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ways in which the motor system can deteriorate Compulsive, repetitive movements are the most frequent: mouthing movements, stereotyped grimacing, protrusion of the tongue, side-to-side or toand-fro tremor of the head, odd vocalizations such as snif ng, snorting, and bleating In some respects these disorders resemble tics (quasivoluntary movements to relieve tension), but careful observation shows that they are not really voluntary Haloperidol and other drugs of this class have an unpredictable therapeutic effect, seeming at times to bene t the patient only by the superimposition of a drug-induced rigidity Old age is thought always to carry a liability to tremulousness, and indeed, one sees this association with some frequency The head, chin, or hands tremble and the voice quavers, yet there is not the usual slowness and poverty of movement, facial impassivity, or exed posture that would stamp the condition as parkinsonian Some instances of tremor are clearly familial, having appeared or worsened only late in life However, the relation of tremulousness to senility is sometimes open to doubt Charcot, in a review of over 2000 elderly inhabitants of the Salpetriere, could nd only about ` 30 with tremor Some cases probably represent the exaggeration or emergence of essential tremor, but many cases cannot be explained on this basis Spastic or spasmodic dysphonia, a disorder of middle and late life characterized by spasm of all the throat muscles on attempted speech, is discussed on page 428 Blepharoclonus or blepharospasm, an involuntary movement of the eyelids, is also described on page 93
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Morphologic and Physiologic Changes in the Aging Nervous System
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These have never been fully established From the third decade of life to the beginning of the tenth decade, the average decline in weight of the male brain is from 1394 to 1161 g, a loss of 233 g The pace of this change, very gradual at rst, accelerates during the sixth or seventh decades The loss of brain weight, which correlates roughly with enlargement of the lateral ventricles and widening of the sulci, is presumably the result of neuronal degeneration and replacement gliosis, although this has not been proved The counting of cerebrocortical neurons is fraught with technical dif culties, even with the use of computer-assisted automated techniques (see the critical review of neuron-counting studies by Coleman and Flood) Most studies, point to a depletion of the neuronal population in the neocortex, especially evident in the seventh, eighth, and ninth decades Cell loss in the limbic system (hippocampus, parahippocampal and cingulate gyri) is of special interest in regard to memory Ball, who measured the neuronal loss in the hippocampus, recorded a linear decrease of 27 percent between 45 and 95 years of age Dam reported a similar degree of cell loss and replacement gliosis These changes seem to proceed without relationship to Alzheimer neuro brillary changes and senile plaques (Kemper) However, recent morphologic work, summarized by Albers and also by Morrison and Hof, suggests that cerebral cell loss with aging is less pronounced than previously thought Furthermore, as pointed out by Morrison, the hippocampus may have only minimal cell loss Moreover, this is partially a result of neurogenesis in this region Brain shrinkage is accounted for in part by the reduction in size of large neurons, not their disappearance There is a more substantial reduction in neuronal number in the substantia nigra, locus ceruleus, and basal forebrain nuclei It may be possible to differentiate
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normal aging from disease in the medial temporal lobe by distinguishing between cell loss in speci c regions (see Small), but novel techniques are required Mueller and colleagues have utilized quantitative volumetric MRI techniques to examine a cohort of 46 nondemented elderly individuals They found small, constant rates of loss of brain volume with aging Moreover, the rates of volume loss in the last decades of life were no greater than in the immediately preceding decades suggesting that large changes in brain volume in the elderly are attributable to the dementing diseases common to this age period Serial MRIs of elderly persons have been found by Rusinick and colleagues to predict which individuals will develop disproportionate atrophy and dementia In particular, hippocampal atrophy increases at the rate of less than 2 percent per year in healthy elderly people, in comparison to 4 to 8 percent a year in early Alzheimer disease This longitudinal method of study is more sensitive than cross-sectional populations studies Among lumbosacral anterior horn cells, sensory ganglion cells, and putaminal and Purkinje cells, neuronal loss amounts to at most 25 percent between youth and old age Not all neuronal groups are equally susceptible For example, the locus ceruleus and substantia nigra, as already commented, lose about 35 percent of their neurons, whereas the vestibular nuclei and inferior olives maintain a fairly constant number of cells throughout life A very subtle loss, decade by decade, of the major systems of nerve cells and myelinated bers of the spinal cord has been demonstrated by Morrison This accelerates after the age of 60 (Tomlinson and Irving) As described above, in normal aging, there is a gradual decline in memory and in some cognitive functions In light of the studies just summarized, it is no longer considered that these changes can be ascribed simply to neuronal loss Rather, they are probably due at least in part to alterations in synaptic connectivity within critical cortical structures Scheibel and coworkers have described a loss of neuronal dendrites in the aging brain, particularly the horizontal dendrites of the third and fth layers of the neocortex However, the Golgi method, which was used in these studies, is dif cult to interpret because of artifacts The morphometric studies of Buell and Coleman have shown that the surviving neurons actually exhibit expanded dendritic trees, suggesting that even aging neurons have the capacity to react to cell loss by developing new synapses Overall, the evidence suggests shrinkage of cells With advancing age, there is an increasing tendency for neuritic (amyloid and neuro lbrillary) plaques to appear in the brains of nondemented individuals At rst the plaques appear in the hippocampus and parahippocampus, but later they become more widespread These are loose aggregates of amorphous argentophilic material containing amyloid They occur in increasing numbers with advancing age; by the end of the ninth decade of life, few brains are without them However, as shown by Tomlinson and colleagues, relatively fewer plaques are present in the brains of mentally intact old people, in contrast to the large numbers in those with Alzheimer disease Even more impressive is the correlation of neuro brillary tangles and Alzheimer disease Very few such tangles are found in the brains of mentally sound individuals, and such as are found are essentially con ned to the hippocampus and adjacent entorhinal cortex By contrast, neuro brillary tangles are far more abundant and diffusely distributed in patients with Alzheimer disease The view is often expressed that neuritic plaques and Alzhei-
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