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ABSTRACT: Age-associated cholinergic dysfunction may contribute to the cognitive decline observed during aging, including a decline in working memory. The current study was designed to determine how healthy aging influences the neural response to working memory before and during pharmacological potentiation of the cholinergic system.
In 13 young and 13 older healthy volunteers, regional cerebral blood flow (rCBF) was measured by using [15O]H2O and positron emission tomography across 10 scans that alternated between a working-memory-for-faces task and rest. In all subjects, the first two scans were obtained during intravenous saline infusion. Seven young and eight older subjects then received intravenous infusion of physostigmine, a cholinesterase inhibitor, and the remaining six young and five older subjects continued to receive saline.
In the placebo condition, task-specific rCBF increases in prefrontal regions were observed in the right middle and inferior frontal cortices in young subjects and in more anterior and ventral prefrontal regions in older individuals. Physostigmine during the working memory task significantly improved performance in both age groups. The right prefrontal regions that were selectively recruited in each age group during the placebo condition showed significantly lower rCBF during physostigmine administration.
Cholinergic enhancement does not affect structurally defined cortical regions but rather modulates neural activity in functionally defined regions, that is, in task-related prefrontal cortical areas that are selectively and distinctively recruited in young and older subjects.
American Journal of Psychiatry 12/2005; 162(11):2061-70. · 12.54 Impact Factor
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ABSTRACT: To identify changes in brain functions associated with the development of dementia, brain metabolism and cognition were assessed repeatedly in 12 adults with Down syndrome (DS) using positron emission tomography and neuropsychological tests. Ten subjects remained non-demented (ND) and showed no significant changes over time in cognitive measures or in cerebral metabolism. Two subjects developed dementia after 7 years. Brain functions were relatively stable prior to the onset of dementia; after the onset of dementia, both cognitive function and glucose metabolism in parietal and temporal brain regions known to be vulnerable to Alzheimer disease (AD) showed a rapid linear decline. These findings support the concept that brain functions are stable over time in ND individuals with DS and that decline of brain functions in DS subjects with dementia follows two distinct phases that correspond to the clinical progression of AD. This may have implications for timing of new therapeutic strategies.
(C) Lippincott-Raven Publishers.
Neuroreport 11/1996; 7(18). · 1.66 Impact Factor
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ABSTRACT: A subgroup of patients with probable Alzheimer disease (AD) reported a history of isolated visual disturbances (VS) early in the course of disease, without the characteristic memory complaints. Brain imaging and neuropathologic studies indicated that this subgroup had larger involvement of visual cortical areas and relative sparing of temporal. frontal, and limbic structures compared with classic AD. Consistent with these findings, the authors hypothesized that the cognitive deficits in this subgroup would be distinctly different from those seen in more typical AD patients. The authors studied 10 probable AD patients with VS (AD&±&|S), 22 patients without VS (AD–), and 25 healthy controls with a neuropsychological test battery. Compared with AD–, AD&±&|S patients performed significantly better on tests of verbal memory and had greater impairment on tests of visuospatial skills, suggesting a distinct pattern of cognitive dysfunction consistent with metabolic and neuropathologic reports. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Neuropsychology 03/1996; 10(2):294-300. · 3.82 Impact Factor
