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  • Image not available.Familial aggregation of a disease is suggested when the recurrence risk among relatives of affected persons exceeds that among relatives of unaffected persons.
  • Image not available. In studies of twins, greater concordance for disease among monozygotic twins as compared with dizygotic twins suggests genetically determined susceptibility.
  • Image not available. If subjects with a high degree of inbreeding have an elevated risk of disease, an autosomal recessive pattern of inheritance may be suggested.
  • Image not available. Co-segregation refers to the tendency of alleles that are situated closely together on the chromosomes to be inherited together.
  • Image not available. Linkage of a marker gene (with a known location in the genome) and a disease susceptibility gene can suggest the particular chromosome involved and where on the chromosome the susceptibility gene is likely to be located.
  • Image not available.Segregation analysis of pedigrees is a complex statistical technique used to determine whether a disease has, at least in part, a genetic origin, and if so, the likely pattern of inheritance.

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Image not available. A 70-year-old retired car salesman is brought by his spouse of 50 years to their family physician for evaluation of “forgetfulness.” Over the previous several years, the patient has had increasing difficulty remembering recent events and has become lost when driving, even near his home. More recently, he has often forgotten names and has asked the same questions several times in succession. He is not taking any medications, nor is there any history of alcoholism, use of recreational drugs, exposure to toxins, high blood pressure, or stroke. The patient’s family history is unremarkable, except for a similar course of progressive memory loss and cognitive disability in his mother and in the oldest of his three siblings.

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The patient appears well nourished, without evidence of systemic illness. On mental status examination, the patient does not know the year, cannot remember any of three objects 5 minutes after learning them, and cannot count backward from 100 by 7. Neurologic examination is otherwise normal. After magnetic resonance imaging and further tests to rule out specific, treatable causes of dementia, a diagnosis of Alzheimer’s disease is made.

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Dementia is characterized by impaired short- and long-term memory, along with disturbances of other cognitive functions (eg, language or visuospatial function). For a diagnosis of dementia to be made, the patient’s loss of cognitive abilities must be of sufficient magnitude to interfere with the individual’s performance of social or occupational activities. More than 60 different clinical disorders are associated with dementia, and Alzheimer’s disease is the most common cause of dementia in many populations. This disease was first reported in 1907 by Alois Alzheimer, who described morphological changes in the brain of a patient who died with progressive dementia. The clinical diagnosis of Alzheimer’s disease is made by excluding other possible causes of dementia, among which vascular disorders predominate.

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The “gold standard” for arriving at a diagnosis of Alzheimer’s disease is a histologic examination of brain tissue. Patients with pathologic confirmation of disease are characterized as ...

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