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Transcript 
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
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