Cerebral metabolic response to passive audiovisual stimulation in patientswith Alzheimer's disease and healthy volunteers assessed by PET

Alzheimer's disease is associated with reductions in resting-state brain me tabolism, as measured by PET, progressing with dementia severity. The purpo se of this study was to see to what extent brain regions with reduced resti ng-state metabolic rates in Alzheimer patients could be activated by a pass ive 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 inh erent viability, and the potential responsiveness of the Alzheimer brain to drug therapy. Methods: Regional cerebral metabolic rates for glucose (rCMR (glc), 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 FD G. Results: In the volunteers, audiovisual stimulation caused significant r CMR(glc) increases in visual and auditory cortical areas but significant de creases in frontal areas. In the mildly demented patients, rCMR(glc) respon ses were within 2 SDs of the mean in volunteers. However, the magnitude of the rCMR(glc) responses during stimulation declined significantly with deme ntia severity in the right occipitotemporal, right and left occipital assoc iation, and left calcarine cortical regions. Conclusion: Functional brain r esponsiveness, evaluated by a passive audiovisual stimulation paradigm with PET, is within normal limits in mildly demented Alzheimer patients but fai ls with worsening dementia severity. Declining responsiveness may account f or the limited success of neurotransmitter replacement therapy in Alzheimer patients with moderate-to-severe dementia,