Cognitive deficit induced by acute tryptophan depletion in patients with Alzheimer's disease.
OBJECTIVE
The study assessed the effects on global cognitive function and mood of a reduction of brain serotonin by means of acute tryptophan depletion in 16 patients with dementia of the Alzheimer type and in 16 cognitively intact comparison subjects.


METHODS
In a double-blind, crossover design, subjects received a tryptophan-free amino acid drink to induce acute tryptophan depletion and, on a separate occasion, a placebo drink containing a balanced mixture of amino acids. On each occasion, ratings of depressed mood were made at baseline and 4 and 7 hours later, and the Modified Mini-Mental State was administered at baseline and 4 hours later.


RESULTS
Patients with dementia of the Alzheimer type had a significantly lower mean score on the Modified Mini-Mental State after acute tryptophan depletion than after receiving placebo. The comparison group showed no difference in mean score on the Modified Mini-Mental State after acute tryptophan depletion and after receiving placebo. No significant changes in mood were found in either group.


CONCLUSIONS
Acute tryptophan depletion significantly impaired cognitive function in patients with dementia of the Alzheimer type. Compromised serotonergic function, in combination with cholinergic deficit, may make an important contribution to cognitive decline in dementia of the Alzheimer type.
Porter
R J
RJ
Academic Department of Psychiatry, University of Newcastle upon Tyne, England.
Lunn
B S
BS
Walker
L L
LL
Gray
J M
JM
Ballard
C G
CG
O'Brien
J T
JT
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D018592:Cross-Over Studies; D003866:Depressive Disorder / Q000097:blood / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D012701:Serotonin / Q000502:physiology; D014364:Tryptophan / Q000097:blood*
D012701:Serotonin; D014364:Tryptophan