| Title: | Disease trajectories before dementia: evidence from a large-scale community-based prospective study |
| Journal: | The British Journal of Psychiatry |
| Published: | 11 Oct 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39391916/ |
| DOI: | https://doi.org/10.1192/bjp.2024.122 |
Publication 13237
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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.</p>
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.</p>
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.</p>
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.</p>
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.</p>
12 Keywords
- Adult
- Aged
- Apolipoprotein E4
- Apolipoproteins E
- Dementia
- Disease Progression
- Female
- Humans
- Male
- Middle Aged
- Prospective Studies
- United Kingdom
9 Authors
- Jialin Li
- Ding Xia
- Mei Cui
- Yingzhe Wang
- Jincheng Li
- Li Jin
- Xingdong Chen
- Chen Suo
- Yanfeng Jiang
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