Major Neurocognitive Disorder

Major neurocognitive disorder (dementia) is an acquired, progressive decline in one or more cognitive domains, sufficient to interfere with independence in everyday activities. It is the clinical syndrome that results from a range of underlying neurodegenerative and, less commonly, other pathological processes.

Alzheimer disease is the commonest single cause. Other important causes are vascular dementia, frontotemporal dementia, and dementia with Lewy bodies. Each has characteristic clinical features and, in some cases, specific management implications.

This entry gives the overarching diagnostic framework and general management principles for the syndrome. It distinguishes major neurocognitive disorder from mild cognitive impairment, a milder but clinically important and potentially precursor condition. It also distinguishes it from delirium, which must always be actively considered and excluded, particularly with any acute change in cognitive status.

Classification and the critical delirium distinction

• Major neurocognitive disorder differs from mild neurocognitive disorder (mild cognitive impairment) by functional impairment. It is sufficient to interfere with independence in instrumental or basic activities of daily living.
• Mild cognitive impairment is objective cognitive decline without this degree of functional impairment. It carries a variable, though generally elevated, risk of later progression to major neurocognitive disorder, so monitor affected individuals.
• Delirium is an acute, fluctuating disturbance of attention and awareness developing over hours to days, reflecting an underlying acute medical cause. Actively consider and exclude it before diagnosing major neurocognitive disorder.
• Delirium can be superimposed on an existing major neurocognitive disorder. It is one of the commonest precipitants of acute deterioration in a patient with known dementia.
• Attend to the acuity and pattern of onset. Assess attention and level of consciousness: these are characteristically impaired in delirium but generally relatively preserved, at least in the earlier stages, in major neurocognitive disorder.
• The two conditions differ fundamentally in mechanism, reversibility, and urgency of management.
• The specific cause carries relevance for prognosis and, in some cases, management. Causes include Alzheimer disease, vascular dementia, frontotemporal dementia, dementia with Lewy bodies, and less commonly a range of other causes, including certain reversible or partially reversible conditions. Make an aetiological diagnosis where feasible, rather than applying the broad label alone.

• Core presentation: progressive decline in one or more cognitive domains (memory, language, executive function, visuospatial function, or social cognition). The pattern and combination of affected domains vary with the underlying cause. There is sufficient functional impairment to interfere with independence in everyday activities.
• Behavioural and psychological symptoms of dementia occur commonly across the course, particularly, though not exclusively, in more moderate to advanced disease. They include agitation, aggression, apathy, depression, anxiety, psychosis (delusions and hallucinations), sleep disturbance, and disinhibition.
• They are a frequent source of significant distress for the individual and carers. They frequently trigger care crisis or care home placement. They warrant careful clinical attention and structured management.
• Presentation and pattern of progression vary by underlying cause:
• Alzheimer disease typically presents with early, prominent episodic memory impairment and gradual, relentless progression.
• Vascular dementia typically presents with a more stepwise decline and relatively greater early prominence of executive dysfunction.
• Frontotemporal dementia typically presents with early, prominent behavioural or language change, with relative preservation of memory in the earlier stages.
• Dementia with Lewy bodies typically presents with fluctuating cognition, visual hallucinations, and parkinsonian motor features.
• Progressive functional decline initially affects complex instrumental activities before progressing to basic activities of daily living. In advanced disease there are significant care needs and, frequently, eventual need for residential or nursing home level care.
• This progressive, severely disabling natural history is common across the syndrome regardless of the underlying cause.

• Clinical assessment is the essential foundation of diagnosis. It comprises a detailed history (ideally with collateral information from a reliable informant), formal structured cognitive assessment, and assessment of functional status and independence in activities of daily living. Follow the general principles for Alzheimer disease.
• Systematically exclude delirium in any patient with acute or subacute cognitive change. This is an essential first step. Assess the acuity and pattern of onset, attention (using a validated screening tool where indicated) and level of consciousness.
• Missing a potentially reversible acute medical cause of delirium is time sensitive and critical, if it is mistakenly attributed to a new or progressing major neurocognitive disorder.
• Screen for reversible or partially reversible contributing causes, including vitamin B12 deficiency and thyroid dysfunction.
• Where indicated by the presentation or risk factors, also consider other metabolic, infective or structural causes. Screen for neurosyphilis or HIV in appropriate clinical contexts. Structural causes include normal pressure hydrocephalus and chronic subdural haematoma, particularly in older patients with a relevant fall history.
• This is a standard component of evaluation. It identifies treatable contributing factors that might meaningfully improve the clinical picture, even where an irreversible primary neurodegenerative process also coexists.
• Structural neuroimaging supports aetiological diagnosis where achievable and clinically relevant.
• Formal neuropsychological assessment characterises the pattern of cognitive domain involvement and helps differentiate the underlying causes. It is particularly useful in diagnostic uncertainty or where the presentation is atypical for the individual's age or the suspected diagnosis.
• Where relevant and available, use the additional biomarker and molecular imaging investigations for Alzheimer disease and the other specific conditions.

• Management principles common across the syndrome, regardless of the underlying cause, start with structured psychosocial support for the affected individual, family and carers.
• Address practical care planning and safety, including driving safety, medication management safety, and home environment safety. Signpost relevant community support services and resources.
• Manage behavioural and psychological symptoms of dementia in a structured, stepwise approach. Non-pharmacological strategies are the essential, preferred first line approach in the great majority of presentations.
• Identify and, where possible, address any specific trigger or unmet need. Pain is frequently underrecognised and undertreated in patients with significant cognitive impairment and communication difficulty. Also consider environmental factors and unmet physical or emotional needs.
• Add structured behavioural and environmental modification strategies, tailored to the individual patient and symptom pattern.
• Reserve pharmacological treatment for symptoms causing significant distress or risk to the patient or others, which have not responded adequately to non-pharmacological approaches.
• Antipsychotic medication carries significant risks in this population, including a well established increased risk of stroke and overall mortality. Discuss this explicitly as part of any decision to use the class.
• Where pharmacological treatment is genuinely required, use the lowest effective dose for the shortest necessary duration.
• Dementia with Lewy bodies carries a marked sensitivity to antipsychotic medication, so take particular caution with this class in that population.
• Arrange regular, structured multidisciplinary follow up. Periodically reassess cognitive and functional status, proactively manage emerging behavioural and psychological symptoms, and support the family and carers throughout the progressive course.
• Engage timely with palliative and end of life care planning and services as the disease progresses to its advanced stages.
• Aetiology specific management considerations apply under each individual underlying condition.