Age-Specific Incidence Rates for Dementia and Alzheimer Disease in NIA-LOAD/NCRAD and EFIGA Families: National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease (NIA-LOAD/NCRAD) and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA)
Open accessAbstract
IMPORTANCE: Late-onset Alzheimer disease (LOAD), defined as onset of symptoms after age 65 years, is the most common form of dementia. Few reports investigate incidence rates in large family-based studies in which the participants were selected for family history of LOAD. OBJECTIVE: To determine the incidence rates of dementia and LOAD in unaffected members in the National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease (NIA-LOAD/NCRAD) and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) family studies. DESIGN, SETTING, AND PARTICIPANTS: Families with 2 or more affected siblings who had a clinical or pathological diagnosis of LOAD were recruited as a part of the NIA-LOAD/NCRAD Family Study. A cohort of Caribbean Hispanics with familial LOAD was recruited in a different study at the Taub Institute for Research on Alzheimer's Disease and the Aging Brain in New York and from clinics in the Dominican Republic as part of the EFIGA study. MAIN OUTCOMES AND MEASURES: Age-specific incidence rates of LOAD were estimated in the unaffected family members in the NIA-LOAD/NCRAD and EFIGA data sets. We restricted analyses to families with follow-up and complete phenotype information, including 396 NIA-LOAD/NCRAD and 242 EFIGA families. Among the 943 at-risk family members in the NIA-LOAD/NCRAD families, 126 (13.4%) developed dementia, of whom 109 (86.5%) met criteria for LOAD. Among 683 at-risk family members in the EFIGA families, 174 (25.5%) developed dementia during the study period, of whom 145 (83.3%) had LOAD. RESULTS: The annual incidence rates of dementia and LOAD in the NIA-LOAD/NCRAD families per person-year were 0.03 and 0.03, respectively, in participants aged 65 to 74 years; 0.07 and 0.06, respectively, in those aged 75 to 84 years; and 0.08 and 0.07, respectively, in those 85 years or older. Incidence rates in the EFIGA families were slightly higher, at 0.03 and 0.02, 0.06 and 0.05, 0.10 and 0.08, and 0.10 and 0.07, respectively, in the same age groups. Contrasting these results with the population-based estimates, the incidence was increased by 3-fold for NIA-LOAD/NCRAD families (standardized incidence ratio, 3.44) and 2-fold among the EFIGA compared with the NIA-LOAD/NCRAD families (1.71). CONCLUSIONS AND RELEVANCE: The incidence rates for familial dementia and LOAD in the NIA-LOAD/NCRAD and EFIGA families are significantly higher than population-based estimates. The incidence rates in all groups increase with age. The higher incidence of LOAD can be explained by segregation of Alzheimer disease-related genes in these families or shared environmental risks.
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Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
Mild Cognitive Impairment: Clinical Characterization and Outcome
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.303 · Cited by 8,980 · see citing works
A New Clinical Scale for the Staging of Dementia
Hughes, C. P., Berg, L., Danziger, W., Coben, L. A., & Martin, R. L. (1982) · British Journal of Psychiatry · doi:10.1192/bjp.140.6.566 · Cited by 7,056 · see citing works
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
Statistical Methods in Cancer Research. Volume II – The Design and Analysis of Cohort Studies
Juul, S. (1989) · Scandinavian Journal of Social Medicine · doi:10.1177/140349488901700214 · Cited by 3,602 · see citing works
Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI.
Hixson, J., & Vernier, D. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)43176-1 · Cited by 2,933 · see citing works
Brookmeyer, R., Gray, S. G., & Kawas, C. H. (1998) · American Journal of Public Health · doi:10.2105/ajph.88.9.1337 · Cited by 1,774 · see citing works
Statistical methods in cancer research. Volume II--The design and analysis of cohort studies.
Breslow, N. E., & Day, N. E. (1987) · PubMed · Cited by 1,684 · see citing works
Influence of education and occupation on the incidence of Alzheimer's disease
Stern, Y. (1994) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1994.03510370056032 · Cited by 1,434 · see citing works
The prevalence of dementia: A quantitative integration of the literature
Jorm, A. F., Korten, A. E., & Henderson, A. S. (1987) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1987.tb02906.x · Cited by 1,301 · see citing works
The Distribution of Chi-Square
Wilson, E. B., & Hilferty, M. M. (1931) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.17.12.684 · Cited by 831 · see citing works
Yoshitake, T., Kiyohara, Y., Kato, I., Ohmura, T., Iwamoto, H., Nakayama, K., Ohmori, S., Nomiyama, K., Kawano, H., Ueda, K., et al. (1995) · Neurology · doi:10.1212/wnl.45.6.1161 · Cited by 829 · see citing works
Tang, M.-X. (1998) · JAMA · doi:10.1001/jama.279.10.751 · Cited by 771 · see citing works
Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan
Tang, M. ‐., Cross, P. S., Andrews, H., Jacobs, D. M., Small, S. A., Bell, K., Merchant, C., Lantigua, R., Costa, R., Stern, Y., et al. (2001) · Neurology · doi:10.1212/wnl.56.1.49 · Cited by 721 · see citing works
Self-citationCanadian study of health and aging: study methods and prevalence of dementia.
(1994) · Europe PMC (PubMed Central) · Cited by 613 · see citing works
Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study
Bachman, D. L., Wolf, P. A., Linn, R., Knoefel, J. E., CobbS, J., Belanger, A., D'Agostino, R. B., & White, L. R. (1992) · Neurology · doi:10.1212/wnl.42.1.115 · Cited by 527 · see citing works
Incidence of dementia and probable Alzheimer's disease in a general population: The Framingham Study
Bachman, D. L., Wolf, P. A., Linn, R. T., Knoefel, J. E., Cobb, J. L., Belanger, A. J., White, L. R., & D'Agostino, R. B. (1993) · Neurology · doi:10.1212/wnl.43.3_part_1.515 · Cited by 470 · see citing works
Age-Specific Incidence of Alzheimer's Disease in a Community Population
Hebert, L. E. (1995) · JAMA · doi:10.1001/jama.1995.03520410048025 · Cited by 462 · see citing works
Locus‐specific mutation databases for neurodegenerative brain diseases
Cruts, M., Theuns, J., & Broeckhoven, C. V. (2012) · Human Mutation · doi:10.1002/humu.22117 · Cited by 462 · see citing works
Genome-wide patterns of population structure and admixture among Hispanic/Latino populations
Bryc, K., Velez, C., Karafet, T., Moreno-Estrada, A., Reynolds, A., Auton, A., Hammer, M., Bustamante, C. D., & Ostrer, H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914618107 · Cited by 442 · see citing works
Rates of dementia in three ethnoracial groups
Gurland, B. J., Wilder, D. E., Lantigua, R., Stern, Y., Chen, J., Killeffer, E. H. P., & Mayeux, R. P. (1999) · International Journal of Geriatric Psychiatry · doi:10.1002/(sici)1099-1166(199906)14:6 · Cited by 417 · see citing works
Self-citationLetenneur, L., Gilleron, V, Commenges, D., Helmer, C., Orgogozo, J. M., & Dartigues, J. F. (1999) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.66.2.177 · Cited by 406 · see citing works
Risk of Dementia Among White and African American Relatives of Patients With Alzheimer Disease
Green, R. C. (2002) · JAMA · doi:10.1001/jama.287.3.329 · Cited by 391 · see citing works
Cruchaga, C., Chakraverty, S., Mayo, K., Vallania, F. L. M., Mitra, R. D., Faber, K., Williamson, J., Bird, T., Diaz-Arrastia, R., Foroud, T. M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031039 · Cited by 320 · see citing works
Self-citationApolipoprotein E and alzheimer's disease: Ethnic variation in genotypic risks
Maestre, G. E., Ottman, R., Stern, Y., Gurland, B. J., Chun, M. R., Tang, M., Shelanski, M. L., Tycko, B., & Mayeux, R. P. (1995) · Annals of Neurology · doi:10.1002/ana.410370217 · Cited by 244 · see citing works
Self-citationLee, J. H., Cheng, R., Barral, S., Reitz, C., Medrano, M., Lantigua, R., Jiménez-Velazquez, I. Z., Rogaeva, E., St. George-Hyslop, P. H., & Mayeux, R. (2011) · Archives of Neurology · doi:10.1001/archneurol.2010.292 · Cited by 190 · see citing works
Self-citationIncidence of Clinically Diagnosed Subtypes of Dementia in an Elderly Population
Brayne, C., Gill, C., Huppert, F. A., Barkley, C., Gehlhaar, E., Girling, D. M., O’Connor, D., & Paykel, E. S. (1995) · The British Journal of Psychiatry · doi:10.1192/bjp.167.2.255 · Cited by 145 · see citing works
Low education and childhood rural residence
Hall, K. S., Gao, S., Unverzagt, F. W., & Hendrie, H. C. (2000) · Neurology · doi:10.1212/wnl.54.1.95 · Cited by 143 · see citing works
Teresi, J. A., Golden, R. R., Cross, P. S., Gurland, B. J., Kleinman, M., & Wilder, D. (1995) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(94)00159-n · Cited by 140 · see citing works
Liu, H. C., Chou, P., Lin, K. N., Wang, S. J., Fuh, J., Lin, H.-H., Liu, C. Y., Wu, G. S., Larson, E. B., White, L. R., et al. (1994) · Psychological Medicine · doi:10.1017/s0033291700027914 · Cited by 127 · see citing works
Kokmen, E., Chandra, V., & Schoenberg, B. S. (1988) · Neurology · doi:10.1212/wnl.38.6.975 · Cited by 127 · see citing works
Organic Brain Syndrome and Aging
Jarvik, L. F. (1980) · Archives of General Psychiatry · doi:10.1001/archpsyc.1980.01780160050005 · Cited by 87 · see citing works
Sources of Variability in Prevalence Rates of Alzheimer's Disease
Corrada, M. M., Brookmeyer, R., & Kawas, C. H. (1995) · International Journal of Epidemiology · doi:10.1093/ije/24.5.1000 · Cited by 86 · see citing works
Incidence and Causes of Nondegenerative Nonvascular Dementia
Knopman, D. S., Petersen, R. C., Cha, R. H., Edland, S. D., & Rocca, W. A. (2006) · Archives of Neurology · doi:10.1001/archneur.63.2.218 · Cited by 83 · see citing works
Incidence of severe dementia in an urban sample followed from 70 to 79 years of age
Nilsson, L. V. (1984) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1984.tb01237.x · Cited by 80 · see citing works
Prevalence of Alzheimer's type dementia in an elderly Arab population
Bowirrat, A., Treves, T. A., Friedland, R. P., & Korczyn, A. D. (2001) · European Journal of Neurology · doi:10.1046/j.1468-1331.2001.00183.x · Cited by 77 · see citing works
Prevalence Estimation of Dementia in a Rural Area of Korea
Woo, J. I., Lee, J. H., Yoo, K., Kim, C., Kim, Y., & Shin, Y. S. (1998) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1998.tb02753.x · Cited by 70 · see citing works
Changing Patterns in the Prevalence of Dementia in a Japanese Community: The Hisayama Study
Kiyohara, Y., Yoshitake, T., Kato, I., Ohmura, T., Kawano, H., Ueda, K., & Fujishima, M. (2009) · Gerontology · doi:10.1159/000213625 · Cited by 66 · see citing works
Prevalence of Alzheimer's Disease and Other Dementing Disorders in Pamplona, Spain
Manubens, J. M., Martínez‐Lage, J. M., Lacruz, F. A., Muruzábal, J. C., Larumbe, R., Guarch, C., Urrutia, T., Sarrasqueta, P., Martínez‐Lage, P., & Rocca, W. A. (1995) · Neuroepidemiology · doi:10.1159/000109791 · Cited by 65 · see citing works
The prevalence of dementia in Girona.
Pousa, S. L., Reglà, J. L., Franch, J. V., & Lozano Fernández de Pinedo, L. (1995) · PubMed · Cited by 36 · see citing works
Senile dementia of the Alzheimer type in the Lundby study
Hagnell, O., Fränck, A., Gräsbeck, A., Öhman, R., Otterbeck, L., & Rosman, B. (1992) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/bf02190258 · Cited by 28 · see citing works
Corso, E. A., Campo, G., Triglio, A., Napoli, A., Reggio, A., & Lanaia, F. (1992) · The Italian Journal of Neurological Sciences · doi:10.1007/bf02224392 · Cited by 17 · see citing works
APOE and AD concordance in twin pairs as predictors of AD in first-degree relatives
Steffens, D. C., Plassman, B. L., Helms, M. J., et al. (2000) · Neurology · doi:10.1212/wnl.54.3.593 · Cited by 15 · see citing works
Senile dementia of the Alzheimer type in the lundby study
Hagnell, O., Fränck, A., Gräsbeck, A., Öhman, R., Öjesjö, L., Otterbeck, L., & Rorsman, B. (1991) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/bf02219715 · Cited by 13 · see citing works
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Zhong, G., Wang, Y., Zhang, Y., Guo, J. J., & Zhao, Y. (2015) · PLOS ONE · doi:10.1371/journal.pone.0118333 · Cited by 362 · see citing works
Genetic architecture of Alzheimer's disease
Neuner, S. M., TCW, J., & Goate, A. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104976 · Cited by 126 · see citing works
“Likewise, familial inheritance of AD is typically associated with early-onset forms of the disease, but large families with multiple individuals affected by LOAD are prevalent [27, 28].”
BackgroundSelf-citation
- Authors
- Vardarajan, B. N., Faber, K. M., Bird, T. D., Bennett, D. A., Rosenberg, R., Boeve, B. F., Graff-Radford, N. R., Goate, A. M., Farlow, M., Sweet, R. A., Lantigua, R., Medrano, M. Z., Ottman, R., Schaid, D. J., Foroud, T. M., & Mayeux, R.
- Affiliations
- Columbia University Irving Medical Center (US)
- Indiana University Indianapolis (US)
- University of Washington (US)
- Rush University Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
- Mayo Clinic (US)
- Department of Neurology, Mayo Clinic, Jacksonville, Florida
- Washington University in St. Louis (US)
- Indiana University School of Medicine (US)
- University of Pittsburgh (US)
- Pontificia Universidad Católica Madre y Maestra (DO)
- Corresponding author
- Mayeux, Richard
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2014-03-01
- Volume
- 71
- Issue
- 3
- Pages
- 315
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC4000602
- OpenAlex
- W2044447672
- Cited by
- 73
- References
- 45
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 8 · 2023: 4 · 2022: 8 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 8 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 3
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR001108, 5r37ag015473-15)
- National Institute on Aging (R01AG017917, P30AG012300, P50AG005133, R37-AG015473, RF1AG015473, U01AG006786, R01AG015819, U24 AG21886, R01AG041797, P50AG008702, R01AG027224, R01AG032306, U24AG026395, U24AG056270, U24AG021886, P50AG016574)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- late-onset Alzheimer's disease, dementia, age-specific incidence, familial Alzheimer's disease, Caribbean Hispanics, older adults, family history of dementia
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Dominican Republic, Female, Follow-Up Studies, Humans, Male, New York, United States, Incidence, Age of Onset, Genetic Predisposition to Disease, Apolipoprotein E4, National Institute on Aging (U.S.)
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