Novel food-based approach for prevention of age-associated cognitive decline inolder adults with obesity

超重和肥胖的老年人容易出现认知能力下降，患痴呆症的风险是常人的两倍

Older adults with overweight and obesity are vulnerable cognitive decline, and have twice the risk of dementia and Alzheimer's Disease compared to adults without overweight or obesity. However, research on nutritional interventions to support cognitive health has been fragmented, and largely restricted to testing individual nutrition factors or generally healthy dietary patterns. The overarching goal of this proposal, responding to PAR-18-877, is to identify effective nutrition-based interventions to improve cognitive and brain functioning in older adults with overweight and obesity. Our central hypothesis is that age-sensitive cognitive functions and cerebral blood flow (CBF, an important biomarker of brain health) can be significantly increased in older adults with overweight or obesity by consumption of a novel multiple-component nutrition supplement (MCNS) used alone or in combination with a behavioral weight loss (WL) intervention. The scientific premise is that older adults with overweight and obesity have pathophysiological changes in the brain secondary to excess weight that damage brain structure and function, and as a result are particularly susceptible to nutritional deficiencies and oxidative stress; thus, optimal nutritional interventions for cognitive health should provide a comprehensive panel of nutrients and other food constituents to support structural and functional remodeling while reducing inflammation and oxidative damage. The project is proposed by a multidisciplinary team with expertise in all aspects of the research. The conceptual basis of the work is supported by our recent compelling data demonstrating effectiveness of a MCNS for improving executive function and cerebral blood flow in young children, which is a landmark advance because less comprehensive supplement formulations have been found to be ineffective. A 1-year randomized placebo-controlled trial will be conducted in 268 older adults with overweight and obesity, low intakes of target nutrients, and normal cognition or mild cognitive impairment. A 2x2 factorial design will randomize participants to: i) a MCNS supplement containing flavanols including epicatechin and catechin, essential micronutrients and omega-3 fatty acids, or to an isocaloric placebo; and b) to receive a behavioral WL intervention or an attentional Control. The primary outcome will be change in a composite cognitive z-score of well-established standardized scores on 5 neuropsychological tests. We hypothesize improved cognitive function in participants randomized to MCNS, WL and MCNS+WL compared to Controls, with greatest mean benefits in MCNS+WL participants. The primary analysis is intention-to-treat. Linear mixed-effects models will be applied to assess the effects of MCNS, WL, and MCNS+WL vs. Control and MCNS+WL vs. MCNS and WL alone. Additional cognitive tests will be drawn for other reliable sources, and microvascular cerebral blood flow and macrovascular cerebral blood flow velocity will be measured using diffuse correlation spectroscopy and transcranial Doppler ultrasound. This research will identify practical nutrition-based interventions for improving cognitive health in vulnerable older adults to support transformational advances in public health initiatives.