Date of Graduation


Document Type


Degree Name

Doctor of Philosophy in Health, Sport and Exercise Science (PhD)

Degree Level



Health, Human Performance and Recreation


Michelle Gray

Committee Member

Nicholas Greene

Second Committee Member

Tyrone Washington

Third Committee Member

Samantha Robinson


Alzheimer's disease, Blood Biomarkers, Cognition, Genetics, Physical Function


Alzheimer’s disease and related dementia (ADRD) rates are expected to triple by the year 2050. Early detection and specific mitigation efforts are warranted to blunt the alarming rate. Physical function (PF) declines with age, but higher physical function is associated with better cognitive functioning in middle-to- older age individuals. Moreover, greater physical activity (PA) is associated with better global cognition; however, Apoliporotein e4 carriers may not gain the same benefits with exercise. Additionally, plasma phosphorylated tau 217 (p-tau217) has been identified as a novel diagnostic ADRD biomarker which needs further research to examine associations with risk factors. Therefore, the aims of this investigation were (1) Understand if higher physical function clusters produce better cognitive outcomes and blood biomarker profiles compared to lower functioning clusters among at-risk individuals, (2) Evaluate the ApoE gene’s mitigating effect on physical activity and blood biomarkers, (3) Examine the associations between risk factors and p-tau217. Participants (n=216;73.1% female; 45-75years) enrolled in the study and completed a DXA scan, venous blood draw, RBANS, handgrip, sit-to-stand power with tendo, dual-task (4-meter and 10-meter), 6-minute walk distance test, nine behavioral risk surveys, and 6 digital cognitive tests. A hierarchal cluster analysis was utilized to identify PF cluster for participants, a one-way ANCOVA was used to assess differences in cognition among clusters. A 2x2 factorial ANCOVA to examine interactions between PA and genetics. A multiple linear regression was used to evaluate risk factors (independent variables) on p-tau217 (dependent variable). Cluster 1 (C1; n =29) was characterized with the highest strength, power, faster dual-task walking time, and higher aerobic capacity, Cluster 3 (C3; n =113) had the lowest values among PF variables, Cluster 2 (C3; n = 74) was in-between C1 and C3. C1 had significantly higher global cognitive, visuospatial scores, digital executive functioning and associative learning compared to C2 (p < 0.05). C3 and C1 had significantly higher values on line orientation task and figure recall than C2 (p < 0.05). Moreover, physically active ApoE carriers had lower body mass index scores compared to physically inactive carriers where the opposite was seen among non-carriers (p < 0.05). Lastly, the regression model accounted for 84% of the variance for p-tau217 (p = .01), SF-12 accounted for 9% of that model as the only significant predictor (p < 0.05). The results from this current study demonstrate that individuals with higher physical functioning output among clustered variables have higher global cognitive scores than individuals with lower physical functioning output, lower BMI scores were found among physically active ApoE carriers, and quality of life may be directly linked to ptau217. Examining physical functioning variables together may be a valuable tool when assessing cognitive decline among at-risk individuals. However, larger sample sizes and longitudinal data is needed to substantiate these claims.