Porth's Essentials of Pathophysiology, 4e

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Nervous System

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inheritance exhibiting the earliest age (younger than 70 years). The APoE genotype is not, however, an abso- lute determinant of who will develop AD. Just how these different APo alleles influence the risk of AD continues to remain poorly understood. Manifestations Alzheimer-type dementia follows an insidious and pro- gressive course. The hallmark symptoms are loss of short-term memory and denial of such memory loss, with eventual disorientation, impaired abstract think- ing, apraxias, and changes in personality and affect. 70 Various stages of the disease have been recognized; all are characterized by progressive degenerative changes. The initial changes are often subtle, characterized by a short-term memory loss that often is difficult to differ- entiate from the normal memory loss that often occurs in the elderly, and usually is reported by caregivers and denied by the person. Although most elderly persons have trouble retrieving from memory incidental infor- mation and proper names, persons with AD randomly forget important and unimportant details. They forget where things are placed, get lost easily, and have trouble remembering appointments and performing novel tasks. Mild changes in personality, such as lack of spontane- ity, social withdrawal, and loss of a previous sense of humor, occur during this stage. As the disease progresses, the person with AD enters the moderate stage. This stage may last several years and is marked by a more global impairment of cogni- tive functioning. During this stage, there are changes in higher cortical functioning needed for language, spatial relationships, and problem solving. Depression may occur in persons who are aware of their deficits. There is extreme confusion, disorientation, lack of insight, and inability to carry out the activities of daily living. Personal hygiene is neglected, and language becomes impaired because of difficulty in remembering and retrieving words. Behavioral changes can include agitation, sleep problems, restlessness and wander- ing, aggression, and suspiciousness. Some persons may become hostile and abusive toward family members. Persons who enter this stage become unable to live alone and should be assisted in making decisions about supervised placement with family members or friends or in a community-based facility. Severe AD is the last stage of the disease. It is char- acterized by a loss of ability to respond to the envi- ronment. Individuals in this stage require total care and spend most of their time bedridden. Death can occur as a result of complications related to chronic debilitation. Diagnosis andTreatment Alzheimer disease is essentially a diagnosis of exclusion. There are no peripheral biochemical markers or tests for the disease. The diagnosis can be confirmed only by microscopic examination of tissue obtained from a cerebral biopsy or at autopsy. The diagnosis is based on clinical findings.

A diagnosis of Alzheimer disease requires the pres- ence of dementia established by clinical examination and documented by results of a Mini-Mental State Examination, Blessed Dementia Test, or similar men- tal status test; no disturbance in consciousness; onset between 40 and 90 years of age, most often after 65 years of age; and absence of systemic or brain disor- ders that could account for the memory or cognitive def- icits. Brain imaging, CT scan, or MRI is done to exclude other brain disease. Metabolic screening should be done for known reversible causes of dementia such as vita- min B 12 deficiency, thyroid dysfunction, and electrolyte imbalance. There is no curative treatment for Alzheimer dis- ease. 70 Drugs are used primarily to slow the progression and to control depression, agitation, or sleep disorders. Two major goals of care are maintaining the person’s socialization and providing support for the family. Self-help groups that provide support for family and friends have become available, with support from the AD and Related Disorders Association. Day care and respite centers are available in many areas to provide relief for caregivers and appropriate stimulation for the patient. Although there is no current drug therapy that is curative for Alzheimer disease, cholinesterase inhibi- tors have been shown to be effective in slowing the progression of the disease by potentiating the action of available acetylcholine. 71,72 These drugs (e.g., donepezil, rivastigmine, galantamine) inhibit acetylcholinesterase, preventing the metabolism of endogenous acetylcholine, and are used in the early stages of the disease for mild cognitive impairment. Again, such therapy does not halt the disease but can slow its progression. Memantine, an N -methyl- d -aspartate antagonist, has been approved by the FDA for treatment of moderate to severe AD. 72 This medication may act by interfering with the glutama- tergic excitotoxicity caused by the ischemia (discussed under mechanisms of brain injury) and amyloid depos- its associated with the disease, or it may provide symp- tomatic improvement through effects on the function of hippocampal neurons. This medication, like the cholin- esterase inhibitors, modestly delays functional loss. Other treatments for Alzheimer disease include agents that are thought to have a neuroprotective effect. 70 A β seems to exert its neurotoxic effects through a variety of secondary mechanisms, including oxidative injury and lipid peroxidation of cell membranes, and inflam- mation. Several strategies have involved the use of anti- inflammatory agents and antioxidants (vitamins E and C). Several, but not all, epidemiologic studies provide evidence supporting the concept that vitamin E and vita- min C have a role in delaying the onset of AD. In some, but not all, trials, G. biloba had small but statistically significant effects compared with placebo in persons with Alzheimer disease. Psychotropic medications, such as antipsychotics and mood stabilizers, may be used to assist in the behavioral management of the disease. Interventions also include environmental adjustments, behavioral intervention, and education and support for caregivers.