Alzheimer's Disease Treatment — Procedure Guide, Recovery & Risks | MyMedicPlus

Alzheimer's disease (AD) is the most common neurodegenerative cause of dementia, accounting for 60-70% of all dementia cases worldwide. It is a progressive, irreversible disease characterised by the accumulation of amyloid-beta plaques between neurons and neurofibrillary tau tangles within neurons, leading to synaptic dysfunction, neuroinflammation, and ultimately neuronal death — particularly in the hippocampus, entorhinal cortex, and association areas of the cerebral cortex. Current pharmacological treatments are primarily symptomatic, targeting the cholinergic deficit — loss of cholinergic neurons in the nucleus basalis of Meynert — with acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine), and the glutamatergic excitotoxicity pathway with the NMDA receptor partial antagonist memantine. Disease-modifying therapies targeting amyloid, including lecanemab and donanemab, have demonstrated statistically significant but modest slowing of disease progression in early-stage patients and have received accelerated FDA approval in the USA. Non-pharmacological approaches — structured cognitive stimulation, occupational therapy, behavioural management, carer education, and appropriate management of sleep, nutrition, pain, and comorbidities — form an essential and evidence-based component of comprehensive dementia care throughout all disease stages. Emerging therapies targeting tau pathology, neuroinflammation, and synaptic protection are in late-stage clinical trials and represent the next frontier of disease-modifying treatment for Alzheimer's disease.

Symptomatic pharmacological treatment is indicated from mild cognitive impairment (MCI) due to AD through to severe AD. Acetylcholinesterase inhibitors (AChEIs) are the standard of care from mild-to-moderate stage (MMSE score 10-26), providing symptomatic benefit in cognitive, functional, and neuropsychiatric domains. Donepezil 10 mg once daily is also licensed for severe Alzheimer's disease. Memantine, an NMDA receptor partial antagonist, is indicated for moderate-to-severe AD (MMSE under 20) and can be used in combination with an AChEI. Novel anti-amyloid immunotherapies (lecanemab, donanemab) target patients in the earliest stages — MCI or mild dementia — with confirmed amyloid pathology on PET scanning or CSF biomarker analysis; they are not appropriate for moderate or severe disease. Non-pharmacological interventions including cognitive stimulation therapy (CST) are recommended for all patients with mild-to-moderate dementia regardless of pharmacotherapy status. Carers and family members benefit from structured education, psychological support, and respite care services throughout the disease course.

Cholinesterase inhibitor initiation follows a stepwise approach to minimise cholinergic side effects. Donepezil is started at 5 mg once daily at bedtime and increased to 10 mg after 4-6 weeks if tolerated, then to 23 mg (in the USA) for moderate-severe disease. Rivastigmine is initiated at 4.6 mg/24h transdermal patch and titrated to 9.5 mg/24h, then to 13.3 mg/24h; the patch formulation achieves significantly better GI tolerability than oral capsules and is preferred for patients with GI sensitivity. Galantamine is started at 8 mg/day in a prolonged-release formulation and increased to 16 mg/day at 4 weeks, then 24 mg/day at 8 weeks. Memantine is initiated at 5 mg/day and increased by 5 mg weekly to a target dose of 20 mg/day in twice-daily or once-daily modified-release formulation. Anti-amyloid therapies such as lecanemab are administered as intravenous infusions every two weeks, with mandatory amyloid PET or CSF confirmation prior to initiation and MRI monitoring for amyloid-related imaging abnormalities (ARIA). Non-pharmacological interventions including cognitive stimulation therapy are delivered by trained therapists in structured group or individual sessions twice weekly. Behavioural and psychological symptoms of dementia (BPSD) such as agitation, psychosis, sleep disturbance, and depression are managed with non-pharmacological strategies first, with selective pharmacotherapy reserved for severe or refractory cases.

Cholinesterase inhibitors slow the rate of cognitive and functional decline by an effect size equivalent to delaying deterioration by approximately 2-3 months compared to placebo over a 6-12 month treatment period, as measured on ADAS-cog and ADCS-ADL scales. This translates into meaningful preservation of activities of daily living, reduced carer burden, and delayed institutionalisation. Memantine reduces agitation and reduces the emergence of behavioural symptoms in moderate-to-severe disease, and combination therapy (AChEI plus memantine) provides additive benefit over either agent alone in advanced disease. Cognitive stimulation therapy delivers measurable improvements in quality of life and cognitive function comparable to pharmacotherapy in mild-to-moderate disease, with strong evidence from the UK NICE-recommended CST programme. Lecanemab reduced clinical decline by 27% compared to placebo over 18 months in early AD in the CLARITY AD trial (NEJM 2023). Early diagnosis and treatment, combined with proactive management of cardiovascular risk factors (hypertension, diabetes, obesity, smoking) — which independently accelerate Alzheimer's pathology — provides the greatest total long-term benefit.

Cholinesterase inhibitors cause predominantly cholinergic GI side effects — nausea, vomiting, diarrhoea, and anorexia — in 10-25% of patients during dose initiation or escalation. These are usually transient and can be minimised by administering the dose with food, using the transdermal route (rivastigmine patch), and slow titration. Cardiac side effects include bradycardia and syncope (1-3%), clinically relevant in patients with pre-existing sinoatrial or atrioventricular conduction disease; ECG review before initiation is recommended in older patients. Nightmares and sleep disruption occur with evening dosing of donepezil in some patients; switching to morning dosing resolves this in most cases. Memantine is generally well-tolerated; dizziness, headache, and constipation occur in under 5%. Anti-amyloid therapies carry a risk of amyloid-related imaging abnormalities (ARIA): ARIA-E (vasogenic oedema) occurs in approximately 12-35% and ARIA-H (microhaemorrhages) in 14-17% of lecanemab-treated patients, most of which are radiologically detected and asymptomatic; symptomatic ARIA requires treatment interruption. APOE4 homozygous carriers have substantially higher ARIA risk and require careful risk-benefit counselling before anti-amyloid therapy.

Alzheimer's disease management is a lifelong commitment rather than a time-limited intervention. Cognitive and functional status is reviewed every 6 months using validated scales including the MMSE, MoCA, ADCS-ADL, or Clinician's Interview-Based Impression of Change (CIBIC+), alongside carer-reported functional assessment. Pharmacological therapy is reviewed at each visit for efficacy, tolerability, and continued appropriateness; many patients continue AChEI therapy into severe disease stages where behavioural benefits and reduced hospitalisation rates have been demonstrated. Falls risk assessment, nutrition and weight monitoring, swallowing evaluation, depression screening, and pain assessment form integral components of regular review. Advanced care planning — including lasting power of attorney, resuscitation preferences, and future care wishes — should be initiated while the patient retains decision-making capacity at the mild stage. Carer wellbeing is addressed through access to respite care, carer support groups, and psychological therapy, as carer burnout and depression are common and independently worsen patient outcomes. Driving assessment and cessation guidance is mandated in most jurisdictions once cognitive impairment reaches moderate severity.