Lucan · Conditions

Alzheimer's dementia

Australian guidance: eTG Neurology — Dementia + RACGP

1. Definition and epidemiology

Alzheimer's dementia (AD) is a progressive neurodegenerative disorder characterised by insidious onset of cognitive decline severe enough to impair daily functioning, most consistently affecting episodic memory first before extending to other cognitive domains and behaviour. In Australia, dementia affects approximately 421,000 people and is the second leading cause of death; Alzheimer's disease accounts for 60 to 70 percent of all dementia diagnoses. Prevalence doubles roughly every five years after age 65, and the condition disproportionately affects women, who represent approximately two thirds of those living with dementia in Australia.

2. Pathophysiology

Per Robbins Ch 28, two cardinal lesions define AD at the molecular level: extracellular amyloid plaques and intraneuronal neurofibrillary tangles. Amyloid plaques form when amyloid precursor protein (APP) is sequentially cleaved by beta-secretase and gamma-secretase, generating amyloid beta (Abeta) peptides, particularly the aggregation-prone Abeta-42 species, which self-assemble into oligomers and then insoluble fibrils surrounded by dystrophic neurites. Neurofibrillary tangles are composed of hyperphosphorylated tau protein, a microtubule-associated protein that, once destabilised, forms paired helical filaments that accumulate in the neuronal perikaryon and processes. The amyloid cascade hypothesis posits that Abeta accumulation is the initiating event, with tau pathology and neuroinflammation driving neuronal loss downstream. Synaptic dysfunction precedes neuronal death; cholinergic neurons of the nucleus basalis of Meynert are preferentially affected early, explaining the rationale for cholinesterase inhibitor therapy. Macroscopic changes include cortical atrophy that is most pronounced in the hippocampus, entorhinal cortex, and association cortices, with relative sparing of the primary motor and sensory cortices until late disease.

3. Clinical presentation and diagnostic criteria

AD presents insidiously in adults aged 65 or older (late onset) or rarely before 65 (early onset, most often familial). The hallmark early symptom is impaired acquisition of new information: the patient repeats questions, misplaces objects, and cannot recall recent events despite intact remote memory. Visuospatial difficulties (getting lost in familiar environments), word-finding difficulty (anomia), and impaired executive function follow. Behavioural and psychological symptoms of dementia (BPSD) including depression, anxiety, apathy, agitation, and psychosis are common at all stages and are a major driver of carer burden.

Diagnostic criteria (DSM-5 / National Institute on Aging criteria) require: major neurocognitive disorder affecting at least two cognitive domains with gradual onset and progressive decline, causing functional dependence, not better explained by delirium or another psychiatric disorder, with AD aetiology supported by biomarkers or genetic mutation (APOE e4, APP, PSEN1, PSEN2 mutations). Standardised cognitive testing uses the Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA); MoCA is preferred for earlier detection (cutoff less than 26 of 30).

4. Investigations and AU-specific cutoffs

A stepwise approach is used. First exclude reversible causes of cognitive impairment with: full blood count, renal function and electrolytes, liver function tests, thyroid stimulating hormone, vitamin B12 and folate, fasting blood glucose, and urinalysis. Brain imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is indicated to exclude structural lesions (subdural haematoma, tumour, normal pressure hydrocephalus) and to identify medial temporal lobe atrophy on MRI that supports an AD diagnosis.

In Australia, cerebrospinal fluid (CSF) biomarkers (low Abeta-42, elevated total tau and phospho-tau) or positron emission tomography (PET) amyloid and tau imaging are used selectively in specialist settings for diagnostic certainty or clinical trial enrolment; these are not yet standard in general practice. Functional assessment tools including the Functional Activities Questionnaire (FAQ) and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) are recommended for tracking functional impairment. The RACGP Silver Book recommends staging dementia (mild/moderate/severe) to guide management intensity and planning.

Genetic testing for APOE e4 is not recommended routinely given limited actionability; autosomal dominant mutations (PSEN1, PSEN2, APP) are tested only when strong family history suggests early-onset familial AD.

5. Management

Management is multimodal, combining pharmacological and non-pharmacological strategies, and should be person-centred with ongoing assessment of patient preferences and capacity.

Non-pharmacological interventions are first-line for BPSD. These include cognitive stimulation therapy, structured physical activity, reminiscence therapy, music therapy, tailored meaningful activities, and optimising sensory inputs (hearing aids, spectacles). Environmental modifications (clear labelling, consistent routines, adequate lighting) reduce agitation and wandering risk. Carer education and support via services such as Dementia Australia (formerly Alzheimer's Australia) and the National Dementia Helpline (1800 100 500) are strongly recommended. Advance care planning and goals of care conversations should occur while the patient retains capacity.

Pharmacological treatment of BPSD should be used only when non-pharmacological measures have failed, the behaviour poses risk of harm, and after informed consent from the patient or substitute decision maker. Antipsychotics carry a boxed warning for increased mortality in elderly patients with dementia-related psychosis and are reserved for severe or dangerous BPSD.

6. Pharmacology and AU PBS notes

Cholinesterase inhibitors are the standard first-line pharmacological treatment for mild to moderate AD. Donepezil (Aricept, generic) at 5 mg daily for four weeks then 10 mg daily is PBS-listed (streamlined authority) for moderate-to-severe AD (MMSE 10 to 24); the 23 mg extended-release formulation is not PBS-listed. Rivastigmine (Exelon) is available orally or as a transdermal patch (4.6 mg per 24 hours titrating to 9.5 mg per 24 hours) and is preferred when gastrointestinal tolerability is a concern; also PBS-listed. Galantamine (Reminyl ER) extended-release 8 mg daily titrating to 16 to 24 mg daily is also PBS-listed. Common adverse effects across the class include nausea, vomiting, diarrhoea, bradycardia, and syncope; slow titration reduces tolerability issues.

NMDA receptor antagonist. Memantine (Ebixa, Namenda) 5 mg daily titrating to 20 mg daily is PBS-listed (Authority Required) for moderate-to-severe AD (MMSE 3 to 14) or when cholinesterase inhibitors are contraindicated or not tolerated. Combination of memantine with a cholinesterase inhibitor is used in moderate-to-severe disease. Adverse effects are generally mild: dizziness, headache, confusion.

BPSD pharmacotherapy. Low-dose risperidone (0.25 to 1 mg daily) has the strongest evidence for AD-related psychosis and aggression and is the only antipsychotic with a TGA-approved indication for BPSD. It is not PBS-listed for this indication and requires specialist or Severe Behaviour Response Team input in residential aged care. Mirtazapine (15 to 30 mg nocte) or citalopram (10 to 20 mg daily, lower doses due to QTc risk) may be used for depression or agitation. Melatonin 2 mg modified-release may assist sleep disturbance (not PBS-listed for dementia specifically).

7. Complications and monitoring

Complications include rapid functional decline, falls and fractures secondary to gait disturbance, aspiration pneumonia (a leading cause of death), delirium superimposed on dementia (which accelerates underlying progression), urinary incontinence, pressure injuries, nutritional compromise, and caregiver burnout.

Monitoring schedule: cognitive function reviewed three to six monthly using MMSE or MoCA; medication efficacy and tolerability reviewed six monthly; annual functional assessment with FAQ; regular review of cardiovascular risk factors (hypertension, diabetes, hyperlipidaemia) that may accelerate progression; hearing and vision testing annually; falls risk assessment at each visit; annual advance care planning review; driving assessment, as per RACGP and Austroads fitness to drive standards, is mandatory once diagnosis is established, with notification obligations depending on state jurisdiction. Deprescribing of anticholinergic medications, sedating antihistamines, and benzodiazepines is a priority given their disproportionate harm in this population.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.