Adaptive Working Memory and Physical Exercise Training to Improve Brain and Mitochondrial Function in MCI

University Of Maryland Baltimore, Baltimore MD

Investigators

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Abstract

Project Summary With the aging population, the prevalence of dementia will more than double in the next three decades in the U.S. Globally, an estimated 75 million individuals will have dementia by 2030; caring for these individuals will have a global cost of 2 trillion USD. According to the WHO, the increasing number of individuals with dementia alone could overwhelm the global health care system and undermine social and economic development. Therefore, effective treatment or prevention for dementia is urgently needed. Currently, no curative treatment for dementia exists despite numerous clinical trials and research studies related to dementia. However, recent data indicate that improved nutrition and physical activity might have contributed to the declined incidence of dementia in the U.S. and in Europe. Hence, the current proposed project aims to evaluate the brain changes and some of the possible underlying mechanisms associated with the combined adaptive working memory training and progressive aerobic exercise training to improve brain function in healthy elderly and in those with mild cognitive improvement (MCI). This project fits well within the goals of the National Alzheimer’s Plan of Action (NAPA), especially with regards to “Prevent and Effectively Treat Alzheimer's Disease by 2025.” The proposed administrative supplement fits well within the overarching University of Maryland Older Americans Independence Center (UM-OAIC) goal which is to build on the sciences and therapeutic applications of exercise and rehabilitation. Specifically, we propose the following two specific aims: Aim 1: To evaluate how the combination of Cogmed® training and exercise training will improve brain structure (on structural MRI), brain blood flow (on perfusion MRI) and on cognitive tests, both in MCI and non-MCI older adults. Study design: 18 individuals with MCI (age>50-80 years), who have higher risk for developing dementia or AD, will be compared to 18 healthy individuals without cognitive deficits, of similar age range, race, sex proportions, and socioeconomic status (SES), before and after a 3x/week x 16 weeks aerobic exercise program, along with an adaptive working memory training program (Cogmed® 5x/week, 25 sessions/ over 5-8 weeks). Aim 2: To evaluate potential mechanism(s) that might contribute to the improved brain structure, brain blood flow or cognition by studying these changes with mitochondrial function / respiration in platelets, biomarkers for neurodegeneration in the brain [NAA and glutamate on proton spectroscopy (1H MRS)] and in the periphery (plasma Aβ-40, Aβ-42, Tau, NFL). Findings from this exploratory pilot project will provide the necessary preliminary data to refine and direct a future larger trial (e.g., using a 2 x 2 design, with or without Cogmed® or exercise training, for the intervention(s) in MCI subjects and controls) using these approaches.