Clinical Trial: Genes, Exercise, Neurocognitive and Neurodegeneration: Community-Based Approach

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Genes, Exercise, Neurocognitive and Neurodegeneration: Community-Based Approach

Brief Summary: Whereas the advantageous effects of exercise-training on memory is increasingly recognized, the practicality and clinical usefulness of such interventions in community-dwelling older African Americans (AA)s Mild Cognitively Impaired (MCI) subjects, and the mechanism by which an effect occurs need elucidation. Because aerobic-exercise can improve emerging cardiovascular (CVD)-related risk factors for cognitive decline such as lipids, inflammatory cytokines and glucose homeostasis; the Investigators will examine training effects on these and related biomarkers. The imperative for this study is further underscored by the fact that, AAs: i) have high rates of dementia, and ii) have paucity of cross-sectional, and lack prospective data on the effects of exercise on cognition. To overcome barriers to recruitment and retention, enhance compliance with a long exercise program (3-times/week), and maximize the use of available resources, the Investigators will use a community-based approach. Therefore, the primary objectives of this study build on the Investigators' experience, and will compare the effects of aerobic-exercise to stretch-exercise (control) in community-dwelling AA MCI subjects. Following the initial 6 months active intervention, the aerobic-exercise group will follow a prescribed but free living 40 minutes, 3 time/week exercise regimen while the control group returns to usual care plus stretch-exercise for additional 12 months. This study will facilitate the estimation of sample size for a larger confirmatory study in AAs. A newly acquired direct oversight of the DC Ward-6 Senior Wellness Center and its infrastructures by the Howard University Division of Geriatrics will provide additional resources and access to the community. In addition to the Investigator's feasibility aims, the Investigators will determine performance on cognitive tasks using the Alzheimer's Disease Assessment Scale-Cognitive Sub-scale (ADAS-Cog) and Clinical Dementia Rating Scale (CDR) s

Detailed Summary:

Although anticholinesterase therapies have greatly improved the symptomatic treatment of Alzheimer's disease (AD), they have not been demonstrated to significantly slow the disease progression; and amyloid-directed therapies have produced disappointing results. A promising evidence-based and relatively side-effect free lifestyle approach is emerging as an alternative or adjunct to drug therapy. In cross-section and prospective studies, and a few randomized controlled trials; aerobic exercise-training has been demonstrated to improve cognition in older subjects. However, the mechanisms of these effects remain poorly understood. Because it is now recognized that cardiovascular disease (CVD) risks can catalyze AD development, it is vital to test whether lifestyle adaptation shown to reduce CVD risks can favorably modify cognitive trajectories and markers of neurodegeneration. Such interventions may benefit those at an early and clinically discernible prodromal stage of AD such as mild cognitive impairment (MCI). Notably, such data are currently lacking in African Americans (AA)s who harbor higher rate of CVD risks and AD.

While a laboratory approach to exercise intervention study is required to prove causation, such a design may not lend itself to real-life application, and is demanding for many economically and educationally disadvantaged older AAs experiencing early symptoms of cognitive deterioration. To address this concern, the Investigators seek to initiate an 18-month study, testing real-life applicability of the effects of exercise adaptation on memory in a more ideal community setting. However, those who chose to exercise at an academic center will not be excluded. Collection of outcome measures at baseline, 3-month, 6-month, 9-month, 12-month and 18-month will provide pilot data to inform dose and duration effects of exercise on outcome measures. In addition to aug
Sponsor: Howard University

Current Primary Outcome: Neuropsychological assessments [ Time Frame: Change cognitive measures from baseline at 6 month ]

Neuropsychological battery will be used to assess cognitive domains of interest.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Brain MRI-derived regions of interest assessed by change in regions of interest brain volume [ Time Frame: Change in regions of interest brain volume from baseline at 6 month and 12 month ]
    Brain MRI will be used as a screening tool and a measure brain volume
  • Cardiovascular disease-related markers and biomarkers assessed by change in lipids (mg/dl) [ Time Frame: Change in lipids (mg/dl) from baseline at 3 month, 6 month, 9 month, 12 month and 18 month ]
    Cardiovascular disease related biomarkers.
  • Cardiovascular disease-related markers and biomarkers assessed by change in Nuclear Magnetic Resonance Spectroscopy measured lipids concentrations (nml/L) [ Time Frame: Change in Nuclear Magnetic Resonance (NMR) Spectroscopy measured lipids concentrations (nml/L) from baseline at 3 month, 6 month, 9 month, 12 month and 18 month ]
    Cardiovascular disease related biomarkers.
  • Cardiovascular disease-related markers and biomarkers assessed by change in cytokines' levels (pg/ml) [ Time Frame: Change in cytokines' levels (pg/ml) from baseline at 3 month, 6 month, 9 month, 12 month and 18 month ]
    Cardiovascular disease related biomarkers.
  • Alzheimer's disease-related markers and biomarkers assessed by change in serum levels of Tau (ng/L) and Abeta (ng/L) [ Time Frame: Change in serum levels of Tau (ng/L) and Abeta (ng/L) from baseline to 3 month, 6 month, 9 month, 12 month and 18 month ]
    Cardiovascular disease and Alzheimer's disease related biomarkers.
  • Alzheimer's disease-related markers and biomarkers assessed by change in CSF levels of Tau (ng/L) and Abeta (ng/L) [ Time Frame: Change in CSF levels of Tau (ng/L) and Abeta (ng/L) from baseline to 6 month. ]
    Cardiovascular disease and Alzheimer's Disease related biomarkers.
  • Cardiovascular disease and Alzheimer's disease-related gene-environment interactions. [ Time Frame: Gene expression (fold change) from baseline at 3 month, 6 month, 9 month, 12 month and 18 month ]
    Cardiovascular disease and Alzheimer's disease related gene-environment interactions.
  • Alzheimer's disease-related markers and biomarkers and their gene-environment interactions. [ Time Frame: Genotype at baseline ]
    Cardiovascular disease and Alzheimer's disease gene-environment interactions..
  • Number of participants enrolled [ Time Frame: Number enrolled at baseline, and retained at 3 month, 6 month, 9 month,12 month and 18 month ]
    To test the feasibility of enrollment and retention of participants into a 6 month exercise study
  • Number of participants accepting of spinal tap procedure [ Time Frame: Number of enrolled who had spinal tap at baseline and 6 month ]
    Acceptability of spinal tap procedure


Original Secondary Outcome: Same as current

Information By: Howard University

Dates:
Date Received: March 24, 2015
Date Started: July 2014
Date Completion: December 2019
Last Updated: October 5, 2016
Last Verified: September 2016