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Disease trajectories before dementia: evidence from a large-scale community-based prospective study

Published online by Cambridge University Press:  11 October 2024

Jialin Li ,
Ding Xia ,
Mei Cui ,
Yingzhe Wang ,
Jincheng Li ,
Li Jin ,
Xingdong Chen ,
Chen Suo  and
Yanfeng Jiang Open the ORCID record for Yanfeng Jiang [Opens in a new window]
Jialin Li
Affiliation:
State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
Ding Xia
Affiliation:
Ministry of Education Key Laboratory of Public Health Safety, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
Mei Cui
Affiliation:
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
Yingzhe Wang
Affiliation:
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
Jincheng Li
Affiliation:
State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
Li Jin
Affiliation:
State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
Xingdong Chen
Affiliation:
State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China Yiwu Research Institute of Fudan University, Yiwu, Zhejiang, China National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
Chen Suo
Affiliation:
Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China Ministry of Education Key Laboratory of Public Health Safety, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China Shanghai Institute of Infectious Disease and Biosecurity, Shanghai, China
Yanfeng Jiang*
Affiliation:
State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China International Human Phenome Institutes (Shanghai), Shanghai, China
*
Correspondence: Yanfeng Jiang. Email: [email protected]
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Abstract

Background

Systemic changes in multiple diseases may influence the onset of dementia. However, the specific temporality between exposure diseases and dementia remains uncertain.

Aims

By characterising the full spectrum of temporal disease trajectories before dementia, this study aims to yield a global picture of precursor diseases to dementia and to provide detailed instructions for risk management and primary prevention of dementia.

Method

Using the multicentre, community-based prospective UK Biobank, we constructed disease trajectories before dementia utilising the phenome-wide association analysis, paired directional test and association quantification. Stratified disease trajectories were constructed by dementia subtypes, gender, age of diagnosis and Apolipoprotein E (ApoE) status, respectively.

Results

Our study population comprised 434 266 participants without baseline dementia and 4638 individuals with all-cause dementia. In total, 1253 diseases were extracted as potential components of the disease trajectory before dementia. We identified three clusters of disease trajectories preceding all-cause dementia, initiated by circulatory, metabolic and respiratory diseases occurring approximately 5–15 years before dementia. Cerebral infarction or chronic renal failure following chronic ischaemic heart disease was the specific trajectory before vascular dementia. Apolipoprotein E (ApoE) ε4 non-carriers exhibited more complex trajectories compared with carriers. Lipid metabolism disorders remained in the trajectories regardless of dementia subtypes, gender, age of diagnosis and ApoE status.

Conclusions

This study provides a comprehensive view of the longitudinal disease trajectories before dementia and highlights the potential targets of midlife cardiometabolic dysfunction for dementia screening and prevention.

Keywords

DementiaAlzheimer's diseasevascular dementiadisease trajectorycohort study
Type
Original Article
Information
The British Journal of Psychiatry , Volume 225 , Issue 6 , December 2024 , pp. 538 - 546
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Copyright
Copyright © The Author(s), 2024. Published by Cambridge University Press on behalf of Royal College of Psychiatrists

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Footnotes

†

These authors contributed equally to the article.

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