Lower Physical Activity Modifies the Association Between Perceived Fatigability and Executive Function but Not Memory: the Study of Muscle, Mobility and Aging (SOMMA)

OBJECTIVE: Emerging evidence shows that perceived fatigability, the quantification of vulnerability to fatigue in relation to specific intensity and duration of activities, may be associated with cognitive function. We sought to quantify associations with multiple domains of cognitive function and the role of physical activity (PA). METHODS: SOMMA participants completed the Pittsburgh Fatigability Scale (PFS) Physical and Mental subscales (each range 0-50; higher scores=greater fatigability) and three cognitive function assessments [Digit Symbol Substitution Test (DSST), executive function; Montreal Cognitive Assessment (MoCA), general function; and California Verbal Learning Test (CVLT), memory]. Linear regression quantified associations cross-sectionally between each PFS subscale and cognitive assessment scores adjusting for covariates. Effect modification by volume and intensity of accelerometer-measured PA was assessed. RESULTS: In 873 participants (59.2% women; age 76.3 +/-5.0; 85% White), mean PFS Physical, Mental, and DSST scores were 15.8±8.7, 7.7±7.8, and 55.4±13.7. After adjustments, for each 4-point higher PFS Physical and 3-point higher PFS Mental, participants had nearly one fewer correct DSST items [β coefficient and 95% confidence interval for PFS Physical: -0.69 (-1.09, -0.29); PFS Mental: -0.64 (-0.97, -0.30)]. Volume and intensity of PA modified the association of PFS Mental and DSST (Pinteractions<0.01). All associations were strongest in those with the lowest volume and intensity of PA. PFS was not associated with MoCA or CVLT. DISCUSSION: Greater perceived fatigability may be associated with poorer executive function, but not memory. Individuals with greater perceived fatigability, particularly those less active, might benefit from interventions that reduce fatigability and may beneficially influence cognitive function. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by several grants and agencies. The Study of Muscle, Mobility and Aging is supported by funding from the National Institute on Aging, grant number AG059416. Study infrastructure support was funded in part by NIA Claude D. Pepper Older American Independence Centers at University of Pittsburgh (P30AG024827) and Wake Forest University (P30AG021332) and the Clinical and Translational Science Institutes, funded by the National Center for Advancing Translational Science, at Wake Forest University (UL1 0TR001420). Additionally, the Claude D. Pepper Older Americans Independence Center, Research Registry and Developmental Pilot Grant (NIH P30 AG024827), and the Intramural Research Program, National Institute on Aging supported N.W.G to develop the Pittsburgh Fatigability Scale. The Epidemiology of Aging training grant at the University of Pittsburgh (National Institute on Aging T32 AG000181) supported B.T.S and K.D.M. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All SOMMA participants provided written informed consent and the study was approved by WIRB-Copernicus Group (WCG) Institutional Review Board (study number 20180764), ethical approval for this work was given. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors