Vascular, frontotemporal and Lewy body dementia

• "Vascular dementia" is not one disease but several: post-stroke patterns (multi-infarct, strategic infarct), subcortical small-vessel disease that can be silent, and mixed vascular-plus-degenerative disease.
• Frontotemporal dementia (FTD) is a young-onset syndrome of behavioural change, executive failure, or progressive language loss, with frontal and anterior temporal atrophy on imaging.
• Dementia with Lewy bodies (DLB) is defined by fluctuating cognition, visual hallucinations, parkinsonism and REM sleep behaviour disorder, and is exquisitely sensitive to antipsychotic drugs.
• Normal pressure hydrocephalus is a potentially reversible syndrome of gait apraxia, cognitive decline and urinary urgency with ventriculomegaly; Creutzfeldt-Jakob disease is a rapidly fatal prion disease.
• Neuroimaging and a structured cognitive and neurological assessment separate these from Alzheimer disease and from each other; criteria from NICE NG97, McKeith (2017), Rascovsky (2011) and the AAN practice parameter guide the work-up. ^[10]

By the end of this page you should be able to:

1. Recognise the four main non-Alzheimer dementia syndromes (vascular, frontotemporal, Lewy body, plus normal pressure hydrocephalus and Creutzfeldt-Jakob disease) from their clinical and imaging patterns.
2. Explain the pathophysiology of each and why the symptoms look the way they do.
3. Apply the McKeith, Rascovsky, NINDS-AIREN and diagnostic imaging steps that distinguish them.
4. Manage vascular risk, treat DLB with cholinesterase inhibitors, avoid unsafe antipsychotics, and recognise prion disease and hydrocephalus.
5. Discuss prognosis and carer support across these diseases.

A dementia syndrome is a progressive decline in cognition severe enough to interfere with daily life. These five conditions are the commonest "not Alzheimer" dementias. ^[1][2]

• Vascular dementia (VaD) is cognitive impairment attributed to cerebrovascular disease: one or more infarcts, strategic lesions, small-vessel disease with lacunes and white-matter change, or hypoperfusion. It ranges from multi-infarct dementia to the insidious subcortical form (Binswanger-type disease) and is frequently a mixed pathology. ^[5][8]
• Frontotemporal dementia (FTD) is neurodegeneration beginning in the frontal and/or anterior temporal lobes. The three clinical syndromes are behavioural variant FTD (bvFTD), nonfluent/agrammatic primary progressive aphasia and semantic variant primary progressive aphasia. ^[2][3]
• Dementia with Lewy bodies (DLB) is dementia with alpha-synuclein pathology and Lewy bodies, with onset of cognitive, psychiatric, motor and autonomic features close together (classically parkinsonism occurring within about a year of the dementia). Parkinson disease dementia is a closely related syndrome in which motor disease clearly precedes the dementia by more than a year. ^[1]
• Normal pressure hydrocephalus (NPH) is ventriculomegaly with normal or intermittently raised cerebrospinal fluid (CSF) pressure and the triad of gait disturbance, cognitive decline and urinary dysfunction; it is potentially reversible. ^[6]
• Creutzfeldt-Jakob disease (CJD) is a prion disease: human disease from misfolded prion protein. Sporadic CJD accounts for roughly 85% of cases; inherited and acquired (iatrogenic or variant) forms are rare. ^[7]

Worldwide about 56.9 million people lived with dementia in 2021, projected to exceed 137 million by 2050. ^[5] VaD is the second commonest cause. Pathology-based series place pure VaD at about 15% of all dementia and mixed vascular-plus-degenerative disease at about 16%, with roughly 8.5 million people living with pure VaD and 9.1 million with mixed disease in 2021. ^[5] Incidence after stroke is steeply related to severity: one-year post-stroke dementia rates of about 5.2% after transient ischaemic attack, 8.2% after minor stroke and 34.4% after severe stroke have been reported. ^{[5] [7]}

FTD is commoner at young age: onset is often in the sixth decade (mean about 58 years in the bvFTD series). ^[3] About 26% of bvFTD has a positive family history and roughly 22% carry a pathogenic mutation (most often MAPT or progranulin/GRN). ^[3]

DLB is the second most common degenerative dementia in many older populations; the McKeith consensus emphasises that it is often missed or labelled Alzheimer disease. ^[1] RBD frequently precedes the dementia by years. ^[1]

NPH is a disorder of older adults and is an important reversible cause of cognitive decline. ^[6] CJD is rare (United Kingdom median annual mortality about 1.46 per million for sporadic disease) and usually occurs between ages 50 and 80. ^[7]

Risk factors. VaD shares its risks with stroke: age, hypertension, diabetes, hyperlipidaemia, smoking, obesity, physical inactivity, atrial fibrillation and prior stroke; chronic small-vessel change also relates to metabolic syndrome. ^[5][8] FTD risk is dominated by family history. DLB risk factors are similar to Parkinson disease and Alzheimer disease (age, vascular risk, REM sleep behaviour disorder). ^[1] NPH risk relates to vascular and CSF-dynamic factors. CJD is mostly sporadic; inherited prion disease (10-15% of cases) is autosomal dominant with a 50% transmission risk. ^[7]

Vascular cognitive impairment arises when perfusion is inadequate for neural networks. Large-artery atherothromboembolism and cardiac embolism produce cortical infarcts; chronic hypertension and diabetes damage the long penetrating arterioles, producing lacunes and white-matter ischaemia. Hypoperfusion (heart failure, arrhythmia, severe hypotension) contributes to white-matter change. Mixed disease (vascular plus Alzheimer pathology) explains why many patients have an intermediate picture. ^[8]

FTD arises from frontotemporal lobar degeneration, a group of pathologies including tau aggregates (e.g. Pick disease, corticobasal degeneration, progressive supranuclear palsy) and TDP-43 aggregation, with a minority involving FUS protein. Genetic forms involve MAPT, GRN and C9orf72. ^[3]

DLB is alpha-synuclein aggregation: Lewy bodies in brainstem, limbic and neocortical regions, with reduced dopaminergic transmission (explaining parkinsonism) and cholinergic deficit (explaining cognitive and behavioural symptoms). ^[1] NPH is ventriculomegaly with impaired CSF resorption and glymphatic dysfunction. ^[6] CJD is accumulation of misfolded prion protein with neuronal loss and spongiform change. ^[7]

Vascular dementia has no single lesion; the pattern follows the vessels. Multi-infarct dementia shows stepwise decline after each cortical event, with patchy focal deficits. Strategic-infarct dementia appears after a single lesion in a memory or executive node (thalamus, caudate, genu of the internal capsule). Subcortical vascular disease is the commoner, quieter form: lacunes and white-matter change disrupt frontal-subcortical circuits, producing dysexecutive slowing, gait and bladder symptoms without a clear stroke history (a history of stroke may be absent in up to 40%). ^[8]

FTD disconnects the frontal control networks. Behavioural disinhibition, apathy, loss of empathy and hyperorality follow fronto-temporal and anterior-cingulate involvement; executive failure and relative sparing of episodic memory and visuospatial skill define the neuropsychological signature. ^[3]

DLB combines a cholinergic deficit (producing fluctuating attention, visual processing failure and visual hallucinations), a dopaminergic deficit (parkinsonism) and autonomic failure. Fluctuations are delirium-like; visual hallucinations are usually well-formed people or animals. ^[1]

NPH produces "magnetic", broad-based gait with reduced step height because periventricular long-loop fibres are stretched; cognition and continence follow the same periventricular circuits. ^[6]

CJD is rapidly progressive global brain dysfunction; pathology is heterogeneous, giving atypical presentations. ^[7]

Take a full history from the patient and an informant, with onset, course, vascular risks, sleep, behavioural change and family history. Examination includes cognition (attention, executive function, visuospatial tests rather than memory-only screening), focal neurological signs, parkinsonism, gait, primitive reflexes and cranial nerves. ^[2][10]

• Stepwise or fluctuating course; small steps of decline; focal neurological signs (hemiparesis, sensory loss, dysarthria). ^[8]
• Subcortical form: insidious onset, slow progression, bradyphrenia, apathy, emotional lability, depression, gait disturbance, urinary urgency, often without stroke history. ^[8]
• Cognitive profile: executive dysfunction, slowed processing; memory less impaired than in Alzheimer disease. ^[8]

• bvFTD: progressive personality change, disinhibition, socially inappropriate behaviour, loss of manners, apathy/inertia, loss of sympathy/empathy, perseverative or compulsive behaviour, hyperorality, dietary change; relative sparing of early memory and spatial skills. ^[3]
• Language variants: nonfluent/agrammatic (effortful, halting speech, agrammatism) and semantic (loss of word and object meaning). ^[2]
• Neurological examination may be normal early; primitive reflexes, parkinsonism or motor neuron signs may appear later. ^[3]

• Fluctuating cognition and alertness, with daytime drowsiness, staring and disorganised speech. ^[1]
• Recurrent, well-formed visual hallucinations (up to about 80%). ^[1]
• Spontaneous parkinsonism (eventually over 85%; may be subtle: one cardinal feature is enough). ^[1]
• REM sleep behaviour disorder (dream enactment, chasing/attacking themes); arises years earlier and often quiets later; RBD occurs far more often in autopsy-confirmed DLB than in non-DLB disease. ^[1]
• Supportive clues: sensitivity to antipsychotic drugs, severe autonomic disturbance, syncope, postural hypotension, anosmia, hypersomnia and lower limb restlessness. ^[1]
• Cognitive profile: disproportionate deficits in attention, executive function and visuospatial processing relative to memory and naming. ^[1]

• Gait first: slow, broad-based, short-stepped, unstable gait with a "magnetic" quality and reduced step height. ^[6]
• Cognitive decline, usually subcortical (slowing, attention, executive change) with relative preservation early. ^[6]
• Urinary urgency then incontinence. ^[6]
• Examination otherwise may be unremarkable; parkinsonian features, when present, raise the possibility of mixed synucleinopathy. ^[6]

• Course over weeks to a few months, fast by dementia standards: the classical presentation (about 50%) combines rapidly progressive cognitive decline with cerebellar ataxia, myoclonus and pyramidal/extrapyramidal signs. ^[7]
• Other phenotypes at onset: pure cognitive (~15%), pure ataxic (~10%), psychiatric/behavioural (~5%, including visual hallucinations), pure visual (Heidenhain variant, ~5%), sleep/thalamic (~2%), stroke-like (~2%) and corticobasal (~2%). ^[7]
• Features include memory loss, dysphasia, executive dysfunction, myoclonus, gait and limb ataxia, visual loss or hallucinations, and progression to akinetic mutism. ^[7]
• Onset of sporadic disease is typically between ages 50 and 80; median survival is about 4 to 6 months and most die within a year. ^[7]

Use current validated criteria rather than impression. ^[2][10]

• DLB: the McKeith (2017) fourth consensus criteria. Dementia is essential. Core clinical features (fluctuation, recurrent visual hallucinations, one or more spontaneous parkinsonian features, REM sleep behaviour disorder) define the syndrome. Probable DLB requires two or more core features, or one core feature plus one or more indicative biomarkers (reduced dopamine transporter uptake on SPECT/PET, abnormal 123I-MIBG cardiac scintigraphy, or polysomnographic confirmation of REM sleep without atonia). Possible DLB is one core feature or one or more indicative biomarkers. Supportive (non-diagnostic) features include severe antipsychotic hypersensitivity, postural instability, falls, syncope, severe autonomic dysfunction, hypersomnia, hyposmia, a non-REM parasomnia and systematised delusions. ^[1]
• bvFTD: the Rascovsky (2011) FTDC criteria. "Possible" bvFTD requires progressive behavioural or cognitive deterioration plus three of six features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative or compulsive behaviour, hyperorality, and a dysexecutive neuropsychological profile with relatively spared memory and visuospatial skills). "Probable" bvFTD also requires significant functional decline and imaging consistent with bvFTD (frontal/anterior temporal atrophy on MRI/CT, or frontal/anterior temporal hypoperfusion/hypometabolism on PET/SPECT). "Definite" requires histopathological confirmation or a known pathogenic mutation. Exclusion criteria (medical, psychiatric, or strongly biomarker-positive Alzheimer disease) apply. ^[3]
• VaD: NINDS-AIREN criteria combine (1) a dementia syndrome, (2) evidence of cerebrovascular disease and (3) a causal relationship, inferred from onset within 3 months of a recognised stroke, or abrupt deterioration, or fluctuating/stepwise progression. They are specific (about 80%) but less sensitive (about 58%). Other criteria (DSM-IV, ICD-10, ADDTC) are not interchangeable and select different patients. Always correlate imaging with the clinical picture: "vascular dementia" should not be diagnosed on lesion burden alone. ^[2][8]
• NPH: diagnosis rests on the triad plus ventriculomegaly, after excluding secondary causes; a high-volume (30-50 mL) CSF tap with clear improvement supports shunting. ^[6]
• CJD: probable CJD is rapidly progressive dementia plus myoclonus, visual or cerebellar symptoms, pyramidal/extrapyramidal features or akinetic mutism, with supportive investigations (RT-QuIC in CSF or tissue, caudate/putamen or at least two cortical regions hyperintense on DWI/FLAIR, or periodic sharp-wave complexes on EEG). Definitive diagnosis requires neuropathological or biochemical confirmation of prion disease (usually post mortem). ^[7]

A comparison of the five syndromes and their closest mimics:

• Suspected CJD or rapidly progressive dementia: refer to neurology with access to CSF testing promptly; avoid routine invasive procedures with reuse of instruments. ^[2][7]
• Acute vascular event: manage stroke according to current stroke pathway; prevent recurrence. ^[5]
• DLB with delirium or acute confusion: treat medical triggers and avoid antipsychotics; use a familiar environment and orientation. ^[2][1]
• NPH with sudden gait decline: evaluate for subdural haematoma or intercurrent illness before attributing change to disease. ^[6]

Vascular dementia

• Primary and secondary stroke prevention: rigorous control of hypertension, diabetes, hyperlipidaemia and smoking; antiplatelet therapy after ischaemic stroke/TIA in line with stroke guidelines; atrial fibrillation management and anticoagulation where indicated. ^[5][8]
• Vascular dementia itself is not an indication for cholinesterase inhibitors or memantine unless comorbid Alzheimer disease, Parkinson disease dementia or DLB is suspected; in that case, treat as below. ^[2]
• If a symptomatic cognitive drug is used in mixed disease, doses reported in vascular studies are donepezil 5-10 mg daily, galantamine 16-24 mg daily and memantine 20 mg daily. ^[8]

Frontotemporal dementia

• No disease-modifying drug. Do not use cholinesterase inhibitors or memantine. ^[2]
• Management is non-pharmacological: environmental simplification, behaviour planning, speech and language therapy, occupational therapy, structured day, safety planning and carer education and support. ^[2][3]
• Treat comorbid depression or anxiety with SSRIs where appropriate (common practice; evidence limited in FTD).

Lewy body dementia (treat as for Parkinson disease dementia where motor symptoms predominate)

• Offer donepezil or rivastigmine for mild to moderate disease; consider them in severe disease. ^[2]
• Consider memantine if cholinesterase inhibitors are not tolerated or are contraindicated. ^{[2] [4]}
• Rivastigmine (patch as licensed for Parkinson disease dementia): start 4.6 mg/24 hours, increase after at least 4 weeks to 9.5 mg/24 hours if tolerated; may increase to a maximum of 13.3 mg/24 hours after a further 4 weeks. Re-titrate from 4.6 mg/24 hours if treatment is interrupted for more than 3 days. ^[9]
• Parkinsonism: dopaminergic therapy (levodopa) helps some patients but can worsen hallucinations; balance benefit and psychosis. ^[1][4]
• Antipsychotic sensitivity (crucial). Antipsychotic drugs (especially D2-blocking agents such as phenothiazines, butyrophenones, olanzapine) can worsen motor features and, in DLB, cause severe sensitivity reactions. Their use should be minimised. If truly needed for severe distress or risk, use the lowest effective dose for the shortest time, with reassessment at least every 6 weeks. In Parkinson disease and DLB management, quetiapine or clozapine (lower doses than in other indications) are preferred; olanzapine should not be used. ^[1][2][4]
• Anticholinergic drugs (including many bladder and older "antidepressant" agents) should be avoided because they worsen cognition and can precipitate delirium. ^[2]
• Treat sleep and autonomic symptoms (REM sleep behaviour disorder may respond to melatonin or clonazepam; postural hypotension with non-pharmacological measures and, if needed, midodrine or fludrocortisone). ^[4]

Normal pressure hydrocephalus

• Careful selection for ventriculoperitoneal shunting after the triad, imaging and a predictive CSF removal test. Significant clinical improvement occurs in selected patients. ^[6]
• Even when concomitant neurodegenerative pathology exists, shunt response is often preserved; consider adjunct treatment of parkinsonism (e.g. a levodopa trial) for persistent symptoms. ^[6]

Creutzfeldt-Jakob disease

• No disease-modifying treatment. Palliative and supportive care is the mainstay, with very close multidisciplinary support for patient and carers; disease often progresses over weeks to months. ^[7]
• Practical symptom management for myoclonus, pain, swallowing, communication, nutrition and end-of-life care. ^[7]
• Types of progression should be discussed sensitively and future care plans put in place early. ^[7]

• After any dementia diagnosis, ensure access to a memory service or equivalent multidisciplinary dementia service; single named coordinator; carer education and support; annual review of needs, cognition, function and medicines. ^[2]
• In DLB and Parkinson disease dementia, reassess for antipsychotic necessity at least every 6 weeks if used. ^[2]
• In VaD, continue stroke prevention and cognitive reassessment; monitor for mixed pathology. ^[5]

• All patients with suspected dementia to a specialist dementia diagnostic service. ^[2]
• Rapidly progressive dementia to neurology with CSF examination. ^[2]
• Uncertain subtype with therapeutic implications: SPECT/DaT/MIBG for DLB, MRI for VaD, FDG-PET/perfusion SPECT for FTD. ^[2]
• NPH for neurosurgical assessment where the triad and imaging suggest it. ^[6]
• CJD to a national prion service (UK National Prion Clinic) where available. ^[7]

• VaD: recurrent stroke, mixed pathology, post-stroke cognitive and functional decline, mortality higher than in Alzheimer disease; falls and gait loss in subcortical disease. ^[5][8]
• FTD: carer burden and safeguarding, behavioural disturbance, eventual loss of communication and self-care; motor neuron disease in some. ^[3]
• DLB: neuroleptic sensitivity reactions, falls, syncope, aspiration, autonomic failure, sleep injury from REM sleep behaviour disorder. ^[1]
• NPH: falls and (if untreated) progressive disability; after shunt, subdural haematoma, infection. ^[6]
• CJD: rapid progression to akinetic mutism; myoclonus, swallowing failure and infection. ^[7]

• VaD: survival is shorter than in Alzheimer disease in most series; prevention and control of risk modify the course. ^[8]
• FTD: average survival roughly 7 to 8 years from onset in bvFTD; varies by syndrome and pathology. ^[3]
• DLB: progression varies; the disease often shows substantial cholinergic benefit; median survival similar to or slightly shorter than Alzheimer disease in many cohorts. ^[1]
• NPH: with careful selection, a substantial proportion improve after shunting; comorbid neurodegenerative pathology worsens outcome. ^[6]
• CJD: median survival about 4 to 6 months; the majority die within a year. ^[7]

• VaD is largely preventable: control vascular risk factors (the 2024 Lancet Commission lists 14 modifiable factors accounting for about 45% of overall dementia risk, including hypertension, diabetes, smoking, obesity, physical inactivity and hyperlipidaemia). ^[5]; manage atrial fibrillation. ^[5]
• Perform case-finding only in research contexts; screen high-risk vascular patients in routine care by attending to cognitive and gait symptoms. ^[2]
• FTD: advise genetic counselling and family screening where a pathogenic mutation or strong family history exists; environmental and behavioural prevention is not established. ^[3]
• DLB: no established prevention; treat vascular risk and sleep disorders. ^[1]
• NPH/CJD: no population screening.

• Older adults: polypharmacy, anticholinergic burden and falls dominate; medication reviews are essential, and be alert for subcortical vascular disease masquerading as "just ageing". ^[2]
• Pregnancy/children: FTD and DLB are diseases of older adults; CJD is rare and inherited forms need genetic counselling; NPH in children is usually secondary. ^[7]
• Immunocompromised patients: consider secondary causes of rapid cognitive decline (infection, inflammatory disease) before diagnosing a degenerative dementia. ^[2]
• Young-onset dementia (under 65): think FTD, vascular or inherited causes; a genetic contribution is commoner. ^[2][3]

• A careful history, cognitive examination, gait assessment and a plain CT head separate most of these diagnoses even when MRI is unavailable; MRI subtypes should not delay basic stroke prevention. ^[2][8]
• Treat vascular risk and offer simple multidisciplinary care and carer education; NICE recommends psychosocial and occupational interventions and group cognitive stimulation. ^[2]
• In DLB, avoid antipsychotics if possible and treat with cholinesterase inhibitors where affordable; fall and safety advice matter most. ^[1][2]
• NPH shunting requires a neurosurgical service; otherwise focus on safety and gait training. ^[6]

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