Examining Long-Term Impact of Grape Consumption on Brain Metabolism in Patients with Mild Decline in Cognition: a Double-Blind Placebo-Controlled Longitudinal Study

1084 Objectives: We previously reported that grape consumption by people experiencing decline in cognition leads to the preservation of metabolism in brain regions important to cognitive function over six months in a double-blinded placebo-controlled study (Experimental Gerontology 87, 2017; 121-128). In an ongoing expansion study, we are examining the effect of grape consumption on regional cerebral metabolism with an independent cohort of subjects, measured over one year. Methods: Twenty subjects underwent neuroimaging and neuropsychological evaluations after being randomized into two groups to consume an active grape formulation (36 grams of reconstituted freeze-dried grape powder) or a placebo formulation free of polyphenols, twice daily for 12 months. Changes in brain metabolism occurring with each therapy regimen were assessed by brain PET scans with the radiotracer [F-18] fluorodeoxyglucose (FDG) from time of initial evaluation to after one year of consumption of grape or placebo formulation. Cognitive performance was measured through neuropsychological assessments performed at baseline, 6 and 12 months after initiation of therapy. Activity in 47 standardized volumes of interest (sVOI’s) were measured to identify areas of significant change in cerebral metabolism occurring over one year, and regionally quantify the magnitudes of change in those areas in each study arm, all as normalized to each individual’s pontine metabolism. Results were analyzed by one-tailed paired t-tests to examine regional metabolic decline within each arm and by unpaired two-tailed t-tests to examine the significance of differences between arms. Results: By the time of this analysis, 19 subjects have completed the year-long trial, with the 20th subject due to undergo one-year evaluations in early 2021. Of completing subjects, nine are in one randomized arm (age 74 ± 6 years, mean ± SD), and ten are in the other (age 76 ± 6 years). While there were no significant declines in regional metabolism in any of the 47 sVOI’s in the first group, subjects in the second group demonstrated the most significant decreases in frontal and temporal cortical regions, including the left superior frontal cortex (p=0.004), right inferior frontal cortex (p=0.002), right posterior medial temporal cortex (p=0.003), and left inferior lateral anterior temporal cortex (p=0.004), changing by -14%, -15%, -7%, -12%, respectively. Moreover, direct statistical comparison between arms demonstrated that the changes in metabolism differed significantly (p<0.05) between active and placebo formulations for both frontal and the medial temporal areas of the brain, as well as 11 other frontal and temporal cortical areas, all in the direction of greater decline in the second randomized arm (with all investigators and subjects remaining blinded as to which arm corresponds to each formulation, until completion of the protocol by the last subject). Conclusions: Twice-daily consumption of grapes for one year by subjects with mild decline in cognition was associated with significant change in the longitudinal trajectory of metabolism in frontal and temporal cortical regions, known to functionally decline in the early stages of neurodegenerative processes leading to dementia.