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Alzheimer's Association International Conference 2026

July 12-15, 2026 | London, United Kingdom, and Online

3922

Genetically Predicted Lung Function Is Associated With Dementia Risk Through Glymphatic-related Imaging Markers

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Poster Presenter

Jie Zhang

Authors

Jie Zhang, Haonan Xie, Kaisi Ren, Luxi Jiang

Affiliations

Zhejiang Provincial People's Hospital

Part of Topic

Genetically Predicted Lung Function Is Associated With Dementia Risk Through Glymphatic-related Imaging Markers

Jie Zhang1, Haonan Xie1, Kaisi Ren1, Luxi Jiang2
1Department of Rehabilitation, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, China;
2Department of Respiratory Medicine, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, China

Key Points:

•Higher genetically predicted FVC is associated with better glymphatic function;

•Higher ALPS indices are associated with lower risks of dementia, particularly AD and dementia in other diseases;

•DTI-ALPS may represent a promising imaging biomarker linking pulmonary health and brain aging.

Introduction:

•Reduced lung function has been associated with dementia in observational studies.

•Glymphatic system plays a key role in brain waste clearance and may contribute to neurodegeneration.

•Whether impaired pulmonary function influences dementia risk through glymphatic dysfunction remains unknown.

Methods:

•Two-sample Mendelian randomization analysis using GWAS summary statistics.

•Exposure: Lung function (FVC, FEV1, PEF, FEV1/FVC).

•Mediators: Glymphatic-related imaging markers (DTI-ALPS and EPVS).

•Outcomes: Overall dementia, and subtypes pf dementia

•Analysis: Univariable MR and two-step mediation.

Results:

•Higher genetically predicted FVC was associated with higher mean ALPS index (β=0.09, P=0.003), but not with EPVS.

•Higher ALPS indices were associated with lower risks of overall dementia, AD, and dementia in other diseases (OR=0.58, P=0.013), but not VaD.

•Higher FVC was associated with a reduced risk of dementia in other diseases (OR=0.72, P=0.017).

•Mediation analysis suggested a possible pathway via ALPS (mediation proportion ≈14–16%; P>0.05).

Conclusions:

•Preserved pulmonary function is genetically associated with more favorable glymphatic-related imaging markers.

•DTI-ALPS, rather than EPVS, showed consistent associations with both lung function and dementia outcomes.

•These findings support a potential lung–brain axis involving glymphatic function that warrants further investigation.

References:
•Xiao T, et al. Lung Function Impairment and the Risk of Incident Dementia: The Rotterdam Study. J Alzheimers Dis, 2021, 82(2): 621-30;
•Grande G, et al. Lung function in relation to brain aging and cognitive transitions in older adults: A population-based cohort study. Alzheimers Dement, 2024, 20(8): 5662-73.
•Zhou L, et al. Association of impaired lung function with dementia, and brain magnetic resonance imaging indices: a large population-based longitudinal study. Age Ageing, 2022, 51(11).

Correspondence:Jie Zhang,
zhangjie91@zju.edu.cn
Zhejiang Provincial People’s Hospital
Hangzhou, 310014

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