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Alzheimer's Disease

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

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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.

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Dementia (overview)AgeingParkinson's diseaseDepression (risk factor)CVD (risk factor)Longevity science

About this hub. Produced by the GMJ News Editorial Team as a public-good service. Every statistic is linked to its primary source. Documents are preserved in the GMJ Repository with full attribution. Georgian Medical Journal · Contact the editorial team
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