ICD-116D80	DEMENTIA DUE TO ALZHEIMER DISEASE Dementia due to Alzheimer disease
ICD-10F00	Dementia in Alzheimer disease
DSM-5-TRG30.9 + F02.8x	Major Neurocognitive Disorder Due to Alzheimer's Disease

1. Definition and nosology

Dementia due to Alzheimer's disease (ICD-11: 6D80; DSM-5-TR: G30.9 + F02.8x Major Neurocognitive Disorder due to Alzheimer's Disease) — gradual and persistent cognitive decline, initially episodic memory, then multiple cognitive domains and significant impairment of daily functioning. Most common cause of dementia (60–70%).

2. History

• Alzheimer A. (1906) — first clinical and pathohistological description.
• Amyloid hypothesis (Hardy J., Higgins G.A. Science 1992).
• NICE NG97 (2018) — dementia clinical guideline.
• FDA — aducanumab (2021, controversial), lecanemab (2023), donanemab (2024) — anti-amyloid antibodies.

3. Epidemiology

• Global 55 mln+ dementia patients (WHO 2023); 60–70% Alzheimer's.
• Prevalence by age: 65 years 5%, 80+ years 25%+.
• Sex: higher in females (related to life expectancy).
• Comorbidity: cardiovascular, depression, anxiety, BPSD (behavioral and psychological symptoms of dementia).

4. Aetiology and pathogenesis

• Familial Alzheimer's (1%): APP, PSEN1, PSEN2 mutations (early onset, dominant).
• Sporadic (99%) – multiple genes (ApoE4 strongest risk; LOAD GWAS loci).
• Modifiable factors (Lancet Commission 2024) — alongside age, ApoE4: low education, hearing loss, hypertension, obesity, smoking, depression, physical inactivity, social isolation, diabetes, air pollution, alcohol, TBI, vision loss, high LDL.
• Pathogenesis — amyloid-β plaques + tau neurofibrillary tangles + neuroinflammation.

5. Clinical features

• Typical onset — episodic memory decline (difficulty retaining new information).
• Stages:
  • Early — memory, anomia, orientation difficulty;
  • Moderate — visual-spatial, executive function, daily activities require support;
  • Late — speech severely limited, loss of recognition of relatives, restricted mobility, feeding and swallowing difficulties.
• BPSD — agitation, aggression, delusions (particularly theft), hallucinations, depression, anxiety, sleep disturbances, sundowning.
• Atypical forms: posterior cortical atrophy (visuospatial dominant), logopenic primary progressive aphasia (language dominant).

6. Diagnosis

6.1 Unified diagnostic criteria

A. Major NCD criteria (≥ 1 cognitive domain significant decline + impairment in daily activities).

B. Clinical characteristics consistent with Alzheimer's (gradual, continuous decline, memory predominant).

C. Probable AD — genetic mutation and/or 3 elements (memory + 1+ cognitive domain, sustained decline, no other cause).

D. Possible AD — criteria not fully met, but atypical clinical presentation or comorbidity.

6.2 Source-specific clarifications

• NIA-AA Research Framework (Jack C.R. 2018) — biomarker-based diagnosis (ATN — amyloid, tau, neurodegeneration).
• NICE NG97 — based on clinical diagnosis; biomarkers selective.
• AAN — diagnostic tools.

6.3 Diagnostic algorithm

1. Clinical interview + informant.
2. MoCA, MMSE, ACE-III.
3. Neuropsychological battery.
4. Laboratory — B12, folate, TSH, liver, kidney, glucose, HIV/syphilis (medical cause exclusion).
5. Brain MRI (atrophy, vascular changes, other pathology).
6. Biomarkers (selective, if clinical suspicion):
   • CSF amyloid-β42 (low), tau (high);
   • Amyloid PET, tau PET;
   • Blood biomarkers (p-tau217, GFAP) — are under development.
7. Comorbid depression screening (GDS).

6.4 Differential diagnosis

7. Examination and assessment

• MoCA, MMSE, ACE-III, neuropsychological.
• Laboratory panel.
• MRI, biomarkers.
• BPSD scales (NPI — Neuropsychiatric Inventory).

8. Treatment

8.1 General Principles (NICE NG97 · AAN · APA)

1. AChEI (donepezil, galantamine, rivastigmine) — for mild-to-moderate Alzheimer; modestly slows cognitive decline. Donepezil 5–10 mg (later 23 mg), rivastigmine patch.
2. Memantine (NMDA antagonist) — for moderate-to-severe Alzheimer's; combination with AChEI.
3. Anti-amyloid antibodies (lecanemab, donanemab) — FDA approval for early symptomatic AD (lecanemab 2023, donanemab 2024); reduces clinical decline rate by ~25%; ARIA (Amyloid-Related Imaging Abnormalities – oedema, cerebral microhaemorrhage) risk high (especially in ApoE4 homozygotes); MRI monitoring crucial; infusion. Clinical benefit is debated.
4. Management of BPSD:
   • First-line — non-pharmacological (environment, social support, physical activity, music therapy);
   • In refractory cases — atypical antipsychotic (risperidone, quetiapine) at low dose, short-term; FDA black box — antipsychotics increase mortality in elderly dementia patients (stroke, cardiovascular).
   • SSRI — comorbid depression/anxiety;
   • Trazodone — for sleep disturbance;
   • Benzodiazepine — is contraindicated (falls, cognitive decline).
5. Carer support and psychoeducation – a critical component.
6. Lifestyle — physical activity, cognitive stimulation, social connections.
7. Advance directives — care and decision-making planning.

8.2 Source-specific clarifications

• NICE NG97 (2018) — AChEI for mild-moderate; memantine for moderate-severe; combination selective.
• Livingston G. et al. Lancet Commission 2024 — 14 modifiable risk factors.
• FDA Lecanemab 2023, Donanemab 2024 — for early AD; ARIA monitoring.
• APA — guidelines for antipsychotic use in the elderly.

Treatment methods

1. Acetylcholinesterase Inhibitors (AChEI) — Donepezil, Galantamine, Rivastigmine — Acetylcholinesterase inhibitor; synaptic acetylcholine increase. NICE NG97.
2. Memantine — NMDA antagonist; reduces excitotoxicity.
3. Lecanemab, Donanemab — Anti-amyloid monoclonal antibodies; for early AD; ARIA monitoring.
4. Non-Pharmacological Interventions for BPSD — Validation therapy, music therapy, reminiscence therapy, ABC analysis.
5. FINGER Multimodal Intervention (FINGER — Finnish Geriatric Intervention Study) — For prophylaxis.
6. Carer Support — Psychoeducation, respite, legal-financial planning.

9. Prognosis

• After diagnosis, median life expectancy is 8–10 years.
• Rapid course, family history, altered by ApoE4.
• Comorbid cardiovascular mortality.

10. Myths and misconceptions

Myth 1: “Alzheimer's is normal aging”

Evidence: Alzheimer's is a disease; normal aging can occur without cognitive decline; up to 45% of dementia cases are attributable to modifiable factors (Lancet Commission 2024).

Myth 2: “Dementia is inevitable, prevention is impossible”

Evidence: Lancet Commission 2024 — management of modifiable factors can delay up to 45% of potential dementia cases.

Myth 3: “Lecanemab cures Alzheimer's”

Evidence: Reduces clinical decline rate by ~25% (moderate effect); ARIA and infusion risks significant; not “cure.”

Myth 4: “Antipsychotics are safe for elderly dementia patients”

Evidence: FDA black box — antipsychotics increase mortality in elderly dementia patients (stroke, cardiovascular); only for severe agitation/psychosis, short-term.

Myth 5: “Ginkgo biloba is a prophylaxis for dementia”

Evidence: Cochrane (Birks J. 2009) — ginkgo shows no evidence of efficacy for dementia.

Myth 6: “Coconut oil cures Alzheimer's”

Evidence: No clinical evidence; promotion in popular media, not a clinical recommendation.

Myth 7: The patient should not be told the diagnosis of dementia

Evidence: NICE — patient has the right to diagnosis; early decision-making, advance documents important.

11. Sources

1. WHO. ICD-11. 6D80 Dementia due to Alzheimer disease. 2024.
2. APA. DSM-5-TR. 2022.
3. NICE NG97. Dementia: assessment, management and support. 2018.
4. Livingston G. et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet 2024;404(10452):572–628.
5. Jack C.R. et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimer's Dement 2018;14(4):535–562.
6. van Dyck C.H. et al. Lecanemab in Early Alzheimer's Disease. NEJM 2023;388(1):9–21.
7. Sims J.R. et al. Donanemab in Early Symptomatic Alzheimer Disease (TRAILBLAZER-ALZ 2). JAMA 2023;330(6):512–527.
8. FDA Black Box Warning — antipsychotics in elderly with dementia. 2005.
9. Birks J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2009;(1):CD003120.