Alden L Gross1,2, Qian-Li Xue3,4,5, Karen Bandeen-Roche4,5, Linda P Fried6, Ravi Varadhan7, Mara A McAdams-DeMarco3, Jeremy Walston4, Michelle C Carlson2. 1. Department of Epidemiology, agross14@jhu.edu. 2. Department of Mental Health. 3. Department of Epidemiology. 4. Division of Geriatric Medicine and Gerontology, Department of Medicine, and. 5. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 6. Department of Epidemiology, Columbia University Mailman School of Public Health, New York. 7. Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Care Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
Abstract
BACKGROUND: Clinical cognitive impairment and physical frailty often co-occur. However, it is unclear whether preclinical impairment or decline in cognitive domains are associated with onset of physical frailty. We tested this hypothesis and further hypothesized that preclinical impairment and decline in executive functioning are more strongly associated with frailty onset than memory or general cognitive performance. METHODS: We used 9 years of data from the Women's Health and Aging Study II (six visits) that longitudinally measured psychomotor speed and executive functioning using the Trail Making Test, parts A and B, respectively, and immediate and delayed word-list recall from the Hopkins Verbal Learning Test. We used Cox proportional hazards models to regress time to frailty on indicators for impairment on these cognitive tests and on rates of change of the tests. Models adjusted for depressive symptoms, age, years of education, and race. RESULTS: Of the 331 women initially free of dementia and frailty, 44 (13%) developed frailty. A binary indicator of impaired executive functioning (Trail Making Test, part B [TMT-B]) was most strongly associated with hazard, or risk, of frailty onset (hazard ratio [HR] = 3.3, 95% confidence interval [CI] = 1.4, 7.6) after adjustment for covariates and other tests. Adjusting for baseline cognitive performance, faster deterioration on TMT-B (HR = 0.6, 95% CI = 0.4, 1.0) was additionally associated with hazard of frailty onset. CONCLUSIONS: Findings inform the association of executive functioning with transitions to frailty, suggesting both impairments in and declines in executive functioning are associated with risk of frailty onset. It remains to be determined whether these associations are causal or whether shared aging related or other mechanisms are involved.
BACKGROUND: Clinical cognitive impairment and physical frailty often co-occur. However, it is unclear whether preclinical impairment or decline in cognitive domains are associated with onset of physical frailty. We tested this hypothesis and further hypothesized that preclinical impairment and decline in executive functioning are more strongly associated with frailty onset than memory or general cognitive performance. METHODS: We used 9 years of data from the Women's Health and Aging Study II (six visits) that longitudinally measured psychomotor speed and executive functioning using the Trail Making Test, parts A and B, respectively, and immediate and delayed word-list recall from the Hopkins Verbal Learning Test. We used Cox proportional hazards models to regress time to frailty on indicators for impairment on these cognitive tests and on rates of change of the tests. Models adjusted for depressive symptoms, age, years of education, and race. RESULTS: Of the 331 women initially free of dementia and frailty, 44 (13%) developed frailty. A binary indicator of impaired executive functioning (Trail Making Test, part B [TMT-B]) was most strongly associated with hazard, or risk, of frailty onset (hazard ratio [HR] = 3.3, 95% confidence interval [CI] = 1.4, 7.6) after adjustment for covariates and other tests. Adjusting for baseline cognitive performance, faster deterioration on TMT-B (HR = 0.6, 95% CI = 0.4, 1.0) was additionally associated with hazard of frailty onset. CONCLUSIONS: Findings inform the association of executive functioning with transitions to frailty, suggesting both impairments in and declines in executive functioning are associated with risk of frailty onset. It remains to be determined whether these associations are causal or whether shared aging related or other mechanisms are involved.
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