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Apolipoprotein E genotype and lifetime cognitive decline

Published online by Cambridge University Press:  01 February 2008

Nicholas A. Kozauer*
Affiliation:
Division of Geriatric and Neuropsychiatry, Johns Hopkins School of Medicine, Baltimore, U.S.A.
Michelle M. Mielke
Affiliation:
Department of Psychiatry, Division of Geriatric Psychiatry and Neuropsychiatr, Johns Hopkins School of Medicine, Baltimore, U.S.A.
Gary Kwun Chuen Chan
Affiliation:
Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, U.S.A.
George W. Rebok
Affiliation:
Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, U.S.A.
Constantine G. Lyketsos
Affiliation:
The Johns Hopkins Bayview Medical Center Department of Psychiatry and Division of Geriatric and Neuropsychiatry, The Johns Hopkins Hospital, Baltimore, U.S.A.
*
Correspondence should be addressed to: Dr. Nicholas A. Kozauer, Division of Geriatric and Neuropsychiatry, Johns Hopkins School of Medicine, 550 N. Broadway, Suite 308, Baltimore, MD 21205. Phone +1 410 502 3748; Fax +1 410 614 8042. Email: nkozaue1@jhmi.edu.

Abstract

Objective: The relationship of apolipoprotein E (APOE) genotype to lifetime cognitive decline was examined over 22 years in a large community-based population study.

Method: The sample for the present study was derived from follow-up of a probability sample of the adult household residents of East Baltimore. From the Baltimore cohort of the Epidemiologic Catchment Area Study, genotype data were collected on 818 participants at the study's fourth wave between 2003 and 2004. Participants were administered the Mini-mental State Examination (MMSE) at all four study waves. Three tests of verbal learning – immediate recall, delayed recall, and word recognition – were completed at waves 3 and 4. The 659 participants for whom genetic data were available had also completed cognitive testing at all time points. Test scores and changes in these scores were examined by APOE genotype group (x/x or 4/x) in younger and older subcohorts defined by age at wave 4 (< or ≥ age 65).

Results: Cross-sectional wave 4 scores on all four cognitive tasks were lower in APOEε4 carriers when compared to non-carriers. In longitudinal univariate models ε4 carriers in the younger cohort demonstrated a greater annual rate of decline on a delayed recall task and MMSE. After adjusting for covariates only the decline in the delayed recall task was significant.

Conclusion: We report an association between APOE genotype and decline in delayed recall and possibly MMSE over this extended time period limited to younger individuals. The lack of an association between APOE and decline in older individuals is likely to be the result of survival bias. Although a clear association exists between APOE genotype and cognitive decline or dementia in late life, these findings suggest that over the lifespan the relationship between APOE and cognitive decline is more complicated.

Type
Research Article
Copyright
Copyright © International Psychogeriatric Association 2007

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References

Baxter, L. C., Caselli, R. J., Johnson, S. C., Reiman, E., Osborne, D. 2003. Apolipoprotein E epsilon 4 affects new learning in cognitively normal individuals at risk for Alzheimer's disease. Neurobiology of Aging, 24, 947952.CrossRefGoogle ScholarPubMed
Blair, C. K. et al. 2005. APOE genotype and cognitive decline in a middle-aged cohort. Neurology, 64, 268276.CrossRefGoogle Scholar
Bretsky, P., Guralnik, J. M., Launer, L., Albert, M., Seeman, T. E. 2003. The role of APOE-ε4 in longitudinal cognitive decline: MacArthur Studies of Successful Aging. Neurology, 60, 10771081.CrossRefGoogle ScholarPubMed
Brookmeyer, R., Gray, S. and Kawas, C. 1998. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. American Journal of Public Health, 88,13371342.CrossRefGoogle ScholarPubMed
Caselli, R. J. et al. 1999. Preclinical memory decline in cognitively normal apolipoprotein E- ε4 homozygotes. Neurology, 53, 201207.CrossRefGoogle ScholarPubMed
Cohen, R. M., Small, C., Lalonde, F., Friz, J. and Sunderland, T. 2001. Effect of apolipoprotein E genotype on hippocampal volume loss in aging healthy women. Neurology, 57, 22232228.CrossRefGoogle ScholarPubMed
Collie, A. et al. 2001. Memory decline in healthy older people: implications for identifying mild cognitive impairment. Neurology, 56, 15331538.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Corder, E. H. et al. 1994 Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nature Genetics, 7, 180184.CrossRefGoogle ScholarPubMed
Coroni-Huntley, J. et al. 1993. Established populations for epidemiologic studies of the elderly: study design and methodology. Aging (Milan), 5, 2737.Google Scholar
Dik, M. G., Jonker, C., Bouter, L. M., Geerlings, M. I., van Kamp, G. J. and Deeg, D. J. 2000. APOE-ε4 is associated with memory decline in cognitively impaired elderly. Neurology, 54, 14921497.CrossRefGoogle ScholarPubMed
Eaton, W. W. and Kessler, L. G. 1985. Epidemiologic Field Methods in Psychiatry: The NIMH Epidemiologic Catchment Area Program. Orlando, FL: Academic Press.Google Scholar
Eaton, W. W. et al. 1997. Natural history of Diagnostic Interview Schedule/DSM-IV major depression. The Baltimore Epidemiologic Catchment Area follow-up. Archives of General Psychiatry, 54, 993999.CrossRefGoogle ScholarPubMed
Fassbender, K., Masters, C. and Beyreuther, K. 2001. Alzheimer's disease: molecular concepts and therapeutic targets. Naturwissenschaften, 6, 261267.Google Scholar
Feskens, E. J., Havekes, L. M., Kalmijn, S., de Knijff, P., Launer, L. J. and Kromhout, D. 1994. Apolipoprotein ε4 allele and cognitive decline in elderly men. BMJ, 309, 12021206.CrossRefGoogle Scholar
Fillenbaum, G. G., Landerman, L. R., Blazer, D. G., Saunders, A. M., Harris, T. B. and Launer, L. J. 2001. The relationship of APOE genotype to cognitive functioning in older African-American and Caucasian community residents. Journal of the American Geriatrics Society, 49, 11481155.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Gomez-Isla, T. et al. 1996 Clinical and pathological correlates of apolipoprotein E ε4 in Alzheimer's disease. Annals of Neurology, 39, 6270.CrossRefGoogle Scholar
Helkala, E. L. et al. 1996 Memory functions in human subjects with different apolipoprotein E phenotypes during a 3-year population-based follow-up study. Neuroscience Letters, 204, 177180.CrossRefGoogle ScholarPubMed
Hyman, B. T. 1996. Apolipoprotein E genotype: utility in clinical practice in Alzheimer's disease. Journal of the American Geriatrics Society, 44, 14691471.CrossRefGoogle ScholarPubMed
Hyman, B. T. et al. 1995 Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome). Proceedings of the National Academy of Science, U.S.A., 92, 3586–3590.Google Scholar
Jonker, C., Schmand, B., Lindeboom, J., Havekes, L. M. and Launer, L. J. 1998. Association between apolipoprotein E ε4 and the rate of cognitive decline in community dwelling elderly individuals with and without dementia. Archives of Neurology, 55, 10651069.CrossRefGoogle ScholarPubMed
Kang, J. H., Logroscino, G., De Vivo, I., Hunter, D. and Grodstein, F. 2005. Apolipoprotein E, cardiovascular disease and cognitive function in aging women. Neurobiology of Aging, 26, 475484.CrossRefGoogle ScholarPubMed
Khachaturian, A. S., Corcoran, C. D., Mayer, L. S., Zandi, P. P. and Breitner, J. C. 2004. Cache County Study Investigators. Apolipoprotein E ε4 count affects age at onset of Alzheimer disease, but not lifetime susceptibility: The Cache County Study. Archives of General Psychiatry, 61, 518524.CrossRefGoogle Scholar
Kuller, L. et al. 1998. Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study. Stroke, 29, 388398.CrossRefGoogle ScholarPubMed
Lahoz, C. et al. 2001. Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study. Atherosclerosis, 154, 529537.CrossRefGoogle ScholarPubMed
Laird, N. M. and Ware, J. H. 1982. Random-effects models for longitudinal data. Biometrics, 38, 963974.CrossRefGoogle ScholarPubMed
Mayeux, R., Small, S. A., Tang, M., Tycko, B. and Stern, Y. 2001. Memory performance in healthy elderly without Alzheimer's disease: effects of time and apolipoprotein-E. Neurobiology of Aging, 22, 683689.CrossRefGoogle ScholarPubMed
McCarron, M. O., Delong, D. and Alberts, M. J. 1999. APOE genotype as a risk factor for ischemic cerebrovascular disease: a meta-analysis. Neurology, 53, 13081311.CrossRefGoogle ScholarPubMed
Mortensen, E. L. and Hogh, P. 2001. A gender difference in the association between APOE genotype and age-related cognitive decline, Neurology, 57, 8995.CrossRefGoogle ScholarPubMed
O'Hara, R., Yesavage, J. A., Kraemer, H. C., Mauricio, M., Friedman, L. F. and Murphy, G. M. Jr. 1998 The APOE ε4 allele is associated with decline on delayed recall performance in community-dwelling older adults. Journal of the American Geriatrics Society, 46, 14931498.CrossRefGoogle ScholarPubMed
Ohm, T. G., Kirca, M., Bohl, J., Scharnagl, H., Gross, W. and Marz, W. 1995. Apolipoprotein E polymorphism influences not only cerebral senile plaque load but also Alzheimer-type neurofibrillary tangle formation. Neuroscience, 66, 583587.CrossRefGoogle Scholar
Pirttila, T. et al. 1997. Apolipoprotein E genotype and amyloid load in Alzheimer disease and control brains. Neurobiology of Aging, 18, 121127.CrossRefGoogle ScholarPubMed
Polvikoski, T. et al. 1995. Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. The New England Journal of Medicine, 333, 12421247.CrossRefGoogle ScholarPubMed
Riley, K. P., Snowdon, D. A., Saunders, A. M., Roses, A. D., Mortimer, J. A. and Nanayakkara, N. 2000 Cognitive function and apolipoprotein E in very old adults: findings from the Nun Study. Journals of Gerontology Series B: Biological Sciences and Medical Sciences, 55, S69S75.CrossRefGoogle ScholarPubMed
Robins, L. N., Helzer, J. E., Croughan, J. and Ratcliff, K. 1981 National Institute of Mental Health Diagnostic Interview Schedule: its history, characteristics, and validity. Archives of General Psychiatry, 38, 381389.CrossRefGoogle ScholarPubMed
Saunders, A. M. et al. 1993. Association of apolipoprotein E allele ε4 with late-onset familial and sporadic Alzheimer's disease. Neurology, 43, 14671472.CrossRefGoogle Scholar
Schmechel, D. E. et al. 1993. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proceedings of the National Academy of Science, U.S.A., 90, 9649–9653.Google Scholar
Sparks, D. L. 1997. Coronary artery disease, hypertension, ApoE, and cholesterol: a link to Alzheimer's disease? Annals of the New York Academy of Science, 826, 128146.CrossRefGoogle ScholarPubMed
Stengard, J. H., Weiss, K. M. and Sing, C. F. 1998. An ecological study of association between coronary heart disease mortality rates in men and the relative frequencies of common allelic variations in the gene coding for apolipoprotein E. Human Genetics, 103, 234241.CrossRefGoogle ScholarPubMed
St.George-Hyslop, P. H. 2000. Genetic factors in the genesis of Alzheimer's disease. Annals of the New York Academy of Science, 924, 17.CrossRefGoogle Scholar
Talbot, C., Lendon, C., Craddock, N., Shears, S., Morris, J.C. and Goate, A. 1994. Protection against Alzheimer's disease with apoE ε2. Lancet, 343, 14321433.CrossRefGoogle Scholar
Tombaugh, T. N. and McIntyre, N. J. 1992. The mini-mental state examination: a comprehensive review. Journal of the American Geriatrics Society, 40, 922935.CrossRefGoogle ScholarPubMed
Wilson, P. W., Schaefer, E. J., Larson, M. G. and Ordovas, J. M. 1996. Apolipoprotein E alleles and risk of coronary disease. A meta-analysis. Arteriosclerosis, Thrombosis, and Vascular Biology, 16, 12501255.CrossRefGoogle ScholarPubMed
Wilson, R. S. et al. 2002. The apolipoprotein ε 4 allele and decline in different cognitive systems during a 6-year period. Archives of Neurology, 59, 11541160.CrossRefGoogle Scholar
Winnock, M., Letenneur, L., Jacqmin-Gadda, H., Dallongeville, J., Amouyel, P. and Dartigues, J. F. 2002. Longitudinal analysis of the effect of apolipoprotein E epsilon4 and education on cognitive performance in elderly subjects: the PAQUID study. Journal of Neurology, Neurosurgery, and Psychiatry, 72, 794797.CrossRefGoogle ScholarPubMed
Yaffe, K., Cauley, J., Sands, L. and Browner, W. 1997. Apolipoprotein E phenotype and cognitive decline in a prospective study of elderly community women. Archives of Neurology, 54, 11101114.CrossRefGoogle Scholar