A 68-year-old man with a 3-year history of progressive memory loss and cognitive decline is brought to the psychiatric outpatient clinic by his daughter. He has been increasingly forgetful, with difficulty recognizing family members and managing finances. His vital signs are stable, and he has no fever or acute illness. What is the most common cause of dementia in this clinical presentation?

## Most Common Cause of Dementia **Key Point:** Alzheimer's disease (AD) accounts for 60–80% of all dementia cases and is the most common neurodegenerative cause of cognitive decline in the elderly. ### Epidemiology and Pathology **High-Yield:** Alzheimer's disease is characterized by: - Insidious onset with progressive memory loss (especially episodic memory early) - Amyloid-β plaques and tau neurofibrillary tangles in the brain - Neuronal loss and cerebral atrophy, particularly in the hippocampus and temporal lobes - Typical age of onset: 65 years and older (though early-onset AD can occur before 65) ### Clinical Features of AD vs Other Dementias | Feature | Alzheimer's Disease | Vascular Dementia | Lewy Body Dementia | Frontotemporal Dementia | | --- | --- | --- | --- | --- | | **Onset** | Insidious, progressive | Stepwise, abrupt | Insidious, fluctuating | Insidious, early personality change | | **Memory Loss** | Early and prominent | Variable; may spare memory | Late; visual hallucinations prominent | Late; language/behavior early | | **Vascular Risk Factors** | Not required | Present (HTN, DM, stroke) | Absent | Absent | | **Hallucinations** | Absent or late | Absent | Early and frequent (visual) | Absent | | **Parkinsonian Signs** | Absent | Absent | Common (rigidity, bradykinesia) | Absent | | **Prevalence** | 60–80% of dementias | 15–20% | 5–10% | 2–3% | **Clinical Pearl:** The patient in this vignette presents with a classic insidious, progressive course of memory loss without acute features, vascular risk factors, visual hallucinations, or early behavioral/language changes—all pointing to Alzheimer's disease as the most likely diagnosis. ### Why AD is Most Common 1. **Age-related prevalence:** Risk doubles every 5 years after age 65 2. **Genetic predisposition:** APOE4 allele is a major risk factor 3. **Pathological hallmark:** Amyloid-β and tau accumulation is the defining neuropathology 4. **Exclusion of other causes:** AD is diagnosed when other causes of dementia are ruled out **Mnemonic:** **3 A's of Alzheimer's** — **A**mnestic (early memory loss), **A**myloid-β and tau (pathology), **A**ge-related (most common in elderly) [cite:Harrison 21e Ch 391]