Genetic propensity for cerebral amyloidosis and risk of mild cognitive impairment and Alzheimer's disease within a cognitive reserve framework

被引：7

作者：

Mourtzi, Niki ^{[1
]}

Charisis, Sokratis ^{[1
,2
]}

Tsapanou, Angeliki ^{[1
,3
]}

Ntanasi, Eva ^{[1
,4
]}

Hatzimanolis, Alexandros ^{[5
]}

Ramirez, Alfredo ^{[6
,7
,8
,9
,10
,11
,12
]}

Heilmann-Heimbach, Stefanie

Grenier-Boley, Benjamin ^{[13
]}

Lambert, Jean-Charles ^{[13
]}

Yannakoulia, Mary ^{[4
,14
]}

Kosmidis, Mary

Dardiotis, Efthimios ^{[15
]}

Hadjigeorgiou, Georgiios ^{[16
]}

Sakka, Paraskevi ^{[17
]}

Georgakis, Marios ^{[18
,19
,20
,21
]}

Yaakov, Stern ^{[3
]}

Scarmeas, Nikolaos ^{[1
,3
]}

机构：

[1] Natl & Kapodistrian Univ Athens, Aiginit Hosp, Dept Neurol, Med Sch, Athens, Greece

[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX USA

[3] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, Dept Neurol, Gertrude H Sergievsky Ctr, New York, NY USA

[4] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece

[5] Natl & Kapodistrian Univ Athens, Eginit Hosp, Dept Psychiat, Med Sch, Athens, Greece

[6] Univ Cologne, Fac Med, Div Neurogenet & Mol Psychiat, Dept Psychiat & Psychotherapy, Cologne, Germany

[7] Univ Hosp Bonn, Dept Neurodegenerat Dis & Geriatr Psychiat, Bonn, Germany

[8] German Ctr Neurodegenerat Dis DZNE Bonn, Bonn, Germany

[9] Glenn Biggs Inst Alzheimers & Neurodegenerat Dis, Dept Psychiat, San Antonio, TX USA

[10] Univ Cologne, Excellence Cluster Cellular Stress Responses Agin, Cologne, Germany

[11] Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany

[12] Univ Hosp Bonn, Bonn, Germany

[13] Univ Lille, INSERM, U1167 RID AGE Facteurs Risque & Determinants Mol, Inst Pasteur Lille,CHU Lille, Lille, France

[14] Aristotle Univ Thessaloniki, Sch Psychol, Lab Cognit Neurosci, Thessaloniki, Greece

[15] Univ Thessaly, Univ Hosp Larissa, Sch Hlth Sci, Dept Neurol, Larisa, Greece

[16] Univ Cyprus, Sch Med, Dept Neurol, Nicosia, Cyprus

[17] Athens Assoc Alzheimers Dis & Related Disorders, Maroussi, Greece

[18] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA USA

[19] Broad Inst MIT & Harvard, Program Med & Populat Genet, Boston, MA USA

[20] MIT, Boston, MA USA

[21] Ludwig Maximilians Univ LMU Munich, Univ Hosp, Inst Stroke & Dementia Res ISD, Munich, Germany

来源：

ALZHEIMERS & DEMENTIA | 2023年 / 19卷 / 09期

基金：

芬兰科学院;

关键词：

Alzheimer's disease; cognitive decline; cognitive reserve; polygenic risk score; OLDER-ADULTS; BETA BURDEN; EDUCATION; DEMENTIA; DEPOSITION; DECLINE; IDENTIFICATION; HERITABILITY; ASSOCIATION; OCCUPATION;

D O I：

10.1002/alz.12980

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

INTRODUCTION: We constructed a polygenic risk score (PRS) for beta-amyloid (PRSA beta 42) to proxy AD pathology and investigated its association with incident Alzheimer's disease (AD)/amnestic mild cognitive impairment (aMCI) and the influence of cognitive reserve (CR), proxied by educational years, on the relationship between PRSA beta 42 and AD/aMCI risk. METHODS: A total of 618 cognitive-normal participants were followed-up for 2.92 years. The association of PRSA beta 42 and CR with AD/aMCI incidence was examined with COX models. Then we examined the additive interaction between PRSA beta 42 and CR and the CR effect across participants with different PRSA beta 42 levels. RESULTS: Higher PRSA beta 42 and CR were associated with a 33.9% higher risk and 8.3% less risk for AD/aMCI, respectively. An additive interaction between PRSA beta 42 and CR was observed. High CR was associated with 62.6% less risk of AD/aMCI incidence only in the high-PRSA beta 42 group. DISCUSSION: A super-additive effect of PRSA beta 42 and CR on AD/aMCI risk was observed. CR influence was evident in participants with high PRSA beta 42.

引用

页码：3794 / 3805

页数：12

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