Studies on the cognitive effects of normal aging typically assume that any decrements found in their older subjects are due to the process of normal aging. However, as people age they often develop diseases for which they take multiple medications. Among the medications often prescribed for diseases common in the elderly is a class of drugs (those with an anticholinergic effect) that impairs the same fundamental cognitive mechanisms (working-memory capacity, processing speed and inhibition) currently theorized to underlie the cognitive decline associated with normal aging. Studies of cognitive aging have rarely controlled for the effects of such drugs and thus it is possible that a substantial portion of the cognitive decline thought to be a normal part of aging may instead be due to the anticholinergic effects of medications that older subjects are taking. To test this possibility we will recruit 175 normal elderly subjects and 30 education-matched young individuals. Subjects will be given tests of working memory, information processing speed and inhibitory efficiency as well as tests of higher-level cognitive abilities: episodic memory, language comprehension and reasoning. We will obtain a blood sample from which we will determine each subject's cumulative anticholinergic load from all drugs, as well as their levels of caffeine and nicotine metabolites and their APOE genotype. Two years later, we will repeat the cognitive testing and blood measures to determine whether any change in SA level from baseline is reflected in subjects' cognitive performance. The repeat testing will also allow us to determine whether any of the subjects show signs of an incipient dementia. This study will examine whether the cognitive performance of the older subjects varies as a function of their serum anticholinergic level and if so, whether this effect is moderated by their intake of caffeine and / or nicotine or by their APOE genotype. We will also examine whether the decrements that anticholinergic drugs produce in higher-level cognitive abilities are mediated through decreases in working memory, processing speed or inhibitory efficiency.
