Pathophysiology — a brief primer

AD is a progressive neurodegenerative disorder characterised by accumulation of amyloid-β plaques and tau-containing neurofibrillary tangles, synaptic dysfunction and progressive neuronal loss. Pathology typically begins in medial temporal lobes (hippocampus) and spreads to association cortices, producing an evolving cognitive syndrome.

Clinical stages & cognitive profile

• Preclinical AD: biomarker changes may be present without cognitive symptoms.
• Mild cognitive impairment (prodromal AD): primary deficits in episodic memory with preserved independence (subjective memory complaints, measurable deficits on testing).
• Major NCD due to AD (mild → moderate → severe): progressive impairment across memory, language, visuospatial function and executive skills, culminating in loss of independence.

Early hallmark: impaired episodic memory (impaired new learning and recall). Later, language difficulties, apraxia, visuospatial dysfunction, behavioural changes and motor features may appear.

Neuropsychiatric & behavioural symptoms

• Apathy and withdrawal.
• Depression and anxiety.
• Agitation, aggression and disinhibition (common in moderate stages).
• Psychosis — mainly visual hallucinations in mixed or Lewy body overlap.
• Sleep disturbances and sundowning.

Assessment — clinical priorities

1. Comprehensive history including onset, trajectory, functional impact and collateral input from family/caregivers.
2. Brief cognitive screening: MoCA or ACE-III preferred for sensitivity to early AD.
3. Domain-specific neuropsychological testing where diagnostic clarity is required.
4. Medication review and assessment for reversible contributors (delirium, depression, B12 deficiency, thyroid dysfunction).

Investigations & biomarkers

• Structural imaging (MRI) — medial temporal atrophy, cortical thinning.
• CSF biomarkers — low Aβ42, high total tau and phosphorylated tau support AD pathology.
• Molecular imaging (amyloid PET, tau PET) — useful in selected cases for diagnostic confirmation or research contexts.
• Blood-based biomarkers (emerging) such as plasma phosphorylated-tau are increasingly available in specialist settings.

Treatment — pharmacological strategies

• Symptomatic therapies: cholinesterase inhibitors (donepezil, rivastigmine, galantamine) for mild–moderate AD; memantine for moderate–severe AD to address cognitive and functional symptoms.
• Emerging disease-modifying approaches: therapies targeting amyloid or tau are under investigation or limited to specialist pathways; discuss potential benefits and risks with neurology and patient/family.
• Psychiatric symptom management: SSRIs for depression/anxiety; antipsychotics only when necessary for severe psychosis or aggression, at lowest effective dose with monitoring.

Non-pharmacological & rehabilitative care

• Cognitive stimulation therapy and cognitive rehabilitation tailored to deficits.
• Occupational therapy for ADL support, environmental modification and assistive technology.
• Exercise, social engagement and structured routines to maintain function and mood.
• Caregiver education, respite and support groups — essential for sustainable care.

Key takeaways

• AD typically begins with episodic memory impairment and progresses to involve multiple cognitive domains and independence loss.
• Diagnosis combines clinical assessment with imaging and biomarkers when indicated.
• Treatment includes symptomatic pharmacotherapy, non-pharmacological interventions, risk reduction and comprehensive care planning.
• Early involvement of multidisciplinary services and caregiver support improves outcomes and quality of life.