Vascular dementia is a progressive cognitive decline resulting from cerebrovascular disease, including strokes or chronic small vessel ischemia, that impairs memory, reasoning, and executive function.

Exam domain	One-glance essentials
Definition / diagnosis	Vascular cognitive impairment/dementia is acquired cognitive decline caused predominantly by cerebrovascular disease *Probable VCID requires clinical evidence of vascular causation plus supportive neuroimaging* ^[1]
Epidemiology / risks	Hypertension is the most important modifiable risk factor; also diabetes, dyslipidaemia, smoking, AF and prior stroke ^[2] CADASIL: NOTCH3 mutation, migraine with aura, young strokes and anterior-temporal white-matter disease
Core mechanism	Large/strategic infarcts, cumulative lacunes, haemorrhage or chronic small-vessel ischaemia disrupt cognitive networks ^[1] Frontal-subcortical disconnection → executive dysfunction, slowed processing and retrieval failure Mixed vascular + Alzheimer pathology is common and lowers the injury threshold
Clinical picture	Classic multi-infarct pattern: abrupt/stepwise decline with plateaus; subcortical disease may be insidious ^[1] Executive/attention deficits exceed memory storage loss; recall often improves with cues Focal signs, pseudobulbar palsy, early gait disorder, emotional lability and urinary urgency support VaD
Investigations	MoCA is preferred for executive/attention deficits; exclude delirium and reversible causes *MRI preferred: infarcts, ≥2 lacunes, strategic lesion or confluent WMH (Fazekas 2–3)* ^[1] Identify mechanism with ECG/Holter, echocardiography and carotid/CTA/MRA as indicated
Management	Prevent the next vascular event: lifestyle, BP/diabetes/lipid control, smoking cessation and exercise ^[2] Antiplatelet for non-cardioembolic ischaemic stroke; anticoagulate AF when appropriate Cognitive drugs have limited benefit in pure VaD; consider mainly when mixed AD pathology is likely ^[2]
Complications	Recurrent stroke drives stepwise deterioration IHD, heart failure, aspiration from pseudobulbar dysphagia, falls, delirium and immobility complications About 50% of deaths are attributed to IHD in the cited senior notes ^[3]
Prevention / follow-up	VaD is highly preventable: aggressive vascular risk-factor control and secondary stroke prevention Physiotherapy, falls prevention, swallow assessment and continence care reduce avoidable complications Review driving, medication adherence and advance care planning while insight is preserved
Exam traps	Stepwise decline is classic but not mandatory: subcortical VaD can progress gradually ^[1] Vascular lesions alone do not prove causation; correlate burden/location with the syndrome Acute fluctuation = delirium, and gait + incontinence + ventriculomegaly may be treatable NPH Antiplatelets are not routine cognitive therapy and may be harmful in haemorrhagic disease

References

^[1] Lecture slides: GC 241. Reference (2) - New vascular neurocognitive disorder criteria JAMA.pdf ^[2] Senior notes: Ryan Ho Neurology.pdf (Section 5.4.2 Vascular Dementia, p. 132) ^[3] Senior notes: Ryan Ho Psychiatry.pdf (Section 4.2.3 Vascular Dementia, pp. 92–93)

Vascular Dementia (VaD) — Definition, Epidemiology, Risk Factors, Anatomy, Etiology, Pathophysiology, Classification, and Clinical Features

Vascular dementia (VaD) — or more accurately, Vascular Cognitive Impairment and Dementia (VCID) — refers to a syndrome of acquired cognitive decline sufficient to impair daily functioning, caused by cerebrovascular disease (CeVD) of any type. The name tells you the condition: "vascular" = blood vessels, "dementia" = loss of mind (Latin: de- = away, mens = mind).

"Dementia arising from multiple infarcts and chronic ischaemia" ^[1]^[2]

The modern terminology has evolved from the older "multi-infarct dementia" to the broader concept of VCID, which captures the full spectrum from mild vascular cognitive impairment (VCI) through to frank vascular dementia. This is important because vascular pathology can cause cognitive problems well before a patient meets dementia criteria.

Key Terminology Shift (VasCog-2-WSO 2025)

The 2025 VasCog-2-WSO consensus criteria formally use "Vascular Cognitive Impairment and Dementia (VCID)" to encompass both vascular MCI and vascular dementia, and encourage identifying multiple co-existing pathologies (e.g., mixed VaD + AD) rather than forcing a single diagnosis. ^[3]

Formal diagnostic framework (VasCog-2-WSO / DSM-5 alignment):

Mild Cognitive Impairment (MCI): Acquired decline in ≥1 cognitive domain with preserved functional independence ^[3]
Dementia (Major Neurocognitive Disorder): Acquired decline in ≥1 cognitive domain that is severe enough to interfere with independence in everyday activities ^[3]
When the predominant etiology is cerebrovascular → Vascular MCI or Vascular Dementia

2. Epidemiology

VaD accounts for approximately 15–17% of all dementias — the second most common cause of dementia after Alzheimer's disease (AD) ^[1]^[2]^[4]
Onset typically in late 60s–70s ^[2]
Prevalence increases sharply with age, roughly doubling every 5 years after age 65 (similar to AD but with a slightly older age distribution)
In Hong Kong, the proportion of vascular dementia is reported to be slightly higher than Western populations (~20–30% in some Asian series), likely reflecting the high prevalence of hypertension and stroke in the Chinese population ^[5]
Post-stroke dementia: approximately 20–30% of stroke survivors develop dementia within 3–6 months of their index stroke; recurrent stroke further increases this risk to > 30%

Historically reported as slightly more common in males (reflecting higher stroke incidence in men), although this gap narrows with age as women's stroke risk rises post-menopause
In East Asian populations (including Hong Kong Chinese), intracranial atherosclerosis is more prevalent than extracranial disease, contributing to a relatively higher burden of subcortical small-vessel disease

Mixed dementia (VaD + AD co-pathology) is extremely common — autopsy studies suggest that 30–60% of dementia cases have both vascular and neurodegenerative pathology
The VasCog-2-WSO criteria explicitly encourage identifying multiple pathologies and stating the most clinically salient etiology ^[3]

3. Risk Factors

The risk factors for VaD are essentially the risk factors for cerebrovascular disease — this is intuitive because VaD is the cognitive consequence of vascular brain injury.

Risk factors: vascular RFs, i.e. HTN, stroke, IHD, peripheral vascular disease ^[1]^[2]

Risk Factor	Mechanism
Age	Cumulative vascular damage, increased arterial stiffness, reduced cerebral autoregulatory reserve
Sex (male > female until ~75y)	Hormonal protection in premenopausal women; equalizes post-menopause
Genetic factors	APOE ε4 (increases both AD and vascular risk); CADASIL (NOTCH3 mutation — autosomal dominant); CARASIL (autosomal recessive); COL4A1 mutations
Family history of stroke/dementia	Shared genetic and environmental risk
Ethnicity	East Asians: higher intracranial atherosclerosis; African descent: higher HTN prevalence

Risk Factor	Pathophysiological Link to VaD
Hypertension	Most important modifiable RF. Promotes arteriolosclerosis → small vessel disease → lacunar infarcts + white matter ischaemia; also promotes large vessel atherosclerosis
Diabetes mellitus	Accelerates atherosclerosis; promotes microvascular disease; hyperglycaemia is directly neurotoxic during ischaemia
Hyperlipidaemia	Drives atherosclerotic plaque formation in extra- and intracranial arteries
Smoking	Endothelial dysfunction, prothrombotic state, accelerates atherosclerosis
Atrial fibrillation	Cardioembolic stroke — one of the most potent risk factors for post-stroke VaD
Prior stroke/TIA	Direct evidence of established cerebrovascular disease; each stroke event compounds cognitive damage
Heart failure / IHD	Reduced cardiac output → chronic cerebral hypoperfusion; embolic risk
Peripheral vascular disease	Marker of systemic atherosclerotic burden
Obesity and physical inactivity	Synergistic with above risk factors; direct pro-inflammatory effects
Excessive alcohol	Hypertension, cardiomyopathy, direct neurotoxicity
Obstructive sleep apnoea	Nocturnal hypoxia, BP surges → endothelial damage and white matter ischaemia

High Yield — Prevention = Treatment

Unlike AD where disease-modifying therapies remain limited, VaD is the most preventable form of dementia because its risk factors are largely modifiable. Aggressive cardiovascular risk factor management is the cornerstone of both prevention and management.

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) ^[2]^[3]:

Gene: NOTCH3 mutation (chromosome 19)
Pathology: Progressive vasculopathy of small cerebral vessels with granular osmiophilic material (GOM) deposits in vessel walls
Clinical features: Recurrent subcortical lacunar strokes (onset typically 30s–50s), migraine with aura, progressive subcortical dementia, psychiatric disturbance, pseudobulbar palsy
MRI: Confluent white matter hyperintensities (especially anterior temporal poles — a distinguishing feature), lacunar infarcts, microbleeds
Significance: Serves as a model of pure vascular cognitive impairment without Alzheimer co-pathology ^[3]

4. Relevant Anatomy and Cerebrovascular Supply

Understanding VaD requires understanding the vascular anatomy of the brain — because which vessels are affected determines which cognitive domains are impaired.

Key anatomical points relevant to VaD:

Structure	Supply Territory	Cognitive Consequence of Infarction
ACA	Medial frontal and parietal cortex, corpus callosum	Executive dysfunction, abulia, apathy, alien hand syndrome
MCA	Lateral frontal, temporal, parietal cortex; basal ganglia (lenticulostriate arteries)	Aphasia (dominant hemisphere), neglect (non-dominant), hemiparesis
PCA	Occipital lobe, medial temporal lobe, thalamus (thalamoperforating arteries)	Visual field defects, anterograde amnesia (hippocampal), thalamic dementia
Lenticulostriate arteries (from MCA)	Basal ganglia, internal capsule	Subcortical dementia, motor deficits
Thalamoperforating arteries (from PCA/basilar tip)	Thalamus	A single strategic thalamic infarct may be sufficient for vascular dementia ^[3]
Pontine perforators (from basilar)	Pons	Pseudobulbar palsy, gait disturbance
Periventricular white matter (long penetrating arteries)	Deep white matter connecting cortical regions	Disconnection syndromes, slowed processing, executive dysfunction

Not all brain regions are equal in their contribution to cognition. Certain structures are so critical that even a single small infarct in the right location can produce dementia:

Thalamus (especially bilateral mediodorsal or anterior nuclei) — "relay station" connecting hippocampus to frontal cortex
Angular gyrus (dominant hemisphere) — integration hub for language, spatial processing
Medial temporal lobe / hippocampus — memory consolidation
Caudate nucleus — part of frontostriatal circuits mediating executive function
Anterior cingulate — attention and motivation
Basal forebrain — cholinergic projection neurons (analogous to AD cholinergic deficit)

"Multiple infarcts or a single extensive or strategically placed infarct, for example in the thalamus, may be sufficient for vascular dementia" ^[3]

The deep periventricular white matter is supplied by long penetrating arterioles that are end-arteries (no collateral supply). This makes them uniquely vulnerable to:

Hypertensive arteriolar damage (lipohyalinosis, fibrinoid necrosis)
Chronic hypoperfusion from arterial stiffness and reduced cardiac output

The consequence is chronic subcortical ischaemia — progressive demyelination and axonal loss in the white matter, visible as white matter hyperintensities (WMH) on MRI FLAIR sequences.

5. Etiology and Pathophysiology

5.1 Mechanisms of Vascular Cognitive Impairment

VaD can result from the following mechanisms ^[1]^[2]:

Usually cortical but may also be subcortical ^[1]^[2]
Result from atherothrombosis or cardioembolism affecting major cerebral arteries
Pathophysiology: Acute occlusion → ischaemic necrosis of cortical/subcortical tissue → loss of neurons and connections → cognitive deficit corresponding to the territory affected
A single large stroke (e.g., dominant MCA territory) or multiple strokes can each cause dementia
Temporal relationship: Cognitive decline is temporally related to the stroke event(s) — "onset is abrupt and cognitive deficits persist beyond 3 months after the stroke" ^[3]

Exclusively subcortical (basal ganglia, thalamus, internal capsule, cerebellum, brainstem) ^[1]^[2]
Result from lipohyalinosis of small penetrating arteries (most commonly from chronic hypertension)
Pathophysiology: Thickening and hyaline degeneration of arteriolar walls → luminal narrowing → occlusion → small deep infarcts (lacunes, typically < 15mm)
Individually, each lacune may be clinically silent or cause only minor deficits — but cumulative lacunar burden produces progressive cognitive decline
"Multiple lacunes (≥ 2) outside the brainstem; 1 lacune may be sufficient if strategically placed or in combination with extensive white matter hyperintensities" ^[3]

Affects periventricular white matter but without discrete episodes of stroke ^[2]
Pathophysiology: Chronic hypoperfusion of deep white matter supplied by end-arterioles → progressive demyelination and gliosis → disruption of cortical–subcortical connections
Results in the classic subcortical dementia picture: psychomotor slowing, executive dysfunction, gait disturbance
On MRI: extensive confluent white matter hyperintensities (Fazekas score 2–3)
"White matter hyperintensities, particularly if they are extensive and confluent (Fazekas score of 2 or 3)" ^[3]

Intracerebral haemorrhage (ICH): Hypertensive ICH (especially deep/basal ganglia) or lobar ICH (often from cerebral amyloid angiopathy)
"Intracerebral hemorrhage; one may be sufficient if large and/or in a lobar location or otherwise strategically placed, or two or more intracerebral hemorrhages" ^[3]
Cerebral amyloid angiopathy (CAA): Amyloid-β deposition in vessel walls → recurrent lobar microbleeds and haemorrhages → cumulative cortical damage
Cerebral microbleeds and cortical superficial siderosis are supportive neuroimaging features ^[3]

CADASIL: AD (autosomal dominant) form with mutated NOTCH3, associated with vasculopathic changes in small cerebral vessels ^[2]
Other rare forms: CARASIL, HERNS, PADMAL, RVCL, COL4A1-related disorders ^[3]

Global cerebral hypoperfusion (cardiac arrest, severe heart failure, severe hypotension) → watershed zone infarcts between major arterial territories
Pathophysiology: Border zones (e.g., ACA-MCA junction, MCA-PCA junction) have the most tenuous blood supply → most vulnerable during systemic hypoperfusion
Can contribute to or unmask vascular cognitive impairment, especially in patients with pre-existing cerebrovascular disease

The common final pathway in VaD is disruption of neural circuits essential for cognition, particularly:

Frontal-subcortical circuits (most commonly affected in VaD):
- Prefrontal cortex → caudate → globus pallidus → thalamus → back to prefrontal cortex
- Mediates executive function, motivation, personality
- Disrupted by subcortical lacunes, white matter ischaemia, or thalamic infarcts
- This explains why executive dysfunction and psychomotor slowing are the hallmark cognitive deficits in VaD (rather than the memory impairment that predominates in AD)
Cholinergic pathways:
- Basal forebrain cholinergic neurons (nucleus basalis of Meynert) project widely to cortex
- Ischaemic damage to these neurons or their white matter projections → cholinergic deficit
- This provides the rationale for cholinesterase inhibitor use in VaD (though evidence is limited)
Cortical–cortical connections:
- White matter tracts connecting cortical association areas
- Disrupted by diffuse white matter ischaemia → "disconnection syndrome"

Why Does VaD Affect Executive Function More Than Memory?

In AD, the hippocampus is the primary target → impaired memory consolidation. In VaD, the primary targets are subcortical structures and their white matter connections to the frontal lobes → impaired executive function, processing speed, and attention. Memory in VaD, where present, typically involves inefficient encoding and/or retrieval (vs consolidation and storage in Alzheimer disease) — meaning patients with VaD can often retrieve memories with prompting/cues, whereas AD patients cannot because the memory was never properly consolidated. ^[3]

Not everyone with the same vascular burden develops VaD. This is because:

Cognitive reserve (education, occupational complexity, mental stimulation) provides a buffer
There is a threshold effect — a certain volume of infarcted or ischaemic tissue must be reached before clinical dementia manifests
The location of damage matters as much as the volume (strategic infarcts)
Co-existing Alzheimer pathology lowers the threshold — less vascular damage is needed to produce clinical dementia if AD pathology is also present (this is why mixed dementia is so common)

6. Classification

Subtype	Mechanism	Typical Imaging	Clinical Pattern
Post-stroke dementia	Large cortical infarct(s)	Territorial infarcts on CT/MRI	Abrupt onset, often with clear focal deficits; stepwise decline with further strokes
Multi-infarct dementia	Multiple lacunar infarcts	Multiple lacunes in deep grey/white matter	Stepwise or fluctuating course; subcortical features predominate
Subcortical ischaemic VaD (Binswanger's)	Chronic small vessel disease	Confluent periventricular WMH, lacunes	Insidious onset; slowly progressive; executive/processing speed deficits
Strategic infarct dementia	Single infarct in critical location	Single infarct (thalamus, angular gyrus, caudate, etc.)	Abrupt onset; cognitive profile depends on location
Haemorrhagic VaD	ICH, lobar haemorrhage, CAA	ICH, microbleeds, haemosiderin	Variable depending on location and recurrence
Hypoperfusion dementia	Global or focal hypoperfusion	Watershed infarcts, hippocampal sclerosis	Often after cardiac arrest/severe hypotension; variable
Hereditary (e.g., CADASIL)	Genetic small vessel disease	Anterior temporal WMH, lacunes, microbleeds	Young-onset; migraine, strokes, progressive subcortical dementia ^[2]^[3]

Subtypes of VCID: Hemorrhagic, ischemic, or mixed hemorrhagic-ischemic ^[3]

Level of Certainty:

Probable VCID: Clinical criteria supported by neuroimaging OR both clinical and genetic evidence of cerebrovascular disease ^[3]
Possible VCID: Clinical criteria met but neuroimaging and/or genetic evidence is not available ^[3]

Multiple or Mixed Causation:

VCID with 1 or more concomitant neurodegenerative disease(s) (e.g., AD, DLB) ^[3]
VCID with additional non-neurodegenerative pathology (e.g., traumatic brain injury) ^[3]
VCID with contribution from depression ^[3]

Preclinical/At-Risk VCID:

Significant incidental neuroimaging evidence of CeVD meeting VCID neuroimaging criteria, WITHOUT satisfying criteria for cognitive impairment ^[3]

Cortical syndrome vs Subcortical syndrome ^[1]

Feature	Cortical VaD	Subcortical VaD
Mechanism	Large vessel territorial infarcts	Small vessel disease (lacunes + WMH)
Cognitive profile	Medial frontal: executive dysfunction, abulia, apathy; Left parietal: aphasia, apraxia, agnosia; Right parietal: hemineglect, confusion, visuospatial/constructional apraxia; Medial temporal: anterograde amnesia ^[1]	Personality and mood changes, apathy, depression, emotional incontinence, relatively mild memory deficits ^[1]; Slowed processing speed, impaired attention, executive dysfunction
Neurological signs	Focal cortical signs corresponding to infarct territory	Focal motor signs, early apraxic or Parkinsonian gait, unsteadiness and falls, pseudobulbar palsy ^[1]
Autonomic features	Usually absent	Early urinary frequency or urgency ^[1]
Course	Stepwise (with each stroke event)	More insidious and slowly progressive

Vascular MCI (Mild Cognitive Impairment): Cognitive decline from vascular cause with preserved functional independence
Vascular Dementia: Cognitive decline sufficient to impair independence in everyday activities

Presenile (early onset, < 65y): Consider genetic causes (CADASIL, CARASIL), early-onset hypertensive disease, vasculitis
Senile (late onset, > 65y): Most common; typically from cumulative atherosclerotic and hypertensive small vessel disease ^[4]

7. Clinical Features

The clinical course of VaD differs fundamentally from AD, and this is one of the most important differentiating features:

Feature	Vascular Dementia	Alzheimer's Disease
Onset	Abrupt (post-stroke) or insidious (subcortical SVD) ^[3]	Insidious
Course	Stepwise deterioration (with each vascular event) or fluctuating course; subcortical SVD may be slowly progressive ^[1]^[3]	Gradually progressive
Insight	Usually preserved insight into illness (at least initially) ^[4]	Lost early
Personality	More personality changes and labile mood cf AD ^[4]	Personality preserved until later stages

High Yield — Stepwise vs Gradual Decline

The stepwise deterioration pattern (periods of relative stability punctuated by sudden worsening with each new vascular event) is the classic course of multi-infarct VaD. However, subcortical ischaemic VaD may present with a gradual onset and slowly progressive course, mimicking AD. The GC lecture reference emphasizes that both patterns exist and that subcortical VaD can have "gradual onset and slowly progressive course, typically predominant in some combination of attention and processing speed, and/or executive functioning." ^[3]

7.2 Symptoms (with Pathophysiological Basis)

Symptom	Pathophysiological Basis	Details
Executive dysfunction	Disruption of frontal-subcortical circuits by subcortical infarcts/WMH	Hallmark of VaD. Difficulty with planning, sequencing, set-shifting, problem-solving, multitasking. Tested by: clock drawing, Trail Making B, verbal fluency
Impaired attention and processing speed	White matter disconnection slows signal transmission between cortical regions	Distractibility, slowness of thought, difficulty sustaining attention. Often the earliest deficit in subcortical VaD
Memory impairment	Usually secondary to retrieval inefficiency (not hippocampal storage failure as in AD)	"Memory impairment, where present, typically involves inefficient encoding and/or retrieval (vs consolidation and storage in AD)" ^[3]. Patients benefit from cueing/prompting — this distinguishes VaD from AD
Aphasia	Left MCA territory or dominant parietal cortical infarct	In cortical VaD; fluent or non-fluent depending on infarct location
Visuospatial dysfunction	Right parietal cortical infarct or diffuse subcortical damage	Difficulty with spatial orientation, constructional tasks
Apraxia	Cortical infarct (dominant parietal) or frontal-subcortical disconnection	Inability to perform learned motor tasks despite intact motor function

Symptom	Pathophysiological Basis
Apathy	Disruption of anterior cingulate–frontal circuits; most common neuropsychiatric feature in subcortical VaD. Patients appear unmotivated, disengaged — often mistaken for depression
Depressive symptoms	Ischaemic damage to frontostriatal mood-regulating circuits; also a reactive phenomenon to disability. "Personality and mood changes, particularly apathy, depressive symptoms and emotional lability... are common in vascular cognitive impairment and dementia" ^[3]
Emotional lability / Pseudobulbar affect	Bilateral corticobulbar (upper motor neuron) pathway damage → loss of cortical inhibition of brainstem emotional centres → involuntary laughing or crying disproportionate to the underlying emotional state
Psychomotor retardation	Global subcortical–frontal slowing from white matter disease
Personality changes	Frontal lobe circuit disruption; may include disinhibition, irritability, aggression
Psychotic symptoms (delusions, hallucinations)	Less common than in DLB; when present, usually referential/persecutory

Apathy ≠ Depression

A common exam mistake: apathy and depression are distinct entities. Apathy is loss of motivation without sadness; depression is low mood with sadness, guilt, and often preserved motivation but inability to act. Both are common in VaD, and they can co-exist, but they require different management.

Symptom	Pathophysiological Basis
Gait disturbance (apraxic/Parkinsonian gait)	Subcortical white matter and basal ganglia ischaemia disrupts motor programming. "Gait-balance disorders are common in vascular cognitive impairment and dementia" ^[3]. The gait is typically broad-based, magnetic (feet seem stuck to the floor), with small shuffling steps — sometimes called "lower body Parkinsonism" or "marche à petits pas"
Unsteadiness and falls	Combination of gait apraxia, impaired proprioception from white matter lesions, and co-existing peripheral neuropathy (especially in diabetics) ^[1]
Focal motor deficits (hemiparesis)	Residual from prior cortical or subcortical strokes
Pseudobulbar palsy	Bilateral upper motor neuron damage to corticobulbar pathways → "supranuclear weakness of muscles of face, tongue and pharynx, spastic dysarthria, swallowing difficulties" ^[3]
Extrapyramidal features	Basal ganglia ischaemia → Parkinsonian features (rigidity, bradykinesia) without tremor (vascular Parkinsonism)

Symptom	Pathophysiological Basis
Early urinary frequency or urgency	Disruption of pontine micturition centre connections or frontal lobe inhibitory control over the bladder ^[1]. This is an early feature distinguishing subcortical VaD from AD, where incontinence occurs late

7.3 Signs (with Pathophysiological Basis)

On examination, look for evidence of cerebrovascular disease, cardiovascular disease, and neurological deficits:

Sign	Significance / Pathophysiology
Hemiparesis, lower facial weakness	Residual corticospinal tract damage from prior stroke ^[3]
Babinski sign (upgoing plantar)	Upper motor neuron damage
Pronator drift	Subtle contralateral corticospinal tract lesion
Sensory deficit (hemisensory)	Thalamic or cortical sensory infarct
Visual field defect (homonymous hemianopia)	PCA territory or optic radiation infarct
Pseudobulbar palsy	Brisk jaw jerk, spastic tongue, spastic dysarthria, dysphagia, emotional incontinence — from bilateral UMN corticobulbar damage ^[3]
Cerebellar signs	Limb ataxia from posterior circulation infarcts ^[3]
Parkinsonian gait	Broad-based, magnetic, shuffling — vascular Parkinsonism from subcortical damage ^[1]
Primitive reflexes (grasp, palmomental, snout)	Frontal lobe or diffuse cortical dysfunction — non-specific but supports advanced disease

Sign	Why You Look For It
Hypertension	Most important modifiable risk factor; check BP in both arms
Atrial fibrillation (irregularly irregular pulse)	Major source of cardioembolism
Carotid bruits	Suggests extracranial carotid stenosis; though note bruits correlate poorly with degree of stenosis
Signs of heart failure	Reduced cardiac output → chronic cerebral hypoperfusion
Peripheral vascular disease (absent foot pulses, ulcers)	Marker of systemic atherosclerosis

Domain	Expected Findings in VaD	Test
Attention	Impaired early	Serial 7s, digit span, months backward
Processing speed	Slowed	Trail Making A, timed tasks
Executive function	Disproportionately impaired	Clock drawing, Trail Making B, verbal fluency, Luria sequences, similarities/proverbs
Memory	Relatively preserved or shows retrieval pattern (improves with cues)	Word list recall with recognition testing
Language	May show dysphasia if dominant hemisphere involved	Naming, repetition, comprehension
Visuospatial	May be impaired	Copy intersecting pentagons, cube drawing

The Hachinski Ischaemic Score (HIS) was developed to help distinguish VaD from AD at the bedside ^[1]:

Feature	Score
Abrupt onset	2
Stepwise deterioration	1
Fluctuating course	2
Nocturnal confusion	1
Relative preservation of personality	1
Depression	1
Somatic complaints	1
Emotional incontinence	1
History of hypertension	1
History of strokes	2
Evidence of associated atherosclerosis	1
Focal neurological symptoms	2
Focal neurological signs	2

Score ≥ 7: Suggests vascular dementia
Score ≤ 4: Suggests Alzheimer's disease
Score 5–6: Indeterminate / suggests mixed dementia

Limitations of Hachinski Score

The HIS was designed for multi-infarct VaD and performs less well for subcortical ischaemic VaD (which may lack abrupt onset, strokes, or focal signs). Modern neuroimaging has largely supplanted it, but it remains a useful bedside screening tool and is commonly tested in exams.

Feature	Vascular Dementia	Alzheimer's Disease	Dementia with Lewy Bodies
Onset	Abrupt or insidious (subcortical)	Insidious	Insidious
Course	Stepwise / fluctuating / slowly progressive	Gradually progressive	Fluctuating cognition with marked variation
Prominent early deficit	Executive function, attention, processing speed	Memory (episodic, anterograde)	Visual hallucinations, Parkinsonism, fluctuations
Memory pattern	Retrieval > consolidation (improves with cues)	Consolidation deficit (no improvement with cues)	Variable
Insight	Preserved	Lost early	Variable
Neurological signs	Focal signs, gait disturbance, pseudobulbar palsy	Usually absent until late	Parkinsonism, REM sleep behaviour disorder
Mood/behaviour	Apathy, depression, emotional lability early	Behavioural changes later	Visual hallucinations, paranoia
Neuroimaging	Infarcts, WMH, lacunes	Hippocampal/medial temporal atrophy	Relatively preserved hippocampi; DaT scan abnormal
Cerebral perfusion SPECT	Patchy, asymmetric hypoperfusion ^[6]	Bilateral posterior temporal + parietal hypoperfusion ^[6]	Occipital hypoperfusion

Different types of dementia typically present with different patterns of perfusion changes — e.g., bilateral posterior temporal and parietal in AD; bilateral frontal and temporal in FTD ^[6]

9. Important Concepts and Supplementary Points

Modern understanding recognizes that vascular pathology exists on a spectrum from risk factor to cause. Many patients have vascular brain lesions that contribute to but may not fully cause their dementia — especially when Alzheimer pathology coexists. The VasCog-2-WSO criteria address this by encouraging clinicians to identify and weight multiple co-existing pathologies.

Post-stroke dementia is a pragmatic clinical term for dementia that develops after a clinically evident stroke. Important points:

Not all post-stroke dementia is "vascular" — the stroke may unmask pre-existing subclinical AD
The 3-month window is used: "cognitive deficits persist beyond 3 months after the stroke" ^[3]
Delirium in the acute post-stroke period must resolve before VaD can be diagnosed

The Fazekas scale grades white matter hyperintensities on MRI FLAIR:

Grade 0: Absent
Grade 1: Punctate foci
Grade 2: Beginning confluence
Grade 3: Large confluent areas

"Extensive and confluent may correspond to a Fazekas score of 2 or 3; or by region: periventricular Fazekas = 3 and/or deep Fazekas = 2 or 3" ^[3]

"Dementia is the leading risk factor for delirium, and 2/3 of delirium occurs in dementia patients" ^[7]. VaD patients are particularly susceptible to delirium because:

They have reduced cognitive reserve
They often have multiple comorbidities (infections, medications, metabolic derangements)
Acute-on-chronic presentations are common — always consider delirium superimposed on dementia when a VaD patient acutely deteriorates

High Yield Summary

Key Points for Exam:

VaD is the second most common cause of dementia (~15–17%), caused by cerebrovascular disease
Risk factors = cardiovascular risk factors (HTN is the most important modifiable RF)
Three main mechanisms: (a) large artery infarcts, (b) small artery lacunar infarcts, (c) chronic subcortical ischaemia — plus hemorrhagic, strategic infarct, and genetic forms
Clinical hallmarks that distinguish VaD from AD:
- Stepwise deterioration (or insidious if subcortical SVD)
- Executive dysfunction > memory impairment
- Preserved insight
- Focal neurological signs, gait disturbance, pseudobulbar palsy
- Emotional lability, apathy, depression
- Early urinary symptoms
Memory in VaD = retrieval deficit (improves with cues) vs AD = consolidation deficit (does not improve with cues)
Neuroimaging is essential: infarcts, lacunes, WMH (Fazekas ≥ 2-3)
VasCog-2-WSO 2025 criteria: require (A) clinical evidence + (B) neuroimaging evidence of CeVD; classify as probable/possible; encourage identifying mixed pathologies
CADASIL (NOTCH3 mutation) = genetic model of pure VaD
Hachinski score ≥ 7 suggests VaD, ≤ 4 suggests AD
VaD is the most preventable form of dementia — aggressive cardiovascular risk management is key

Active Recall - Vascular Dementia (Definition, Epidemiology, RF, Pathophysiology, Classification, Clinical Features)

^[1] Senior notes: Ryan Ho Neurology.pdf (Section 5.4.2 Vascular Dementia, p.132) ^[2] Senior notes: Ryan Ho Psychiatry.pdf (Section 4.2.3 Vascular Dementia, p.92) ^[3] Lecture slides: GC 241. Reference (2) - New vascular neurocognitive disorder criteria JAMA.pdf (VasCog-2-WSO 2025 consensus criteria, Boxes 1-3) ^[4] Senior notes: Ryan Ho Psychiatry.pdf (Dementia classification table, p.81) ^[5] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Stroke section, p.1210) ^[6] Senior notes: Ryan Ho Diagnostic Radiology.pdf (Cerebral perfusion study, p.69) ^[7] Senior notes: Ryan Ho Fundamentals.pdf (Delirium section, p.325)

Differential Diagnosis of Vascular Dementia

When a patient presents with cognitive decline and you suspect vascular dementia, the real clinical question is: "Is this truly VaD, or could this be something else — or something in addition?" The differential diagnosis of VaD is essentially the differential of any dementia syndrome, but you must also think about non-dementia mimics (especially delirium and depression, which are reversible).

Think of it in two tiers:

Other causes of dementia (neurodegenerative and non-neurodegenerative)
Non-dementia mimics of cognitive decline (delirium, depression, amnestic syndromes, focal lesions)

1. Other Causes of Dementia — The "Big Five" + Others

AD accounts for ~50–70% of all dementia ^[8]. This is far and away the most common alternative diagnosis, and distinguishing it from VaD is one of the most frequently tested clinical skills.

Feature	Vascular Dementia	Alzheimer's Disease
Onset	Abrupt (post-stroke) or insidious (subcortical SVD) ^[3]	Insidious onset with slow deterioration ^[8]
Course	Stepwise deterioration with periods of improvement ^[1]^[2]	Steadily progressive, gradual decline without extended plateaus ^[8]
Prominent early deficit	Executive function, attention, processing speed ^[2]	Memory impairment most prominent in early stages, typically anterograde, recent, episodic ^[9]
Memory pattern	Inefficient encoding and/or retrieval (improves with cues) ^[3]	Impaired consolidation and storage (does NOT improve with cues) ^[3]
Insight	Usually preserved ^[4]	Lost early
Neurological signs	Focal motor signs, gait disturbance, pseudobulbar palsy ^[1]	Absence of neurological signs of focal damage occurring early in the illness ^[8]
Mood/behaviour	Apathy, depression, emotional lability early ^[2]	Behavioural changes in later stages
Neuroimaging	Infarcts, lacunes, WMH (Fazekas ≥ 2–3) ^[3]	Unilateral or bilateral perihippocampal atrophy (early), generalized atrophy (late) ^[9]
Perfusion SPECT	Patchy, asymmetric hypoperfusion ^[6]	Bilateral posterior temporal + parietal hypoperfusion ^[6]

Why is distinguishing them so important? Because in practice, pure VaD and pure AD often coexist — mixed dementia is the most common neuropathological finding in elderly patients with dementia. The VasCog-2-WSO criteria explicitly state: "VCID with 1 or more concomitant neurodegenerative disease(s) (e.g., Alzheimer disease, dementia with Lewy bodies)" and encourage clinicians to "state which etiology is clinically more salient" ^[3].

VasCog-2-WSO: Features Suggesting AD as Alternative or Co-Existing Etiology

"Insidious early onset of cognitive, perceptual and motor symptoms suggestive of AD in the absence of corresponding focal vascular lesions (infarct or small vessel disease) on brain imaging or history of vascular events" ^[3]. Supportive biomarkers include: CSF or plasma Aβ42:40 ratio, p-tau181, p-tau217; PET amyloid imaging; autosomal mutation associated with AD; or being homozygous for APOE ε4 ^[3].

The Hachinski Ischaemic Score helps at the bedside: ≥ 7 suggests multi-infarct VaD; ≤ 4 suggests AD; 5–6 suggests mixed dementia ^[2]. However, as discussed previously, it was designed for multi-infarct disease and performs less well for subcortical ischaemic VaD.

DLB accounts for ~5–10% of dementias. It is an α-synucleinopathy characterised by Lewy body inclusions in cortical and subcortical neurons.

Feature	How to Distinguish from VaD
Core features	Fluctuating cognition with pronounced variation in attention and alertness; recurrent well-formed visual hallucinations (VH); REM sleep behaviour disorder (RBD); spontaneous Parkinsonism
Cognitive profile	Prominent visuospatial and attentional deficits; memory may be relatively preserved early (similar to VaD in this respect)
Movement disorder	Spontaneous Parkinsonism with symmetrical onset — differs from vascular Parkinsonism which is typically "lower body" predominant
Neuroimaging	Relatively preserved hippocampi (vs AD); no significant vascular lesion burden; abnormal dopamine transporter (DaT) scan
Key differentiator	"Early and prominent movement disorder suggestive of dementia with Lewy bodies or other α-synucleinopathy" should raise concern that VaD is not the primary pathology ^[3]

The VasCog-2-WSO criteria list "the presence of biomarkers of dementia with Lewy bodies, including dopamine transporter imaging and α-synuclein seed amplification assay in cerebrospinal fluid" as features that may suggest an alternative etiology ^[3].

DLB vs VaD — A Common Exam Trap

Both DLB and VaD can have cognitive fluctuations and Parkinsonism. The key distinguishing features are: (1) in DLB, visual hallucinations are early, recurrent, and well-formed; in VaD, psychosis is less common and less vivid. (2) DLB Parkinsonism affects upper and lower body symmetrically; vascular Parkinsonism predominantly affects gait ("lower body Parkinsonism") with relative sparing of upper limbs.

FTD accounts for ~5–10% of dementias overall but is the second most common cause of presenile (< 65y) dementia. It encompasses behavioural variant FTD (bvFTD) and primary progressive aphasias.

Feature	How to Distinguish from VaD
Age of onset	Typically younger (45–65y) vs VaD (late 60s–70s)
Prominent early features	Behavioural changes, disinhibition, antisocial behaviour, irresponsibility (bvFTD) or progressive language deficits (PPA) ^[4]
Memory	Relatively preserved in early stages
Neuroimaging	Frontal and/or anterior temporal atrophy (often asymmetric); SPECT shows bilateral frontal + temporal hypoperfusion ^[6]
Cerebrovascular disease	Absent or minimal cerebrovascular lesions on CT or MRI ^[3]

Key principle: FTD presents with personality/behavioural changes first (anterior dementia), while VaD subcortical type presents with apathy and psychomotor slowing first — both can appear as "frontal" syndromes, but the underlying neuroimaging is completely different.

PDD is diagnosed when dementia develops > 1 year after established motor Parkinson's disease (the "1-year rule" distinguishes PDD from DLB) ^[4]^[10]
Similar to DLB in clinical features (Lewy body spectrum) ^[4]
Unlike VaD, motor features precede cognitive decline by years, and the Parkinsonism is levodopa-responsive (vascular Parkinsonism is typically poorly levodopa-responsive)

This is a critically important differential because it is potentially reversible.

Feature	NPH	VaD (Subcortical Type)
Classic triad	Frontal dementia, apraxic gait ("magnetic"), urinary incontinence ^[4] — "wet, wacky, and wobbly"	Also has gait disturbance + urinary symptoms + executive dysfunction
Neuroimaging	ALL ventricles enlarged disproportionate to sulcal effacement; periventricular lucency especially on FLAIR ^[4]	Lacunes, WMH; ventricles may enlarge but proportionate to sulcal widening (ex vacuo dilatation)
Key test	CSF tap test (large volume LP): transient improvement in gait = positive	No improvement with LP
Age	Commonest in 50–70y ^[4]	Late 60s–70s

Why this matters: The overlap between subcortical VaD and NPH is enormous — both have gait apraxia, incontinence, and frontal-executive dysfunction. The imaging distinction (disproportionately large ventricles with tight sulci in NPH vs proportionate atrophy in VaD) and the CSF tap test are critical.

High Yield — NPH vs Subcortical VaD

If you see the triad of gait disturbance + dementia + incontinence with ventriculomegaly out of proportion to sulcal widening on imaging, think NPH first — it is treatable with VP shunt. Do not mistake it for VaD. Conversely, extensive white matter hyperintensities and lacunes with proportionate ventriculomegaly point towards VaD.

Feature	CJD	VaD
Speed of decline	Rapidly progressive dementia (in months) ^[4]	Stepwise or slowly progressive (years)
Neurological features	Myoclonic jerks, seizures, cerebellar ataxia ^[4]	Focal signs related to strokes
MRI	Cortical ribboning on DWI/FLAIR ^[4]	Infarcts, lacunes, WMH
CSF	14-3-3 protein positive; RT-QuIC assay positive	Normal (unless recent stroke)
Age	Variable; variant CJD: young onset with early psychiatric symptoms ^[4]	Late 60s–70s

CJD should be suspected whenever dementia progresses rapidly — over weeks to months rather than months to years. VaD can occasionally have a stuttering rapid course (e.g., recurrent strokes in quick succession), but CJD's myoclonus and cortical ribboning on DWI are distinctive.

2. Non-Dementia Mimics — "Reversible" Causes of Cognitive Decline

These are arguably more important clinically than distinguishing between types of dementia, because they are treatable.

"Commonly confused with delirium" ^[11]. This is the first diagnosis to rule out in any patient presenting with cognitive change.

Feature	Delirium	Dementia (including VaD)
Onset	Acute (hours to days) ^[11]^[12]	Insidious or stepwise (weeks–years)
Course	Fluctuating with diurnal variation (worse at night) ^[12]	Relatively stable day-to-day (though DLB and VaD can fluctuate)
Consciousness	Impaired/clouded	Typically clear (until very late stages)
Attention	Characteristically impaired — hallmark ^[12]	Impaired in VaD but not the defining feature
Hallucinations	Common, especially visual hallucinations ^[12]	VH prominent in DLB; less common in VaD/AD
Precipitant	Usually precipitated by acute medical illness, new drug, infection, metabolic derangement ^[11]	No acute precipitant
Reversibility	Reversible when precipitant treated	Progressive

"Acute onset and fluctuating course of symptoms" is the hallmark of delirium that distinguishes it from dementia exacerbation ^[12].

Delirium Superimposed on Dementia

"Dementia is the leading risk factor for delirium, and 2/3 of delirium occurs in dementia patients" ^[7]. A VaD patient who suddenly deteriorates is delirium-until-proven-otherwise. Always search for and treat the precipitant (UTI, pneumonia, constipation, new medication, metabolic derangement, pain) before attributing the deterioration to progression of VaD.

Depression is the most important mimic ('pseudodementia'), accounts for ~10% of presumed dementia ^[11].

Feature	Depression	VaD
Onset	More well-defined, more rapid decline ^[11]	Variable
Self-report	Tends to complain/worry of poor memory more ^[11]	VaD patients may have preserved insight but less anxious about it
Testing behaviour	Tends to give less effort; "don't know" answers ^[11]	VaD patients try hard but give incorrect answers
Cognition	Poor concentration and attention; language and motor skills slow but not impaired ^[11]	True cognitive deficits (aphasia, apraxia, etc.)
Mood features	Morning dysphoria, anhedonia, guilt, suicidal ideation, psychomotor retardation	Apathy (distinct from sadness), emotional lability

Why this is particularly tricky in VaD: Depressive symptoms are very common in VaD itself — "apathy, depressive symptoms and emotional lability... are common in vascular cognitive impairment and dementia" ^[3]. The VasCog-2-WSO criteria removed major depression as an exclusion criterion for VCID because "there is considerable overlap between depression and VCID symptoms in later life" ^[3]. In practice, if depression is suspected, a trial of antidepressant treatment may be warranted before concluding on a diagnosis of dementia ^[11].

These must be systematically excluded in every patient presenting with cognitive decline. Think of the mnemonic DEMENTIA:

Letter	Cause	How to Exclude
D	Drugs (anticholinergics, sedatives, polypharmacy)	Medication review
E	Emotional (depression — see above)	Psychiatric assessment
M	Metabolic (hypothyroidism, B12/folate deficiency, hypercalcaemia, hepatic/renal encephalopathy, Addison's, Cushing's)	TFT, B12, folate, Ca, RFT, LFT, cortisol
E	Eyes and Ears (sensory deprivation mimicking cognitive decline)	Visual and hearing assessment
N	Normal pressure hydrocephalus	CT/MRI brain (see above)
T	Tumour / Trauma (brain tumour, chronic subdural haematoma)	CT/MRI brain
I	Infection (neurosyphilis, HIV-associated neurocognitive disorder, chronic meningitis)	VDRL/RPR, HIV test, CSF if indicated
A	Alcohol / Autoimmune (Wernicke-Korsakoff, autoimmune encephalitis)	History, thiamine levels, autoimmune antibodies

Minimum investigations for any new dementia (per NICE guidelines): CBC, serum B12 and folate, TFT, RFT, calcium, glucose, CT/MRI brain ^[11]

"By definition, associated with severe disruption of memory with minimal involvement of other domains. Confabulation may be prominent, especially in diencephalic amnesias" ^[11].

Wernicke-Korsakoff syndrome: thiamine deficiency (alcoholism, malnutrition) → mammillary body and thalamic damage → anterograde and retrograde amnesia with confabulation, but other cognitive domains relatively preserved
Distinguished from VaD because the deficit is isolated to memory without the broader executive/motor/autonomic features

"Progressive memory deficit, dementia ± depression, mania, psychosis" — occurs ~10–25 years after primary syphilis infection ^[13]. In Hong Kong, while syphilis incidence is lower than in some regions, it should still be considered in any unexplained dementia, especially with psychiatric features or pupillary abnormalities (Argyll-Robertson pupils). Diagnosed by serology and CSF VDRL.

These are less commonly confused with VaD but worth mentioning:

Condition	Key Distinguishing Features from VaD
Multiple system atrophy (MSA)	Prominent autonomic failure + cerebellar/Parkinsonian features; poor or no response to levodopa ^[10]; imaging: putaminal rim (MSA-P), hot cross bun sign (MSA-C)
Progressive supranuclear palsy (PSP)	Supranuclear vertical gaze palsy (initially downward); early falls; hummingbird sign on MRI ^[10]
Corticobasal degeneration (CBD)	Progressive asymmetric movement disorder; alien limb phenomenon; ideomotor apraxia ^[10]
Huntington's disease	Autosomal dominant; CAG repeat expansion on chromosome 4; chorea + psychiatric features + dementia; caudate atrophy ^[14]

Differential	Key Differentiating Feature(s)
Alzheimer's Disease	Insidious onset, gradual progression; memory (consolidation) > executive; no focal signs; hippocampal atrophy
Mixed Dementia (VaD + AD)	Features of both; very common; state which is more salient
Dementia with Lewy Bodies	Visual hallucinations, cognitive fluctuations, Parkinsonism, RBD; DaT scan abnormal
Frontotemporal Dementia	Young onset; personality/behavioural changes first; frontal/temporal atrophy; no vascular lesions
Normal Pressure Hydrocephalus	Gait + dementia + incontinence; disproportionate ventriculomegaly; improves with LP
CJD	Rapidly progressive (months); myoclonus; cortical ribboning on DWI
Delirium	Acute onset, fluctuating consciousness, precipitant identified; REVERSIBLE
Depression (pseudodementia)	"Don't know" answers, excessive worry about memory; REVERSIBLE
Metabolic/toxic	B12/folate deficiency, hypothyroidism, hypercalcaemia, drugs; REVERSIBLE
Structural lesion	Chronic subdural haematoma, brain tumour; CT/MRI diagnostic; POTENTIALLY REVERSIBLE
Neurosyphilis	History, Argyll-Robertson pupils; serology + CSF; TREATABLE

High Yield — The Clinical Approach to the Differential

Rule out delirium first — it is acute, fluctuating, and has a treatable precipitant.
Screen for depression — it mimics dementia and is treatable.
Exclude reversible causes — bloods (B12, TFT, Ca, RFT, glucose), medication review, neuroimaging (SDH, tumour, NPH).
Determine the dementia subtype — using history (onset, course), cognitive profile (executive vs memory), neurological examination (focal signs, Parkinsonism, gait), and neuroimaging (infarcts/WMH vs atrophy vs ventriculomegaly).
Consider mixed pathology — especially VaD + AD, which is the rule rather than the exception in elderly patients.

Active Recall - Differential Diagnosis of Vascular Dementia

References

^[1] Senior notes: Ryan Ho Neurology.pdf (Section 5.4.2 Vascular Dementia, p.132) ^[2] Senior notes: Ryan Ho Psychiatry.pdf (Section 4.2.3 Vascular Dementia, p.93) ^[3] Lecture slides: GC 241. Reference (2) - New vascular neurocognitive disorder criteria JAMA.pdf (VasCog-2-WSO 2025 consensus criteria, Boxes 1–3 and Discussion) ^[4] Senior notes: Ryan Ho Psychiatry.pdf (Dementia classification and aetiology table, p.82) ^[6] Senior notes: Ryan Ho Diagnostic Radiology.pdf (Cerebral perfusion study, p.69) ^[7] Senior notes: Ryan Ho Fundamentals.pdf (Delirium section, p.325) ^[8] Senior notes: Ryan Ho Psychiatry.pdf (AD diagnostic criteria ICD-10/DSM-5, p.92) ^[9] Senior notes: Ryan Ho Neurology.pdf (Alzheimer's Disease clinical features, p.131) ^[10] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Parkinson-plus syndromes, p.1298) ^[11] Senior notes: Ryan Ho Psychiatry.pdf (Dementia differential diagnosis and approach, p.88) ^[12] AOS material: AOS - Geriatrics.pdf (Delirium vs dementia, p.3–4) ^[13] Senior notes: Ryan Ho Urogenital.pdf (Neurosyphilis, p.246) ^[14] Senior notes: learning_points_output.txt (Neurology – Two Cases of Movement Disorders)

Diagnostic Criteria, Diagnostic Algorithm, and Investigations for Vascular Dementia

1. Diagnostic Criteria

Diagnosing vascular dementia requires satisfying two independent requirements simultaneously: (1) the patient has dementia (or MCI), and (2) the predominant cause is cerebrovascular disease. Let's walk through each framework.

1.1 Step 1 — Establish Cognitive Impairment (Dementia or MCI)

Before you can call anything "vascular dementia," you first need to prove there is dementia at all. The criteria below apply to any cause of dementia.

A. Evidence of significant cognitive decline from a previous level of performance in ≥ 1 cognitive domains (out of 6) based on: (1) clinical evidence of decline in cognitive function; and (2) impairment in cognitive performance, preferably documented by standardized assessment ^[15]

B. The cognitive deficits interfere with independence in everyday activities (i.e. at a minimum require assistance with complex instrumental ADLs) ^[15]

C. The cognitive deficits do not occur exclusively in the context of a delirium ^[15]

D. The cognitive deficits are not better explained by another mental disorder (e.g. major depressive disorder, schizophrenia) ^[15]

The six cognitive domains in DSM-5 are:

Learning and memory
Language
Executive function
Complex attention
Perceptual–motor function
Social cognition

Primary requirement is evidence of a decline in both memory and thinking which is sufficient to impair personal ADL... Evidence of clear consciousness is required... Above symptoms and impairments should have been evident for at least 6 months ^[15]

DSM-5 vs ICD-10 — Key Difference

DSM-5 requires decline in only ≥ 1 cognitive domain and does not mandate memory impairment — this is important for VaD, where executive dysfunction may be the sole early deficit. ICD-10 requires both memory AND thinking impairment, which may miss early subcortical VaD where memory is relatively preserved.

Mild Cognitive Impairment (Both A and B necessary): ^[3]

A. Acquired decline from a documented or inferred previous level of performance in ≥ 1 cognitive domains as evidenced by:
- 1. Concerns of the person, knowledgeable informant or clinician of mild levels of decline
- 2. Evidence of modest deficits on objective cognitive assessment (typically 1–2 SDs below norms, i.e. 3rd–16th percentile) ^[3]
B. The cognitive deficits are insufficient to interfere with independence in everyday activities ^[3]

Dementia: Same as above but cognitive deficits are sufficient to interfere with independence ^[3].

1.2 Step 2 — Establish Vascular Etiology (VasCog-2-WSO 2025 Criteria)

This is where we prove that the cognitive impairment is caused by cerebrovascular disease. The VasCog-2-WSO criteria (2025) are the most current and are provided as a GC reference — treat them as especially high yield.

Both A and B are required. Features under C suggest multiple contributing etiologies or an alternative etiology. ^[3]

A.1 — Post-stroke cognitive decline:

"The onset of the cognitive deficits is temporally related to ≥ 1 clinical strokes. Onset is abrupt and cognitive deficits persist beyond 3 months after the stroke. Multiple strokes may be associated with a stepwise or fluctuating course." ^[3]

Evidence of stroke can be:

a. Documented history of a stroke, with cognitive decline temporally associated with the event ^[3]
b. Physical signs consistent with stroke — "hemiparesis, lower facial weakness, Babinski sign, pronator drift, sensory deficit, visual field defect, pseudobulbar syndrome — supranuclear weakness of muscles of face, tongue and pharynx, spastic dysarthria, swallowing difficulties — and cerebellar signs e.g. limb ataxia" ^[3]

A.2 — Subcortical ischaemic pathology (no clinical stroke history):

"In the absence of history of a stroke or TIA, evidence for decline from subcortical ischemic pathology may be associated with a picture of gradual onset and slowly progressive course, typically predominant in some combination of attention and processing speed, and/or executive functioning" ^[3]

"Memory impairment, where present, typically involves inefficient encoding and/or retrieval (vs consolidation and storage in AD)" ^[3]

Supportive features: "Personality and mood changes, particularly apathy, depressive symptoms and emotional lability, and gait-balance disorders are common in vascular cognitive impairment and dementia" ^[3]

Neuroimaging Finding	Details / Guidance
1. Multiple infarcts or a single extensive or strategically placed infarct	"For example in the thalamus, may be sufficient for vascular dementia" ^[3]
2. Multiple lacunes (≥ 2) outside the brainstem	"1 lacune may be sufficient if strategically placed or in combination with extensive white matter hyperintensities" ^[3]
3. White matter hyperintensities, particularly if extensive and confluent	"Extensive and confluent may correspond to a Fazekas score of 2 or 3; or by region: periventricular Fazekas = 3 and/or deep Fazekas = 2 or 3" ^[3]
4. Intracerebral hemorrhage	"One may be sufficient if large and/or in a lobar location or otherwise strategically placed, or two or more intracerebral hemorrhages" ^[3]

Supportive features (not sufficient alone):

Cerebral microbleeds and cortical superficial siderosis ^[3]
Abnormalities meeting criteria of cerebral amyloid angiopathy (e.g. Boston criteria version 2.0) ^[3]

Category	Features
Clinical	Insidious early onset suggestive of AD without corresponding vascular lesions; Early prominent movement disorder suggestive of DLB/α-synucleinopathy; Features of another primary neurological disorder (MS, encephalitis, toxic/metabolic) ^[3]
Neuroimaging	Absent or minimal cerebrovascular lesions on CT or MRI ^[3]
Biomarkers for AD	CSF/plasma Aβ42:40 ratio, p-tau181, p-tau217; amyloid PET; autosomal AD mutation; APOE ε4 homozygosity ^[3]
Biomarkers for DLB	Dopamine transporter imaging; α-synuclein seed amplification assay in CSF ^[3]

Probable VCID: (a) Clinical criteria supported by neuroimaging; OR (b) Both clinical and genetic evidence of cerebrovascular disease ^[3]

Possible VCID: Clinical criteria met but neuroimaging and/or genetic evidence is not available ^[3]

VasCog-2-WSO 2025 — What's New vs Previous Criteria?

Key changes from VasCog-1 (2014): (1) Inclusion of preclinical/at-risk VCID category for incidental CeVD on imaging without cognitive impairment. (2) Incorporation of AD and DLB biomarkers to identify mixed pathology. (3) Removal of major depression as an exclusion criterion due to the recognised overlap between depression and VCID. (4) Genetic disorders (e.g. CADASIL) now accepted as sufficient for probable VCID without requiring neuroimaging. (5) Added mixed hemorrhagic-ischemic subtype. ^[3]

The Hachinski score is used for distinguishing VaD from AD at the bedside ^[1]^[2]:

Feature	Score
Abrupt onset	2
Stepwise deterioration	1
Fluctuating course	2
Nocturnal confusion	1
Relative preservation of personality	1
Depression	1
Somatic complaints	1
Emotional incontinence	1
History of hypertension	1
History of strokes	2
Evidence of associated atherosclerosis	1
Focal neurological symptoms	2
Focal neurological signs	2

Interpretation: ≥ 7 = multi-infarct VaD; 5–6 = mixed; ≤ 4 = AD ^[2]

The approach to a patient with suspected vascular dementia follows a logical sequence: Confirm cognitive impairment → Exclude reversible causes and delirium → Determine the dementia subtype → Confirm vascular etiology → Assess for mixed pathology.

3. Investigation Modalities

Investigations in suspected VaD serve three purposes:

Exclude reversible causes of cognitive decline
Confirm the presence and extent of cerebrovascular disease (neuroimaging)
Identify the underlying vascular mechanism (vascular/cardiac imaging) and risk factors

Tool	Details	Key Points
Montreal Cognitive Assessment (MoCA)	30-point test; tests executive function, visuospatial, attention, language, abstraction, memory, orientation	"MoCA more appropriate" for VaD ^[2] because it has greater sensitivity for executive dysfunction and attention deficits (the hallmark deficits of VaD) compared with MMSE
Mini-Mental State Examination (MMSE)	30-point test; heavier on memory and orientation	Less sensitive for subcortical/VaD patterns because it under-tests executive function; more useful for AD screening
Addenbrooke's Cognitive Examination (ACE-III)	100-point test covering all domains; subdomains scored separately	Useful in research; allows domain-specific profiling
Clock Drawing Test	Screens executive function, visuospatial ability, planning	Quick bedside screen; abnormalities highly suggestive of frontal/executive dysfunction
Trail Making Test B	Set-shifting, attention, processing speed	Disproportionately impaired in VaD vs AD
Verbal Fluency	Phonemic and semantic categories	Frontal-executive measure; impaired early in VaD

Why MoCA Over MMSE in VaD?

The MMSE gives heavy weighting to orientation and memory recall, which may be relatively preserved in early subcortical VaD. The MoCA tests executive function (Trail Making, abstraction, verbal fluency), visuospatial skills (cube drawing, clock), and attention (serial subtraction, digit span) — all domains preferentially affected in VaD. A patient can score 26/30 on MMSE while scoring 18/30 on MoCA because the MMSE misses their executive deficits.

"Minimum Ix included in NICE guidelines" ^[11]

Investigation	What You're Looking For	Why
CBC	Anaemia (B12/folate def), infection, haematological malignancy	Severe anaemia → cerebral hypoperfusion; polycythaemia → hyperviscosity and stroke risk
Serum B12 and folate	Deficiency → subacute combined degeneration, cognitive impairment	B12 deficiency causes demyelination; reversible if caught early
TFT	Hypothyroidism	Causes cognitive slowing, apathy — mimics subcortical dementia; fully reversible
RFT (urea, creatinine, eGFR)	Renal impairment / uraemic encephalopathy	Also assesses baseline renal function before contrast imaging
Calcium	Hypercalcaemia	Causes confusion, lethargy — reversible
Glucose / HbA1c	Diabetes mellitus	Both a reversible cause of acute confusion (hypo/hyperglycaemia) and a major vascular risk factor
LFT	Hepatic encephalopathy, alcohol-related damage	Chronic liver disease → hepatic encephalopathy; also marker of alcohol excess
Lipid profile	Dyslipidaemia	Vascular risk factor assessment
ESR / CRP	Vasculitis, infection, systemic inflammation	Cerebral vasculitis can mimic multi-infarct VaD
VDRL / RPR (if indicated)	Neurosyphilis	Treatable cause of dementia
HIV test (if risk factors)	HIV-associated neurocognitive disorder	Treatable

3.3 Structural Neuroimaging — The Cornerstone of VaD Diagnosis

Neuroimaging is essential — you cannot diagnose probable VCID without it.

Feature	Findings in VaD	Interpretation
Old infarcts	Hypodense areas in cortical or subcortical regions	Indicate prior completed stroke
Lacunar infarcts	Small (< 15mm) hypodense lesions in basal ganglia, thalamus, internal capsule, pons	Evidence of small vessel disease ^[16]
White matter lesions	Periventricular hypodensity ("leukoaraiosis")	Chronic subcortical ischaemia
Cerebral atrophy	Widened sulci, dilated ventricles	Non-specific; proportionate atrophy suggests neurodegeneration; disproportionate ventriculomegaly suggests NPH
Haemorrhage	Hyperdense areas (acute); hypodense (chronic with haemosiderin)	ICH or old lobar haemorrhage

Advantages: Fast, widely available, good for acute exclusions (SDH, tumour, acute haemorrhage) Limitations: Low sensitivity for small vessel disease, white matter changes, and microbleeds — MRI is more sensitive for small vessel diseases ^[2]

"MRI (preferable) or CT" for VCID diagnosis ^[3]

Sequence	What It Shows in VaD	Key Findings
T1-weighted	Anatomy, grey matter atrophy	Old infarcts appear hypointense; lacunar cavities visible
T2-weighted	Fluid appears bright; detects oedema, gliosis	White matter lesions appear hyperintense ^[2]
FLAIR (Fluid-Attenuated Inversion Recovery)	Suppresses CSF signal → white matter lesions stand out clearly	White matter hyperintensities (WMH) are the hallmark — grade using Fazekas scale ^[3]
DWI (Diffusion-Weighted Imaging)	Detects acute/recent ischaemia	Acute infarcts appear bright (restricted diffusion); helps identify recent subclinical strokes
SWI / T2 (Susceptibility-Weighted Imaging)*	Detects blood products	Cerebral microbleeds appear as small dark dots; cortical superficial siderosis ^[3]

The Fazekas Scale for White Matter Hyperintensities:

Grade	Periventricular WMH	Deep WMH
0	Absent	Absent
1	Caps or thin lining	Punctate foci
2	Smooth halo	Beginning confluence
3	Irregular extending into deep WM	Large confluent areas

"Extensive and confluent may correspond to a Fazekas score of 2 or 3; or by region: periventricular Fazekas = 3 and/or deep Fazekas = 2 or 3" — this is what satisfies criterion B.3 ^[3]

High Yield — MRI Findings Summary for VaD

On MRI, look for: (1) Old cortical or subcortical infarcts (T1 hypointense, T2/FLAIR hyperintense). (2) Lacunes (small CSF-signal cavities in deep grey matter). (3) Extensive confluent WMH on FLAIR (Fazekas ≥ 2). (4) Cerebral microbleeds on SWI (especially deep/basal ganglia location = hypertensive; lobar location = CAA). (5) Perivascular space enlargement. (6) Brain atrophy. This constellation of findings is collectively referred to as cerebral small vessel disease (CSVD) ^[1]^[2]^[3].

3.4 Functional Neuroimaging — Distinguishing Dementia Subtypes

"Different types of dementia typically present with different patterns of perfusion changes. Visualization of hypoperfusion to specific areas indicates brain degeneration in those areas" ^[6]

Dementia Type	SPECT Perfusion Pattern
VaD	Patchy, asymmetric, multifocal hypoperfusion (corresponds to infarcts and ischaemic zones)
Alzheimer's Disease	Bilateral posterior temporal + parietal hypoperfusion ^[6]
Frontotemporal Dementia	Bilateral frontal + temporal hypoperfusion ^[6]
DLB	Occipital hypoperfusion (differentiates from AD)

Clinical indication: When structural imaging is equivocal or when differentiating between dementia subtypes, especially VaD vs AD vs FTD ^[6].

Measures regional cerebral glucose metabolism (a proxy for neuronal activity)
VaD: Multifocal, asymmetric hypometabolism corresponding to infarct sites
AD: Bilateral temporoparietal and posterior cingulate hypometabolism
FTD: Frontal ± anterior temporal hypometabolism
More sensitive than SPECT but less available and more expensive

Detects brain amyloid-β deposition in vivo
VaD (pure): Negative amyloid PET (no significant amyloid burden)
AD or Mixed VaD+AD: Positive amyloid PET
"Imaging brain amyloid levels (i.e. using positron emission tomography) at accepted Centiloid/standardized uptake value ratio thresholds" — supports AD as alternative/co-existing etiology ^[3]

3.5 Vascular Imaging — Identifying the Mechanism

Once VaD is diagnosed, you need to identify the underlying vascular mechanism to guide secondary prevention.

Non-invasive, first-line vascular imaging ^[17]
Detects and quantifies extracranial carotid and vertebral artery stenosis
Identifies plaque morphology (ulcerated plaques = higher embolic risk)
Limitations: Operator-dependent; cannot assess intracranial vessels

Rapid, widely available assessment of both extracranial and intracranial arteries
Identifies significant stenoses, occlusions, aneurysms, dissection
"CT angiography (CTA)" is standard in stroke workup ^[17]
Limitation: Contrast nephropathy risk, radiation dose ^[17]

No ionising radiation; can be done with or without gadolinium contrast
Good for intracranial vessel assessment (especially important in the Hong Kong Chinese population where intracranial atherosclerosis is more prevalent than extracranial disease)
"MR angiography (MRA)" ^[17]

"Gold standard for assessment of vascular lesion. Interventional procedure → stenting/coiling. Cons: inherent risk → stroke, dissection, infection, bleeding" ^[17]

Reserved for planned intervention or when non-invasive imaging is inconclusive
Not used routinely for dementia workup

Cardioembolism is a major cause of cortical infarcts leading to post-stroke VaD. These investigations identify embolic sources:

Investigation	What It Detects	When to Order
12-lead ECG	Atrial fibrillation (most common cardioembolic source), old MI, LVH	All patients — baseline
24h/48h Holter monitor or prolonged cardiac monitoring	Paroxysmal AF	When ECG is normal but embolic stroke is suspected
Transthoracic echocardiography (TTE)	Valvular disease, LV dysfunction, intracardiac thrombus, wall motion abnormalities	Suspected cardioembolic source
Transoesophageal echocardiography (TOE)	Patent foramen ovale (PFO), left atrial appendage thrombus, aortic arch atheroma	When TTE is non-diagnostic or paradoxical embolism suspected

Test	Indication	Key Findings
CSF Aβ42:40 ratio, p-tau181, p-tau217	Distinguish VaD from AD; identify mixed pathology	"Cerebrospinal or plasma Aβ and p-tau-derived species... at levels consistent with brain amyloid pathology" — if positive, suggests AD co-pathology ^[3]
Plasma Aβ42:40 ratio, p-tau217	Non-invasive alternative to CSF biomarkers; rapidly emerging	Same interpretation as CSF; increasingly validated
CSF 14-3-3 protein, RT-QuIC	Suspected CJD	Positive in prion disease (rapidly progressive dementia)
VDRL on CSF	Suspected neurosyphilis	Positive = neurosyphilis confirmed
Genetic testing (NOTCH3)	Suspected CADASIL	Confirms diagnosis in young-onset small vessel disease

Investigation	Purpose
Fasting glucose, HbA1c	Diabetes screening and control assessment
Fasting lipid profile	Dyslipidaemia — target for statin therapy
Renal function	CKD is an independent cardiovascular risk factor
ECG	AF, LVH, old MI
Vasculitic screen (ANA, ANCA, ESR, CRP)	If young-onset multi-infarct pattern or systemic features suggest CNS vasculitis
Thrombophilia screen	If young-onset stroke with no other cause; protein C/S, antithrombin III, antiphospholipid antibodies

VaD Subtype	Key Imaging Findings	Vascular Assessment	Clinical Clue
Post-stroke (large vessel)	Large territorial infarcts (cortical)	Carotid USS/CTA shows stenosis; or echo shows AF/thrombus	Abrupt onset post-stroke; hemiparesis, aphasia
Multi-infarct (lacunar)	Multiple lacunes in BG, thalamus, IC ^[1]	Often HTN-related; may have intracranial stenosis on MRA	Stepwise; subcortical signs
Subcortical ischaemic (Binswanger's)	Extensive confluent WMH (Fazekas 2–3) ^[3]; few or no lacunes	HTN; often no significant large vessel disease	Insidious; processing speed/executive dysfunction
Strategic infarct	Single infarct in thalamus, caudate, angular gyrus	Source-specific	Abrupt onset disproportionate to infarct size
Haemorrhagic	ICH ± microbleeds (deep = HTN; lobar = CAA)	BP assessment; SWI for microbleed pattern	History of ICH; if lobar, consider amyloid angiopathy
CADASIL	Anterior temporal pole WMH, lacunes, microbleeds	NOTCH3 mutation on genetic testing	Young onset; migraine with aura; family history

High Yield Summary — Diagnostic Criteria and Investigations

VasCog-2-WSO 2025 requires BOTH (A) clinical evidence of vascular etiology AND (B) neuroimaging evidence of cerebrovascular disease for probable VCID ^[3]
Two clinical pathways — A.1: post-stroke cognitive decline (abrupt, persists > 3 months); A.2: subcortical ischaemic (gradual onset, attention/processing speed/executive dysfunction predominant) ^[3]
MRI is preferred over CT — more sensitive for white matter hyperintensities, lacunes, and microbleeds ^[2]^[3]
Fazekas score ≥ 2–3 satisfies neuroimaging criterion for extensive WMH ^[3]
MoCA is more appropriate than MMSE for VaD because it better tests executive function ^[2]
Always exclude reversible causes: B12, folate, TFT, Ca, glucose, medication review ^[11]
Always exclude delirium before diagnosing any dementia
Hachinski score ≥ 7 supports VaD; ≤ 4 supports AD ^[2]
SPECT pattern for VaD = patchy, asymmetric, multifocal hypoperfusion (vs bilateral posterior temporal + parietal in AD) ^[6]
VasCog-2-WSO incorporates AD and DLB biomarkers to identify mixed pathology — this reflects the clinical reality that mixed dementia is the rule in elderly patients ^[3]

Active Recall - Diagnostic Criteria, Algorithm, and Investigations for Vascular Dementia

References

Management of Vascular Dementia

The management of vascular dementia is fundamentally different from Alzheimer's disease in one crucial respect: the primary treatment target is the underlying cerebrovascular disease, not just the cognitive symptoms. Think of it this way — in AD, you're trying to slow a neurodegenerative process you don't fully understand; in VaD, you're dealing with a vascular disease where the risk factors are well-characterised and modifiable. This makes VaD the most preventable and potentially modifiable form of dementia.

Management is structured around four pillars:

Vascular risk factor management (primary and secondary prevention — the most important)
Pharmacological treatment for cognition (limited evidence but commonly used)
Management of behavioural and psychological symptoms of dementia (BPSD)
Non-pharmacological / supportive interventions (multidisciplinary, patient and carer-centred)

2. Pillar 1 — Vascular Risk Factor Management (The Cornerstone)

"RF management: healthy lifestyle, HTN, DM, statins, aspirin" ^[1]^[2]

"Apart from lifestyle changes, most of the RF management interventions are probably more effective in preventing further stroke events than dementia" ^[1]

This footnote from the senior notes is worth understanding deeply: we know that controlling vascular risk factors prevents further strokes, and preventing further strokes should logically prevent further cognitive decline. However, the evidence that risk factor control reverses existing VaD or significantly slows its progression (beyond stroke prevention) is more limited. Nevertheless, risk factor management remains the most evidence-based intervention we have.

Intervention	Mechanism / Rationale	Practical Advice
Regular physical exercise	Improves cerebral perfusion, endothelial function, insulin sensitivity, reduces BP; promotes neuroplasticity and brain-derived neurotrophic factor (BDNF) release	≥ 150 min/week moderate-intensity aerobic activity; adapted to patient's mobility
Healthy diet	Mediterranean and DASH diets reduce cardiovascular events; rich in antioxidants, anti-inflammatory compounds	High fruits/vegetables, whole grains, fish; low saturated fat, salt, processed food
Smoking cessation	Smoking accelerates atherosclerosis, endothelial damage, prothrombotic state	Counselling, nicotine replacement therapy, varenicline/bupropion if needed
Alcohol moderation	Excessive alcohol → hypertension, cardiomyopathy, direct neurotoxicity; moderate alcohol may be neutral or mildly protective	≤ 14 units/week; avoid binge drinking
Weight management	Obesity synergises with HTN, DM, dyslipidaemia	BMI target 18.5–24.9
Cognitive and social engagement	Builds cognitive reserve; reduces depression and isolation	Encourage social activities, cognitive stimulation, hobbies
Sleep optimisation	OSA → nocturnal hypoxia → endothelial damage, BP surges	Screen for OSA; CPAP if diagnosed

Hypertension is the single most important modifiable risk factor for VaD. Chronic hypertension drives arteriolar lipohyalinosis (small vessel disease), accelerates large vessel atherosclerosis, and increases risk of both ischaemic and haemorrhagic stroke.

Aspect	Details
Target BP	Generally < 130/80 mmHg for secondary stroke prevention (per AHA/ASA guidelines); individualise in frail elderly — avoid excessive lowering that may cause falls or worsen cerebral hypoperfusion
First-line agents	ACEi/ARB (renoprotective, especially in DM); CCB (amlodipine — good evidence in stroke prevention); Thiazide diuretics (indapamide — PROGRESS trial showed 43% stroke risk reduction with perindopril + indapamide)
Cautions in elderly	Start low, go slow; monitor for orthostatic hypotension (risk of falls → hip fractures → further cognitive decline from hospitalisation/delirium); avoid over-aggressive targets in patients > 80y with significant frailty

The J-Curve in Dementia Patients

Over-aggressive BP lowering in elderly VaD patients can paradoxically worsen cognitive function by reducing cerebral perfusion below autoregulatory thresholds. Cerebral autoregulation is often impaired in patients with chronic hypertension and cerebrovascular disease — their brain requires a higher perfusion pressure. Balance is key: treat hypertension, but avoid symptomatic hypotension.

"Aspirin" ^[1]

Aspect	Details
Indication	Secondary prevention of ischaemic stroke / TIA — i.e., patients with evidence of prior ischaemic cerebrovascular events
First-line	Aspirin 80–100 mg daily (irreversibly inhibits COX-1 → blocks thromboxane A2 → ↓platelet aggregation)
Alternative	Clopidogrel 75 mg daily (blocks P2Y12 ADP receptor on platelets) — used if aspirin-intolerant or as per local guidelines
Dual antiplatelet therapy (DAPT)	Aspirin + clopidogrel for 21 days post-minor stroke/TIA (CHANCE/POINT trials), then switch to single agent — not for long-term use (↑bleeding risk)
NOT indicated	In haemorrhagic VaD (ICH-related) — antiplatelets would increase re-bleeding risk

Aspect	Details
Indication	Atrial fibrillation — the most important cardioembolic risk factor for stroke and post-stroke VaD
First-line	DOACs (dabigatran, rivarelbaban, apixaban, edoxaban) — preferred over warfarin due to lower ICH risk, no routine monitoring, fewer drug interactions
Warfarin	INR target 2.0–3.0; used if DOACs contraindicated (e.g., mechanical valve, severe CKD)
CHA₂DS₂-VASc score	Used to stratify AF patients for anticoagulation need; most VaD patients with AF will score ≥ 2 (age, HTN, stroke history) and require anticoagulation
Contraindication	Active bleeding, recent ICH (especially CAA-related — discuss risk-benefit on case-by-case basis with haematology/neurology), severe thrombocytopaenia

The AF–VaD Dilemma After ICH

Some VaD patients have AF (needing anticoagulation to prevent cardioembolic stroke) AND a history of ICH (where anticoagulation increases re-bleeding risk). This is a genuine clinical dilemma requiring multidisciplinary discussion. Left atrial appendage occlusion (LAAO) devices (e.g., Watchman) may be considered as an alternative to lifelong anticoagulation in these patients.

"Statins" ^[1]

Aspect	Details
Indication	Secondary prevention in patients with atherosclerotic cerebrovascular disease; LDL target < 1.8 mmol/L (or ≥ 50% reduction from baseline)
Mechanism	HMG-CoA reductase inhibitors → ↓cholesterol synthesis → ↑hepatic LDL receptor expression → ↓circulating LDL; also pleiotropic effects: anti-inflammatory, endothelial function improvement, plaque stabilisation
First-line	Atorvastatin 40–80 mg or rosuvastatin 20–40 mg (high-intensity)
Cautions	Myopathy (monitor for muscle pain, check CK if symptomatic), hepatotoxicity (baseline LFT), drug interactions (CYP3A4 — avoid simvastatin with certain medications)
Evidence for cognition	No strong evidence that statins directly improve cognition in VaD; benefit is primarily through stroke prevention

Aspect	Details
Target	HbA1c < 7% (53 mmol/mol) for most; individualise — less stringent (< 8%) in frail elderly to avoid hypoglycaemia
Why	DM accelerates micro- and macrovascular disease; hyperglycaemia worsens ischaemic brain injury; hypoglycaemia also directly harms cognition
Preferred agents	Metformin (first-line); SGLT2 inhibitors and GLP-1 agonists have demonstrated cardiovascular outcome benefit

Aspect	Details
Carotid endarterectomy (CEA)	Symptomatic carotid stenosis ≥ 70% (NASCET criteria) — reduces future stroke risk. Consider for 50–69% stenosis in select patients
Carotid artery stenting (CAS)	Alternative if surgically high-risk
Relevance to VaD	Restoring carotid flow may prevent future embolic/haemodynamic strokes that would worsen cognitive decline; does NOT reverse established dementia

3. Pillar 2 — Pharmacological Therapy for Cognition

"Pharmacological therapy: anticholinesterase and NMDA receptor antagonists" ^[1]

"Evidence for use of these drugs in VaD is limited, but they are often used due to well-known co-association between AD and VaD and the clinical difficulty in differentiating between the two" ^[1]

This is an important exam point. The rationale for using AD drugs in VaD is:

Mixed pathology is extremely common — most elderly patients with VaD also have some Alzheimer pathology, so treating the AD component may help
Cholinergic deficit exists in VaD too — ischaemic damage to basal forebrain cholinergic neurons and their white matter projections produces a cholinergic deficit (not just an AD phenomenon)
Excitotoxicity from glutamate release during ischaemia provides a rationale for memantine

"Cholinesterase inhibitors, e.g. donepezil (Aricept), galantamine (Reminyl), rivastigmine (Exelon)" ^[2]

Aspect	Details
Drugs	Donepezil (Aricept), galantamine (Reminyl), rivastigmine (Exelon) ^[2]
Mechanism	"↓ACh breakdown at synapses → ↑cholinergic transmission (based on cholinergic hypothesis)" ^[2]. The name "cholinesterase inhibitor" tells you: they inhibit the enzyme (acetylcholinesterase) that breaks down acetylcholine → more ACh available at the synapse
Indication	Mild to moderate dementia; used in VaD especially when mixed pathology (VaD + AD) is suspected. "Small benefit of uncertain clinical significance" in pure VaD ^[2]
Evidence in VaD	Two large RCTs (donepezil in VaD): statistically significant but clinically modest improvements in ADAS-Cog (~2 points) and global impression; not formally licensed for pure VaD in many jurisdictions
Effect	"Modest improvement in cognition (MMSE 1.37 points, ADAS-Cog 2.7 points at 6–12mo), neuropsychiatric symptoms, ADLs, delay decline for ~2mo/y but little evidence for long-term effect" ^[2]
Side effects	"Very commonly GI upset (diarrhoea, N/V), anorexia/weight loss, bradycardia/↓BP, sleep disturbances" ^[2]
Contraindications	Sick sinus syndrome, second/third-degree heart block (due to vagotonic bradycardia); active peptic ulcer (cholinergic stimulation increases gastric acid); severe hepatic impairment; caution with NSAIDs (GI bleeding risk)
Practical points	Start low dose, titrate slowly over weeks; take donepezil at bedtime (if insomnia → switch to morning); rivastigmine patch may reduce GI side effects

Why does a cholinergic drug cause bradycardia? Acetylcholine acts on muscarinic M2 receptors in the heart → slows SA node firing and AV conduction → bradycardia. By increasing ACh throughout the body (not just the brain), ChEIs have systemic parasympathetic effects.

Why GI upset? ACh stimulates muscarinic M3 receptors on GI smooth muscle → increased motility (diarrhoea, cramps) and on gastric parietal cells → increased acid secretion (nausea).

"NMDA antagonists, e.g. Memantine (Ebixa)" ^[2]

Aspect	Details
Drug	Memantine (Ebixa) ^[2]
Mechanism	"Block excitatory Glu transmission by NMDAr → ↓excitotoxicity (esp in vascular dementia)" ^[2]. During ischaemia, excessive glutamate release overstimulates NMDA receptors → massive Ca²⁺ influx → neuronal death (excitotoxicity). Memantine is a low-affinity, voltage-dependent, uncompetitive NMDA receptor antagonist — it blocks pathological tonic activation while allowing physiological phasic signalling needed for learning
Indication	"Moderate to advanced dementia" ^[2]; in VaD, may have particular rationale due to the ischaemic excitotoxicity mechanism
Effect	"Modest benefit in moderate/advanced dementia (but limited evidence for mild dementia), may have synergistic effect with cholinesterase inhibitor" ^[2]
Side effects	"Uncommon, dizziness, confusion/hallucinations (rare)" ^[2]
Contraindications	Severe renal impairment (renally excreted — reduce dose if eGFR 5–29); epilepsy (theoretical seizure threshold lowering); caution with other NMDA antagonists (amantadine, ketamine, dextromethorphan)
Practical points	Start 5 mg daily, titrate by 5 mg weekly to target 20 mg daily; can be combined with ChEI

Why Memantine Has a Particular Rationale in VaD

In pure AD, the cholinergic hypothesis is the dominant treatment rationale. In VaD, chronic ischaemia causes ongoing glutamate excitotoxicity — NMDA receptor overactivation kills neurons through calcium overload. Memantine directly targets this mechanism. This is why the senior notes specifically note "esp in vascular dementia" for the excitotoxicity rationale ^[2]. However, the clinical evidence for memantine in pure VaD remains modest.

Drug Class	Examples	MoA	Indication	Evidence in VaD
ChEI	Donepezil, galantamine, rivastigmine	↓ACh breakdown → ↑cholinergic transmission	Mild–moderate dementia; especially mixed VaD+AD	Small benefit, uncertain clinical significance in pure VaD
NMDA antagonist	Memantine	Blocks glutamate excitotoxicity via NMDA receptor	Moderate–severe dementia	Modest; particular rationale in VaD due to ischaemic excitotoxicity
Combination	ChEI + Memantine	Complementary mechanisms	Moderate–severe, especially if monotherapy insufficient	May have synergistic benefit

4. Pillar 3 — Management of Behavioural and Psychological Symptoms of Dementia (BPSD)

BPSD affects up to 90% of dementia patients at some point and is often the most distressing aspect for carers. In VaD, common BPSD includes apathy, depression, emotional lability, agitation, anxiety, psychosis, and sleep disturbance.

"Supportive: behavioural Tx, pain control, antidepressants, anxiolytics, antipsychotics" ^[1]

Always identify and treat underlying causes first — pain, constipation, urinary retention, infection, medication side effects, environmental factors (overstimulation/understimulation)
Non-pharmacological approaches are ALWAYS first-line
Pharmacological therapy only when non-pharmacological measures fail and symptoms are severe enough to cause harm or significant distress
"Start low, go slow, and review regularly" — minimise polypharmacy

Intervention	Target Symptoms	Mechanism
Person-centred care	All BPSD	Understanding the patient's perspective, preferences, and triggers; maintaining dignity
Environmental modification	Agitation, wandering, sundowning	Reduce noise, adequate lighting (especially at night), familiar objects, consistent routines
Music therapy	Agitation, anxiety, depression	Reduces cortisol, promotes relaxation; familiar music evokes positive memories
Aromatherapy	Agitation	Lavender and melissa oils have modest evidence for calming effect
Reminiscence therapy	Depression, apathy	Discussing past experiences using prompts (photos, music, objects)
Validation therapy	Agitation, distress	Acknowledging and validating the patient's feelings rather than correcting them
Physical activity	Agitation, depression, sleep disturbance	Reduces arousal, improves mood, promotes nighttime sleep
Pain assessment and management	Agitation, aggression (often unrecognised pain)	Use validated pain scales for cognitively impaired patients (e.g., Abbey Pain Scale); treat with simple analgesia (paracetamol)

Class	Drug Examples	Indication	Mechanism	Key Cautions
SSRIs	Sertraline, citalopram, escitalopram	Depression, anxiety, emotional lability	Selective serotonin reuptake inhibition → ↑serotonergic transmission	First-line pharmacological for depression/anxiety in dementia; fewer anticholinergic effects than TCAs; monitor for hyponatraemia (SIADH), GI bleeding (especially with aspirin)
Mirtazapine	—	Depression with insomnia, poor appetite	NaSSA: ↑noradrenaline and serotonin; H1 blockade → sedation, appetite stimulation	Weight gain; sedation (can be useful if insomnia is a problem)
Trazodone	—	Insomnia, agitation	5-HT2A antagonist + weak SERT inhibition; sedating	Useful for sleep disturbance; less anticholinergic; risk of postural hypotension
Antipsychotics	Risperidone, quetiapine, haloperidol	Agitation, aggression, psychosis (only when severe and causing risk of harm)	D2 receptor antagonism	Use with extreme caution: increased risk of stroke and death in elderly dementia patients (1.5–2× mortality); use lowest effective dose for shortest possible duration; risperidone is the only antipsychotic with some regulatory approval for BPSD in some jurisdictions
Anxiolytics	Lorazepam (short-acting benzo)	Acute severe agitation/anxiety as rescue	GABA-A receptor potentiation → sedation	Short-term only; risk of over-sedation, falls, paradoxical disinhibition, respiratory depression; avoid long-acting benzodiazepines (accumulation in elderly)

Antipsychotics in Dementia — The Black Box Warning

Both typical and atypical antipsychotics carry an FDA/EMA black box warning for increased mortality in elderly patients with dementia (primarily from cardiovascular events and infections). They should be used only when BPSD causes significant risk of harm to the patient or others, and only after non-pharmacological approaches have been exhausted. Document the indication, expected duration, and plan for review. Aim to taper and discontinue within 6–12 weeks if possible.

Special considerations for antipsychotics in VaD:

VaD patients are at higher cerebrovascular risk than AD patients → antipsychotic-associated stroke risk is particularly concerning
Avoid in DLB or mixed VaD/DLB — severe neuroleptic sensitivity reactions (severe Parkinsonism, rigidity, obtundation); if an antipsychotic is absolutely necessary, quetiapine at the lowest dose is preferred in suspected Lewy body spectrum

Drugs to AVOID in dementia patients:

Drug Class	Why to Avoid
Anticholinergics (e.g., oxybutynin, chlorpheniramine, TCAs)	Worsen cognition by blocking ACh (directly counteracting ChEIs); cause delirium, constipation, urinary retention
Benzodiazepines (long-acting, e.g., diazepam, nitrazepam)	Over-sedation, falls, respiratory depression, paradoxical agitation; accumulate in elderly
Centrally-acting antihistamines	Anticholinergic and sedating properties

5. Pillar 4 — Non-Pharmacological and Supportive Care

This pillar is equally important as the pharmacological interventions and is central to maintaining quality of life.

Intervention	Description	Evidence
Cognitive stimulation therapy (CST)	Group-based activity sessions involving themed activities, discussions, puzzles over 7 weeks	Best evidence of any non-pharmacological intervention; NICE-recommended; modest cognitive benefit equivalent to ChEIs
Cognitive rehabilitation	Goal-oriented, personalised strategies to maintain function in specific everyday activities	Helps with specific functional tasks; requires OT/neuropsych input
Cognitive training	Repeated practice of standardised tasks targeting specific domains	Less evidence for generalised benefit; may help with trained tasks

Team Member	Role
Geriatrician / Neurologist / Psychiatrist	Diagnosis, medication management, monitoring
Occupational therapist	Home safety assessment, adaptive equipment, maintaining ADLs
Physiotherapist	Gait and balance training (critical in VaD with gait apraxia), falls prevention, exercise programmes
Speech and language therapist	Swallowing assessment (especially with pseudobulbar palsy), communication strategies
Social worker	Community resources, day care, respite, financial and legal advice (e.g., enduring power of attorney)
Psychologist	Neuropsychological assessment, psychological interventions for BPSD
Nurse specialist / dementia care coordinator	Care coordination, patient and carer education, ongoing monitoring
Dietitian	Nutritional assessment and support, especially with dysphagia or weight loss

Education: Help carers understand the disease, its course, and what to expect
Respite care: Day programmes, temporary residential care to prevent carer burnout
Carer support groups: Peer support, shared experience
Psychological support: Carers of dementia patients have high rates of depression and anxiety

Issue	Management
Driving	Assess fitness to drive; in Hong Kong, medical professionals can advise the Transport Department if a patient is unfit to drive; VaD patients with significant cognitive/motor impairment should not drive
Wandering	ID bracelets, GPS tracking devices, secure door alarms, structured routines
Falls prevention	Home safety assessment, remove trip hazards, assistive devices, physiotherapy; especially important in VaD due to gait apraxia
Medication management	Dosette boxes, supervised administration, simplify regimens
Financial and legal planning	Encourage early while patient has capacity: enduring power of attorney, advance directives
Fire safety	Supervised cooking, smoke alarms, remove gas appliances if unsafe

Discuss early while the patient still has capacity and insight (VaD patients often have preserved insight early)
Document preferences regarding future treatments: resuscitation status, artificial feeding, hospitalisation
Enduring power of attorney: Appoint while patient has capacity
End-of-life: Focus on comfort, dignity, symptom control (pain, agitation, secretions); avoid futile interventions

"Disease course: stepwise progression with periods of deterioration and improvements" ^[2]

"Life expectancy: variable but usually shorter than AD (~5y), with ~50% dying from IHD" ^[2]

Aspect	Details
Average survival	~5 years from diagnosis (shorter than AD's 7–10 years) — because VaD patients have heavy systemic cardiovascular disease
Cause of death	~50% die from IHD ^[2]; also stroke, heart failure, pneumonia, other complications of immobility
Factors affecting prognosis	Extent of vascular disease, adequacy of risk factor control, presence of co-existing AD pathology, age at onset, baseline functional status

Stage	Key Management Priorities
Preclinical/At-Risk	Aggressive vascular risk factor management; lifestyle modification; monitoring
Mild VaD	All of above + cognitive stimulation therapy; consider ChEI if mixed pathology suspected; occupational therapy; driving assessment; advance care planning
Moderate VaD	All of above + memantine consideration; BPSD management (non-pharmacological first); physiotherapy for gait; swallowing assessment; carer support intensification
Severe VaD	Focus shifts to comfort and quality of life; palliative approach; advanced BPSD management; dysphagia management; continence care; end-of-life planning

High Yield Summary — Management of Vascular Dementia

VaD is the most preventable form of dementia — vascular risk factor management is the cornerstone of treatment ^[1]
Key RF interventions: healthy lifestyle, antihypertensives, statins, aspirin/anticoagulation, glycaemic control, smoking cessation ^[1]
ChEIs (donepezil, galantamine, rivastigmine): small benefit of uncertain clinical significance in pure VaD; used because mixed VaD+AD is common and hard to distinguish ^[1]^[2]
Memantine: blocks glutamate excitotoxicity via NMDA receptor; particular rationale in VaD; modest benefit in moderate-severe dementia; may be synergistic with ChEIs ^[2]
BPSD: always non-pharmacological first; antipsychotics carry black box warning for increased stroke and mortality in elderly dementia patients — use only for severe symptoms, lowest dose, shortest duration
Multidisciplinary approach: OT, PT, SLT, social work, carer support are all essential
Prognosis: ~5 years average survival from diagnosis; ~50% die from IHD ^[2]
Advance care planning should be discussed early while the patient has preserved insight

Active Recall - Management of Vascular Dementia

References

^[1] Senior notes: Ryan Ho Neurology.pdf (Section 5.4.2 Vascular Dementia, Management, p.132) ^[2] Senior notes: Ryan Ho Psychiatry.pdf (Sections 4.2.2–4.2.3, Cholinesterase inhibitors, Memantine, Vascular Dementia management and prognosis, p.92–93)

Complications of Vascular Dementia

Vascular dementia is not an isolated cognitive disorder — it exists within the context of systemic cardiovascular disease and progressive brain injury. Understanding its complications requires thinking along two parallel tracks:

Complications arising from the underlying cerebrovascular disease (further strokes, cardiovascular events)
Complications arising from the dementia itself (functional decline, behavioural disturbance, immobility-related consequences)

These two tracks interact in a vicious cycle: further vascular events worsen cognition, while worsening cognition leads to poor medication adherence, reduced mobility, and increased vulnerability to systemic complications.

1. Recurrent Cerebrovascular Events

The single most important complication of VaD — and the major driver of its stepwise progression — is further stroke.

Aspect	Details
Why it happens	The same vascular risk factors that caused the initial cerebrovascular disease persist — hypertension drives ongoing small vessel disease, AF generates ongoing emboli, atherosclerosis progresses
Impact on cognition	Each new stroke event adds to cumulative brain injury → stepwise deterioration ^[1]^[2]. Even clinically "silent" (covert) infarcts on MRI contribute to cognitive decline
Risk	Annual stroke recurrence risk is approximately 5–10% without adequate secondary prevention; higher in the first year post-stroke
Prevention	Aggressive vascular risk factor management — this is why secondary prevention is the cornerstone of VaD management ^[1]

Aspect	Details
Hypertensive ICH	Ongoing poorly controlled hypertension → further deep ICH (basal ganglia, thalamus, pons)
Cerebral amyloid angiopathy (CAA)	Aβ40 predominant: cerebrovascular deposition → ICH → vascular dementia ^[18]. CAA causes recurrent lobar ICH and microbleeds → cumulative cortical damage
Anticoagulant-related ICH	Patients on anticoagulation for AF are at increased bleeding risk; ICH is the most feared complication
Impact	ICH carries high mortality (~40% at 1 month) ^[5] and compounds existing cognitive deficits

"Haemorrhagic transformation: mechanism = reperfusion injury; suspect if power keeps deteriorating after stroke, mostly occurs 2–3 days after stroke" ^[19]

This is particularly relevant in VaD patients who experience a new ischaemic stroke and receive thrombolysis — the combination of antiplatelets/anticoagulants and recent ischaemia increases haemorrhagic transformation risk.

2. Cardiovascular Complications

VaD patients have heavy systemic atherosclerotic burden. The same pathology that affects cerebral vessels affects coronary and peripheral arteries.

"Life expectancy: variable but usually shorter than AD (~5y), with ~50% dying from IHD" ^[2]

Aspect	Details
Why so common	Shared vascular risk factors (HTN, DM, dyslipidaemia, smoking); systemic atherosclerosis affects coronary arteries simultaneously
Clinical challenge	Dementia patients may not report chest pain clearly (cognitive/language impairment) → MI may present atypically with confusion, falls, dyspnoea, or acute deterioration ("silent MI")
Mortality	~50% of VaD patients die from IHD ^[2] — this makes cardiovascular prevention even more important than trying to treat the cognitive symptoms

Chronic hypertension → left ventricular hypertrophy (LVH) → diastolic dysfunction → heart failure with preserved ejection fraction (HFpEF) ^[20]
Heart failure reduces cardiac output → chronic cerebral hypoperfusion → worsens cognitive decline (a vicious cycle)
Fluid overload and nocturnal orthopnoea worsen sleep quality → exacerbate cognitive symptoms

AF is both a risk factor for VaD and an ongoing source of embolic complications
Anticoagulation dilemma: benefits (stroke prevention) vs risks (bleeding, falls in dementia patients with gait disturbance)

Marker of systemic atherosclerosis; associated with reduced mobility → further deconditioning and functional decline

3. Complications of Immobility and Functional Decline

As VaD progresses, patients become increasingly immobile — both from motor deficits (hemiparesis, gait apraxia, Parkinsonism) and from cognitive decline (apathy, inability to initiate movement). Immobility triggers a cascade of systemic complications.

Aspect	Details
Why it occurs	Pseudobulbar palsy — bilateral corticobulbar pathway damage → supranuclear weakness of pharyngeal muscles → impaired swallowing coordination ^[1]^[3]. Also cortical stroke affecting swallowing centres
Consequence	Silent aspiration → aspiration pneumonia — one of the leading causes of death in advanced VaD
Management	Speech and language therapy assessment; modified diet textures (thickened fluids, pureed food); upright feeding position; oral hygiene; consider NG or PEG feeding in advanced disease (with careful ethical discussion)

"Dysphagia and aspiration pneumonia" are listed as major complications of stroke ^[19]^[21]

Aspect	Details
Why	Immobility → venous stasis (Virchow's triad); paretic limbs have particularly reduced venous return
Prevention	"VTE prophylaxis: elastic stockings (or low dose SC heparin)" ^[21]; early mobilisation; physiotherapy
Clinical challenge	DVT may present subtly in cognitively impaired patients (unable to report leg pain); PE may present as acute confusion or unexplained tachycardia

Aspect	Details
Why	Immobility + malnutrition + incontinence → sustained pressure on bony prominences (sacrum, heels, trochanters) → tissue ischaemia → necrosis
Prevention	"Pressure sores: reposition weak limbs, frequent turning, use of cushions, egg-crater/air mattress" ^[21]; adequate nutrition; keep skin dry; pressure-relieving devices
Complications of pressure ulcers	Secondary infection → cellulitis → sepsis; chronic wound requiring surgical debridement

Prolonged immobility → muscle shortening, joint capsule fibrosis → fixed flexion contractures (especially at hips, knees, elbows)
Prevention: regular passive range-of-motion exercises, physiotherapy, correct positioning

Aspect	Details
Why VaD patients are at high fall risk	Multiple compounding factors: gait apraxia / Parkinsonian gait ^[1]; postural instability; visual field defects from prior strokes; orthostatic hypotension (from antihypertensives, autonomic dysfunction); cognitive impairment (impaired judgement, spatial awareness); polypharmacy (sedatives, antipsychotics)
Consequences	Hip fractures (high morbidity and mortality in elderly — 30-day mortality ~10%); head injury (risk of subdural haematoma — especially if on anticoagulation); wrist fractures
Management	Falls risk assessment; physiotherapy for gait training and balance; occupational therapy for home safety; medication review (reduce sedatives); hip protectors; osteoporosis screening and treatment

Falls → Subdural Haematoma → Worsening Dementia

A VaD patient on anticoagulation who falls and hits their head is at high risk of chronic subdural haematoma (SDH). This presents insidiously with worsening confusion — which may be mistakenly attributed to dementia progression rather than a treatable surgical condition. Always CT brain in a dementia patient with unexplained acute/subacute cognitive deterioration, especially if on anticoagulation or antiplatelet therapy.

5. Neuropsychiatric Complications

"Prevalence of depression observed at any time after stroke = 29%" ^[22]

"Depression at 3 months after stroke is correlated with a poor outcome at 1 year" ^[22]

Aspect	Details
Prevalence in VaD	Higher than in AD; "more commonly associated with depression, labile mood, apathy, anxiety and pseudobulbar affect" ^[2]
Pathophysiology	(1) Ischaemic disruption of frontostriatal serotonergic/noradrenergic mood circuits (biological "vascular depression" hypothesis); (2) Reactive depression to disability and loss of independence; (3) Shared vascular risk factors
Impact	Worsens cognition, reduces motivation for rehabilitation, increases carer burden, increases mortality
Predictors	Disability, anxiety, pre-stroke depression, cognitive impairment, severity of stroke ^[22]
Management	SSRIs (sertraline, escitalopram) first-line; avoid TCAs (anticholinergic → worsen cognition); psychological support; exercise

The most common neuropsychiatric symptom in subcortical VaD
Distinct from depression — loss of motivation without sadness
Pathophysiology: disruption of anterior cingulate → frontal motivational circuits by subcortical white matter disease
No good pharmacological treatment; cognitive stimulation, structured routines, and engagement strategies may help

"Pseudobulbar affect = pathological laughing or crying" ^[2]

Involuntary, exaggerated emotional expression disproportionate or incongruent with the underlying emotional state
Pathophysiology: bilateral upper motor neuron damage to corticobulbar pathways → loss of cortical inhibition of brainstem emotional centres
Distressing for patients and carers; often misinterpreted as depression or mania
Management: dextromethorphan/quinidine combination is licensed in some jurisdictions; SSRIs may also help; importantly, education of patient and carers that this is a neurological symptom, not a psychiatric one

More common in moderate-to-severe VaD
Often triggered by unrecognised pain, constipation, urinary retention, infection, environmental overstimulation, medication effects
Management: identify and treat triggers first → non-pharmacological approaches → pharmacological only as last resort (with the caveats about antipsychotic risks discussed in Management)

Dementia is the leading risk factor for delirium ^[7]
VaD patients are particularly vulnerable due to: reduced cognitive reserve, polypharmacy, multiple comorbidities, frequent hospitalisations
Any acute deterioration in a VaD patient should prompt a delirium screen and search for precipitants (infection, metabolic derangement, new drug, constipation, urinary retention, pain)

Infection	Why Common in VaD	Prevention
Aspiration pneumonia	Pseudobulbar palsy → dysphagia → aspiration ^[1]^[21]	Swallowing assessment, modified diet, oral hygiene, upright positioning
Urinary tract infection (UTI)	Neurogenic bladder (from subcortical white matter disease) → urinary retention/incontinence → catheter use → CAUTI ^[21]	Avoid unnecessary catheterisation; intermittent catheterisation preferred; bladder training; good perineal hygiene
Skin and soft tissue infections	Pressure ulcers → portal of entry for bacteria	Pressure ulcer prevention (see above)

Complication	Mechanism	Management
Malnutrition / Weight loss	Dysphagia (inadequate oral intake), apathy (reduced motivation to eat), forgetting to eat (cognitive decline), depression (anorexia), medication side effects (ChEIs cause anorexia/nausea)	Dietitian assessment; calorie-dense foods; oral nutritional supplements; assisted feeding; consider NG/PEG in selected cases
Dehydration	Reduced thirst perception in elderly; inability to independently access fluids; dysphagia limiting fluid intake; diuretic use for HTN/HF	Encourage regular fluid intake; assisted drinking; IV/SC fluids if needed

Aspect	Details
Why	Cortical infarcts create epileptogenic foci (ischaemic scar tissue → abnormal neuronal excitability); prevalence of post-stroke epilepsy ~5–10%
Timing	Early seizures (< 7 days post-stroke) are usually provoked and may not recur; late seizures (> 7 days) are more likely to recur and constitute post-stroke epilepsy
Management	"Prophylactic anticonvulsants are not recommended" for stroke ^[19]; if seizures occur, treat with standard antiepileptic drugs (levetiracetam preferred in elderly — fewer drug interactions and less hepatic metabolism; avoid phenytoin long-term due to cognitive side effects and drug interactions)

In advanced VaD, patients become bedbound and fully dependent:

Complication	Details
Complete functional dependence	Unable to perform any ADLs; requires full nursing care
Loss of communication	Severe aphasia, dysarthria, or global cognitive impairment → inability to express needs → unrecognised pain, hunger, thirst
Terminal pneumonia	Recurrent aspiration → eventually fatal; often the terminal event
Cachexia	Progressive weight loss from combined dysphagia, malnutrition, immobility, and systemic inflammation
Multi-organ complications	Renal impairment (CKD from hypertensive nephrosclerosis + dehydration), cardiac events (IHD, HF), infections

While not a "complication" in the traditional medical sense, carer burden is a critical consequence of VaD:

Aspect	Details
Psychological	Depression (30–40% of carers), anxiety, chronic stress, grief for the "living loss" of the person they knew
Physical	Sleep deprivation (from patient's nocturnal agitation), back injuries (from lifting), neglect of own health
Social and financial	Social isolation, loss of employment, financial strain from care costs
Management	Carer education, respite services, support groups, counselling, financial assistance programmes

System	Key Complications
Cerebrovascular	Recurrent ischaemic stroke, ICH, haemorrhagic transformation, progressive small vessel disease
Cardiovascular	IHD/MI (~50% cause of death), heart failure, AF-related events
Neuropsychiatric	Depression, apathy, pseudobulbar affect, agitation/psychosis, delirium superimposed on dementia
Respiratory	Aspiration pneumonia (leading cause of death in advanced VaD)
Musculoskeletal	Falls → fractures (especially hip), contractures
Genitourinary	Neurogenic bladder → incontinence → UTI
Nutritional	Malnutrition, dehydration, weight loss
Dermatological	Pressure ulcers → secondary infection → sepsis
Thromboembolic	DVT/PE from immobility
Neurological	Post-stroke seizures
Carer	Depression, burnout, social isolation

High Yield Summary — Complications of Vascular Dementia

Recurrent stroke is the major driver of stepwise decline and the most important complication to prevent through secondary vascular risk factor management ^[1]
~50% of VaD patients die from IHD — cardiovascular disease, not the dementia itself, is the leading cause of death ^[2]
Aspiration pneumonia (from pseudobulbar dysphagia) is the leading cause of death in advanced VaD
Depression affects ~29% of stroke patients and is higher in VaD than AD; it worsens cognition and outcomes ^[22]
Delirium superimposed on dementia — any acute cognitive deterioration must prompt a delirium screen; dementia is the leading RF for delirium ^[7]
Falls are extremely common due to gait apraxia, polypharmacy, and cognitive impairment — beware chronic subdural haematoma in anticoagulated patients who fall
Immobility complications (DVT/PE, pressure ulcers, contractures, infections) are preventable with proactive nursing and allied health care
Prognosis is worse than AD — average survival ~5 years from diagnosis, reflecting the heavy systemic cardiovascular burden ^[2]

Active Recall - Complications of Vascular Dementia

References

^[1] Senior notes: Ryan Ho Neurology.pdf (Section 5.4.2 Vascular Dementia, p.132) ^[2] Senior notes: Ryan Ho Psychiatry.pdf (Section 4.2.3 Vascular Dementia, prognosis, p.93) ^[3] Lecture slides: GC 241. Reference (2) - New vascular neurocognitive disorder criteria JAMA.pdf (VasCog-2-WSO 2025, Box 2 — physical signs of stroke including pseudobulbar syndrome) ^[5] Senior notes: Ryan Ho Neurology.pdf (Stroke mortality data, p.74) ^[7] Senior notes: Ryan Ho Fundamentals.pdf (Delirium section, p.325) ^[18] Senior notes: Maksim Medicine Notes.pdf (Dementia and amyloid — Aβ40 vs Aβ42, p.245) ^[19] Senior notes: Maksim Medicine Notes.pdf (Complications of acute ischaemic stroke, p.243) ^[20] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Complications of hypertension, p.335) ^[21] Senior notes: Ryan Ho Neurology.pdf (Prevention and treatment of stroke complications, p.82) ^[22] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (Post-stroke depression, p.1238)

High Yield Summary

Key Points for Exam:

VaD is the second most common cause of dementia (~15–17%), caused by cerebrovascular disease
Risk factors = cardiovascular risk factors (HTN is the most important modifiable RF)
Three main mechanisms: (a) large artery infarcts, (b) small artery lacunar infarcts, (c) chronic subcortical ischaemia — plus hemorrhagic, strategic infarct, and genetic forms
Clinical hallmarks that distinguish VaD from AD:
- Stepwise deterioration (or insidious if subcortical SVD)
- Executive dysfunction > memory impairment
- Preserved insight
- Focal neurological signs, gait disturbance, pseudobulbar palsy
- Emotional lability, apathy, depression
- Early urinary symptoms
Memory in VaD = retrieval deficit (improves with cues) vs AD = consolidation deficit (does not improve with cues)
Neuroimaging is essential: infarcts, lacunes, WMH (Fazekas ≥ 2-3)
VasCog-2-WSO 2025 criteria: require (A) clinical evidence + (B) neuroimaging evidence of CeVD; classify as probable/possible; encourage identifying mixed pathologies
CADASIL (NOTCH3 mutation) = genetic model of pure VaD
Hachinski score ≥ 7 suggests VaD, ≤ 4 suggests AD
VaD is the most preventable form of dementia — aggressive cardiovascular risk management is key

High Yield Summary — Diagnostic Criteria and Investigations

VasCog-2-WSO 2025 requires BOTH (A) clinical evidence of vascular etiology AND (B) neuroimaging evidence of cerebrovascular disease for probable VCID ^[3]
Two clinical pathways — A.1: post-stroke cognitive decline (abrupt, persists > 3 months); A.2: subcortical ischaemic (gradual onset, attention/processing speed/executive dysfunction predominant) ^[3]
MRI is preferred over CT — more sensitive for white matter hyperintensities, lacunes, and microbleeds ^[2]^[3]
Fazekas score ≥ 2–3 satisfies neuroimaging criterion for extensive WMH ^[3]
MoCA is more appropriate than MMSE for VaD because it better tests executive function ^[2]
Always exclude reversible causes: B12, folate, TFT, Ca, glucose, medication review ^[11]
Always exclude delirium before diagnosing any dementia
Hachinski score ≥ 7 supports VaD; ≤ 4 supports AD ^[2]
SPECT pattern for VaD = patchy, asymmetric, multifocal hypoperfusion (vs bilateral posterior temporal + parietal in AD) ^[6]
VasCog-2-WSO incorporates AD and DLB biomarkers to identify mixed pathology — this reflects the clinical reality that mixed dementia is the rule in elderly patients ^[3]

High Yield Summary — Management of Vascular Dementia

VaD is the most preventable form of dementia — vascular risk factor management is the cornerstone of treatment ^[1]
Key RF interventions: healthy lifestyle, antihypertensives, statins, aspirin/anticoagulation, glycaemic control, smoking cessation ^[1]
ChEIs (donepezil, galantamine, rivastigmine): small benefit of uncertain clinical significance in pure VaD; used because mixed VaD+AD is common and hard to distinguish ^[1]^[2]
Memantine: blocks glutamate excitotoxicity via NMDA receptor; particular rationale in VaD; modest benefit in moderate-severe dementia; may be synergistic with ChEIs ^[2]
BPSD: always non-pharmacological first; antipsychotics carry black box warning for increased stroke and mortality in elderly dementia patients — use only for severe symptoms, lowest dose, shortest duration
Multidisciplinary approach: OT, PT, SLT, social work, carer support are all essential
Prognosis: ~5 years average survival from diagnosis; ~50% die from IHD ^[2]
Advance care planning should be discussed early while the patient has preserved insight

High Yield Summary — Complications of Vascular Dementia

Recurrent stroke is the major driver of stepwise decline and the most important complication to prevent through secondary vascular risk factor management ^[1]
~50% of VaD patients die from IHD — cardiovascular disease, not the dementia itself, is the leading cause of death ^[2]
Aspiration pneumonia (from pseudobulbar dysphagia) is the leading cause of death in advanced VaD
Depression affects ~29% of stroke patients and is higher in VaD than AD; it worsens cognition and outcomes ^[22]
Delirium superimposed on dementia — any acute cognitive deterioration must prompt a delirium screen; dementia is the leading RF for delirium ^[7]
Falls are extremely common due to gait apraxia, polypharmacy, and cognitive impairment — beware chronic subdural haematoma in anticoagulated patients who fall
Immobility complications (DVT/PE, pressure ulcers, contractures, infections) are preventable with proactive nursing and allied health care
Prognosis is worse than AD — average survival ~5 years from diagnosis, reflecting the heavy systemic cardiovascular burden ^[2]

Vascular Dementia

1. Definition

2. Epidemiology

2.1 Prevalence and Incidence

2.2 Sex and Ethnic Considerations

2.3 Overlap with Alzheimer's Disease (Mixed Dementia)

3. Risk Factors

3.1 Non-Modifiable Risk Factors

3.2 Modifiable Risk Factors (High Yield — These Are the Targets for Prevention)

3.3 CADASIL — The Genetic Archetype of VaD

4. Relevant Anatomy and Cerebrovascular Supply

4.1 Arterial Supply of the Brain

4.2 The Concept of "Strategic" Infarcts

4.3 White Matter and Cerebral Small Vessel Disease

5. Etiology and Pathophysiology

5.1 Mechanisms of Vascular Cognitive Impairment

A. Large Artery Infarcts (Post-Stroke Dementia)

B. Small Artery (Lacunar) Infarcts — Multi-Infarct Dementia

C. Chronic Subcortical Ischaemia (Binswanger's Disease)

D. Haemorrhagic Mechanisms

E. Hereditary Cerebral Small Vessel Disease

F. Hypoperfusion (Watershed/Border-Zone Mechanism)

5.2 Pathophysiology — Integrative Framework

5.3 The Concept of "Cognitive Reserve" and "Threshold" in VaD

6. Classification

6.1 By Mechanism (Pathological Classification)

6.2 By VasCog-2-WSO Framework (2025) [3]

6.3 By Cognitive Syndrome (Cortical vs Subcortical)

6.4 By Severity

6.5 By Age of Onset

7. Clinical Features

7.1 Mode of Onset and Course

7.2 Symptoms (with Pathophysiological Basis)

A. Cognitive Symptoms

B. Neuropsychiatric Symptoms

C. Motor and Gait Symptoms

D. Autonomic Symptoms

7.3 Signs (with Pathophysiological Basis)

A. Neurological Signs

B. Cardiovascular Signs

C. Cognitive Examination Findings

7.4 The Hachinski Ischaemic Score

7.5 Clinical Course Summary

8. Distinguishing VaD from AD and Other Dementias — Key Clinical Pointers

9. Important Concepts and Supplementary Points

9.1 The "Vascular Contribution" vs "Vascular Causation" Debate

9.2 Post-Stroke Cognitive Impairment

9.3 Fazekas Score for White Matter Hyperintensities

9.4 Relationship Between VaD and Delirium

Active Recall - Vascular Dementia (Definition, Epidemiology, RF, Pathophysiology, Classification, Clinical Features)

References

Approach: A Structured Framework

1. Other Causes of Dementia — The "Big Five" + Others

A. Alzheimer's Disease (AD) — The Most Important Differential

B. Dementia with Lewy Bodies (DLB)

C. Frontotemporal Dementia (FTD)

D. Parkinson's Disease Dementia (PDD)

E. Normal Pressure Hydrocephalus (NPH)

F. Creutzfeldt-Jakob Disease (CJD)

2. Non-Dementia Mimics — "Reversible" Causes of Cognitive Decline

A. Delirium

B. Depression ("Pseudodementia")

C. Other Reversible / Treatable Causes

D. Amnestic Syndrome

E. Neurosyphilis (General Paresis of the Insane)

3. "Parkinson-Plus" and Other Neurodegenerative Differentials

4. Summary Table — Key Differentials of VaD at a Glance

Active Recall - Differential Diagnosis of Vascular Dementia

1. Diagnostic Criteria

1.1 Step 1 — Establish Cognitive Impairment (Dementia or MCI)

DSM-5 Criteria for Major Neurocognitive Disorder (Dementia) [15]

ICD-10 Criteria for Dementia [15]

VasCog-2-WSO Criteria for MCI and Dementia (Box 1, 2025) [3]

1.2 Step 2 — Establish Vascular Etiology (VasCog-2-WSO 2025 Criteria)

Criterion A — Clinical Evidence of Vascular Etiology (One of A.1 or A.2) [3]

Criterion B — Neuroimaging Evidence of Cerebrovascular Disease (≥ 1 of the following) [3]

Criterion C — Features Suggesting Alternative or Co-Existing Etiology [3]

Level of Certainty [3]

1.3 Hachinski Ischaemic Score (Bedside Clinical Tool)

2. Diagnostic Algorithm