Randomized Trial of Marine n-3 Polyunsaturated Fatty Acids for the Prevention of Cerebral Small Vessel Disease and Inflammation in Aging (PUFA Trial): Rationale, Design and Baseline Results

Vascular risk factors for age-related cognitive decline are significant, and their management may ultimately prove the most successful strategy for reducing risk and sustaining cognitive health. This randomized, double-blinded, placebo-controlled trial with parallel group allocation to either marine n-3 polyunsaturated fatty acids (n-3 PUFA) or soybean oil placebo assesses the effects on the total volume of accumulation in cerebral white matter hyperintensities (WMH), a potentially modifiable neurovascular component of age-related cognitive decline. Total WMH accumulation over 3 years is the primary endpoint. The safety and efficacy of n-3 PUFA is evaluated in older adults with significant WMH and suboptimum plasma n-3 PUFA as inclusion criteria. One hundred and two non-demented older adults were enrolled with a mean age of 81.1 (±4.4) years, WMH of 19.4 (±16.1) cm3, and a plasma n-3 PUFA of 86.64 (±29.21) µg/mL. 61% were female, 28% were apolipoprotein E epsilon 4 carriers, and the mean mini-mental state exam (MMSE) was 27.9 (±1.7). This trial provides an initial evaluation of n-3 PUFA effects on WMH, a reproducible and valid risk biomarker for cognitive decline, as well as on inflammatory biomarkers thought to play a role in WMH accumulation. We present the baseline results and operational experience of enriching a study population on advanced age, blood n-3 PUFA, and magnetic resonance imaging (MRI) derived WMH with biomarker outcomes (WMH, inflammation markers) in a dementia prevention paradigm

Behavioral RCT using internet- based social interactions: Why some gain and some do not

BackgroundIncreasing social interaction could be a promising intervention for improving the cognitive well- being of socially isolated older adults. However, we expect that the efficacy of a social intervention can differ across subjects due to personality traits, preference for specific activities, and different pathological stages, even within the same clinical diagnosis. For most behavioral intervention studies, the priority of randomized controlled trials is not necessarily to gain a statistically significant intervention effect, but to find which subjects benefit from the specific intervention. Factoring this potential heterogeneity into the efficacy analysis of randomized controlled trials (RCT) will be discussed.MethodsBuilding upon our previously completed NIH- funded project (ClinicalTrials.gov #: NCT01571427), we developed a multi- site RCT to examine whether conversation- based cognitive stimulation has a positive effect on domain- specific cognitive functions and higher- order objectively measured IADL (Instrumental Activities of Daily Living). We target socially isolated older adults with either normal cognition or mild cognitive impairment (Internet- Based Conversational Engagement Clinical Trial (I- CONECT), ClinicalTrials.gov # NCT02871921). The experimental group engages in semi- structured video- chat conversation with trained conversational staff 4 times per week for 6 months (high dose) and twice per week for additional 6 months (maintenance dose). In addition to the main outcomes of neuropsychological test scores, we aim to determine factors which lead to heterogeneities in efficacy including: baseline brain atrophy and connectivity using MRI/fMRI, personality, Apoe genotype, mood and nature of social isolation (emotional vs. structural).ResultsWhile recruiting socially isolated subjects is challenging, as of January, 2020, our study has reached out 26,000 subjects, screened 195 subjects, and 131 subjects were ultimately randomized with 40% of those being eligible for MRI assessment. Baseline recruitment will continue until March of 2021. Carefully considered outcomes, covariates and mediating factors are being collected in this RCT. This presentation will examine some of the key heterogeneities observed in our ongoing baseline sample, and discuss potential implications these differences may have on our future efficacy analysis.ConclusionsOur project serves as a reference for developing individualized, targeted community intervention strategies with high adherence with maintainable life style modifications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163794/1/alz046367.pd