Document Type
Peer-Reviewed Article
Publication Date
7-2023
Abstract
Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90–0.96, p = 3.37 × 10−7). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies.
DOI
10.1111/acel.13808
PMID
37254630
Recommended Citation
Liu, R., Xiang, M., Pilling, L. C., Melzer, D., Wang, L., Manning, K. J., Steffens, D.C., Bowden, J., Fortinsky, R.H., Kuchel, G.A., Rhee, T.G., Diniz, B.S., & Kuo, C. L. (2023). Mid‐life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants. Aging Cell, 22(7), e13808. Doi: 10.1111/acel.13808
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Included in
Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons, Genetic Phenomena Commons
Comments
Online ahead of print, May 30, 2023
Open access under Creative Commons Attribution 4.0 International (CC BY 4.0) license.