Definition & diagnostic threshold

Major Neurocognitive Disorder is diagnosed when there is substantial cognitive decline in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual–motor, social cognition) that is sufficient to interfere with independence in everyday activities and cannot be explained by delirium or other mental disorders.

Common types & characteristic features

• Alzheimer’s disease (AD): insidious onset, progressive episodic memory impairment, medial temporal atrophy on imaging.
• Vascular neurocognitive disorder: stepwise decline, executive dysfunction, focal neurological signs, MRI evidence of vascular lesions.
• Lewy body dementia (DLB): early visuospatial deficits, fluctuating cognition, recurrent visual hallucinations and parkinsonism.
• Parkinson’s disease dementia (PDD): dementia developing in the context of established Parkinson’s disease (motor symptoms precede cognitive decline).
• Frontotemporal dementia (FTD): early behavioural change, disinhibition or language-predominant variants (semantic, non-fluent/agrammatic).
• Mixed etiologies: frequently Alzheimer’s with vascular changes or other overlaps.
• Other causes: traumatic brain injury, prion disease, HIV, normal-pressure hydrocephalus, metabolic and toxic causes.

Clinical presentation — cognitive, behavioural and functional

• Cognitive: memory impairment (especially episodic), executive dysfunction, language difficulties, visuospatial impairment and impaired attention.
• Behavioural: apathy, agitation, disinhibition, psychosis, depression and anxiety.
• Functional: difficulty with instrumental activities (finances, medications, driving) and, in later stages, basic activities of daily living (washing, dressing, feeding).

Assessment pathway

1. Confirm cognitive decline and rule out delirium — use collateral history from family/caregivers to establish baseline and timeline.
2. Screen cognitive tests (MoCA preferred for sensitivity) and consider ACE-III or MMSE for follow-up documentation.
3. Domain-specific neuropsychological testing to characterise the cognitive profile and aid differential diagnosis.
4. Medication review, metabolic screen and assessment for reversible contributors (B12, TSH, glucose, electrolytes, syphilis, HIV where relevant).
5. Neuroimaging — MRI brain to identify atrophy patterns, vascular lesions, NPH or other structural causes; CT when MRI not feasible.
6. Specialist referrals (neurology, geriatrics, psychiatry) for complex or rapidly progressive presentations.

Investigations — essential and targeted

• Blood tests: CBC, electrolytes, renal and liver function, glucose, TSH, B12/folate, vitamin D, lipid profile.
• Infectious screen where indicated: HIV, syphilis, hepatitis.
• Neuroimaging: MRI brain with volumetric sequences; CT head for acute settings.
• CSF biomarkers (amyloid, tau) and PET imaging (FDG-PET, amyloid PET) in selected cases when diagnosis uncertain.

Treatment principles

Management aims to slow progression where possible, treat behavioural and psychiatric symptoms, optimise function and support families with long-term care planning.

Cause-specific treatments

• Alzheimer’s disease: cholinesterase inhibitors (donepezil, rivastigmine, galantamine) for mild–moderate AD; memantine for moderate–severe AD.
• Vascular NCD: aggressive vascular risk factor modification (BP control, statins, diabetes management, smoking cessation) and secondary stroke prevention.
• Lewy body dementia: rivastigmine for cognitive symptoms; antipsychotics used very cautiously due to sensitivity.
• FTD: limited evidence for pharmacotherapy — focus on behavioural management and non-pharmacological strategies.

Symptom-targeted pharmacotherapy

• Antidepressants (SSRIs) for depression or anxiety.
• Antipsychotics for severe psychosis or aggression — lowest effective dose and brief duration, with informed consent and monitoring.
• Medications for sleep disturbances and neuropsychiatric symptoms tailored to risk–benefit profile.

Non-pharmacological interventions

• Cognitive rehabilitation and cognitive stimulation therapy.
• Occupational therapy for ADL support, safety modification and assistive technology.
• Psychosocial interventions: caregiver education, structured routines, reminiscence therapy and social engagement.
• Exercise programs to maintain mobility and reduce fall risk.

Key takeaways

• Major Neurocognitive Disorder is a syndrome with multiple causes; accurate aetiological diagnosis guides treatment and prognosis.
• Assessment requires careful history, cognitive testing, imaging and consideration of reversible causes.
• Combine pharmacological treatments where evidence exists with robust non-pharmacological care and caregiver support.
• Early planning for capacity, legal and long-term care improves outcomes for patients and families.