AS572 - COSMOS Cognition: The effect of dietary flavanols on cognition

Investigator Names and Contact Information

Adam Brickman (amb2139@columbia.edu)

Introduction/Intent

The purpose of this study is to examine whether dietary intake of cocoa flavanols improves cognitive function in older adults and to validate a neuropsychological instrument for remote internet-based testing. The study follows our recent work that isolated dysfunction in the dentate gyrus (DG) subfield of the hippocampus as a source of age-related cognitive decline (1). As part of that effort, we developed a computerized neuropsychological test, the ModBent, performance on which a) shows an age-related decline among neurologically healthy adults across the adult lifespan, b) correlates selectively with DG function, and c) improves monotonically with dietary cocoa flavanol-driven increase in DG function. The current study follows up on this latter observation by testing in a formal randomized clinical trial the impact of dietary flavanol intake on cognitive function. Given our previous observations with the ModBent, which is a novel object recognition memory task, our primary outcome will be performance on this measure. However, we will also interrogate other domains of cognition (e.g., spatial memory, attention/executive function), with a brief battery of computerized neuropsychological tests. These additional tests serve as secondary/exploratory outcomes that will allow us to test the specificity of the expected effect on the ModBent and determine whether other aspects of cognition are also affected. This is a substudy of the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) trial, which is conducted primarily by mail. We will therefore employ a novel internet-based neuropsychological testing scheme to collect the cognitive outcome measures remotely. A second goal of this study is to validate the internet-administered ModBent by comparing performance on the test over the internet with an in-person assessment among a subset of participants who will be evaluated in-clinic. These participants will also be evaluated in-clinic after two years and we will compare cognitive findings derived remotely with those derived in-person. The overall study design is a randomized, double-blind, placebo-controlled factorial trial that includes a high-quality cocoa extract supplement (containing 600 mg/d flavanols, including 80mg (-)-epicatechins versus placebo) in 4,000 individuals aged ≥65 years with four years of treatment and follow-up.

SPECIFIC AIMS

• 1.To test the hypothesis that dietary intake of cocoa flavanols improves performance on the ModBent, a cognitive test of novel object recognition in older adults. This aim will be accomplished with two parallel studies:

  Among a subset of 4,000 individuals enrolled in the COSMOS, participants will be evaluated remotely by an internet-based computerized neuropsychological testing battery, which includes the ModBent as a primary outcome and two other tests as secondary/exploratory outcomes, at baseline and at 1-, 2, and 3-year follow-up. A subset of 500 individuals will be evaluated in clinic with the ModBent and an additional computerized test battery at baseline and 2 years follow-up.

• 2.To validate the ModBent for remote internet-based testing.

  Baseline neuropsychological test scores collected over the internet will be compared with scores derived in-clinic among the subset of 500 participants evaluated in-clinic. These participants will also be evaluated in-clinic after two years and we will compare cognitive findings derived remotely with those derived in-person.