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2023 HSR&D/QUERI National Conference Abstract

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1165 — Cardiorespiratory Fitness and Risk of Alzheimer’s Disease and Related Dementias Among American Veterans

Lead/Presenter: Yan Cheng,  George Washington University
All Authors: Cheng Y (George Washington University), Zamrini E (University of Utah) Faselis C (Washington DC VA Medical Center) Redd D (George Washington University) Shao Y (George Washington University) Morgan CJ (University of Alabama at Birmingham) Sheriff HM (Washington DC VA Medical Center) Ahmed A (Washington DC VA Medical Center) Kokkinos P (Washington DC VA Medical Center) Zeng-Treitler Q (George Washington University)

Objectives:
Alzheimer's disease and related dementias (ADRD) are an urgent public health problem without adequate prevention strategies. Cardiorespiratory fitness (CRF) is associated with improved health and survival. Less is known about its association with ADRD. In this study we examined the association between CRF expressed in metabolic equivalents (METs) and incident ADRD in a large national cohort of US Veterans during 20 years of follow-up.

Methods:
We used a natural language processing (NLP) tool based on a Regular Expression Discovery Extractor (REDEx) algorithm to identify and extract MET values from exercise treadmill test data. We identified 649,605 US Veterans 30-95 years (mean age, 61 years; 6% women; 17% African Americans) free of ADRD who completed a standardized exercise tolerance test between 2000 and 2017 with no evidence of ischemia. We formed five age-and-gender-specific fitness categories based on peak metabolic equivalents (METs) achieved: Least-fit (n = 132,634; METs = 3.8 [STD 0.6]), Low-fit (n = 129,493; METs = 5.8 [STD 1.4]), Moderate-fit (n = 120,988; METs = 7.5 [STD 1.5]), Fit (n = 137,122; METs = 9.2 [STD 1.7]) and High-fit (n = 129,368; METs = 11.7 [STD 2.1]). We examined the association between CRF and ADRD incidence using multivariate Cox regression models and a propensity score-matched cohort of 393,625 Veterans with 78,725 in each fitness category.

Results:
During up to 20 (median 8.3; 5,733,488.6 person-years of observation) years of follow-up, incident ADRD occurred in 44,105 (6.8%) participants, with an incident rate of 7.7/1,000 person-years. Incident ADRD for the Least-fit to High-fit categories were: 9.5, 8.5, 7.4, 7.2 and 6.4, respectively (p < 0.0001). Compared to the Least-fit, multivariable-adjusted hazard ratios (95% confidence intervals) for incident ADRD were: 0.87 (0.85–0.90), 0.80 (0.78–0.83), 0.74 (0.72–0.76) and 0.67 (0.65–0.70), for Low-fit, Moderate-fit, Fit, and High-fit individuals, respectively.

Implications:
The findings of the current study demonstrate an independent, inverse and graded association between CRF and the incidence of ADRD regardless of gender or race.

Impacts:
These findings along with the well-documented health benefits associated with increased CRF support the concept that improving CRF may be a potential and viable strategy to lower risk of incident ADRD. Future studies need to determine strategies to improve fitness and identify individual optimal fitness goals for maximal ADRD risk reduction.