Alzheimer's Disease & Dementia

Definition

Alzheimer's disease is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioral changes. Dementia is a broader term describing significant cognitive impairment interfering with daily functioning, of which Alzheimer's is the most common cause.

Epidemiology

• Most common cause of dementia in older adults
• Prevalence increases with age: affects ~10% of individuals over 65 and ~30% over 85
• Slightly more common in women than men, partly due to longer life expectancy
• Global prevalence is rising with aging populations
• Family history increases risk, particularly with early-onset cases

Etiology

• Neurodegenerative process with amyloid-beta plaque deposition and tau protein tangles
• Genetic factors: mutations in APP, PSEN1, PSEN2 for early-onset; APOE ε4 allele increases late-onset risk
• Age-related neuronal loss and vascular changes
• Environmental and lifestyle factors: cardiovascular risk factors, smoking, low cognitive engagement
• Other comorbidities: diabetes, hypertension, dyslipidemia
• Secondary causes of dementia: vascular, Lewy body, frontotemporal, Parkinson’s disease-related

Pathophysiology

• Accumulation of amyloid-beta plaques disrupts neuronal signaling
• Neurofibrillary tangles of hyperphosphorylated tau cause neuronal death
• Synaptic dysfunction leads to progressive cognitive decline
• Neuroinflammation contributes to neuronal injury
• Cerebral atrophy particularly in hippocampus and cortex
• Cholinergic neuron loss contributes to memory deficits
• Vascular pathology may exacerbate neurodegeneration