Empirically Derived Trajectories to Dementia Over 15 Years of Follow-up Identified by Using Mixed Membership Models

Alzheimer disease is the most common form of dementia in the elderly, and the complex relationships among risk factors produce highly variable natural histories from normal cognition through the prodromal stage of mild cognitive impairment (MCI) to clinical dementia. We used a novel statistical appr...

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Bibliographic Details
Published in:American journal of epidemiology 2015-08, Vol.182 (4), p.366-374
Main Authors: Lecci, Fabrizio, Junker, Brian, Kuller, Lewis H, Lopez, Oscar L, Becker, James T
Format: Article
Language:English
Subjects:
Age Distribution
Aged
Aged, 80 and over
Alzheimer Disease - diagnostic imaging
Alzheimer Disease - epidemiology
Alzheimer Disease - genetics
Alzheimer's disease
Anatomy & physiology
Apolipoprotein E4 - genetics
Cardiovascular Diseases - epidemiology
Cognitive ability
Cognitive Dysfunction - epidemiology
Comorbidity
Dementia
Dementia - classification
Dementia - epidemiology
Dementia - genetics
Diabetes Mellitus - epidemiology
Disease Progression
Female
Follow-Up Studies
Humans
Magnetic Resonance Imaging
Male
Neuroimaging
Practice of Epidemiology
Prevalence
Probability
Proportional Hazards Models
Radiography
Risk Factors
Sex Distribution
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Summary:Alzheimer disease is the most common form of dementia in the elderly, and the complex relationships among risk factors produce highly variable natural histories from normal cognition through the prodromal stage of mild cognitive impairment (MCI) to clinical dementia. We used a novel statistical approach, mixed membership trajectory models, to capture the variety of such pathways in 652 participants in the Cardiovascular Health Study Cognition Study over 22 years of follow-up (1992-2014). We identified 3 trajectories: a "healthy" profile with a peak probability of MCI between 95 and 100 years of age and only a 50% probability of dementia by age 100; an "intermediate" profile with a peak probability of MCI between 85 and 90 years of age and progression to dementia between 90 and 95 years; and an "unhealthy" profile with a peak probability of progressing to MCI between ages 75 and 80 years and to dementia between the ages of 80 and 85 years. Hypertension, education, race, and the ϵ4 allele of the apolipoprotein E gene all affected the closeness of an individual to 1 or more of the canonical trajectories. These results provide new insights into the natural history of Alzheimer disease and evidence for a potential difference in the pathophysiology of the development of dementia.
ISSN:0002-9262
1476-6256
DOI:10.1093/aje/kwv051