BACKGROUND: Although the apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer's disease (AD), it is not clear whether this relationship persists among the oldest old. Several European studies suggest that the effect of the APOE ε4 allele on dementia and mortality disappears in very old age. We describe the APOE allele and genotype frequencies and examine whether the presence of the APOE ε4 or APOE ε2 alleles is related to prevalent dementia, incident dementia, and mortality in a population-based cohort of oldest-old participants in the United States. METHODS: We studied 904 participants aged 90 years and older from The 90+ Study. Eight hundred two (89%) participants were genotyped and included in the prevalent dementia and mortality analyses. The 520 initially nondemented participants were included in the incident dementia analyses and were evaluated for dementia every 6 months. RESULTS: The APOE ε4 allele was significantly associated with prevalent dementia (odds ratio = 2.06) and AD (odds ratio = 2.37) in women but not in men. The APOE ε2 allele was not related to prevalent dementia in either sex. After an average follow-up of 2.4 years, 188 incident dementia cases were identified. Neither the APOE ε4 nor the APOE ε2 allele was related to incident dementia or AD. Five hundred ten (64%) participants died after an average follow-up of 2.3 years, and their mortality was not related to the presence of either the APOE ε2 or APOE ε4 allele. CONCLUSIONS: Our findings suggest that the associations between APOE ε4, dementia, and mortality are age dependent, and that APOE ε4 no longer plays a role in dementia and mortality at very old ages.
BACKGROUND: Although the apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer's disease (AD), it is not clear whether this relationship persists among the oldest old. Several European studies suggest that the effect of the APOE ε4 allele on dementia and mortality disappears in very old age. We describe the APOE allele and genotype frequencies and examine whether the presence of the APOE ε4 or APOE ε2 alleles is related to prevalent dementia, incident dementia, and mortality in a population-based cohort of oldest-old participants in the United States. METHODS: We studied 904 participants aged 90 years and older from The 90+ Study. Eight hundred two (89%) participants were genotyped and included in the prevalent dementia and mortality analyses. The 520 initially nondemented participants were included in the incident dementia analyses and were evaluated for dementia every 6 months. RESULTS: The APOE ε4 allele was significantly associated with prevalent dementia (odds ratio = 2.06) and AD (odds ratio = 2.37) in women but not in men. The APOE ε2 allele was not related to prevalent dementia in either sex. After an average follow-up of 2.4 years, 188 incident dementia cases were identified. Neither the APOE ε4 nor the APOE ε2 allele was related to incident dementia or AD. Five hundred ten (64%) participants died after an average follow-up of 2.3 years, and their mortality was not related to the presence of either the APOE ε2 or APOE ε4 allele. CONCLUSIONS: Our findings suggest that the associations between APOE ε4, dementia, and mortality are age dependent, and that APOE ε4 no longer plays a role in dementia and mortality at very old ages.
Authors: C Lahoz; E J Schaefer; L A Cupples; P W Wilson; D Levy; D Osgood; S Parpos; J Pedro-Botet; J A Daly; J M Ordovas Journal: Atherosclerosis Date: 2001-02-15 Impact factor: 5.162
Authors: A M Koivisto; P Lempiäinen; K Koivisto; E L Helkala; L Mykkänen; J Kuusisto; K Kervinen; Y A Kesäniemi; M Laakso; H Soininen Journal: Neuroepidemiology Date: 2000 Nov-Dec Impact factor: 3.282
Authors: K Juva; A Verkkoniemi; P Viramo; T Polvikoski; K Kainulainen; K Kontula; R Sulkava Journal: Int Psychogeriatr Date: 2000-09 Impact factor: 3.878
Authors: Elizabeth Rose Mayeda; Teresa J Filshtein; Yorghos Tripodis; M Maria Glymour; Alden L Gross Journal: Int J Epidemiol Date: 2018-10-01 Impact factor: 7.196
Authors: Rosebud O Roberts; Ruth H Cha; Michelle M Mielke; Yonas E Geda; Bradley F Boeve; Mary M Machulda; David S Knopman; Ronald C Petersen Journal: Neurology Date: 2015-04-08 Impact factor: 9.910
Authors: Kathleen M Hayden; Sarah A Gaussoin; Jaimie C Hunter; JoAnn E Manson; Bonnie C Sachs; Aladdin H Shadyab; Hilary A Tindle; Yasmin Mossavar-Rahmani; Khyobeni Mozhui; Beverly M Snively; Stephen R Rapp; Susan M Resnick Journal: Int J Geriatr Psychiatry Date: 2019-08-22 Impact factor: 3.485
Authors: Paola Gilsanz; Maria M Corrada; Claudia H Kawas; Elizabeth Rose Mayeda; M Maria Glymour; Charles P Quesenberry; Catherine Lee; Rachel A Whitmer Journal: Alzheimers Dement Date: 2019-02-20 Impact factor: 21.566
Authors: Jiri M G van Bergen; Xu Li; Frances C Quevenco; Anton F Gietl; Valerie Treyer; Sandra E Leh; Rafael Meyer; Alfred Buck; Philipp A Kaufmann; Roger M Nitsch; Peter C M van Zijl; Christoph Hock; Paul G Unschuld Journal: Neurobiol Aging Date: 2017-12-20 Impact factor: 4.673
Authors: J M G van Bergen; X Li; F C Quevenco; A F Gietl; V Treyer; R Meyer; A Buck; P A Kaufmann; R M Nitsch; P C M van Zijl; C Hock; P G Unschuld Journal: Neuroimage Date: 2018-03-13 Impact factor: 6.556
Authors: Janna H Neltner; Erin L Abner; Gregory A Jicha; Frederick A Schmitt; Ela Patel; Leonard W Poon; Gearing Marla; Robert C Green; Adam Davey; Mary Ann Johnson; S Michal Jazwinski; Sangkyu Kim; Daron Davis; John L Woodard; Richard J Kryscio; Linda J Van Eldik; Peter T Nelson Journal: Neurobiol Aging Date: 2015-10-19 Impact factor: 4.673
Authors: John L Robinson; Laura Molina-Porcel; Maria M Corrada; Kevin Raible; Edward B Lee; Virginia M-Y Lee; Claudia H Kawas; John Q Trojanowski Journal: Brain Date: 2014-07-09 Impact factor: 13.501