BACKGROUND: A complex set of interactions between biological, genetic, and environmental factors likely underlies the development of Alzheimer's disease (AD). Identifying which of these factors is most associated with AD is important for early diagnosis and treatment. OBJECTIVE: We sought to examine genetic risk and structural brain volume on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD. METHODS: 686 adults (55-91 years old) completed a 3T MRI scan, baseline cognitive assessments, and biospecimen collection through the Alzheimer's Disease Neuroimaging Initiative. Hierarchical linear regression analyses examined main and interaction effects of medial temporal lobe (MTL) volume and polygenic hazard score (PHS), indicating genetic risk for AD, on a validated episodic memory composite score. RESULTS: Genetic risk moderated the relationship between MTL volume and memory, such that individuals with high PHS and lower hippocampal and entorhinal volume had lower memory composite scores [ΔF (1,677) = 4.057, p = 0.044, ΔR2 = 0.002]. Further analyses showed this effect was driven by the left hippocampus [ΔF(1,677) = 5.256, p = 0.022, ΔR2 = 0.003] and right entorhinal cortex [ΔF (1,677) = 6.078, p = 0.014, ΔR2 = 0.003]. CONCLUSIONS: Among those with high genetic risk for AD, lower volume was associated with poorer memory. Results suggest that the interaction between AD genetic risk and MTL volume increases the likelihood for memory impairment among older adults. Results from this study suggest that genetic risk and brain volume should be considered key factors in tracking cognitive decline.
BACKGROUND: A complex set of interactions between biological, genetic, and environmental factors likely underlies the development of Alzheimer's disease (AD). Identifying which of these factors is most associated with AD is important for early diagnosis and treatment. OBJECTIVE: We sought to examine genetic risk and structural brain volume on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD. METHODS: 686 adults (55-91 years old) completed a 3T MRI scan, baseline cognitive assessments, and biospecimen collection through the Alzheimer's Disease Neuroimaging Initiative. Hierarchical linear regression analyses examined main and interaction effects of medial temporal lobe (MTL) volume and polygenic hazard score (PHS), indicating genetic risk for AD, on a validated episodic memory composite score. RESULTS: Genetic risk moderated the relationship between MTL volume and memory, such that individuals with high PHS and lower hippocampal and entorhinal volume had lower memory composite scores [ΔF (1,677) = 4.057, p = 0.044, ΔR2 = 0.002]. Further analyses showed this effect was driven by the left hippocampus [ΔF(1,677) = 5.256, p = 0.022, ΔR2 = 0.003] and right entorhinal cortex [ΔF (1,677) = 6.078, p = 0.014, ΔR2 = 0.003]. CONCLUSIONS: Among those with high genetic risk for AD, lower volume was associated with poorer memory. Results suggest that the interaction between AD genetic risk and MTL volume increases the likelihood for memory impairment among older adults. Results from this study suggest that genetic risk and brain volume should be considered key factors in tracking cognitive decline.
Authors: Marilyn S Albert; Steven T DeKosky; Dennis Dickson; Bruno Dubois; Howard H Feldman; Nick C Fox; Anthony Gamst; David M Holtzman; William J Jagust; Ronald C Petersen; Peter J Snyder; Maria C Carrillo; Bill Thies; Creighton H Phelps Journal: Alzheimers Dement Date: 2011-04-21 Impact factor: 21.566
Authors: Clifford R Jack; David S Knopman; William J Jagust; Ronald C Petersen; Michael W Weiner; Paul S Aisen; Leslie M Shaw; Prashanthi Vemuri; Heather J Wiste; Stephen D Weigand; Timothy G Lesnick; Vernon S Pankratz; Michael C Donohue; John Q Trojanowski Journal: Lancet Neurol Date: 2013-02 Impact factor: 44.182
Authors: David C Steffens; Martha E Payne; Daniel L Greenberg; Christopher E Byrum; Kathleen A Welsh-Bohmer; H Ryan Wagner; James R MacFall Journal: Am J Geriatr Psychiatry Date: 2002 Jan-Feb Impact factor: 4.105
Authors: W J Strittmatter; A M Saunders; D Schmechel; M Pericak-Vance; J Enghild; G S Salvesen; A D Roses Journal: Proc Natl Acad Sci U S A Date: 1993-03-01 Impact factor: 11.205
Authors: J C Lambert; C A Ibrahim-Verbaas; D Harold; A C Naj; R Sims; C Bellenguez; A L DeStafano; J C Bis; G W Beecham; B Grenier-Boley; G Russo; T A Thorton-Wells; N Jones; A V Smith; V Chouraki; C Thomas; M A Ikram; D Zelenika; B N Vardarajan; Y Kamatani; C F Lin; A Gerrish; H Schmidt; B Kunkle; M L Dunstan; A Ruiz; M T Bihoreau; S H Choi; C Reitz; F Pasquier; C Cruchaga; D Craig; N Amin; C Berr; O L Lopez; P L De Jager; V Deramecourt; J A Johnston; D Evans; S Lovestone; L Letenneur; F J Morón; D C Rubinsztein; G Eiriksdottir; K Sleegers; A M Goate; N Fiévet; M W Huentelman; M Gill; K Brown; M I Kamboh; L Keller; P Barberger-Gateau; B McGuiness; E B Larson; R Green; A J Myers; C Dufouil; S Todd; D Wallon; S Love; E Rogaeva; J Gallacher; P St George-Hyslop; J Clarimon; A Lleo; A Bayer; D W Tsuang; L Yu; M Tsolaki; P Bossù; G Spalletta; P Proitsi; J Collinge; S Sorbi; F Sanchez-Garcia; N C Fox; J Hardy; M C Deniz Naranjo; P Bosco; R Clarke; C Brayne; D Galimberti; M Mancuso; F Matthews; S Moebus; P Mecocci; M Del Zompo; W Maier; H Hampel; A Pilotto; M Bullido; F Panza; P Caffarra; B Nacmias; J R Gilbert; M Mayhaus; L Lannefelt; H Hakonarson; S Pichler; M M Carrasquillo; M Ingelsson; D Beekly; V Alvarez; F Zou; O Valladares; S G Younkin; E Coto; K L Hamilton-Nelson; W Gu; C Razquin; P Pastor; I Mateo; M J Owen; K M Faber; P V Jonsson; O Combarros; M C O'Donovan; L B Cantwell; H Soininen; D Blacker; S Mead; T H Mosley; D A Bennett; T B Harris; L Fratiglioni; C Holmes; R F de Bruijn; P Passmore; T J Montine; K Bettens; J I Rotter; A Brice; K Morgan; T M Foroud; W A Kukull; D Hannequin; J F Powell; M A Nalls; K Ritchie; K L Lunetta; J S Kauwe; E Boerwinkle; M Riemenschneider; M Boada; M Hiltuenen; E R Martin; R Schmidt; D Rujescu; L S Wang; J F Dartigues; R Mayeux; C Tzourio; A Hofman; M M Nöthen; C Graff; B M Psaty; L Jones; J L Haines; P A Holmans; M Lathrop; M A Pericak-Vance; L J Launer; L A Farrer; C M van Duijn; C Van Broeckhoven; V Moskvina; S Seshadri; J Williams; G D Schellenberg; P Amouyel Journal: Nat Genet Date: 2013-10-27 Impact factor: 38.330