Snapshot A 69-year-old gentleman is brought to his primary care provider by his daughter. She states that it seems like he has struggled more and more with every day living. Initially, he forgot simple things such as dates and addresses, but this has progressed over the last few years to an inability to pay his own bills. He has even gotten lost coming home from the grocery store which is one block away from his house. Introduction Degeneration of the cerebral cortex results in diffuse cortical atrophy widening of sulci, narrowing of gyri, expansion of the ventricles ↓ ACh neurotransmission by cholinergic neurons in the nucleus basalis of Meynert Most common cause in dementia in the elderly Causes majority of cases are sporadic allele variations of apolipoprotein E (APOE) on chromosome 19 determine risk ε4 is associated with increased risk ε2 is associated with decreased risk familial early-onset cases can involve presenilin mutations presenilin-1 (chromosome 14) presenilin-2 (chromosome 1) Associated conditions Down syndrome ↑ risk of developing Alzheimer's because the APP gene is located on chromosome 21 commonly presents before age 40 Presentation Symptoms short-term memory loss first symptom progresses to long-term memory loss disorientation behavior and personality changes gradual onset of symptoms in contrast to vascular dementia Evaluation Predominantly a clinical diagnosis of exclusion confirmation is autopsy histology can do a MRI if concerned about another disease process Histologic findings senile/neuritic plaques extracellular Aβ-amyloid core derived from amyloid precursor protein (APP) APP normally degraded via α-cleavage β-cleavage of APP results in Aβ-amyloid neurofibrillary tangles intracellular aggregations of hyperphosphorylated tau protein tau is an insoluble cytoskeletal element (microtubule-associated protein) tangles correlate with degree of dementia Differential Normal pressure hydrocephalus treatment large volume lumbar puncture or ventral-peritoneal shunt Vascular dementia step-wise/sudden progression of symptoms associated with hypertension and focal deficits Treatment See Alzheimer's drugs topic Prognosis, Prevention, and Complications Complications amyloidosis may result in angiopathy results in weakened vessel walls and can lead to rupture with intracranial hemorrhage Most common cause of death is infection mental status changes associated with sepsis are not detected when superimposed on baseline Alzheimer's