Alzheimer disease (Dementia) ✅

Related Subjects: |Behavioural and Psychological (BPSD) Symptoms of Dementia |Alzheimer disease (Dementia)

✅🧠 Alzheimer’s Disease (AD) – the most common cause of dementia, affecting ~10% of people >65 years. Characterised by progressive cognitive decline, memory impairment, and behavioural changes. Diagnosis is clinical, supported by cognitive testing, imaging, and history.

ℹ️ About

• Clinical diagnosis is based on history from patient and informant, cognitive testing (e.g., MMSE, MoCA), and neurological exam.
• ⚠️ Progressive decline in cognition and function, usually insidious.
• Prevalence rises sharply after 80 years of age.

🧬 Aetiology

• Most cases are sporadic; rare familial forms exist (autosomal dominant, Presenilin 1/2, APP).
• Genetic risk: ApoE e4 allele (homozygotes at highest risk).
• Pathophysiology: neuronal loss, synaptic dysfunction, and neurotransmitter deficits (cholinergic, noradrenergic, dopaminergic).

🔬 Pathology

• ⬇️ Acetylcholine in cortex and hippocampus – underpins memory and attention deficits.
• Neurofibrillary tangles: intraneuronal aggregates of hyperphosphorylated tau protein, correlates with disease severity.
• Senile plaques: extracellular β-amyloid deposits, especially in hippocampus and cortex.
• Microglial activation and neuroinflammation contribute to progression.
• Hippocampal atrophy is a hallmark; medial temporal lobe degeneration occurs early.

🖥️ Imaging

• MRI: hippocampal atrophy, cortical thinning, ventricular enlargement; best for disease monitoring.
• CT: less sensitive but may exclude vascular causes.
• PET: amyloid or FDG-PET can support early diagnosis or research settings.
• Functional imaging may show reduced temporoparietal metabolism.

🔎 Diagnosis

• Primarily clinical: history, cognitive testing, examination.
• Rule out reversible causes: B12/folate deficiency, thyroid disease, infection, depression.
• Supportive investigations: MRI/CT, sometimes PET or CSF biomarkers (tau, β-amyloid) in specialist settings.
• Diagnosis is definite only post-mortem; clinically we aim for “probable Alzheimer’s dementia” using criteria such as NIA-AA or DSM-5.

👩‍⚕️ Behavioural & Psychological Symptoms

• Early: anxiety, depression, irritability, sleep disturbance.
• Mid-stage: apathy, agitation, wandering, delusions, hallucinations.
• Late-stage: aggression, psychosis, loss of insight, incontinence, loss of communication.
• Management: non-pharmacological approaches first (routine, structured environment, caregiver support). Pharmacological therapy only if severe distress.

⚠️ Complications

• Falls, fractures, malnutrition, dehydration.
• Infections: urinary tract infections, pneumonia.
• Behavioural crises and caregiver burnout.
• Advanced disease: immobility, pressure ulcers, aspiration, increased mortality (~10% per year).

💊 Management & When to Start Medications

• Referral to memory clinic or specialist for confirmation and treatment planning.
• Cognitive enhancers: Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) for mild-to-moderate disease; memantine (NMDA antagonist) for moderate-to-severe disease.
• Timing: Start cognitive enhancers as soon as functional decline is documented; do not delay for imaging alone. Monitor for response and side effects.
• Non-drug measures: structured daily routine, cognitive stimulation, social engagement, physical activity.
• Behavioural symptoms: non-pharmacological strategies first; antipsychotics reserved for severe agitation or psychosis not responsive to other measures.
• Comorbidity optimisation: cardiovascular risk control, diabetes management, nutrition, and fall prevention.

🌅 End-of-Life Care

• Focus on comfort, dignity, advanced care planning, and symptom management.
• Support for families and carers is essential throughout disease trajectory.

💡 Exam Pearl: Consider Alzheimer’s when: older patient + progressive memory loss + hippocampal atrophy + no stepwise decline (distinguishes from vascular dementia). ✅ NICE-aligned guidance

📚 References & NICE Guidance

• ✅ NICE Guideline NG97 – Dementia: assessment, management and support
  Core clinical guideline covering diagnosis, monitoring, cognitive enhancers, behavioural management and support pathways.
• ✅ NICE Topic Page – Dementia Guidance & Products
  Index of all NICE resources on dementia including guidelines, quality standards, and consultations.
• ✅ NICE Quality Standard QS184 – Dementia
  Priority quality statements for assessment, diagnosis, care planning and support.
• ✅ NICE TA217 – Pharmacological Treatment Appraisal (Donepezil, Rivastigmine, Galantamine, Memantine)
  Evidence appraisal and recommendations on symptomatic medications used in AD.
• 📄 NG97 Full Recommendations (Professional Version)
  Detailed clinical recommendations supporting diagnosis, non‑drug approaches and risk/benefit discussions.