Mid-life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants.
Mid-life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants.
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作者：
端粒磨损是生物衰老的标志之一，可以针对多种衰老相关疾病进行干预，包括阿尔茨海默病和阿尔茨海默病相关痴呆（AD/ADRD）。本研究的目的是评估白细胞端粒长度（TL）与AD/ADRD和AD/ADRD早期标志物（包括认知能力和脑磁共振成像（MRI）表型）的相关性。来自英国生物样本库（n = 435，046）中欧洲血统参与者的数据用于评价中年白细胞TL是否与平均随访12.2年的AD/ADRD事件相关。在没有AD/ADRD和脑成像数据的子样本中（n = 43，390），我们将TL与AD或血管性痴呆病理相关的脑MRI表型相关联。TL较长与AD/ADRD事件风险较低相关（根据SD调整的风险比[aHR]= 0.93，95% CI 0.90-0.96，p = 3.37 × 10−7）。较长的TL也与特定认知领域的更好的认知表现、更大的海马体积、更低的白色高信号总体积、以及更高的各向异性分数和更低的穹窿平均扩散率相关。总之，较长的TL与AD/ADRD、认知障碍和脑结构病变向AD/ADRD发展呈负相关。然而，根据孟德尔随机化分析结果，遗传决定的TL与上述结局之间的关系无统计学显著性。我们的研究结果增加了AD/ADRD优先风险的文献。因果关系需要在机理研究中确定。较长的白细胞端粒长度与AD/ADRD、认知障碍和脑结构病变的风险降低相关。
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. Longer leukocyte telomere length was associated with reduced risks of AD/ADRD, cognitive impairment, and brain structural lesions.
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短白细胞端粒可预测非 APOE ε4 携带者 25 年阿尔茨海默病的发病率。
DOI：
10.1186/s13195-021-00871-y
发表时间：
2021-07-15
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Hackenhaar FS;Josefsson M;Adolfsson AN;Landfors M;Kauppi K;Hultdin M;Adolfsson R;Degerman S;Pudas S
通讯作者：
Pudas S
影响因子：
7.7
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan NA;Thompson JR
通讯作者：
Thompson JR
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S