American Journal of Epidemiology Advance Access originally published online on April 12, 2007
American Journal of Epidemiology 2007 165(11):1231-1238; doi:10.1093/aje/kwm085
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ORIGINAL CONTRIBUTIONS |
Transitions to Mild Cognitive Impairments, Dementia, and Death: Findings from the Nun Study
1 Department of Health Studies and Gerontology, University of Waterloo, Waterloo, Ontario, Canada
2 Division of Behavioural Neuroscience, Department of Psychology, University of Waterloo, Waterloo, Ontario, Canada
3 School of Statistics, National University of Colombia at Medellín, Medellín, Colombia
4 Department of Neurology, University of Kentucky, Lexington, KY
5 Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY
6 Department of Preventive Medicine and Environmental Health, University of Kentucky, Lexington, KY
7 Department of Biostatistics, University of Kentucky, Lexington, KY
8 Department of Statistics, University of Kentucky, Lexington, KY
Correspondence to Dr. Suzanne L. Tyas, Department of Health Studies and Gerontology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada N2L 3G1 (e-mail: styas{at}uwaterloo.ca).
Received for publication July 21, 2006. Accepted for publication October 20, 2006.
The potential of early interventions for dementia has increased interest in cognitive impairments less severe than dementia. However, predictors of the trajectory from intact cognition to dementia have not yet been clearly identified. The purpose of this study was to determine whether known risk factors for dementia increased the risk of mild cognitive impairments or progression from mild cognitive impairments to dementia. A polytomous logistic regression model was used, with parameters governing transitions within transient states (intact cognition, mild cognitive impairments, global impairment) estimated separately from parameters governing the transition from transient to absorbing state (dementia or death). Analyses were based on seven annual examinations (1991–2002) of 470 Nun Study participants aged 
75 years at baseline and living in the United States. Odds of developing dementia increased with age primarily for those with low educational levels. In these women, presence of an apolipoprotein E gene *E4 allele increased the odds more than fourfold by age 95 years. Age, education, and the apolipoprotein E gene were all significantly associated with mild cognitive impairments. Only age, however, was associated with progression to dementia. Thus, risk factors for dementia may operate primarily by predisposing individuals to develop mild cognitive impairments; subsequent progression to dementia then depends on only time and competing mortality.
aged, 80 and over; apolipoproteins E; cognition disorders; cohort studies; dementia; disease progression; Markov chains; risk factors
Abbreviations: APOE, apolipoprotein E gene
Editor's note: An invited commentary on this article appears on page 1239, and the authors' response is published on page 1247.
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Related articles in Am. J. Epidemiol.:
- Tyas et al. Respond to "Predictors of Rate of Change in Disease Progression"
- Suzanne L. Tyas, Juan Carlos Salazar, David A. Snowdon, Mark F. Desrosiers, Kathryn P. Riley, Marta S. Mendiondo, and Richard J. Kryscio
Am. J. Epidemiol. 2007 165: 1247.[Extract] [FREE Full Text] - Invited Commentary: When Bad Genes Look Good—APOE*E4, Cognitive Decline, and Diagnostic Thresholds
- M. Maria Glymour
Am. J. Epidemiol. 2007 165: 1239-1246.[Abstract] [FREE Full Text]
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M. M. Glymour Invited Commentary: When Bad Genes Look Good--APOE*E4, Cognitive Decline, and Diagnostic Thresholds Am. J. Epidemiol., June 1, 2007; 165(11): 1239 - 1246. [Abstract] [Full Text] [PDF]
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