Fitness on White Matter and Cognition in Aging
Condition: Cognitive Decline; Executive Dysfunction; Cardiovascular Risk Factor
MeSH terms: Cognitive Dysfunction
Study type: Observational

Summary: 
      Cardiorespiratory fitness (CRF) is associated with decreased risk for mild cognitive
      impairment (MCI) and dementia. CRF is linked with more conserved gray and white matter (WM)
      volume, improved WM microstructural integrity, and better cognitive performance among healthy
      older adults. Additional research is needed to determine: (1) which WM tracts are most
      strongly related to CRF, (2) whether CRF-related benefits on WM translate to enhanced
      cognitive functioning, and (3) factors that mediate and moderate CRF effects. Higher CRF was
      hypothesized to be associated with stronger WM integrity, both globally and locally in WM
      tracts that connect frontal brain regions. The neuroprotective effects were hypothesized to
      be age-dependent, such that the association between CRF and WM integrity would be stronger in
      old age compared to younger age. Finally, higher CRF was hypothesized to predict stronger
      performance on tests of executive functioning (EF), partially mediated by frontal WM
      integrity. Delineation of specific neurocognitive effects of CRF may serve clinicians in
      individually tailoring wellness interventions to meet patients' specific cognitive concerns
      with aging.
    

Detailed description: 
      Sample: Participant data from the "Cross-Sectional Lifespan Connectomics Study" of the Nathan
      Kline Institute - Rockland Sample (NKI-RS) will be analyzed for the present study. Zip
      code-based recruitment and monitoring enrollment for key demographic variables (e.g., age,
      sex, ethnicity) were used to maintain adequate representation of Rockland County and prevent
      sampling biases (e.g., cohort effects). NKI-RS eligibility was designed for inclusivity.

      Procedure: All participants completed a medical evaluation, psychiatric interview,
      self-report questionnaires, standardized battery of cognitive tests, and neuroimaging at NKI.
      Complete details about the MRI measurement parameters can be located on the NKI-RS website
      for DTI and MPRAGE and protocols. Quality assurance of raw data, inclusive of monitoring
      standard operating procedures, error-handling, and compiling the data dictionary, is
      maintained by NKI-RS. Raw neuroimaging data was acquired by NKI-RS and processed at Suffolk
      University using TRACULA and FreeSurfer 5.3.

      Statistical Plan: Analyses will be performed on de-identified phenotypic and neuroimaging
      data from adult NKI-RS participants available at the start of this study (October 2016).
      Analyses will evaluate the potential for CRF to modulate decline in WM integrity and EF
      observed with aging. Mixed-effects modeling will investigate the extent to which CRF predicts
      WM integrity, as both a global measurement of fractional anisotropy (FA) and FA within nine
      major WM tracts. Structural equation modeling will examine whether higher FA within frontal
      WM tracts partially mediates a positive relationship between CRF and EF. The role of age and
      clinical characteristics (e.g., cardiovascular risk factors, depression) will also be
      explored as covariates in the link between CRF, WM, and EF.
    

Observational model: Ecologic or Community
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Participants are community-dwelling adults from the "Cross-Sectional Lifespan Connectomics
        Study" of the Nathan Kline Institute - Rockland Sample (NKI-RS)-a large cross-sectional
        sample of adult brain development. NKI prospectively recruited community-dwelling residents
        of Rockland County, New York-a region that is socioeconomically comparable to United States
        demographics.
      
Keywords: Neuroimaging; White matter; Cardiorespiratory fitness; Physical activity; Cognitive aging; Executive function; Cognitive reserve