Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer's disease.
Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer's disease.
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阿尔茨海默病早期纵向认知衰退的遗传效应。
DOI：
10.1038/s41598-021-99310-z
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发表时间：
2021-10-06
影响因子：
4.6
通讯作者：
Hansson O
中科院分区：
文献类型：
--
作者：
Kumar A;Shoai M;Palmqvist S;Stomrud E;Hardy J;Mattsson-Carlgren N;Hansson O
早期阿尔茨海默病（AD）的认知能力下降可能取决于遗传变异。在瑞典BioFINDER研究中，我们使用多基因评分（PGS）（AD，智力和教育程度）预测平均4.2年的纵向认知变化（通过简易精神状态检查（MMSE）[主要结局]和其他认知测试测量）。我们纳入了260名β-淀粉样蛋白（Aβ）阴性认知未受损（CU）个体，121名Aβ阳性CU（临床前AD），50名Aβ阴性轻度认知障碍（MCI）患者和127名Aβ阳性MCI患者（前驱AD）。在Bonferroni校正的p值< 0.05时确定统计学显著性。智力的PGS（beta = 0.1，p = 2.9e−02）对CU和MCI参与者的MMSE下降具有保护作用，无论Aβ状态如何。AD的多基因风险评分（beta =-0.12，p = 9.4e-03）与MMSE的变化率相关，并且部分由Aβ病理学介导（中介效应20%）。教育PGS对认知测量没有影响。与智力相关的遗传变异可缓解认知功能下降，而与Aβ病理学无关，而与AD相关的遗传变异的作用部分由Aβ病理学介导。
Cognitive decline in early-stage Alzheimer’s disease (AD) may depend on genetic variability. In the Swedish BioFINDER study, we used polygenic scores (PGS) (for AD, intelligence, and educational attainment) to predict longitudinal cognitive change (measured by mini-mental state examination (MMSE) [primary outcome] and other cognitive tests) over a mean of 4.2 years. We included 260 β-amyloid (Aβ) negative cognitively unimpaired (CU) individuals, 121 Aβ-positive CU (preclinical AD), 50 Aβ-negative mild cognitive impairment (MCI) patients, and 127 Aβ-positive MCI patients (prodromal AD). Statistical significance was determined at Bonferroni corrected p value < 0.05. The PGS for intelligence (beta = 0.1, p = 2.9e−02) was protective against decline in MMSE in CU and MCI participants regardless of Aβ status. The polygenic risk score for AD (beta = − 0.12, p = 9.4e−03) was correlated with the rate of change in MMSE and was partially mediated by Aβ-pathology (mediation effect 20%). There was no effect of education PGS on cognitive measures. Genetic variants associated with intelligence mitigate cognitive decline independent of Aβ-pathology, while effects of genetic variants associated with AD are partly mediated by Aβ-pathology.
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基因发现和多基因预测，从基因组全基因组协会的教育程度研究中，有110万个人。
影响因子：
30.8
作者：
Lee JJ;Wedow R;Okbay A;Kong E;Maghzian O;Zacher M;Nguyen-Viet TA;Bowers P;Sidorenko J;Karlsson Linnér R;Fontana MA;Kundu T;Lee C;Li H;Li R;Royer R;Timshel PN;Walters RK;Willoughby EA;Yengo L;23andMe Research Team;COGENT (Cognitive Genomics Consortium);Social Science Genetic Association Consortium;Alver M;Bao Y;Clark DW;Day FR;Furlotte NA;Joshi PK;Kemper KE;Kleinman A;Langenberg C;Mägi R;Trampush JW;Verma SS;Wu Y;Lam M;Zhao JH;Zheng Z;Boardman JD;Campbell H;Freese J;Harris KM;Hayward C;Herd P;Kumari M;Lencz T;Luan J;Malhotra AK;Metspalu A;Milani L;Ong KK;Perry JRB;Porteous DJ;Ritchie MD;Smart MC;Smith BH;Tung JY;Wareham NJ;Wilson JF;Beauchamp JP;Conley DC;Esko T;Lehrer SF;Magnusson PKE;Oskarsson S;Pers TH;Robinson MR;Thom K;Watson C;Chabris CF;Meyer MN;Laibson DI;Yang J;Johannesson M;Koellinger PD;Turley P;Visscher PM;Benjamin DJ;Cesarini D
通讯作者：
Cesarini D
影响因子：
5.3
作者：
Janelidze S;Zetterberg H;Mattsson N;Palmqvist S;Vanderstichele H;Lindberg O;van Westen D;Stomrud E;Minthon L;Blennow K;Swedish BioFINDER study group;Hansson O
通讯作者：
Hansson O
DOI：
10.1093/geronb/58.4.p228
发表时间：
2003-07-01
影响因子：
6.2
作者：
Bäckman, L;Jones, S;Fratiglioni, L
通讯作者：
Fratiglioni, L
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
9.9
作者：
Ge, Tian;Sabuncu, Mert R.;Mormino, Elizabeth C.
通讯作者：
Mormino, Elizabeth C.