Alzheimer's disease is the most common cause of dementia globally — accounting for 60-80% of dementia diagnoses. The pathology develops over decades before clinical symptoms emerge. By the time recent memory loss becomes apparent, substantial pathological burden has accumulated.
Hallmark pathology: extracellular amyloid-beta plaques and intracellular hyperphosphorylated tau neurofibrillary tangles. The hippocampus and entorhinal cortex are affected early — explaining why recent memory loss is the cardinal early symptom while remote memories remain preserved. Pathology spreads progressively through cortex with anterior-then-posterior progression in many patients.
The basal forebrain cholinergic system dies early in AD, depriving cortex and hippocampus of acetylcholine essential for attention and memory consolidation. This cholinergic deficit drives much of the cognitive picture and is the rationale for cholinesterase inhibitor treatment.
Clinical presentation: insidious onset of progressive recent memory loss (forgetting recent conversations, repeating questions, misplacing items), with relative preservation of remote memory early. Word-finding difficulties, spatial disorientation (getting lost in familiar places), executive dysfunction, eventual loss of activities of daily living. Behavioral symptoms (agitation, depression, psychosis) emerge variably across the course.
Diagnosis: clinical diagnosis remains primary. Workup: comprehensive neurologic exam, cognitive testing (MoCA more sensitive than MMSE for mild impairment), basic labs (TSH, B12, comprehensive metabolic, sometimes RPR, HIV), MRI to assess for vascular contribution and rule out alternatives (NPH, structural lesions). Biomarker testing (CSF amyloid/tau ratios, amyloid PET) increasingly available for early/atypical presentations.
Treatment — cholinesterase inhibitors: donepezil (5-10 mg), rivastigmine (oral and patch), galantamine. Modest benefit — typically a few months to a year of slowed cognitive decline in patients who respond. Memantine (NMDA modulator) approved for moderate-to-severe disease, often combined with cholinesterase inhibitor.
Anti-amyloid antibodies: lecanemab and donanemab — newer disease-modifying agents that clear amyloid plaques. Modest clinical benefit, real ARIA (amyloid-related imaging abnormalities — edema, microhemorrhages) risk requiring MRI monitoring. Candidates: confirmed amyloid pathology, mild cognitive impairment or mild dementia stage, no significant contraindications. The therapeutic landscape is shifting.
Behavioral and psychological symptoms of dementia (BPSD): address modifiable triggers first — pain (often unrecognized in patients who can't verbalize), constipation, urinary retention, infection, medication side effects, environmental change. Antipsychotics carry black-box mortality warning in dementia — use only when behavior is dangerous and after addressing modifiable factors. SSRIs (citalopram has best evidence per CitAD trial) for behavioral symptoms. Non-pharmacologic interventions central.
Family and caregiver support is essential and often more impactful than medication. Education about the disease, advance care planning, caregiver respite, eventual long-term care decisions. The patient with AD lives within a family system; treating the patient means supporting the system.
When you encounter a patient with progressive memory loss, the diagnosis is often AD but the workup matters — treatable mimics (NPH, B12 deficiency, hypothyroidism, depression) should not be missed. Treatment is modest but real. Family support shapes trajectory.