Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ INTRODUCTION ++ Alzheimer disease (AD) affects ∼7.5 million Americans of all ages and is a progressive illness of unknown cause characterized by loss of cognitive and physical functioning, commonly with behavior symptoms. +++ PATHOPHYSIOLOGY ++ Dominantly inherited forms of AD are fewer than 1% of cases. More than half of young-onset, dominantly inherited cases are attributed to chromosomal alterations that affect processing of the amyloid precursor protein. Genetic susceptibility to late-onset AD is primarily linked to the apolipoprotein E (APOE) genotype, but an interaction of multiple genes with the environment may be at play. AD risk factors include age, decreased reserve capacity of the brain, head injury, Down syndrome, depression, mild cognitive impairment, and risk factors for vascular disease, including hypertension, elevated homocysteine, elevated low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, obesity, metabolic syndrome, and diabetes. Signature findings include intracellular neurofibrillary tangles (NFTs), extracellular amyloid plaques in the cortex and medial temporal lobe, degeneration of neurons and synapses, and cortical atrophy. AD-affected individuals appear to have a higher burden of plaques and NFTs in their younger years compared to age-matched controls. Proposed mechanisms for these changes include: (1) β-amyloid protein aggregation, leading to formation of plaques; (2) hyperphosphorylation of tau protein, leading to NFTs; (3) synaptic failure and depletion of neurotrophin and neurotransmitters; (4) mitochondrial dysfunction; and (5) oxidative stress. The amyloid cascade hypothesis states that there is an imbalance between production and clearance of β-amyloid, with aggregation and accumulation of β-amyloid leading to AD. Whether this is the primary pathology in most forms of AD remains to be shown. Of neurotransmitter deficits, loss of cholinergic activity is most prominent, and it correlates with AD severity. Cholinergic cell loss seems to be a consequence of AD pathology, not the cause of it. Other neurotransmitter considerations include: (1) serotonergic neurons of the raphe nuclei and noradrenergic cells of the locus ceruleus are lost; (2) monoamine oxidase type B activity is increased; (3) glutamate pathways of the cortex and limbic structures are abnormal; and (4) excitatory neurotransmitters, including glutamate, may be neurotoxic. +++ CLINICAL PRESENTATION ++ Cognitive decline is gradual and includes memory loss, aphasia, apraxia, agnosia, disorientation, and impaired executive function. Other non-cognitive symptoms include depression, psychotic symptoms, aggression, motor hyperactivity, uncooperativeness, wandering, and combativeness. Patients become increasingly unable to care for themselves. Table 53-1 shows the stages of AD. ++Table Graphic Jump LocationTABLE 53-1Stages of Alzheimer DiseaseView Table||Download (.pdf) TABLE 53-1 Stages of Alzheimer Disease Mild (MMSE score 26–21) Patient has difficulty remembering recent events. Ability to manage finances, prepare food, and carry out other household activities declines. May get lost while driving. Begins to withdraw from difficult tasks and to give up hobbies. May deny memory problems. Moderate (MMSE score 20–10) Patient requires assistance with activities of daily living. Frequently disoriented with regard to time (date, year, and season). Recall ... Your MyAccess profile is currently affiliated with '[InstitutionA]' and is in the process of switching affiliations to '[InstitutionB]'. Please click ‘Continue’ to continue the affiliation switch, otherwise click ‘Cancel’ to cancel signing in. Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth