title: 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).
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York2Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Badri N
authors.initials: BN
authors.lastname: Vardarajan
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University, Indianapolis.
authors.forename: Kelley M
authors.initials: KM
authors.lastname: Faber
authors.affiliation: Department of Neurology, University of Washington, Seattle5Department of Medicine, University of Washington, Seattle.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bird
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas.
authors.forename: Roger
authors.initials: R
authors.lastname: Rosenberg
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.affiliation: Department of Psychiatry and Genetics, Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri11Hope Center for Neurological Disorders, Washington University, St Louis, Missouri.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
authors.affiliation: Department of Neurology, Indiana University Center for Alzheimer's Disease and Related Disorders, Indianapolis.
authors.forename: Martin
authors.initials: M
authors.lastname: Farlow
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania14Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania15Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York16Department of Medicine, Columbia University, New York, New York.
authors.forename: Rafael
authors.initials: R
authors.lastname: Lantigua
authors.affiliation: Universidad Tecnológica de Santiago, Santiago, Dominican Republic18currently with Department of Geriatrics, Pontificia Universidad Católica Madre y Maestra, Santiago, Dominican Republic.
authors.forename: Martin Z
authors.initials: MZ
authors.lastname: Medrano
authors.affiliation: Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, New York3Department of Medical and Molecular Genetics, Indiana University, Indianapolis19Department of Epidemiology, Columbia University, New York, New York20.
authors.forename: Ruth
authors.initials: R
authors.lastname: Ottman
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schaid
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University, Indianapolis.
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Foroud
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York2Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, New York22Department of Neurolo.
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D004293:Dominican Republic / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D054561:National Institute on Aging (U.S.); D009518:New York / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
chemical_list: D053327:Apolipoprotein E4