BACKGROUND AND PURPOSE: Age and the apolipoprotein E ε4 allele are well-known risk factors for Alzheimer disease, but whether female sex is also a risk factor remains controversial. It is also unclear how these risk factors affect rates of structural brain and clinical decline across the spectrum of preclinical to clinical Alzheimer disease. Our objective is to estimate the effects of apolipoprotein E ε4 and sex on age-specific rates of morphometric and clinical decline in late-onset sporadic Alzheimer disease. MATERIALS AND METHODS: With the use of linear mixed-effects models, we examined the effect of age, apolipoprotein E ε4, and sex on longitudinal brain atrophy and clinical decline among cognitively normal older individuals and individuals with mild cognitive impairment and Alzheimer disease (total = 688). We also evaluated the relationship between these effects and CSF biomarkers of Alzheimer disease pathology. RESULTS: Apolipoprotein E ε4 significantly accelerated rates of decline, and women in all cohorts had higher rates of decline than men. The magnitude of the sex effect on rates of decline was as large as those of ε4, yet their relationship to measures of CSF biomarkers were weaker. CONCLUSIONS: These results indicate that in addition to apolipoprotein E ε4 status, diagnostic and therapeutic strategies should take into account the effect of female sex on the Alzheimer disease process.
BACKGROUND AND PURPOSE:Age and the apolipoprotein E ε4 allele are well-known risk factors for Alzheimer disease, but whether female sex is also a risk factor remains controversial. It is also unclear how these risk factors affect rates of structural brain and clinical decline across the spectrum of preclinical to clinical Alzheimer disease. Our objective is to estimate the effects of apolipoprotein E ε4 and sex on age-specific rates of morphometric and clinical decline in late-onset sporadic Alzheimer disease. MATERIALS AND METHODS: With the use of linear mixed-effects models, we examined the effect of age, apolipoprotein E ε4, and sex on longitudinal brain atrophy and clinical decline among cognitively normal older individuals and individuals with mild cognitive impairment and Alzheimer disease (total = 688). We also evaluated the relationship between these effects and CSF biomarkers of Alzheimer disease pathology. RESULTS:Apolipoprotein E ε4 significantly accelerated rates of decline, and women in all cohorts had higher rates of decline than men. The magnitude of the sex effect on rates of decline was as large as those of ε4, yet their relationship to measures of CSF biomarkers were weaker. CONCLUSIONS: These results indicate that in addition to apolipoprotein E ε4 status, diagnostic and therapeutic strategies should take into account the effect of female sex on the Alzheimer disease process.
Authors: J C Breitner; B W Wyse; J C Anthony; K A Welsh-Bohmer; D C Steffens; M C Norton; J T Tschanz; B L Plassman; M R Meyer; I Skoog; A Khachaturian Journal: Neurology Date: 1999-07-22 Impact factor: 9.910
Authors: K Andersen; L J Launer; M E Dewey; L Letenneur; A Ott; J R Copeland; J F Dartigues; P Kragh-Sorensen; M Baldereschi; C Brayne; A Lobo; J M Martinez-Lage; T Stijnen; A Hofman Journal: Neurology Date: 1999-12-10 Impact factor: 9.910
Authors: E H Corder; A M Saunders; W J Strittmatter; D E Schmechel; P C Gaskell; G W Small; A D Roses; J L Haines; M A Pericak-Vance Journal: Science Date: 1993-08-13 Impact factor: 47.728
Authors: H Xu; G K Gouras; J P Greenfield; B Vincent; J Naslund; L Mazzarelli; G Fried; J N Jovanovic; M Seeger; N R Relkin; F Liao; F Checler; J D Buxbaum; B T Chait; G Thinakaran; S S Sisodia; R Wang; P Greengard; S Gandy Journal: Nat Med Date: 1998-04 Impact factor: 53.440
Authors: Elizabeth H Corder; Estifanos Ghebremedhin; Miles G Taylor; Dietmar R Thal; Thomas G Ohm; Heiko Braak Journal: Ann N Y Acad Sci Date: 2004-06 Impact factor: 5.691
Authors: B L Plassman; K M Langa; G G Fisher; S G Heeringa; D R Weir; M B Ofstedal; J R Burke; M D Hurd; G G Potter; W L Rodgers; D C Steffens; R J Willis; R B Wallace Journal: Neuroepidemiology Date: 2007-10-29 Impact factor: 3.282
Authors: Minjie Wu; Rebecca C Thurston; Dana L Tudorascu; Helmet T Karim; Chester A Mathis; Brian J Lopresti; M Ilyas Kamboh; Ann D Cohen; Beth E Snitz; William E Klunk; Howard J Aizenstein Journal: Neurobiol Aging Date: 2018-12-01 Impact factor: 4.673
Authors: Rachel F Buckley; Elizabeth C Mormino; Rebecca E Amariglio; Michael J Properzi; Jennifer S Rabin; Yen Ying Lim; Kathryn V Papp; Heidi I L Jacobs; Samantha Burnham; Bernard J Hanseeuw; Vincent Doré; Annette Dobson; Colin L Masters; Michael Waller; Christopher C Rowe; Paul Maruff; Michael C Donohue; Dorene M Rentz; Dylan Kirn; Trey Hedden; Jasmeer Chhatwal; Aaron P Schultz; Keith A Johnson; Victor L Villemagne; Reisa A Sperling Journal: Alzheimers Dement Date: 2018-05-24 Impact factor: 21.566
Authors: Rebecca A Nebel; Neelum T Aggarwal; Lisa L Barnes; Aimee Gallagher; Jill M Goldstein; Kejal Kantarci; Monica P Mallampalli; Elizabeth C Mormino; Laura Scott; Wai Haung Yu; Pauline M Maki; Michelle M Mielke Journal: Alzheimers Dement Date: 2018-06-12 Impact factor: 21.566
Authors: Ferenc Deak; Willard M Freeman; Zoltan Ungvari; Anna Csiszar; William E Sonntag Journal: J Gerontol A Biol Sci Med Sci Date: 2015-11-20 Impact factor: 6.053
Authors: Emilie T Reas; Donald J Hagler; Murray J Andrews; Roland R Lee; Anders M Dale; Linda K McEvoy Journal: Neurobiol Aging Date: 2020-07-15 Impact factor: 4.673