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

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

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

Niki Mourtzi et al. Alzheimers Dement. 2023 Sep.

. 2023 Sep;19(9):3794-3805.

doi: 10.1002/alz.12980. Epub 2023 Mar 9.

Authors

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.

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References

REFERENCES

1. Stern Y, Arenaza-Urquijo EM, Bartrés-Faz D, et al. Whitepaper: defining and investigating cognitive reserve, brain reserve and brain maintenance. Alzheimers Dement. 2020;16:1305-1311. doi:10.1016/j.jalz.2018.07.219
1. Scarmeas N, Stern Y. Cognitive reserve and lifestyle. J Clin Exp Neuropsychol. 2003;25:625-633. doi:10.1076/jcen.25.5.625.14576
1. Scarmeas N, Zarahn E, Anderson KE, et al. Cognitive reserve-mediated modulation of positron emission tomographic activations during memory tasks in Alzheimer disease. Arch Neurol. 2004;61:73-78. doi:10.1001/archneur.61.1.73
1. Scarmeas N, Levy G, Tang M-X, Manly J, Stern Y. Influence of leisure activity on the incidence of Alzheimer's Disease. Neurology. 2001;57:2236-2242.
1. Stern Y. Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurol. 2012;11:1006-1012. doi:10.1016/S1474-4422(12)70191-6

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

Affiliations

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

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical