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Cerebral Metabolic Response to Passive Audiovisual Stimulation in Patients with Alzheimer's Disease and Healthy Volunteers Assessed by PET

Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland
Department of Human and Environmental Sciences and Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies, University of Pisa, Pisa, Italy

Correspondence: For correspondence or reprints contact: Pietro Pietrini, MD, PhD, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bldg. 10, Rm. 6C414, 9000 Rockville Pike, Bethesda, MD 20892.

ABSTRACT

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

Key Words: PET • FDG • dementia • brain • activation • cognition

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