Alzheimer's Disease — Causes, Stages, Symptoms & Care Guide — Symptoms, Causes & Treatment | MyMedicPlus

Alzheimer's disease is a progressive neurodegenerative disorder and the most common cause of dementia worldwide, accounting for 60-80% of all dementia cases. It is characterised by the pathological accumulation of amyloid-beta protein (forming extracellular senile plaques) and hyperphosphorylated tau protein (forming intraneuronal neurofibrillary tangles) — both of which disrupt synaptic function, activate neuroinflammatory pathways, and cause progressive neuronal death. The hippocampus (memory formation centre) and entorhinal cortex are affected earliest, explaining why episodic memory loss is typically the first symptom, before involvement spreads to the parietal, temporal, and frontal cortices. Approximately 55 million people worldwide live with dementia, and Alzheimer's is expected to affect 153 million by 2050 as global populations age. Most cases occur after age 65 (late-onset Alzheimer's); early-onset Alzheimer's — occurring in people under 65 — affects approximately 5-10% of cases and is more frequently linked to rare genetic mutations (APP, PSEN1, PSEN2). Alzheimer's disease is the 7th leading cause of death globally, and it imposes an enormous caregiver burden — over 80% of patients with advanced disease require full-time care.

Alzheimer's disease results from the abnormal accumulation of amyloid-beta (from impaired clearance via the blood-brain barrier and glymphatic system) and pathological tau hyperphosphorylation disrupting axonal transport — both processes leading to synaptic dysfunction, neuroinflammation (microglial activation, astrocyte reactivity), and progressive neuronal death. Age is the strongest risk factor — prevalence doubles approximately every 5 years after age 65, reaching 33% in those over 85. Genetics: APOE-e4 allele (chromosome 19) is the most significant genetic risk factor for late-onset Alzheimer's — one copy increases risk 3-fold, two copies (homozygous) increases risk 8-15-fold; however, APOE-e4 is neither necessary nor sufficient. Rare early-onset familial Alzheimer's (<1% of cases) is caused by autosomal dominant mutations in APP (amyloid precursor protein), PSEN1 (presenilin-1), or PSEN2 (presenilin-2). Down syndrome (trisomy 21) causes near-universal Alzheimer's pathology by age 40 due to the extra copy of the APP gene on chromosome 21. Modifiable risk factors (Lancet Commission 2024 — 14 modifiable factors): untreated hypertension in midlife, type 2 diabetes, obesity, physical inactivity, excessive alcohol, smoking, depression, social isolation, low educational attainment, air pollution exposure, traumatic brain injury, hearing loss (in midlife), and high LDL cholesterol.

Alzheimer's disease follows a characteristic progression through three clinical stages. Mild (early) Alzheimer's: the earliest and most distinctive symptom is episodic memory loss — inability to retain new information (forgetting recent conversations, appointments, where items were placed) while long-term memories remain preserved; word-finding difficulties (anomia); mild disorientation (difficulty remembering the date, losing track of time); subtle personality changes including apathy and irritability; and difficulty with complex tasks such as managing finances or planning. People with mild Alzheimer's may still live independently with support. Moderate Alzheimer's: significant memory impairment affecting both recent and remote memories; disorientation in familiar environments (getting lost near home); need for help with activities of daily living (bathing, dressing, cooking); behavioural and psychological symptoms of dementia (BPSD) — agitation, wandering, sleep disturbances, paranoia, delusions, and hallucinations (affecting 80-90% of patients at this stage); communication difficulties with markedly reduced vocabulary. Severe (late) Alzheimer's: complete loss of verbal communication; inability to recognise family members; total dependency for all personal care; immobility; dysphagia (difficulty swallowing — leading to aspiration pneumonia); urinary and faecal incontinence; and extreme vulnerability to infections. Average time from diagnosis to severe disease is 5-8 years.

Diagnosis of Alzheimer's disease is primarily clinical — based on a comprehensive history (often obtained from both patient and informant), cognitive testing, and neuroimaging — with biomarker confirmation increasingly important. Cognitive assessments: MMSE (Mini-Mental State Examination — 30 points, sensitivity ~80% for moderate-severe dementia), MoCA (Montreal Cognitive Assessment — more sensitive for mild cognitive impairment), ACE-III (Addenbrooke's Cognitive Examination), and neuropsychological testing (memory, language, attention, executive function, and visuospatial domains). Blood tests exclude reversible causes of cognitive decline: FBC, renal function, LFTs, calcium, glucose, TFTs (hypothyroidism), vitamin B12 and folate, syphilis serology, HIV. Structural neuroimaging: MRI brain is preferred — shows characteristic bilateral hippocampal and entorhinal cortex atrophy, medial temporal lobe volume loss, and cortical thinning in parietal and temporal regions; CT head excludes structural causes (subdural haematoma, hydrocephalus, tumour). Functional and biomarker imaging: FDG-PET shows reduced glucose metabolism in temporoparietal regions (characteristic hypometabolism pattern); amyloid-PET detects amyloid plaques (now part of diagnostic criteria); tau-PET detects tau tangles and correlates with disease stage. CSF biomarkers: reduced amyloid-beta 1-42, elevated total tau, elevated phospho-tau 181 — the classical Alzheimer's biomarker signature (AT(N) framework). Blood biomarkers: plasma phospho-tau 217, amyloid-beta 42/40 ratio, and GFAP are emerging high-accuracy blood tests now available in specialist centres. Genetic testing (APOE genotyping, PSEN1/PSEN2/APP for early-onset) in appropriate cases.

Treatment of Alzheimer's disease combines symptomatic pharmacological therapy, disease-modifying biologics (for early stages), and comprehensive non-pharmacological care. Symptomatic cognitive therapy: cholinesterase inhibitors — donepezil (5-10 mg/day, approved for all stages), rivastigmine (oral or transdermal patch — 4.6-9.5 mg/24hr, or capsules 1.5-6 mg twice daily), and galantamine (8-24 mg/day) — inhibit acetylcholinesterase to increase synaptic acetylcholine, producing modest but clinically meaningful improvements in cognition, function, and behaviour in mild-to-moderate Alzheimer's. Memantine (10 mg twice daily) — NMDA receptor antagonist regulating glutamate activity — is approved for moderate-to-severe Alzheimer's and can be used in combination with a cholinesterase inhibitor. Disease-modifying therapies (DMTs): lecanemab (Leqembi — anti-amyloid monoclonal antibody) was approved by the FDA in 2023 for early Alzheimer's (MCI or mild dementia with confirmed amyloid pathology), reducing cognitive decline by approximately 27% versus placebo at 18 months but requiring ARIA (amyloid-related imaging abnormalities — brain swelling/microhaemorrhage) monitoring; donanemab (Kisunla) was FDA-approved in 2024 with similar mechanism and outcomes. These are infused every 2-4 weeks and are not suitable for moderate-severe disease. Management of BPSD (behavioural and psychological symptoms): non-pharmacological approaches first (structured activity, routine, environmental modification); low-dose antipsychotics (risperidone 0.25-1 mg — with caution given mortality risk in dementia) or mirtazapine for agitation; antidepressants (sertraline, citalopram) for depression; melatonin for sleep disturbance. Non-pharmacological care: cognitive stimulation therapy (CST), structured exercise programmes, reminiscence therapy, occupational therapy for adaptive daily function, speech and language therapy for dysphagia, and family/caregiver training and support.

As Alzheimer's progresses without adequate supportive care, patients develop complete dependence for all activities of daily living including feeding, toileting, dressing, and mobility. Nutritional complications arise from dysphagia (swallowing difficulty in late stages) — aspiration of food and liquids causes recurrent aspiration pneumonia, which is the most common direct cause of death. Immobility leads to pressure sores (sacrum, heels, trochanters), deep vein thrombosis, and contractures. Urinary tract infections are common due to incontinence and catheter use. Falls and fractures — particularly hip fractures — occur from impaired gait and balance, with resulting surgical complications. Neuropsychiatric symptoms (agitation, psychosis, wandering) cause significant caregiver burden and increase care home placement rates. Caregiver burnout and depression affect 40-60% of family caregivers without professional support. The average survival from diagnosis is 8-10 years, varying considerably from 3 to over 20 years depending on age at diagnosis and comorbidities. Patients with younger-onset Alzheimer's (onset below age 65) may live considerably longer and have greater socioeconomic impact.

Up to 40% of Alzheimer's cases may be preventable through modifiable risk factor reduction. The Lancet Commission 2024 identified 14 modifiable risk factors: midlife hypertension (control to below 130/80 mmHg), obesity (BMI above 30 — increase dementia risk by 30-40%), physical inactivity (at least 150 minutes moderate aerobic exercise weekly reduces risk by 35-38%), type 2 diabetes (good HbA1c control reduces dementia risk), excessive alcohol (more than 14 units/week), smoking (cessation at any age reduces risk), depression (treat actively — contributes 3.9% of attributable dementia risk), social isolation and low social engagement, air pollution exposure, traumatic brain injury (especially repeated concussion in sport — helmets, rule changes), untreated hearing loss (treating hearing loss in midlife reduces risk — use hearing aids), low educational attainment, late-life vision loss, and high LDL cholesterol. The MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay — emphasising leafy greens, berries, nuts, olive oil, whole grains, fish, poultry, legumes, with restriction of red meat, butter, cheese, sweets) is associated with 35-53% reduced Alzheimer's risk and slowed cognitive decline in observational studies. Cognitive engagement — lifelong learning, reading, puzzles, complex work — builds cognitive reserve, delaying symptomatic onset by years.

See a GP for: noticeable memory decline affecting daily life — particularly forgetting recent events while remembering distant memories; getting lost in familiar places; difficulty managing finances, medications, or complex tasks; language difficulties (word-finding problems); personality changes or withdrawal from social activities; or a family member raising concerns about memory or behaviour. Seek urgent medical attention for: sudden onset of confusion or memory loss (which may indicate acute delirium from infection, medication, or stroke — treatable causes that differ from Alzheimer's); or confusion with fever, headache, or neck stiffness (meningitis/encephalitis). Alzheimer's disease has no definitive cure, but early diagnosis enables access to cholinesterase inhibitor medication (donepezil, rivastigmine — which modestly slow symptom progression), carer support services, advance care planning while the person retains capacity, and participation in clinical trials. Early diagnosis is always valuable — don't wait until symptoms are severe before seeking assessment.