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Am J Psychiatry 1997; 154:1063-1069
Copyright © 1997 by American Psychiatric Association
Low glucose metabolism during brain stimulation in older Down's syndrome subjects at risk for Alzheimer's disease prior to dementia
P Pietrini, A Dani, ML Furey, GE Alexander, U Freo, CL Grady, MJ Mentis, D Mangot, EW Simon, B Horwitz, JV Haxby and MB Schapiro
Laboratory of Neurosciences, National Institute on Aging, NIH, Bethesda, MD 20892, USA. pietrini@alw.nih.gov
OBJECTIVE: Down's syndrome is characterized by the genetically programmed
accumulation of substantial Alzheimer's disease neuropathology after age 40
and the development of early dementia years later, providing a unique human
model to investigate the preclinical phases of Alzheimer's disease. Older
nondemented adults with Down's syndrome show normal rates of regional
cerebral glucose metabolism at rest before the onset of dementia,
indicating that their neurons maintain function at rest. The authors
hypothesized that an audiovisual stimulation paradigm, acting as a stress
test, would reveal abnormalities in cerebral glucose metabolism before
dementia in the neocortical parietal and temporal areas most vulnerable to
Alzheimer's disease. METHOD: Regional cerebral glucose metabolism was
assessed by means of positron emission tomography (PET) with
[18F]fluorodeoxyglucose in eight younger (mean age = 35 years, SD = 2) and
eight older (mean age = 50, SD = 7) healthy, nondemented adults with
trisomy 21 Down's syndrome. PET scans were performed at rest and during
audiovisual stimulation in the same scanning session. Levels of general
intellectual functioning and compliance were similar in the two groups.
RESULTS: At rest the two groups showed no difference in glucose metabolism
in any cerebral region. In contrast, during audiovisual stimulation the
older subjects with Down's syndrome had significantly lower glucose
metabolic rates in the parietal and temporal cortical areas. CONCLUSIONS:
Abnormalities in cerebral metabolism during stimulation appeared in the
first cortical regions typically affected in Alzheimer's disease. These
results indicate that a stress test paradigm can detect metabolic
abnormalities in the preclinical stages of Alzheimer's disease despite
normal cerebral metabolism at rest.
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