Skip to main content
×
Home

Trajectories of cognitive decline in Alzheimer's disease

  • Patricia A. Wilkosz (a1), Howard J. Seltman (a2), Bernie Devlin (a1), Elise A. Weamer (a1) (a3), Oscar L. Lopez (a1) (a3), Steven T. DeKosky (a1) (a3) and Robert A. Sweet (a1) (a3) (a4)...
Abstract
ABSTRACT

Background: Late-onset Alzheimer disease (LOAD) is a clinically heterogeneous complex disease defined by progressively disabling cognitive impairment. Psychotic symptoms which affect approximately one-half of LOAD subjects have been associated with more rapid cognitive decline. However, the variety of cognitive trajectories in LOAD, and their correlates, have not been well defined. We therefore used latent class modeling to characterize trajectories of cognitive and behavioral decline in a cohort of AD subjects.

Methods: 201 Caucasian subjects with possible or probable Alzheimer's disease (AD) were evaluated for cognitive and psychotic symptoms at regular intervals for up to 13.5 years. Cognitive symptoms were evaluated serially with the Mini-mental State Examination (MMSE), and psychotic symptoms were rated using the CERAD behavioral rating scale (CBRS). Analyses undertaken were latent class mixture models of quadratic trajectories including a random intercept with initial MMSE score, age, gender, education, and APOE ϵ4 count modeled as concomitant variables. In a secondary analysis, psychosis status was also included.

Results: AD subjects showed six trajectories with significantly different courses and rates of cognitive decline. The concomitant variables included in the best latent class trajectory model were initial MMSE and age. Greater burden of psychotic symptoms increased the probability of following a trajectory of more rapid cognitive decline in all age and initial MMSE groups. APOE ϵ4 was not associated with any trajectory.

Conclusion: Trajectory modeling of longitudinal cognitive and behavioral data may provide enhanced resolution of phenotypic variation in AD.

Copyright
Corresponding author
Correspondence should be addressed to: Robert A. Sweet, M. D., Professor of Psychiatry and Neurology, University of Pittsburgh, Biomedical Science Tower, Rm W-1645, 3811 O'Hara Street, Pittsburgh, PA 15213–2593, U.S.A. Phone +1 412 383 8548; Fax +1 412 624 9910. Email: sweetra@upmc.edu.
References
Hide All
Bacanu S. A., Devlin B., Chowdari K. V., DeKosky S. T., Nimgaonkar V. L. and Sweet R. A. (2005). Heritability of psychosis in Alzheimer disease. American Journal of Geriatric Psychiatry, 13, 624627.
Barnes L. L., Wilson R. S., Schneider J. A., Bienias J. L., Evans D. A. and Bennett D. A. (2003). Gender, cognitive decline, and risk of AD in older persons. Neurology, 60, 17771781.
Berg L. et al. (1998). Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Archives of Neurology, 55, 326335.
Bertram K., McQueen M. B., Mullin K., Blacker D. and Tanzi R. E. (2007). Systematic Meta-Analysis of Alzheimer Disease Genetic Association Studies: The AlzGene Database. Nature Genetics, 39, 1723.
Bretsky P., Guralnik J. M., Launer L., Albert M. and Seeman T. E. (2003). The role of APOE-epsilon4 in longitudinal cognitive decline: MacArthur Studies of Successful Aging. Neurology, 60, 10771081.
Corder E. H. et al. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science, 261, 921923.
Craft S. et al. (1998). Accelerated decline in apolipoprotein E-epsilon4 homozygotes with Alzheimer's disease. Neurology, 51, 149153.
Curran P. J. and Willoughby M. T. (2003). Implications of latent trajectory models for the study of developmental psychopathology. Development and Psychopathology, 15, 581612.
Dodge H. H., Du Y., Saxton J. A. and Ganguli M. (2006). Cognitive domains and trajectories of functional independence in nondemented elderly persons. Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 61, 13301337.
Folstein M. F., Folstein S. E. and McHugh P. R. (1975). Mini mental state: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.
Gruen B. and Leisch F. (2008). FlexMix Version 2: finite mixtures with concomitant variables and varying and constant parameters. Journal of Statistical Software, 28, 135.
Healy D. G. (2006). Case-control studies in the genomic era: a clinician's guide. Lancet Neurology, 5, 701707.
Helgeson V. S., Snyder P. and Seltman H. (2004). Psychological and physical adjustment to breast cancer over 4 years: identifying distinct trajectories of change. Health Psychology, 23, 315.
Hollingworth P. et al. (2007). Increased familial risk and genomewide significant linkage for Alzheimer's disease with psychosis. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 144B, 841848.
Holmans P. et al. (2005). Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 135B, 2432.
Hoyt B. D., Massman P. J., Schatschneider C., Cooke N. and Doody R. S. (2005). Individual growth curve analysis of APOE epsilon 4-associated cognitive decline in Alzheimer disease. Archives of Neurology, 62, 454459.
Jones B. L., Nagin D. S. and Roeder K. (2001). A SAS procedure based on mixture models for estimating developmental trajectories. Sociological Methods and Research, 29, 374393.
Kamboh M. I., Aston C. E. and Hamman R. F. (1995). The relationship of APOE polymorphism and cholesteral levels in normoglycemic and diabetic subjects in biethnic population from the San Luis Valley, Colorado. Atherosclerosis, 112, 145159.
Kleiman T. et al. (2006). Apolipoprotein E ϵ4 allele is unrelated to cognitive or functional decline in Alzheimer's disease: retrospective and prospective analysis. Dementia and Geriatric Cognitive Disorders, 22, 7382.
Leisch E. (2004). FlexMix: a general framework for finite mixture models and latent class regression in R. Journal of Statistical Software, 11, 118.
Lopez O. L., Kuller L. H., Fitzpatrick A., Ives D., Becker J. T. and Beauchamp N. (2003). Evaluation of dementia in the cardiovascular health cognition study. Neuroepidemiology, 22, 112.
Mann U. M., Mohr E., Gearing M. and Chase T. N. (1992). Heterogeneity in Alzheimer's disease: progression rate segregated by distinct neuropsychological and cerebral metabolic profiles. Journal of Neurology, Neurosurgery and Psychiatry, 55, 956959.
Martins C. A., Oulhaj A., de Jager C. A. and Williams J. H. (2005). APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model. Neurology, 65, 18881893.
McKeith I. G. et al. (1996). Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology, 47, 11131124.
McKhann G., Drachman D., Folstein M., Katzman R., Price D. and Stadlan E. M. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology, 34, 939944.
O'Hara R., Sommer B., Way N., Kraemer H. C., Taylor J. and Murphy G. (2008). Slower speed-of-processing of cognitive tasks is associated with presence of the apolipoprotein ϵ4 allele. Journal of Psychiatric Research, 42, 199204.
R Development Core Team (2007). A Language and Environment for Statistical Computing. Vienna: R Foundation for Statistical Computing.
Rasmusson D. X., Carson K. A., Brookmeyer R., Kawas C. and Brandt J. (1996). Predicting rate of cognitive decline in probable Alzheimer's disease. Brain and Cognition, 31, 133147.
Ropacki S. A. and Jeste D. V. (2005). Epidemiology of and risk factors for psychosis of Alzheimer's disease: a review of 55 studies published from 1990 to 2003. American Journal of Psychiatry, 162, 20222030.
Royall D. R., Palmer R., Chiodo L. K. and Polk M. J. (2005). Normal rates of cognitive change in successful aging: the freedom house study. Journal of the International Neuropsychological Society, 11, 899909.
Scarmeas N. et al. (2005). Delusions and hallucinations are associated with worse outcome in Alzheimer disease. Archives of Neurology, 62, 16011608.
Schwarz G. (1978). Estimating the dimension of a model. Annals of Statistics, 6, 461464.
Tariot P. N. et al. (1995). The behavior rating scale for dementia of the Consortium to Establish a Registry for Alzheimer's Disease. American Journal of Psychiatry, 152, 13491357.
Tyas S. L. et al. (2007). Transitions to mild cognitive impairments, dementia, and death: findings from the Nun Study. American Journal of Epidemiology, 165, 12311238.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

International Psychogeriatrics
  • ISSN: 1041-6102
  • EISSN: 1741-203X
  • URL: /core/journals/international-psychogeriatrics
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Full text views

Total number of HTML views: 3
Total number of PDF views: 60 *
Loading metrics...

Abstract views

Total abstract views: 290 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 25th November 2017. This data will be updated every 24 hours.