The goal of this study is to characterize the neurophysiologic mechanisms underlying the age-related decline in human visual cognitive function. This research will delineate specific neurophysiologic measures of subcortical functions that contribute to the age-related decline in cognitive function. It is hypothesized that the impairment of the sub, cortical function of alertness contributes to the age-related decrement in visual cognitive function and is related to right hemisphere dysfunction. Alertness is experimentally modulated in a double blind placebo-controlled drug study using a CNS depressant (diphenhydramine) and CNS stimulant (methylphenidate). Alertness is operationally defined using computerized EEG frequency analysis; slow later"""""""" al eye movements; blink rate; sympathetic nervous system activity (skin blood flow based, on laser Doppler velocimetry); parasympathetic nervous system activity (heart rate, variability). Visual cognitive function is assessed by performance on serial and parallel search tasks and a directed attention task. Measures of cognitive performance include: reaction time; accuracy; variability of reaction time. The hypothesis will be tested with 120 subjects, 60 in each of 2 age groups, 25-35 years and 65-75 years. Subjects will participate on 5 separate mornings. On each morning they will be given either a placebo, 0.5 mg/Kg diphenhydramine, 1 mg/Kg diphenhydramine: 0.1 mg/Kg methylphenidate or 0.2 mg/Kg methylphenidate. They will perform the cognitive tasks before and after administration of each drug condition. The research impacts clinical management of patients with cognitive deficits. Clinicians will be provided with measurement tools to document alertness deficits in cognitively impaired patients with subcortical lesions secondary to aging, focal lesions, neurodegenerative diseases and medications. If deficits in alertness can be measured and contribute to cognitive decline in the elderly, then strategies to increase alertness could be offered by clinicians. This may be particularly helpful in problem areas for the elderly such as driving and ambulation, where intermittent lapses in alertness or attention may produce significant injury. The normative data for cognitive function does not presently account for the subject's level of alertness. Since the level of alertness may account for a large amount of the variability in cognitive function, especially in the elderly and neurologically impaired population, the definition of a measurable state of alertness will improve the sensitivity and specificity of all clinical cognitive testing.
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