Cardiovascular risk burden, dementia risk and brain structural imaging markers: a study from UK Biobank

Yaying Cao; Gaohong Zhu; Chengwu Feng; Jing Chen; Wei Gan; Yuan Ma; Yonghua Hu; Klodian Dhana; Trudy Voortman; Jie Shen; Ting Li; Yan Zheng; Changzheng Yuan; Geng Zong

doi:10.1136/gpsych-2023-101209

Cardiovascular risk burden, dementia risk and brain structural imaging markers: a study from UK Biobank

Gen Psychiatr. 2024 Jan 29;37(1):e101209. doi: 10.1136/gpsych-2023-101209. eCollection 2024.

Authors

Yaying Cao^{1

2}, Gaohong Zhu³, Chengwu Feng², Jing Chen⁴, Wei Gan^{5

6}, Yuan Ma⁷, Yonghua Hu⁸, Klodian Dhana⁹, Trudy Voortman^{10

11}, Jie Shen¹², Ting Li¹³, Yan Zheng^{14

15}, Changzheng Yuan^{12

16}, Geng Zong^{2

17}

Affiliations

¹ Department of Food Nutrition and Health, School of Medicine and Health, Harbin Institute of Technology, Harbin, Heilongjiang, China.
² CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
³ Department of Nuclear Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
⁴ Neurology Department, Zhongshan Hospital Affiliated with Fudan University, Shanghai, China.
⁵ Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.
⁶ Department of Genetics, Novo Nordisk Research Centre Oxford, Oxford, UK.
⁷ Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA.
⁸ Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
⁹ Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA.
¹⁰ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹¹ Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
¹² School of Public Health, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
¹³ First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
¹⁴ State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
¹⁵ Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, China.
¹⁶ The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, Zhejiang, China.
¹⁷ Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Abstract

Background: Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure, while the role of genetics and incident cardiovascular disease (CVD) remains unclear.

Aims: To examine the association of overall cardiovascular risk burden with the risk of major dementia subtypes and volumes of related brain regions in a large sample, and to explore the role of genetics and CVD onset.

Methods: A prospective study among 354 654 participants free of CVD and dementia (2006-2010, mean age 56.4 years) was conducted within the UK Biobank, with brain magnetic resonance imaging (MRI) measurement available for 15 104 participants since 2014. CVD risk burden was evaluated by the Framingham General Cardiovascular Risk Score (FGCRS). Dementia diagnosis was ascertained from inpatient and death register data.

Results: Over a median 12.0-year follow-up, 3998 all-cause dementia cases were identified. Higher FGCRS was associated with increased all-cause dementia risk after adjusting for demographic, major lifestyle, clinical factors and the polygenic risk score (PRS) of Alzheimer's disease. Comparing the high versus low tertile of FGCRS, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.26 (1.12 to 1.41) for all-cause dementia, 1.67 (1.33 to 2.09) for Alzheimer's disease and 1.53 (1.07 to 2.16) for vascular dementia (all p_trend<0.05). Incident stroke and coronary heart disease accounted for 14% (95% CI: 9% to 21%) of the association between FGCRS and all-cause dementia. Interactions were not detected for FGCRS and PRS on the risk of any dementia subtype. We observed an 83% (95% CI: 47% to 128%) higher all-cause dementia risk comparing the high-high versus low-low FGCRS-PRS category. For brain volumes, higher FGCRS was associated with greater log-transformed white matter hyperintensities, smaller cortical volume and smaller grey matter volume.

Conclusions: Our findings suggest that the positive association of cardiovascular risk burden with dementia risk also applies to major dementia subtypes. The association of cardiovascular risk burden with all-cause dementia is largely independent of CVD onset and genetic predisposition to dementia.

Keywords: Ageism; Cognition Disorders; Cohort Studies; Epidemiologic Factors.