Alzheimer' s disease (A.D.) is a progressive disorder associated with disruption of neuronal function and a gradual deterioration in intellectual function and personality. Although memory is one of the primary impairments in Alzheimer's disease, assessment of memory function by itself is not sufficient in assessing longitudinal course. The addition of non-memory measures increases the ability to follow the course of A.D. However, there is a need to develop antemortem markers as a complement to clinical measures to assess the course of A.D. A.D. is characterized by loss of large neurons in the frontal, temporal and parietal cortex; and, cholinergic neurons in the nucleus basalis of Meynert. The loss of these neurons leads to gross morphometric changes such as ventricular dilation, reduction in thickness of the cortex and reduction in size of the Amygdala hippqcapal complex. These changes which were initially noted on post mortem examination can now be visualized using imaging techniques such as computed tomography and magnetic resonance imaging. Preliminary studies using these techniques have documented ventricular enlargement, cerebral atrophy and hippocampal atrophy, in vivo. Further, rapid progression of some of these changes over the course of the illness has been documented. In addition, with the advent of proton magnetic resonance spectroscopy, it has become possible to study physicochemical changes in the brain reflecting cholinergic metabolism and neuronal content. In vitro studies have documented that N-Acetyl Aspartate (NAA) is reduced in A.D. in the temporal and frontal cortex. N-Acetyl Aspartate is primarily present in neurons. The reduction in NAA is believed to reflect neuronal loss. A preliminary In vivo proton MRS study has documented the reduction in NAA. The proposed study is designed to confirm the reduction in NAA and some of the morphometric changes in A.D. and to follow longitudinally the anatomical/ physicochemical changes in patients with A.D. in relation to progression of disease. If progression of physicochemical and morphometric changes is demonstrated then proton MRS and MRI can be used as a compliment to clinical variables in assessing treatment effects in A.D.
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