COGNITIVE &NEUROPHYSIOLOGICAL FUNCTION IN HEALTHY AGING

Aging

Investigators

Abstract

Two families of optical textures were passively presented to healthy volunteers undergoing positron emission tomography (PET) to measure regional cerebral blood flow (rCBF): Random textures in which black and white checks were arranged in a random fashion, and Even textures in which the checks were ordered to produce extended contours and rectangular blocks at multiple spatial scales. In young subjects, repeated alternating presentation of Random and Even textures showed differential rCBF activation in striate cortex in initial presentations, of extrastriate association visual areas in subsequent presentations, and of hippocampus in final presentations, suggesting that the brain can learn to classify differences in visual patterns without direct conscious involvement. In older healthy controls, extrastriate and frontal regions were activated that were not activated in the young subjects, suggesting a reallocation of cortical resources during visual perception with age. In young healthy subjects, physostigmine, an acetylcholinesterase inhibitor, improved performance on a working-memory-for-faces task, seen as a reduced reaction time on the task, and reduced task-specific increments in rCBF measured with PET in the right prefrontal cortex. A correlation analysis showed that the improved performance involved functional alterations regions in cortical networks subserving perceptual processing, memory and attention. Alzheimer disease (AD):A subgroup of Alzheimer disease (AD) patients with early prominent visual disturbances showed cerebral glucose hypometabolism, measured with PET and corrected for atrophy, in parieto-occipital and calcarine cortices, with relative sparing of paralimbic regions, compared to typical AD patients. In this subgroup, postmortem pathology showed a distribution of senile plaques and neurofibrillary tangles consistent with the pattern of metabolic deficits. rCBF in control and AD patients changed in brain visual areas in response to increasing frequency of visually presented pattern flashes. In striate cortex, rCBF increased from 0 to 8 Hz, then decreased, whereas in extrastriate visual cortex, rCBF increased monotonically from 0 to 16 Hz. Flow responses were abnormal in mildly demented AD patients, more so in moderately and severely demented patients, suggesting early and progressive synaptic dysfunction. Brain glucose metabolism was measured with PET at rest and in response to auditory-visual activation in controls and AD patients. The activated metabolic response was within normal limits in mildly demented patients but was reduced in more demented patients. Declining responsiveness may account for limited success of neurotransmitter replacement therapy in AD patients with moderate-severe dementia. A "normal" metabolic response to activation in initial stages of AD was ascribed to selective and potentially reversible downregulation of brain enzymes that mediate mitochondrial oxidative phosphorylation. Reduced responsiveness in later stages was ascribed to irreversible loss of mitochondrial function associated with neuronal death and neurofibrillary tangle formation. Reduced size of the corpus callosum, measured using magnetic resonance imaging (MRI), can be used as a marker of metabolic and cognitive dysfunction in AD. The size of the corpus callosum, which connects right and left cerebral hemispheres, was shown to fall in proportion to reduction in brain metabolism measured with PET in left and right frontal and parietal lobes.