Vascular burden and genetic risk in association with cognitive performance and dementia in a population-based study

Marios K Georgakis; Eva Ntanasi; Alfredo Ramirez; Benjamin Grenier-Boley; Jean-Charles Lambert; Paraskevi Sakka; Mary Yannakoulia; Mary H Kosmidis; Efthimios Dardiotis; Georgios M Hadjigeorgiou; Sokratis Charissis; Niki Mourtzi; Alexandros Hatzimanolis; Nikolaos Scarmeas

doi:10.1016/j.cccb.2022.100145

Vascular burden and genetic risk in association with cognitive performance and dementia in a population-based study

Cereb Circ Cogn Behav. 2022 May 5:3:100145. doi: 10.1016/j.cccb.2022.100145. eCollection 2022.

Authors

Marios K Georgakis^{1

2

3}, Eva Ntanasi^{4

5}, Alfredo Ramirez^{6

7}, Benjamin Grenier-Boley⁸, Jean-Charles Lambert⁸, Paraskevi Sakka⁹, Mary Yannakoulia⁵, Mary H Kosmidis¹⁰, Efthimios Dardiotis¹¹, Georgios M Hadjigeorgiou¹², Sokratis Charissis⁴, Niki Mourtzi⁴, Alexandros Hatzimanolis^{13

14}, Nikolaos Scarmeas^{4

15}

Affiliations

¹ Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University LMU, Feodor-Lynen-Str. 17, Munich 81377, Germany.
² Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
³ Programme in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴ 1st Department of Neurology, Eginition Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.
⁵ Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
⁶ Department of Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany.
⁷ Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, Germany.
⁸ U1167-RID-AGE Facteurs de Risque et Déterminants Moléculaires des Maladies Liés au Vieillissement, University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
⁹ Athens Association of Alzheimer's Disease and Related Disorders, Marousi, Greece.
¹⁰ Lab of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
¹¹ Department of Neurology, Faculty of Medicine, School of Health Sciences, University Hospital of Larissa, University of Thessaly, Larissa, Greece.
¹² Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus.
¹³ Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, Greece.
¹⁴ Theodor-Theohari Cozzika Foundation, Neurobiology Research Institute, Athens, Greece.
¹⁵ Department of Neurology, The Gertrude H. Sergievsky Center, Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.

Abstract

Background and purpose: Vascular risk factors may influence cognitive function and thus represent possible targets for preventive approaches against dementia. Yet it remains unknown, if they associate with cognition independently of the individual genetic risk for dementia.

Methods: In a population-based study of 1172 community-dwelling individuals aged ≥65 years in Greece, we constructed a vascular burden score (VBS; based on presence of hypertension, diabetes, hyperlipidemia, heart disease, and cerebrovascular disease, range 0-5) and a polygenic risk score (PRS) for clinically-diagnosed Alzheimer's disease (AD) based on 23 genetic variants. We then explored in joint models the associations of the PRS for AD and VBS with global cognitive performance, cognitive performance across multiple cognitive domains, and odds of dementia.

Results: The mean age of study participants was 73.9 ± 5.2 years (57.1% females). Both the PRS for AD and VBS were associated with worse global cognitive performance (beta per-SD-increment in PRS: -0.06, 95%CI: -0.10 to -0.02, beta per-point-increment in VBS: -0.05, 95%CI: -0.09 to -0.02), worse performance across individual cognitive domains (memory, executive function, attention, language, visuospatial ability), and higher odds of dementia (OR per-SD increment in PRS: 1.56, 95%CI: 1.17-2.09, OR per-point increment in VBS: 1.38, 95%CI: 1.05-1.81). There was no evidence of an interaction between the two scores. Higher VBS was associated with worse cognitive performance equally across tertiles of the PRS for AD, even among individuals at the highest tertile.

Conclusions: Both genetic risk and vascular burden are independently and additively associated with worse cognitive performance and higher odds of dementia.

Keywords: Cardiovascular prevention; Cognitive decline; Dementia; Genetics; Population-based studies; Vascular risk factors.