Jeannie-Marie S Leoutsakos1, Sarah N Forrester1, Christopher D Corcoran2,3, Maria C Norton2,4,5, Peter V Rabins1, Martin I Steinberg1, Joann T Tschanz2,4, Constantine G Lyketsos1. 1. Department of Psychiatry, Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 2. Center for Epidemiologic Studies, Utah State University, Logan, UT, USA. 3. Department of Mathematics and Statistics, Utah State University, Logan, UT, USA. 4. Department of Psychology, Utah State University, Logan, UT, USA. 5. Department of Family, Consumer and Human Development, Utah State University, Logan, UT, USA.
Abstract
OBJECTIVE: Several longitudinal studies of Alzheimer's disease (AD) report heterogeneity in progression. We sought to identify groups (classes) of progression trajectories in the population-based Cache County Dementia Progression Study (N = 328) and to identify baseline predictors of membership for each group. METHODS: We used parallel-process growth mixture models to identify latent classes of trajectories on the basis of Mini-Mental State Exam (MMSE) and Clinical Dementia Rating sum of boxes scores over time. We then used bias-corrected multinomial logistic regression to model baseline predictors of latent class membership. We constructed receiver operating characteristic curves to demonstrate relative predictive utility of successive sets of predictors. RESULTS: We fit four latent classes; class 1 was the largest (72%) and had the slowest progression. Classes 2 (8%), 3 (11%), and 4 (8%) had more rapid worsening. In univariate analyses, longer dementia duration, presence of psychosis, and worse baseline MMSE and Clinical Dementia Rating sum of boxes were associated with membership in class 2, relative to class 1. Lower education was associated with membership in class 3. In the multivariate model, only MMSE remained a statistically significant predictor of class membership. Receiver operating characteristic areas under the curve were 0.98, 0.88, and 0.67, for classes 2, 3, and 4 relative to class 1. CONCLUSIONS: Heterogeneity in AD course can be usefully characterized using growth mixture models. The majority belonged to a class characterized by slower decline than is typically reported in clinical samples. Class membership could be predicted using baseline covariates. Further study may advance our prediction of AD course at the population level and in turn shed light on the pathophysiology of progression.
OBJECTIVE: Several longitudinal studies of Alzheimer's disease (AD) report heterogeneity in progression. We sought to identify groups (classes) of progression trajectories in the population-based Cache County Dementia Progression Study (N = 328) and to identify baseline predictors of membership for each group. METHODS: We used parallel-process growth mixture models to identify latent classes of trajectories on the basis of Mini-Mental State Exam (MMSE) and ClinicalDementia Rating sum of boxes scores over time. We then used bias-corrected multinomial logistic regression to model baseline predictors of latent class membership. We constructed receiver operating characteristic curves to demonstrate relative predictive utility of successive sets of predictors. RESULTS: We fit four latent classes; class 1 was the largest (72%) and had the slowest progression. Classes 2 (8%), 3 (11%), and 4 (8%) had more rapid worsening. In univariate analyses, longer dementia duration, presence of psychosis, and worse baseline MMSE and ClinicalDementia Rating sum of boxes were associated with membership in class 2, relative to class 1. Lower education was associated with membership in class 3. In the multivariate model, only MMSE remained a statistically significant predictor of class membership. Receiver operating characteristic areas under the curve were 0.98, 0.88, and 0.67, for classes 2, 3, and 4 relative to class 1. CONCLUSIONS: Heterogeneity in AD course can be usefully characterized using growth mixture models. The majority belonged to a class characterized by slower decline than is typically reported in clinical samples. Class membership could be predicted using baseline covariates. Further study may advance our prediction of AD course at the population level and in turn shed light on the pathophysiology of progression.
Authors: M E Peters; P B Rosenberg; M Steinberg; M C Norton; K A Welsh-Bohmer; K M Hayden; J Breitner; J T Tschanz; C G Lyketsos Journal: Am J Geriatr Psychiatry Date: 2013-02-06 Impact factor: 4.105
Authors: Kumar B Rajan; Elizabeth A McAninch; Robert S Wilson; Jennifer Weuve; Lisa L Barnes; Denis A Evans Journal: J Alzheimers Dis Date: 2019 Impact factor: 4.472
Authors: Christine E Walsh; Yang C Yang; Katsuya Oi; Allison Aiello; Daniel Belsky; Kathleen Mullan Harris; Brenda L Plassman Journal: J Gerontol B Psychol Sci Soc Sci Date: 2022-10-06 Impact factor: 4.942
Authors: Helen Hochstetler; Paula T Trzepacz; Shufang Wang; Peng Yu; Michael Case; David B Henley; Elisabeth Degenhardt; Jeannie-Marie Leoutsakos; Constantine G Lyketsos Journal: J Alzheimers Dis Date: 2016 Impact factor: 4.472