Cardiorespiratory fitness mitigates brain atrophy and cognitive decline in preclinical Alzheimer’s disease

Abstract

AbstractBackgroundCardiorespiratory fitness (CRF) may be a mitigating factor for Alzheimer’s Disease (AD) progression. The purpose of this study was to examine the longitudinal associations of CRF with brain atrophy and cognitive function in a late‐middle‐aged cohort of adults at risk for AD.MethodOne hundred and ten adults (mean age = 64.2 ± 5.7 years, 65% female) from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) completed a baseline graded treadmill exercise test, two brain MRI scans (over 4.67 ± 1.17 years) and neurocognitive assessments (2.18 ± .78 neurocognitive tests over 3.26 ± 1.02 years) as part of their WRAP study involvement. The oxygen uptake efficiency slope (OUES) was calculated for each participant and served as the CRF measure. Total gray matter and hippocampal volumes and the preclinical Alzheimer’s cognitive composite (PACC) score were the primary outcome measures. Linear mixed effects models examined the longitudinal associations adjusted for covariates. The CRF x age (i.e., time) interaction was centered and was the term of interest as it would indicate whether longitudinal decline in volumetrics or cognition differed as a function of CRF.ResultBaseline OUES values were 1.16 ± 0.28. Total gray matter and hippocampal volume declined at a rate of ‐0.73 ± 0.90% and ‐0.16 ± 1.30% per year, and cognitive trajectories decline ‐.047 points (standardized score) per year. The CRF × age interaction was significant for total gray matter volume (β=.26 SE .11; p=.020; Figure 1) and PACC score (β=.07 SE .03; p=.049; Figure 2), but not hippocampal volume (β=.002 SE .002; p=.347). These findings were most pronounced among APOE‐e4 carriers (p<.05).ConclusionCRF may be a modifiable physiological attribute to target during the preclinical stage of AD in effort to delay disease progression.