Jasmine Nettiksimmons1, Hilsa Ayonayon2, Tamara Harris2, Caroline Phillips2, Caterina Rosano2, Suzanne Satterfield2, Kristine Yaffe2. 1. From the Departments of Psychiatry (J.N.) and Epidemiology and Biostatistics (H.A.), University of California-San Francisco; Laboratory of Epidemiology and Population Sciences, Intramural Research Program (T.H.), and Neuroepidemiology Section (C.P.), National Institute on Aging; Center for Aging and Population Health (C.R.), Department of Epidemiology, University of Pittsburgh, PA; Department of Preventive Medicine (S.S.), University of Tennessee Health Science Center; and Departments of Psychiatry, Neurology, and Epidemiology and Biostatistics (K.Y.), University of California-San Francisco, San Francisco Veterans Affairs Medical Center. jasmine.nettiksimmons@ucsf.edu. 2. From the Departments of Psychiatry (J.N.) and Epidemiology and Biostatistics (H.A.), University of California-San Francisco; Laboratory of Epidemiology and Population Sciences, Intramural Research Program (T.H.), and Neuroepidemiology Section (C.P.), National Institute on Aging; Center for Aging and Population Health (C.R.), Department of Epidemiology, University of Pittsburgh, PA; Department of Preventive Medicine (S.S.), University of Tennessee Health Science Center; and Departments of Psychiatry, Neurology, and Epidemiology and Biostatistics (K.Y.), University of California-San Francisco, San Francisco Veterans Affairs Medical Center.
Abstract
OBJECTIVE: We sought to develop and validate a risk index for prospective cognitive decline in older adults based on blood-derived markers. METHODS: The index was based on 8 markers that have been previously associated with cognitive aging: APOE genotype, plasma β-amyloid 42/40 ratio, telomere length, cystatin C, glucose, C-reactive protein, interleukin-6, and albumin. The outcome was person-specific cognitive slopes (Modified Mini-Mental State Examination) from 11 years of follow-up. A total of 1,445 older adults comprised the development sample. An index based on dichotomized markers was divided into low-, medium-, and high-risk categories; the risk categories were validated with the remaining sample (n = 739) using linear regression. Amyloid was measured on a subsample (n = 865) and was included only in a secondary index. RESULTS: The risk categories showed significant differences from each other and were predictive of prospective cognitive decline in the validation sample, even after adjustment for age and baseline cognitive score: the low-risk group (24.8%) declined 0.32 points/y (95% confidence interval [CI]: -0.46, -0.19), the medium-risk group (58.7%) declined 0.55 points/y (95% CI: -0.65, 0.45), and the high-risk group (16.6%) declined 0.69 points/y (95% CI: -0.85, -0.54). Using the secondary index, which included β-amyloid 42/40 (validation n = 279), the low-risk group (26.9%) declined 0.20 points/y (95% CI: -0.42, 0.01), the medium-risk group (61.3%) declined 0.55 points/y (95% CI: -0.72, -0.38), and the high-risk group (11.8%) declined 0.83 points/y (95% CI: -1.14, -0.51). CONCLUSIONS: A risk index based on 8 blood-based markers was modestly able to predict cognitive decline over an 11-year follow-up. Further validation in other cohorts is necessary.
OBJECTIVE: We sought to develop and validate a risk index for prospective cognitive decline in older adults based on blood-derived markers. METHODS: The index was based on 8 markers that have been previously associated with cognitive aging: APOE genotype, plasma β-amyloid 42/40 ratio, telomere length, cystatin C, glucose, C-reactive protein, interleukin-6, and albumin. The outcome was person-specific cognitive slopes (Modified Mini-Mental State Examination) from 11 years of follow-up. A total of 1,445 older adults comprised the development sample. An index based on dichotomized markers was divided into low-, medium-, and high-risk categories; the risk categories were validated with the remaining sample (n = 739) using linear regression. Amyloid was measured on a subsample (n = 865) and was included only in a secondary index. RESULTS: The risk categories showed significant differences from each other and were predictive of prospective cognitive decline in the validation sample, even after adjustment for age and baseline cognitive score: the low-risk group (24.8%) declined 0.32 points/y (95% confidence interval [CI]: -0.46, -0.19), the medium-risk group (58.7%) declined 0.55 points/y (95% CI: -0.65, 0.45), and the high-risk group (16.6%) declined 0.69 points/y (95% CI: -0.85, -0.54). Using the secondary index, which included β-amyloid 42/40 (validation n = 279), the low-risk group (26.9%) declined 0.20 points/y (95% CI: -0.42, 0.01), the medium-risk group (61.3%) declined 0.55 points/y (95% CI: -0.72, -0.38), and the high-risk group (11.8%) declined 0.83 points/y (95% CI: -1.14, -0.51). CONCLUSIONS: A risk index based on 8 blood-based markers was modestly able to predict cognitive decline over an 11-year follow-up. Further validation in other cohorts is necessary.
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