Chapter 37: Alzheimer’s Disease – Cognitive Drug Treatments

The underlying pathology involves cortical atrophy and neuronal loss, driven by the accumulation of hallmark brain lesions: β-amyloid plaques and neurofibrillary tangles, the latter formed from hyperphosphorylated tau protein. These destructive changes impair neurotransmitter systems, notably leading to decreased acetylcholine and excessive glutamate stimulation. While advanced age is the primary risk factor, the text also discusses genetic predisposition, including the ApoE-e4 allele and specific mutations in the amyloid precursor protein (APP), presenilin-1, and presenilin-2 genes. Clinical diagnosis requires standardized cognitive assessments (like the MMSE or MOCA) and ruling out reversible causes of dementia, while definitive confirmation relies on autopsy. Pharmacologic treatment aims to maximize functional ability and slow decline, as AD is currently incurable. First-line therapy for mild-to-moderate AD utilizes Cholinesterase Inhibitors (CIs)—donepezil, rivastigmine, and galantamine—to enhance cholinergic function. For patients with moderate-to-severe disease, the NMDA receptor antagonist memantine is introduced, often in conjunction with a CI. Beyond cognitive management, the chapter addresses noncognitive symptoms like psychosis, agitation, and depression. Antipsychotic agents must be used cautiously due to a black box warning regarding increased mortality risk. Monitoring of therapy involves assessing cognitive status every three to six months and evaluating the patient's ability to perform daily living activities (ADLs), while nonpharmacologic interventions such as support groups, caregiver education, and maintaining routine are essential for overall management.