Prospective Randomized Placebo‐Controlled Trial of Long‐Term Durability of Effect of One Year of Grape Consumption on Preventing Decline of Cerebral Function

• Published in: Alzheimer's & dementia Vol. 19; no. S23
• Main Authors: Liu, Stephen S., Lu, Josephine L., Alcantara, April R., Varughese, Deepu V., Silverman, Daniel H.
• Format: Journal Article
• Language: English
• Published: 01.12.2023
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1002/alz.077247

Background Long‐term impact of one year of grape consumption on regional brain metabolism and associated neuropsychologic status was examined across multiple years of follow‐up. Method Twenty subjects (74.6±5.4 years) were randomized to consume an active grape formulation (36g reconstituted freeze‐dried grape powder) or placebo (matched for sweetness and appearance but free of polyphenols) twice daily for one year. Changes in brain metabolism were assessed by PET with radiotracer [F‐18]fluorodeoxyglucose and cognitive performance was measured through neuropsychological testing, at baseline, 1 year after initiating consumption of grape or placebo formulation, and again 2 to 3 years after completing the randomized regimen in half of the subjects on each arm, with all subjects remaining blinded to which regimen they had been assigned until after final assessments. Activity in 47 standardized volumes of interest (sVOI’s) were measured, voxel‐based analyses using statistical parametric mapping were conducted, and associations were examined between interval changes in metabolism and neuropsychologic status. Result During the year while consuming formulations, subjects randomized to placebo underwent metabolic decline in 27 sVOI’s, including particularly inferior posterior temporal (p = 0.006) and inferior frontal (p = 0.004) areas, correlating with neuropsychologic decline, while significant (p<0.05) decline was seen in none of the 47 sVOI’s in the active formulation group. Voxel‐based analyses corroborated differential metabolic decline in placebo and active formulation groups, and direct difference‐of‐differences analyses further documented significantly more decline in the placebo group. Moreover, a significant difference in regional metabolism persisted at the end of follow‐up, after having discontinued randomized formulations for 28.1±5.7 months (40.0±5.4 after baseline), with mean medial temporal sVOI’s demonstrating significant decline in the group that had been randomized to placebo (‐4.6%, p = 0.009), but not in the group that had been in the active arm (‐1.5%, N.S.). Difference of magnitudes of long‐term metabolic decline between arms was significant in direct difference‐of‐differences analysis, and correlated with neuropsychologic decline (p<0.001) in both inferior posterior temporal and inferior frontal regions. Conclusion Subjects randomized to consume reconstituted grapes twice daily enjoyed long‐term protection from loss of cerebral function, as assessed more than two years beyond the last consumed dose.