What is Alzheimer's disease?

Alzheimer's disease is the most common cause of dementia — accounting for approximately 60-70% of all dementia cases — and is characterised by progressive, irreversible loss of memory, language, reasoning, and the ability to perform daily activities. The pathological hallmarks are amyloid-beta plaques (protein deposits between neurons) and tau neurofibrillary tangles (twisted protein fibres inside neurons), leading to neuronal death and brain atrophy. Alzheimer's affects approximately 33 million people specifically — part of the 55 million living with dementia globally (WHO 2024). Cases are projected to triple to 153 million by 2050 as populations age.

What are lecanemab and donanemab?

Lecanemab (Leqembi, January 2023) and donanemab (Kisunla, July 2024) are the first approved disease-modifying treatments for Alzheimer's disease — drugs that target the underlying biological cause (amyloid-beta accumulation) rather than just symptoms. Both are monoclonal antibodies given by IV infusion that clear amyloid plaques from the brain. Clinical trial results: lecanemab slowed cognitive and functional decline by approximately 27% over 18 months; donanemab slowed decline by approximately 35% in patients with low-medium tau. These drugs work only in early Alzheimer's (MCI or mild dementia with confirmed amyloid pathology). The side effect ARIA (amyloid-related imaging abnormalities — brain swelling or microbleeds on MRI) occurs in approximately 30-35% of patients and requires regular MRI monitoring.

What are the symptoms and stages of Alzheimer's?

Alzheimer's progresses through stages: Preclinical: amyloid and tau accumulate for 15-20 years before symptoms appear — now detectable with biomarkers. MCI (mild cognitive impairment) due to Alzheimer's: memory problems noticeable to the person and close contacts but not affecting daily function significantly — the window for anti-amyloid therapy. Mild Alzheimer's: memory loss affecting daily life; word-finding difficulty; disorientation; difficulty with complex tasks. Moderate: increasing confusion; difficulty recognising family; need for daily assistance; behavioural changes (agitation, sleep disturbance). Severe: dependent for all activities; loss of speech; swallowing difficulty; vulnerability to infections (pneumonia — most common cause of death).

What can prevent or delay Alzheimer's?

The Lancet 2024 Commission identified 14 modifiable risk factors that could theoretically prevent or delay approximately 45% of dementia cases: hearing loss (use hearing aids); low education; depression; physical inactivity; smoking; excessive alcohol; hypertension; obesity; diabetes; social isolation; traumatic brain injury; air pollution; high LDL cholesterol (new 2024); untreated vision loss (new 2024). The interventions with strongest evidence: treating hearing impairment (greatest population attributable fraction); physical exercise (protective effect in multiple large cohort studies); blood pressure control in mid-life; treating depression; staying cognitively and socially active. These are achievable at population level without pharmaceuticals.

How is Alzheimer's diagnosed?

The diagnosis of Alzheimer's has evolved from a clinical diagnosis of exclusion to a biological diagnosis: Clinical: cognitive assessment (MMSE, MoCA); history of progressive cognitive decline; functional impairment. Structural neuroimaging: MRI brain (hippocampal atrophy — a sign but not diagnostic). Biomarker confirmation (increasingly standard): CSF analysis (low Aβ42, elevated p-tau181 and total tau); plasma p-tau 217 (blood test — >90% accuracy, transforming scalability); amyloid PET scan (definitive amyloid visualisation, required for anti-amyloid antibody eligibility). Tau PET: stages tau pathology (Braak staging). The AT(N) framework: A (amyloid), T (tau), N (neurodegeneration) — biomarker-based biological definition of Alzheimer's.

How does GMJ News cover Alzheimer's disease?

GMJ News covers WHO dementia data, the amyloid cascade hypothesis, lecanemab and donanemab 2023-2024 breakthroughs, ARIA safety monitoring, CSF and blood biomarkers, the Lancet 2024 Commission 14 modifiable risk factors, APOE ε4 genetics, and Georgia's dementia care priorities. Alzheimer's disease — the defining neurological epidemic of the ageing 21st century — is directly relevant to PHIG's ageing programme and Georgia's growing elderly population.

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Alzheimer's Disease

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

Summary Statistics Glossary GMJ news FAQ Documents Organizations Research

Alzheimer's disease — the most common cause of dementia, accounting for 60-70% of the estimated 55 million people living with dementia globally — has entered a transformational era with the FDA approval of lecanemab (Leqembi, January 2023) and donanemab (Kisunla, July 2024): the first disease-modifying therapies that clear amyloid-beta plaques from the brain and slow clinical decline by 27-35% in early Alzheimer's disease, validating the amyloid cascade hypothesis after decades of failed trials (WHO/Lancet 2024). WHO launched updated global guidelines on dementia risk reduction in July 2026, while the Lancet 2024 Commission identified 14 modifiable risk factors — including the newly added LDL cholesterol and vision loss — through which approximately 45% of dementia cases could theoretically be prevented or delayed.

Key messages

55M with dementia — 45% potentially preventable

55 million people live with dementia globally; Alzheimer's causes 60-70% of cases. The Lancet Commission 2024 identified 14 modifiable risk factors through which approximately 45% of dementia could theoretically be prevented or delayed (WHO/Lancet 2024).

Lecanemab + donanemab — first disease-modifying treatments

Lecanemab (Leqembi, FDA January 2023) and donanemab (Kisunla, FDA July 2024) are the first approved drugs that clear amyloid-beta plaques from the brain and slow clinical decline by 27-35% in early Alzheimer's — validating the amyloid cascade hypothesis after decades of failed trials.

ARIA — the critical safety concern

Amyloid-related imaging abnormalities (ARIA) — brain microhaemorrhages or oedema on MRI from amyloid-clearing antibodies — occur in approximately 30-35% of treated patients. Most are asymptomatic, but symptomatic ARIA (headache, confusion, seizure) requires treatment suspension. Regular MRI monitoring is mandatory.

Biomarker diagnosis — the new standard

Alzheimer's is no longer a clinical diagnosis of exclusion. Amyloid PET scan, tau PET and CSF biomarkers (amyloid-beta 42/40 ratio, phospho-tau 181, total tau) now define biological Alzheimer's — enabling pre-dementia diagnosis in the MCI and even preclinical stages (normal cognition with amyloid pathology).

14 modifiable risk factors — prevention is possible

Lancet 2024: 12 established + 2 new risk factors (LDL cholesterol; vision loss). Addressing these: hearing loss (hearing aids), social isolation, cognitive inactivity, physical inactivity, smoking, alcohol, hypertension, obesity, diabetes, depression, TBI, air pollution, low education, high LDL, vision loss — could prevent up to 45% of dementia cases.

APOE ε4 — the strongest genetic risk factor

APOE ε4 allele: one copy increases Alzheimer's risk approximately 3-5 fold; two copies (homozygous) approximately 8-12 fold. APOE ε4 also affects amyloid-clearing antibody response — homozygous carriers have higher ARIA risk. APOE genotyping is increasingly part of Alzheimer's clinical trials and emerging precision medicine approaches.

Key statistics

55M

people living with dementia globally; 60-70% Alzheimer's (WHO 2024)

WHO 2024

153M

projected dementia cases by 2050 (tripling) without prevention

Lancet 2024

45%

of dementia cases potentially preventable/delayed via 14 risk factors

Lancet 2024

27-35%

clinical decline slowed by lecanemab/donanemab vs placebo

NEJM 2023/2024

Jan 2023

lecanemab FDA approval — first amyloid-clearing Alzheimer's drug

FDA 2023

July 2026

WHO updated guidelines on dementia risk reduction launched

WHO July 2026

Dementia causes by type — global proportion (WHO/Lancet)

Source: WHO/Lancet. Alzheimer's disease dominates; mixed dementia (Alzheimer's + vascular) increasingly recognised.

Glossary of key terms

Amyloid cascade hypothesis
WHO/LancetThe central hypothesis of Alzheimer's pathophysiology: aberrant processing of amyloid precursor protein (APP) → accumulation of amyloid-beta peptides (particularly Aβ42) → oligomer formation → fibril formation → amyloid plaques → downstream tau hyperphosphorylation → neurofibrillary tangles → neuronal death → clinical dementia. Validated by: (1) genetic mutations causing early-onset Alzheimer's all involve the amyloid pathway; (2) Down syndrome (trisomy 21 — extra APP copy) uniformly develops Alzheimer's by age 50; (3) amyloid-clearing antibodies slow clinical progression.

Lecanemab (Leqembi)
FDA/EMA 2023An anti-amyloid monoclonal antibody (Eisai/Biogen) targeting amyloid protofibrils. CLARITY AD phase 3 trial: 27% slowing of cognitive decline vs placebo over 18 months in early Alzheimer's (MCI/mild dementia). FDA full approval January 2023. IV infusion every 2 weeks. ARIA (amyloid-related imaging abnormalities) occurred in approximately 35% (most asymptomatic). MRI monitoring required.

Donanemab (Kisunla)
FDA July 2024An anti-amyloid monoclonal antibody (Eli Lilly) targeting pyroglutamate-modified amyloid. TRAILBLAZER-ALZ2 phase 3: 35% slowing of decline in low-medium tau patients (22% in all comers). Novel feature: discontinuation after amyloid clearance confirmed — limited treatment duration. FDA approved July 2024. ARIA in approximately 36%.

ARIA (amyloid-related imaging abnormalities)
FDA/NeurologyBrain imaging findings from amyloid-clearing antibody treatment: ARIA-E (oedema/effusions — sulcal fluid or parenchymal swelling on FLAIR MRI); ARIA-H (microhaemorrhages/haemosiderin deposits on GRE/SWI MRI). Usually asymptomatic; symptomatic ARIA: headache, confusion, dizziness, visual disturbance, nausea (rarely seizures). Management: temporary drug suspension; restart after ARIA resolution. Risk factors: APOE ε4 (homozygous highest risk); anticoagulation.

CSF and blood biomarkers
Alzheimer's AssociationCSF: Aβ42 (reduced — amyloid sequestered in plaques); Aβ42/40 ratio (most accurate); phospho-tau 181 (elevated — tau hyperphosphorylation); total tau (neuronal damage). Blood biomarkers (plasma): plasma Aβ42/40; plasma p-tau 217 (most sensitive — >90% accuracy for Alzheimer's pathology) — now enabling blood-based Alzheimer's diagnosis, transforming scalability of testing. Amyloid PET: definitive amyloid visualisation; expensive; criteria for lecanemab/donanemab eligibility.

Lancet 2024 Commission — 14 risk factors
Lancet 2024The 12 established risk factors from 2020 (low education, hearing loss, hypertension, obesity, smoking, depression, physical inactivity, diabetes, social isolation, excessive alcohol, TBI, air pollution) plus two new additions in 2024: high LDL cholesterol (evidence strengthened for mid-life LDL as modifiable risk factor) and vision loss (untreated vision impairment in later life — now added; hearing aids and glasses both reduce dementia risk). Together: up to 45% of dementia attributable to these factors.