Frederick W. Unverzagt - US grants

DESCRIPTION (provided by applicant): Dementia is an age-related condition that affects 10% of the population over age 70. It is associated with loss of functional independence and high care costs (estimated at $159 billion in 2010). Prior to becoming demented, most patients pass through a stage called Mild Cognitive Impairment (MCI) in which deficits are mild and care costs are lower. We are proposing a pilot study of a behavioral intervention in MCI patients. If the proposed pilot study, designed to be consistent with current recommended approaches to establishing trial feasibility, is able to achieve its aims, it will provide a conceptual and practcal rationale to support a large, multi-site, randomized clinical trial (RCT) that tests the efficacy o combined physical and cognitive training in delaying time to a clinical diagnosis of dementia. a 2 x 2 factorial design with a home-based cognitive intervention (Cog-I) or cognitive control (Cog-C) and a home-based physical exercise intervention (Phys-I) or physical exercise control (Phys-C) enrolling older adults with MCI receiving meals under Title III of the Older Americans Act. The Phys-I intervention includes physical exercise focused on aerobic and resistance training for 45 minutes. The Cog-I intervention consists of computer based modules focused on executive cognitive ability for 45 minutes. The Phys-C intervention consists of 45 minutes of stretching while the Cog-C intervention consists of 45 minutes of educational programs and completion of puzzles and word games (Cog-C). Each of the 4 treatment conditions consists of 3 90-minute per week sessions for 12 weeks (36 sessions total). The aims are: 1) establish feasibility, monitor adherence to interventions and outcomes, and monitor safety and acceptability; 2) determine if combined treatment (Cog-I + Phys-I) has a positive effect on cognitive test performance vs. control (Cog-C + Phys-C); 3) estimate whether age, APOE, education, and baseline cognitive status are associated with response to treatment; and 4) examine mechanisms of action of the experimental intervention by tracking pre-post changes in trophic factors (BDNF and VEGF) and inflammatory markers (CRP, IL-6, TNF-alpha). Identification of treatments that delay progression of MCI is of enormous public health significance as such interventions have potential to delay the onset of dementia and its attendant functional and financial losses.

In April 2015, the Institute of Medicine called for clinical trials and multi-component interventions to prevent cognitive decline among at-risk adults. We here propose a pilot randomized trial of high polyphenol foods combined with speed of processing cognitive training in older adults with low education. Low education is the top modifiable risk factor for Alzheimer disease (AD). Low cognitive reserve is a leading hypothesis for low education's effects on early cognitive decline. Specific dietary components, here referred to as MIND foods,? have emerged as key interventions for enhancing cognitive reserve. Randomized trials support that just 12 weeks of consumption of MIND foods improves short-term cognition, including speed of processing. Similarly, 12 weeks of speed of processing training has broad effects and has been hypothesized to improve cognitive reserve. Our secondary analysis of existing trial data showed that cognitive training effects were largest in those with low education. At this time, there are no published trials of speed of processing training among older adults with low education nor are there any trials of speed of processing training combined with MIND foods. Using a 2 x 2 factorial design, we propose a randomized controlled trial of the efficacy of speed training and MIND foods in maintaining or improving brain and cognitive health in older adults with low education and no dementia. Older adults seeking primary care who have low education will be recruited and randomized to one of four arms: MIND food + Speed training, MIND food + Speed training control, MIND food control + Speed training, or MIND food control + Speed training control. We refer to the MIND and Speed combination as MINDSpeed, while the combination of MIND food control and speed training control we refer to as Double Control. Twelve weeks of access, support, and incentives for trainings and food will be facilitated by tablet applications created with users by our user-interface design team. The primary specific aim of this pilot clinical trial is to determine MINDSpeed effects on an executive cognitive composite (ECC) score relative to Double Control. Secondary aims are to determine: 1) MIND and Speed treatment effects on ECC vs Double Control and MINDSpeed, 2) feasibility (i.e., adherence, satisfaction, adverse events, costs), 3) treatment effect modifiers (e.g., education, age, baseline cognitive status, APOE ?4 carrier status), and 4) mechanisms of inflammation, oxidative stress, and hippocampal volume. The ultimate goal of this line of research is to enhance cognitive reserve through MIND foods and brain training and thereby delay AD.