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

Niki Mourtzi; Sokratis Charisis; Angeliki Tsapanou; Eva Ntanasi; Alexandros Hatzimanolis; Alfredo Ramirez; Stefanie Heilmann-Heimbach; Benjamin Grenier-Boley; Jean-Charles Lambert; Mary Yannakoulia; Mary Kosmidis; Efthimios Dardiotis; Georgiios Hadjigeorgiou; Paraskevi Sakka; Marios Georgakis; Stern Yaakov; Nikolaos Scarmeas

doi:10.1002/alz.12980

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

Alzheimers Dement. 2023 Sep;19(9):3794-3805. doi: 10.1002/alz.12980. Epub 2023 Mar 9.

Authors

Niki Mourtzi¹, Sokratis Charisis^{1

2}, Angeliki Tsapanou^{1

3}, Eva Ntanasi^{1

4}, Alexandros Hatzimanolis⁵, Alfredo Ramirez^{6

7

8

9

10}, Stefanie Heilmann-Heimbach¹¹, Benjamin Grenier-Boley¹², Jean-Charles Lambert¹², Mary Yannakoulia⁴, Mary Kosmidis¹³, Efthimios Dardiotis¹⁴, Georgiios Hadjigeorgiou¹⁵, Paraskevi Sakka¹⁶, Marios Georgakis^{17

18

19}, Stern Yaakov³, Nikolaos Scarmeas^{1

3}

Affiliations

¹ 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.
² Department of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
³ Department of Neurology, The Gertrude H. Sergievsky Center, Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
⁴ Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
⁵ Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, Greece.
⁶ Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany.
⁷ Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
⁸ German Center for Neurodegenerative Diseases (DZNE Bonn), Bonn, Germany.
⁹ Department of Psychiatry, Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, Texas, USA.
¹⁰ Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
¹¹ Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
¹² Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE facteurs de risque et déterminants moléculaires des maladies liés au vieillissement, Lille, France.
¹³ Lab of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
¹⁴ Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
¹⁵ Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus.
¹⁶ Athens Association of Alzheimer's Disease and Related Disorders, Marousi, Greece.
¹⁷ Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹⁸ Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of Technology, Boston, Massachusetts, USA.
¹⁹ Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.

PMID: 36895094
DOI: 10.1002/alz.12980

Abstract

Introduction: We constructed a polygenic risk score (PRS) for β-amyloid (PRSAβ42) 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 PRSAβ42 and AD/aMCI risk.

Methods: A total of 618 cognitive-normal participants were followed-up for 2.92 years. The association of PRSAβ42 and CR with AD/aMCI incidence was examined with COX models. Then we examined the additive interaction between PRSAβ42 and CR and the CR effect across participants with different PRSAβ42 levels.

Results: Higher PRSAβ42 and CR were associated with a 33.9% higher risk and 8.3% less risk for AD/aMCI, respectively. An additive interaction between PRSAβ42 and CR was observed. High CR was associated with 62.6% less risk of AD/aMCI incidence only in the high-PRSAβ42 group.

Discussion: A super-additive effect of PRSAβ42 and CR on AD/aMCI risk was observed. CR influence was evident in participants with high PRSAβ42.

Keywords: Alzheimer's disease; cognitive decline; cognitive reserve; polygenic risk score.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / complications
Amyloidosis*
Cognitive Dysfunction* / complications
Cognitive Dysfunction* / genetics
Cognitive Reserve*
Humans
Neuropsychological Tests