P Bretsky1, J M Guralnik, L Launer, M Albert, T E Seeman. 1. Department of Preventive Medicine, Keck School of Medicine, USC/Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA. pbretsky@usc.edu
Abstract
BACKGROUND: While a genetic risk factor for late-onset AD, the effects of the epsilon4 allele of the APOE gene on cognitive functioning more generally remain unclear. OBJECTIVE: To assess the role of the epsilon4 allele of the APOE gene in longitudinal cognitive decline. METHODS: Multiple measures of cognitive function were assessed longitudinally in the MacArthur Successful Aging Study, a population-based cohort free of frank impairment at baseline. Subjects were 965 Caucasian and African American men and women from Durham NC, East Boston, MA, and New Haven, CT, aged 70 to 79 years, recruited in 1988 through 1989, who completed two follow-up evaluations, one at 3 years and another at 7 years. RESULTS: At the first follow-up, modest but significant declines in naming and spatial ability were associated with the APOE-epsilon4 genotype. By the second follow-up, more pronounced and significant associations were noted between the APOE-epsilon4 genotype and cognitive decline from six of the eight cognitive outcomes. After 7 years, APOE-epsilon4 allele carriers were twice as likely to have declined on a global cognitive score (odds ratio = 2.0; 95% CI: 1.1, 3.6) as noncarriers. CONCLUSIONS: APOE-epsilon4 is associated with cognitive decline among a high-functioning elderly cohort, with effects most pronounced after 7 years of follow-up. Hence, the epsilon4 allele either may function as a risk factor for cognitive impairment in normal aging across a broad spectrum of domains or may exert detectable effects early in a long prodromal AD trajectory.
BACKGROUND: While a genetic risk factor for late-onset AD, the effects of the epsilon4 allele of the APOE gene on cognitive functioning more generally remain unclear. OBJECTIVE: To assess the role of the epsilon4 allele of the APOE gene in longitudinal cognitive decline. METHODS: Multiple measures of cognitive function were assessed longitudinally in the MacArthur Successful Aging Study, a population-based cohort free of frank impairment at baseline. Subjects were 965 Caucasian and African American men and women from Durham NC, East Boston, MA, and New Haven, CT, aged 70 to 79 years, recruited in 1988 through 1989, who completed two follow-up evaluations, one at 3 years and another at 7 years. RESULTS: At the first follow-up, modest but significant declines in naming and spatial ability were associated with the APOE-epsilon4 genotype. By the second follow-up, more pronounced and significant associations were noted between the APOE-epsilon4 genotype and cognitive decline from six of the eight cognitive outcomes. After 7 years, APOE-epsilon4 allele carriers were twice as likely to have declined on a global cognitive score (odds ratio = 2.0; 95% CI: 1.1, 3.6) as noncarriers. CONCLUSIONS:APOE-epsilon4 is associated with cognitive decline among a high-functioning elderly cohort, with effects most pronounced after 7 years of follow-up. Hence, the epsilon4 allele either may function as a risk factor for cognitive impairment in normal aging across a broad spectrum of domains or may exert detectable effects early in a long prodromal AD trajectory.
Authors: May A Beydoun; Adel Boueiz; Marwan S Abougergi; Melissa H Kitner-Triolo; Hind A Beydoun; Susan M Resnick; Richard O'Brien; Alan B Zonderman Journal: Neurobiol Aging Date: 2010-07-08 Impact factor: 4.673
Authors: G C Chiang; P S Insel; D Tosun; N Schuff; D Truran-Sacrey; S T Raptentsetsang; C R Jack; P S Aisen; R C Petersen; M W Weiner Journal: Neurology Date: 2010-10-27 Impact factor: 9.910
Authors: Christina E Wierenga; Nikki H Stricker; Ashley McCauley; Alan Simmons; Amy J Jak; Yu-Ling Chang; Lisa Delano-Wood; Katherine J Bangen; David P Salmon; Mark W Bondi Journal: Neuroimage Date: 2010-03-16 Impact factor: 6.556
Authors: Joann T Tschanz; Roxane Pfister; Joseph Wanzek; Chris Corcoran; Ken Smith; Brian T Tschanz; David C Steffens; Truls Østbye; Kathleen A Welsh-Bohmer; Maria C Norton Journal: Int J Geriatr Psychiatry Date: 2012-10-04 Impact factor: 3.485
Authors: A Caroli; C Testa; C Geroldi; F Nobili; L R Barnden; U P Guerra; M Bonetti; G B Frisoni Journal: J Neurol Date: 2007-11-09 Impact factor: 4.849
Authors: Kumar B Rajan; Robert S Wilson; Kimberly A Skarupski; Carlos F Mendes de Leon; Denis A Evans Journal: Psychosom Med Date: 2014-01-16 Impact factor: 4.312
Authors: Paul K Crane; Kaavya Narasimhalu; Laura E Gibbons; Dan M Mungas; Sebastien Haneuse; Eric B Larson; Lewis Kuller; Kathleen Hall; Gerald van Belle Journal: J Clin Epidemiol Date: 2008-05-05 Impact factor: 6.437
Authors: Kathleen M Hayden; Peter P Zandi; Nancy A West; Joann T Tschanz; Maria C Norton; Chris Corcoran; John C S Breitner; Kathleen A Welsh-Bohmer Journal: Arch Neurol Date: 2009-11