Geula & Mesulam, Cerebral Cortex 1996, 6:165-177 Age-matched controlAlzheimer’s disease.

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Presentation transcript:

Geula & Mesulam, Cerebral Cortex 1996, 6: Age-matched controlAlzheimer’s disease

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). Attentional functions of the cortical cholinergic input system:

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?

Human cortex Rat cortex Cortical cholinergic inputs and cognitive function