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Dementia

A comprehensive guide to the types, clinical features, assessment, and management of dementia — including Alzheimer's disease, vascular dementia, Dementia with Lewy Bodies, and frontotemporal dementia.

Author's note: This document was written by Dr Alok Kumar Rana, MBBS, PG Diploma in Hospital Management, MRCPsych (UK) — Specialty Registrar in Old Age Psychiatry, Herefordshire PCT NHS Trust (January 2009). Content is intended for qualified medical professionals only.

Definition

Dementia is a progressive and largely irreversible clinical syndrome characterised by widespread impairment of mental function. It can manifest as some or all of the following:

  • Memory loss (particularly short-term memory in Alzheimer's disease)
  • Language impairment (aphasia)
  • Disorientation in time, place, or person
  • Changes in personality
  • Difficulties with activities of daily living (ADLs)
  • Self-neglect
  • Psychiatric symptoms — apathy, depression, psychosis
  • Behavioural and psychological symptoms of dementia (BPSD) — aggression, sleep disturbance, disinhibited sexual behaviour, wandering

Classification of Dementia

(i) Cortical and Subcortical Dementia

A) Cortical dementias: Alzheimer's disease (AD), frontotemporal dementia (FTD), Creutzfeldt-Jakob disease (CJD).

B) Subcortical dementias: Parkinson's disease dementia, Huntington's disease, normal pressure hydrocephalus, multiple sclerosis.

C) Mixed cortical and subcortical: Vascular dementia, Dementia with Lewy Bodies (DLB), corticobasal degeneration, neurosyphilis.

Memory Language Maths Personality Mood Co-ordination Speed Movements
Cortical Severe, early Dysphasia, early Impaired early Indifferent Normal Normal Normal Rare
Subcortical Moderate Normal Preserved Apathetic, inert Flat, depressed Impaired Slowed Common: choreiform or tremor

(ii) Presenile and Senile Dementia

  • Presenile (early-onset) dementia: Onset before age 65. More commonly due to Alzheimer's disease (familial forms), frontotemporal dementia, or rarer causes.
  • Senile (late-onset) dementia: Onset at age 65 or over. The most common form worldwide; Alzheimer's disease accounts for the majority of cases.

Alzheimer's Disease (AD)

Alzheimer's disease is the most common cause of dementia, accounting for approximately 50–60% of all cases. It is characterised by cortical atrophy, loss of cholinergic neurons (particularly from the nucleus basalis of Meynert), the accumulation of amyloid plaques (extracellular), and neurofibrillary tangles of hyperphosphorylated tau protein (intracellular). This cholinergic deficit forms the basis for acetylcholinesterase inhibitor (AChEI) therapy.

The core clinical symptom of AD is cognitive impairment, which is clinically heterogeneous. Cognitive decline is classically described using the "4 As":

  • Amnesia: Memory loss in AD is early and inevitable. Characteristically, recent memories (episodic memory) are lost before remote (long-term) memories — the patient may recall events from decades ago while being unable to recall what they had for breakfast. With disease progression, even remote and emotionally charged memories are eventually lost.
  • Aphasia: Language problems are common at presentation. Word-finding difficulties (nominal dysphasia) are the earliest phenomena, accompanied by circumlocutions (talking around a word they cannot recall). As the disorder progresses, syntax is affected, speech becomes increasingly paraphasic, and eventually comprehension is impaired.
  • Agnosia: Difficulty in recognising objects, faces, or sounds despite intact sensory function. One particular agnosia in AD is loss of recognition of one's own face in a mirror (autoprosopagnosia), which can lead to distressing behaviours such as talking to or becoming frightened of their reflection (the "mirror sign").
  • Apraxia: Difficulties with complex tasks that are not due to motor impairment. Typically, dressing apraxia or difficulties with kitchen tasks are noticed first, progressing to loss of ability for more fundamental activities of daily living.

Additional cognitive impairments in AD include visuospatial difficulties (topographical disorientation, wandering and becoming lost), impaired calculation, attentional deficits, and executive dysfunction.

Functional Impairment in Alzheimer's Disease

Although cognitive decline is the core symptom of AD, it is functional deterioration that has the greatest impact on the patient and drives most of their care needs, including nursing home admission. Activities of daily living (ADLs) are divided into:

  • Instrumental ADLs (first affected): Managing finances, using transport, cooking, housework, managing medication
  • Basic ADLs (affected later): Dressing, washing, toileting, feeding, and mobility

Neuropsychiatric Symptoms of Alzheimer's Disease

Mood: The relationship between AD and depression is complex. Depression is both a risk factor for AD and occurs as part of the condition. Approximately 10% of patients have a full major depressive episode; up to 50% have some depressive features. Elation and hypomania occur but are less common (around 3.5%).

Psychosis: Psychotic symptoms occur in 10–50% of patients. The most common delusion is the delusion of theft — the patient, having mislaid an object due to amnesia, is convinced it has been stolen. Patients may also become convinced that a family member is trying to harm them. Visual hallucinations are more common than auditory hallucinations in AD; when prominent, this should raise the possibility of Dementia with Lewy Bodies.

Misidentification syndromes: Capgras syndrome (the belief that a known person has been replaced by an identical impostor) may occur. Failing to recognise one's own face in a mirror (autoprosopagnosia) is a relatively specific feature of AD.

Personality change: An almost inevitable accompaniment of AD. Family members often describe this as a "living bereavement" — the person remains physically present, but the person once known has fundamentally changed. Changes most commonly involve loss of awareness of and normal responsiveness to the environment, apathy, and emotional blunting.

Vascular Dementia

Vascular dementia is the second most common cause of dementia, accounting for 10–50% of cases depending on the geographic region and diagnostic criteria. It results from cerebrovascular disease and ischaemic or haemorrhagic damage to the brain. It is important to recognise because its vascular risk factors may be modifiable, and patients may benefit from specific interventions.

Vascular dementia is not simply multi-infarct dementia — it encompasses a range of vascular mechanisms including large vessel disease (multi-infarct dementia), small vessel disease (lacunar infarcts, white matter changes), single strategic infarcts in areas such as the thalamus or hippocampus, and hypoxic-ischaemic events.

Risk Factors for Vascular Dementia

  • Vascular: Hypertension, atrial fibrillation, myocardial infarction, diabetes, dyslipidaemia, smoking, generalised atherosclerosis
  • Demographic: Increasing age; men have a slightly higher prevalence
  • Genetic: Family history; CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
  • Stroke-related: Type, site, and size of cerebrovascular event

Clinical Features of Vascular Dementia (ICD-10)

ICD-10 criteria require: evidence of focal brain damage (focal neurological signs or neuroimaging evidence of cerebrovascular disease), unequal distribution of cognitive deficits across different domains, and significant cerebrovascular disease judged to be aetiologically related to the dementia.

Traditionally, vascular dementia has a relatively abrupt onset (days to weeks), stepwise deterioration (periods of worsening with partial recovery), and a fluctuating course. The mean duration is approximately 5 years. Survival is less than for the general population or those with Alzheimer's disease, due to the co-morbid cardiovascular disease.

Frontotemporal Dementia (FTD)

Frontotemporal dementia results from degeneration primarily affecting the frontal and temporal lobes. It includes Pick's disease (characterised by Pick cells and Pick bodies in neurones) and frontal-lobe degeneration of non-Alzheimer type. It is the most common cause of early-onset dementia.

The first clinical manifestations usually appear in the presenium — most commonly between ages 45 and 70 years. Memory is relatively preserved in the early stages, in contrast to Alzheimer's disease.

Clinical Features of Frontotemporal Dementia

  • Early changes in personality and behaviour: loss of personal and social awareness, neglect of personal hygiene, tactlessness, antisocial behaviour, loss of empathy
  • Emotional shallowness and blunting — egocentric, rigid, lacking in concern for family and friends
  • Stereotyped and perseverative behaviours: wandering, clapping, humming, hoarding objects, complex rituals involving washing and dressing
  • Features of Klüver-Bucy syndrome: blunted affect, hyperorality, unrestrained sexuality
  • Progressive impairment of expressive speech — with relative preservation of comprehension initially
  • Disinhibition and socially inappropriate behaviour that can be mistaken for a psychiatric disorder (mania, schizophrenia, personality disorder)

The clinical onset is insidious and the course slowly progressive. The duration of FTD ranges from 3 to 17 years.

Dementia with Lewy Bodies (DLB)

Lewy bodies are spherical neuronal inclusions composed of alpha-synuclein protein, first described by Friedrich Lewy. They are found in the substantia nigra in Parkinson's disease and in the cerebral cortex in DLB. DLB accounts for just under 20% of all dementia cases at neuropathological autopsy.

Core Clinical Features of DLB (McKeith Criteria)

  • Fluctuating cognition — marked variation in attention and alertness, often apparent on a day-to-day basis; patients may have periods of appearing almost normal and then periods of profound confusion
  • Recurrent, well-formed visual hallucinations — typically vivid, detailed, and persistent; usually of people or animals; present in approximately two-thirds of patients
  • Spontaneous features of Parkinsonism — bradykinesia, rigidity, tremor (postural rather than resting is more common than in idiopathic Parkinson's disease)
  • REM sleep behaviour disorder — acting out dreams (a newly recognised core feature)

Critical prescribing warning: Patients with DLB are exquisitely sensitive to conventional (typical) antipsychotics (e.g. haloperidol) and may develop severe, life-threatening neuroleptic sensitivity reactions — characterised by sudden deterioration of consciousness, severe Parkinsonism, and autonomic instability. Even atypical antipsychotics must be used with extreme caution. This is one of the most important clinical distinctions between DLB and Alzheimer's disease.

Assessment Tools

  • MMSE (Mini-Mental State Examination): 30-point scale assessing orientation, registration, attention, recall, and language. Widely used but limited sensitivity for mild dementia. Scores: 25–30 = no cognitive impairment; 21–24 = mild dementia; 10–20 = moderate dementia; 0–9 = severe dementia. Copyright restrictions now limit its use.
  • MoCA (Montreal Cognitive Assessment): 30-point scale, more sensitive than MMSE for mild cognitive impairment and frontal/executive deficits. Freely available at mocatest.org. Score below 26 suggests cognitive impairment.
  • ACE-III (Addenbrooke's Cognitive Examination III): 100-point scale; highly sensitive and specific; covers attention, memory, fluency, language, and visuospatial abilities.
  • Clock Drawing Test: Simple screening test; particularly sensitive for visuospatial and executive dysfunction.

Investigations

  • Full blood count, renal function, liver function, thyroid function tests, vitamin B12 and folate, calcium, glucose — to exclude reversible causes of cognitive impairment
  • Syphilis serology (VDRL/TPHA) and HIV testing where clinically indicated
  • Urinalysis (delirium must be excluded)
  • CT head (to exclude space-occupying lesions, hydrocephalus, cerebrovascular disease)
  • MRI brain (more sensitive — can show hippocampal atrophy in AD, white matter changes in vascular dementia, frontal lobe atrophy in FTD)
  • DaTSCAN (dopamine transporter SPECT) — to support diagnosis of DLB vs Alzheimer's disease
  • Neuropsychological assessment — detailed formal cognitive testing
  • CSF biomarkers (amyloid and tau) in specialist settings for uncertain diagnoses

Pharmacological Management

Acetylcholinesterase Inhibitors (AChEIs)

AChEIs work by inhibiting the enzyme acetylcholinesterase, increasing the availability of acetylcholine at synaptic junctions. This partially compensates for the cholinergic deficit characteristic of Alzheimer's disease and DLB. NICE recommends AChEIs for mild to moderate Alzheimer's disease and for DLB.

  • Donepezil (Aricept) — 5 mg once daily, increasing to 10 mg daily after 4 weeks; suitable across all stages of AD; once-daily dosing
  • Rivastigmine (Exelon) — 1.5 mg twice daily, increasing gradually; also available as a transdermal patch (preferred for patients prone to GI side effects); licensed for Parkinson's disease dementia and may be preferred in DLB
  • Galantamine (Reminyl) — also acts as a nicotinic receptor modulator; 4 mg twice daily, increasing to 8–12 mg twice daily; XL formulation available for once-daily dosing

Common side effects of AChEIs: nausea, vomiting, diarrhoea, bradycardia (ECG monitoring recommended), and vivid dreams. These can be minimised by slow dose titration.

Memantine

Memantine is an NMDA (N-methyl-D-aspartate) receptor antagonist that blocks excessive glutamatergic activity, which is thought to contribute to neuronal excitotoxicity in Alzheimer's disease. NICE recommends memantine for moderate to severe AD (as an alternative or in addition to AChEIs) and for severe AD. Dose: 5 mg once daily, increasing by 5 mg weekly to 20 mg once daily. Side effects: dizziness, headache, constipation, hypertension; generally well tolerated.

Management of Behavioural and Psychological Symptoms of Dementia (BPSD)

BPSD (including agitation, aggression, wandering, sleep disturbance, and psychosis) are among the most distressing aspects of dementia for patients, carers, and care staff. Non-pharmacological approaches should always be tried first:

  • Person-centred care approaches
  • Structured activity and meaningful occupation
  • Environmental modification (lighting, wayfinding cues)
  • Music therapy, aromatherapy, and reminiscence therapy
  • Carer support and training

If pharmacological treatment is required for BPSD:

  • AChEIs and memantine have modest effects on agitation and psychosis in AD
  • Antipsychotics (e.g. quetiapine, risperidone) may be used with caution for severe agitation or psychosis in AD — risks include increased risk of stroke (1–2%) and death; they should be used at the lowest effective dose for the shortest possible time, with regular review
  • Conventional antipsychotics are absolutely contraindicated in DLB due to the risk of severe neuroleptic sensitivity reactions
  • SSRIs (sertraline, citalopram) for depression and agitation in dementia

Frequently Asked Questions

What is the most common cause of dementia?

Alzheimer's disease is the most common cause of dementia, accounting for approximately 50–60% of all cases. The second most common is vascular dementia (10–20%), followed by Dementia with Lewy Bodies (10–15%), and frontotemporal dementia (5–10%). Mixed pathology — particularly Alzheimer's disease co-existing with vascular dementia — is very common at post-mortem and probably accounts for many clinically ambiguous presentations. In people under 65 years of age (early-onset or presenile dementia), frontotemporal dementia becomes a relatively more common cause.

How does Dementia with Lewy Bodies differ from Alzheimer's disease?

Key distinguishing features of DLB compared to Alzheimer's disease include: fluctuating cognition with pronounced variation in attention (not present in AD); prominent, recurrent, well-formed visual hallucinations (much more common in DLB); spontaneous Parkinsonism; and REM sleep behaviour disorder. Memory impairment is less prominent and less consistent in early DLB than in early AD — executive and visuospatial deficits may be more prominent. DaTSCAN shows reduced dopamine transporter uptake in DLB but not in AD. Crucially, patients with DLB are extremely sensitive to antipsychotics — conventional antipsychotics can cause life-threatening neuroleptic malignant syndrome-like reactions and must be avoided.

What are acetylcholinesterase inhibitors and how do they work?

Acetylcholinesterase inhibitors (AChEIs) — donepezil, rivastigmine, and galantamine — work by blocking the enzyme acetylcholinesterase, which normally breaks down acetylcholine in the synaptic cleft. By inhibiting this enzyme, AChEIs increase the concentration of acetylcholine available at cholinergic synapses, partially compensating for the cholinergic deficit in Alzheimer's disease (caused by loss of neurons from the nucleus basalis of Meynert). They have a modest but clinically meaningful effect on cognition, functional ability, and behaviour. NICE recommends them for mild to moderate Alzheimer's disease and for Dementia with Lewy Bodies (rivastigmine is particularly preferred in Parkinson's disease dementia).

What is the MMSE and what are its limitations?

The MMSE (Mini-Mental State Examination), developed by Folstein et al. (1975), is a 30-point cognitive screening tool assessing orientation, registration, attention and calculation, recall, and language. Scores of 24–30 are generally normal, 18–23 suggest mild cognitive impairment or mild dementia, and below 18 indicates moderate to severe dementia. Limitations include: poor sensitivity for mild dementia and early frontotemporal dementia; educational and cultural bias (scores are influenced by education level and first language); inability to detect executive dysfunction; copyright restrictions (PAR, Inc.) limiting free clinical use. The MoCA (Montreal Cognitive Assessment) is now preferred in many centres as it is more sensitive for mild cognitive impairment and is freely available.

What is the STOMP programme?

STOMP (Stopping Over-Medication of People with a learning disability, autism, or both) is an NHS England programme that highlights the inappropriately high rates of psychotropic medication prescribed to people with intellectual disabilities and/or autism, often for behavioural problems rather than a specific mental health condition. STOMP encourages clinicians, patients, carers, and families to review all psychotropic medications, ensure they are only used when there is a clear clinical indication, and to consider non-pharmacological interventions first. Although primarily focused on people with intellectual disabilities, the principles of minimising unnecessary psychotropic prescribing in dementia are closely aligned.

When should antipsychotics be used for BPSD, and when are they contraindicated?

Antipsychotics for behavioural and psychological symptoms of dementia (BPSD) should only be used when non-pharmacological approaches have been tried and have failed, and when the patient is at risk of harming themselves or others. NICE recommends risperidone (the only antipsychotic licensed for BPSD) at the lowest effective dose for the shortest possible time (initially no longer than 6 weeks), with regular review. All antipsychotics in people with dementia carry an increased risk of stroke (approximately doubled) and death. Conventional antipsychotics (haloperidol, chlorpromazine) are absolutely contraindicated in DLB due to the risk of severe, potentially fatal neuroleptic sensitivity reactions. Even atypical antipsychotics must be used cautiously in DLB.

What investigations are recommended in the workup of new dementia?

NICE NG97 recommends the following baseline investigations for all patients with suspected dementia: full blood count; urea, creatinine, and electrolytes; liver function tests; thyroid function tests; serum calcium; blood glucose; vitamin B12 and folate levels; urinalysis. Structural brain imaging (CT or MRI) is recommended for all patients to exclude reversible causes (brain tumour, subdural haematoma, normal pressure hydrocephalus) and to support the diagnosis of dementia subtype. MRI is preferred over CT where accessible, as it provides superior characterisation of hippocampal atrophy, white matter changes, and cortical thinning. Functional imaging (FDG-PET, SPECT) and CSF biomarkers may be used in specialist memory clinic settings when the diagnosis is uncertain.

References

  1. National Institute for Health and Care Excellence. Dementia: assessment, management and support for people living with dementia and their carers. NICE Guideline NG97. NICE, 2018. Available at: nice.org.uk/guidance/ng97
  2. Alzheimer's Society. Dementia UK. 3rd ed. Alzheimer's Society, 2014. alzheimers.org.uk
  3. McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017;89(1):88–100.
  4. Gelder M, Cowen P, Harrison P. Shorter Oxford Textbook of Psychiatry. 7th ed. Oxford University Press, 2020.
  5. Kaplan HI, Sadock BJ. Concise Textbook of Psychiatry. 2nd ed. Williams & Wilkins, 1996.
  6. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders. WHO, Geneva, 1992.
  7. Folstein MF, Folstein SE, McHugh PR. "Mini-Mental State": A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–198.
  8. Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–699.