Maryam Iraniparast, From the School of Public Health Sciences (M.I., C.J.M., S.L.T.), Department of Statistics and Actuarial Science (Y.S., Y.W., L.Z.), and School of Pharmacy (C.J.M.), University of Waterloo, Canada; School of Statistics and Data Science (Y.W.), Nankai University, Tianjin, China; Departments of Statistics and Biostatistics and Sanders-Brown Center on Aging (R.J.K.), University of Kentucky, Lexington; Department of Medicine, Section of Geriatric Medicine, Max Rady College of Medicine (P.D.S.), and Centre on Aging (P.D.S.), University of Manitoba, Winnipeg, Canada; and Department of Laboratory Medicine and Pathology (K.S.S.), University of New Mexico School of Medicine, Albuquerque
Yidan Shi, From the School of Public Health Sciences (M.I., C.J.M., S.L.T.), Department of Statistics and Actuarial Science (Y.S., Y.W., L.Z.), and School of Pharmacy (C.J.M.), University of Waterloo, Canada; School of Statistics and Data Science (Y.W.), Nankai University, Tianjin, China; Departments of Statistics and Biostatistics and Sanders-Brown Center on Aging (R.J.K.), University of Kentucky, Lexington; Department of Medicine, Section of Geriatric Medicine, Max Rady College of Medicine (P.D.S.), and Centre on Aging (P.D.S.), University of Manitoba, Winnipeg, Canada; and Department of Laboratory Medicine and Pathology (K.S.S.), University of New Mexico School of Medicine, Albuquerque
Ying Wu, From the School of Public Health Sciences (M.I., C.J.M., S.L.T.), Department of Statistics and Actuarial Science (Y.S., Y.W., L.Z.), and School of Pharmacy (C.J.M.), University of Waterloo, Canada; School of Statistics and Data Science (Y.W.), Nankai University, Tianjin, China; Departments of Statistics and Biostatistics and Sanders-Brown Center on Aging (R.J.K.), University of Kentucky, Lexington; Department of Medicine, Section of Geriatric Medicine, Max Rady College of Medicine (P.D.S.), and Centre on Aging (P.D.S.), University of Manitoba, Winnipeg, Canada; and Department of Laboratory Medicine and Pathology (K.S.S.), University of New Mexico School of Medicine, Albuquerque
Leilei Zeng, From the School of Public Health Sciences (M.I., C.J.M., S.L.T.), Department of Statistics and Actuarial Science (Y.S., Y.W., L.Z.), and School of Pharmacy (C.J.M.), University of Waterloo, Canada; School of Statistics and Data Science (Y.W.), Nankai University, Tianjin, China; Departments of Statistics and Biostatistics and Sanders-Brown Center on Aging (R.J.K.), University of Kentucky, Lexington; Department of Medicine, Section of Geriatric Medicine, Max Rady College of Medicine (P.D.S.), and Centre on Aging (P.D.S.), University of Manitoba, Winnipeg, Canada; and Department of Laboratory Medicine and Pathology (K.S.S.), University of New Mexico School of Medicine, Albuquerque
Colleen J. Maxwell, From the School of Public Health Sciences (M.I., C.J.M., S.L.T.), Department of Statistics and Actuarial Science (Y.S., Y.W., L.Z.), and School of Pharmacy (C.J.M.), University of Waterloo, Canada; School of Statistics and Data Science (Y.W.), Nankai University, Tianjin, China; Departments of Statistics and Biostatistics and Sanders-Brown Center on Aging (R.J.K.), University of Kentucky, Lexington; Department of Medicine, Section of Geriatric Medicine, Max Rady College of Medicine (P.D.S.), and Centre on Aging (P.D.S.), University of Manitoba, Winnipeg, Canada; and Department of Laboratory Medicine and Pathology (K.S.S.), University of New Mexico School of Medicine, Albuquerque
Richard J. Kryscio, From the School of Public Health Sciences (M.I., C.J.M., S.L.T.), Department of Statistics and Actuarial Science (Y.S., Y.W., L.Z.), and School of Pharmacy (C.J.M.), University of Waterloo, Canada; School of Statistics and Data Science (Y.W.), Nankai University, Tianjin, China; Departments of Statistics and Biostatistics and Sanders-Brown Center on Aging (R.J.K.), University of Kentucky, Lexington; Department of Medicine, Section of Geriatric Medicine, Max Rady College of Medicine (P.D.S.), and Centre on Aging (P.D.S.), University of Manitoba, Winnipeg, Canada; and Department of Laboratory Medicine and Pathology (K.S.S.), University of New Mexico School of Medicine, Albuquerque
Philip D. St John, From the School of Public Health Sciences (M.I., C.J.M., S.L.T.), Department of Statistics and Actuarial Science (Y.S., Y.W., L.Z.), and School of Pharmacy (C.J.M.), University of Waterloo, Canada; School of Statistics and Data Science (Y.W.), Nankai University, Tianjin, China; Departments of Statistics and Biostatistics and Sanders-Brown Center on Aging (R.J.K.), University of Kentucky, Lexington; Department of Medicine, Section of Geriatric Medicine, Max Rady College of Medicine (P.D.S.), and Centre on Aging (P.D.S.), University of Manitoba, Winnipeg, Canada; and Department of Laboratory Medicine and Pathology (K.S.S.), University of New Mexico School of Medicine, Albuquerque
Karen S. SantaCruz, From the School of Public Health Sciences (M.I., C.J.M., S.L.T.), Department of Statistics and Actuarial Science (Y.S., Y.W., L.Z.), and School of Pharmacy (C.J.M.), University of Waterloo, Canada; School of Statistics and Data Science (Y.W.), Nankai University, Tianjin, China; Departments of Statistics and Biostatistics and Sanders-Brown Center on Aging (R.J.K.), University of Kentucky, Lexington; Department of Medicine, Section of Geriatric Medicine, Max Rady College of Medicine (P.D.S.), and Centre on Aging (P.D.S.), University of Manitoba, Winnipeg, Canada; and Department of Laboratory Medicine and Pathology (K.S.S.), University of New Mexico School of Medicine, Albuquerque
Suzanne L. Tyas, From the School of Public Health Sciences (M.I., C.J.M., S.L.T.), Department of Statistics and Actuarial Science (Y.S., Y.W., L.Z.), and School of Pharmacy (C.J.M.), University of Waterloo, Canada; School of Statistics and Data Science (Y.W.), Nankai University, Tianjin, China; Departments of Statistics and Biostatistics and Sanders-Brown Center on Aging (R.J.K.), University of Kentucky, Lexington; Department of Medicine, Section of Geriatric Medicine, Max Rady College of Medicine (P.D.S.), and Centre on Aging (P.D.S.), University of Manitoba, Winnipeg, Canada; and Department of Laboratory Medicine and Pathology (K.S.S.), University of New Mexico School of Medicine, Albuquerque. styas@uwaterloo.ca

Document Type

Article

Publication Date

3-15-2022

Abstract

BACKGROUND AND OBJECTIVES: Little is known about the effect of education or other indicators of cognitive reserve on the rate of reversion from mild cognitive impairment (MCI) to normal cognition (NC) or the relative rate (RR) of reversion from MCI to NC vs progression from MCI to dementia. Our objectives were to (1) estimate transition rates from MCI to NC and dementia and (2) determine the effect of age,

METHODS: We estimated instantaneous transition rates between NC, MCI, and dementia after accounting for transition to death across up to 12 assessments in the Nun Study, a cohort study of religious sisters aged 75+ years. We estimated RRs of reversion vs progression for age,

RESULTS: Of the 619 participants, 472 were assessed with MCI during the study period. Of these 472, 143 (30.3%) experienced at least one reverse transition to NC, and 120 of the 143 (83.9%) never developed dementia (mean follow-up = 8.6 years). In models adjusted for age group and

DISCUSSION: Knowledge of frequent reversion from MCI to NC may alleviate concerns of inevitable cognitive decline in those with MCI. Identification of characteristics predicting the rate of reversion from MCI to NC vs progression from MCI to dementia may guide population-level interventions targeting these characteristics to prevent or postpone MCI and dementia. Research on cognitive trajectories would benefit from incorporating predictors of reverse transitions and competing events, such as death, into statistical modeling. These results may inform the design and interpretation of MCI clinical trials, given that a substantial proportion of participants may experience improvement without intervention.

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