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mer type of neuro brillary changes simply represent an acceleration of the natural aging process in the brain We are more inclined to the idea that the plaques and neuro brillary changes represent an acquired age-linked disease, analogous in this respect to certain cerebrovascular diseases In support of this latter view are several observations First, Homo sapiens is the only animal species in which Alzheimer neuro brillary changes and neuritic plaques are regularly found in the aging brain A few plaque-like structures (but no neuro brillary changes) have been seen occasionally in old dogs and monkeys but not in mice or rats It seems unbiologic that human aging should differ from that of all other animal species Second, some of the most severe forms of Alzheimer disease occur in middle adult life, long before the senium Third, these histopathologic changes in variable proportion occur in a number of other diseases unrelated to aging, such as dementia pugilistica ( punch-drunk state), Down syndrome, postencephalitic Parkinson disease, and progressive supranuclear palsy Fourth, neuro brillary tangles can be reproduced in the experimental animal by such toxins as aluminum, vincristine, vinblastine, and colchicine Finally, a small proportion of Alzheimer cases are de nitely familial Alzheimer disease is therefore more appropriately considered with degenerative diseases (see Chap 39, where the entire subject is discussed further) Virtually every molecular structure within the cell is subject to age-related biochemical modi cations, such as the formation of carbonyl proteins, glycation of sugars, and oxidative changes in lipids Some of these subcellular phenomena contribute to the aging process (see Smith CD et al and Mrak et al for details), as do the cumulation of mitochondrial DNA mutations and shortened lengths of the telomeres Among the visible biochemical alterations is an increasing accumulation of lipofuscin granules in the cytoplasm of neurons, sometimes extreme in degree Also, there is an age-related neuronal accumulation of iron and other pigment bodies Granulovacuolar changes are a regular nding in aging hippocampi, regardless of the mental state of the individual The accumulation of amyloid-containing concretions (corpora amylaceae) around nerve roots and diffusely in the subpial space is yet another aging effect Cerebral atherosclerosis is, of course, a frequent nding in the elderly, but it does not parallel aging with any degree of precision, being severe in some 30- to 40-year-old individuals and practically absent in some octogenarians In the normotensive individual, it tends to occur in scattered, discrete plaques mostly in the aorta and cervical arteries (carotid bifurcation and higher segments), proximal middle cerebral arteries, and at the vertebrobasilar junction and basilar portions of the cerebral arterial system In the hypertensive and diabetic, it is more diffuse and extends into ner branches of the cerebral and cerebellar arteries One or more cerebral ischemic softenings (infarcts) are found in about 25 percent of all individuals more than 70 years of age who have been carefully examined postmortem In addition to atherosclerotic disease, the basilar arteries become somewhat larger and more tortuous and opaque in the elderly Cerebral blood ow has been extensively investigated in the elderly population Most studies have shown that ow declines with age and that the cerebral metabolic rate declines in parallel There is also an age-related increase in cerebrovascular resistance Declines in ow are somewhat greater in the cortex than in white matter and greater in prefrontal regions than in other parts of the hemispheres Obrist demonstrated a 28 percent reduction in cerebral ow by age 80 It is noteworthy, however, that every cohort. zxing.net code 128 Free BarCode API for . NET - CodePlex Archive
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