Cerebral metabolic response to passive audiovisual stimulation in patients with Alzheimer's disease and healthy volunteers assessed by PET.
Alzheimer's disease is associated with reductions in resting-state brain metabolism, as measured by PET, progressing with dementia severity. The purpose of this study was to see to what extent brain regions with reduced resting-state metabolic rates in Alzheimer patients could be activated by a passive audiovisual stimulation test and to compare the result with activation in age-matched healthy volunteers. The extent of activation in Alzheimer's disease is considered to reflect the integrity of synaptic function, or inherent viability, and the potential responsiveness of the Alzheimer brain to drug therapy.


METHODS
Regional cerebral metabolic rates for glucose (rCMRglc, in mg/ 100 g tissue/min) were measured in the resting state (eyes and ears covered) and during passive audiovisual stimulation (watching a movie) in 15 otherwise healthy Alzheimer patients of differing dementia severity (Mattis Dementia Rating Scale score, 23-128) and in 14 age-matched healthy volunteers (score, 141 +/- 3) using PET with 2 sequential injections of FDG.


RESULTS
In the volunteers, audiovisual stimulation caused significant rCMRglc increases in visual and auditory cortical areas but significant decreases in frontal areas. In the mildly demented patients, rCMRglc responses were within 2 SDs of the mean in volunteers. However, the magnitude of the rCMRglc responses during stimulation declined significantly with dementia severity in the right occipitotemporal, right and left occipital association, and left calcarine cortical regions.


CONCLUSIONS
Functional brain responsiveness, evaluated by a passive audiovisual stimulation paradigm with PET, is within normal limits in mildly demented Alzheimer patients but fails with worsening dementia severity. Declining responsiveness may account for the limited success of neurotransmitter replacement therapy in Alzheimer patients with moderate-to-severe dementia.
Pietrini
P
P
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
Alexander
G E
GE
Furey
M L
ML
Dani
A
A
Mentis
M J
MJ
Horwitz
B
B
Guazzelli
M
M
Shapiro
M B
MB
Rapoport
S I
SI
D000161:Acoustic Stimulation; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D010775:Photic Stimulation; D019275:Radiopharmaceuticals; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose