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Age-matched control Alzheimer’s disease Geula & Mesulam, Cerebral Cortex 1996, 6:165-177 Attentional functions of the cortical cholinergic input system: The attentional abilities which depend on the integrity of cortical cholinergic inputs range from: • the detection, selection, and discrimination of stimuli and associations (sustained and selective attention) to • the regulation of processing capacity (divided attention). EVIDENCE LINKING CORTICAL ACh RELEASE TO ATTENTION • HUMANS: CORRELATION BETWEEN COGNITIVE DEFICITS IN ALZHEIMER’S DISEASE AND LOSS OF BASAL FOREBRAIN CHOLINERGIC NEURONS; DRUGS THAT INCREASE ACh RELEASE CAN FACILITATE ATTENTION • RATS: DRUGS OR LESIONS THAT DECREASE CORTICAL ACh RELEASE IMPAIR ATTENTIONAL PROCESSING & THESE DEFICITS CAN BE ATTENUATED WITH DRUGS THAT POTENTIATE STIMULATE ACh RELEASE; CORTICAL ACh RELEASE IS STIMULATED DURING PERFORMANCE OF ATTENTIONAL TASKS CORTICAL ACh AND ALZHEIMER’S DISEASE THE HUNDRED BILLION $$$$ QUESTION! IF THE COGNITIVE DEFICITS IN ALZHEIMER’S DISEASE REFLECT DECREASED CORTICAL ACh, THEN WHY AREN’T DRUGS THAT INCREASE CORTICAL ACh RELEASE MORE THERAPEUTIC? Cortical cholinergic inputs and cognitive function Human cortex Rat cortex