Neuropathologic data from patients with Alzheimer's disease indicate the
presence of neurofibrillary tangles in hypothalamic regions associated with
regulation of pituitary hormone release. The authors explored the
hypothesis that cholinergic projections to hypothalamic nuclei controlling
pituitary growth hormone (GH) release degenerate in Alzheimer's disease.
Integrity of cholinergic regulation was tested by assaying the GH response
to a presynaptic cholinergic challenge. After administration of the choline
esterase inhibitor edrophonium, the peak GH response was 14 ng/ml in
healthy elderly control subjects and only 2 ng/ml in Alzheimer's patients.
The magnitude of GH blunting was correlated with cognitive and functional
deficits. Possible implications of these data for enhanced accuracy in the
diagnosis of dementia are discussed.