Dataset Information

Telomere Length and Magnetic Resonance Imaging Findings of Vascular Brain Injury and Central Brain Atrophy: The Strong Heart Study.

ABSTRACT: Telomeres are repeating regions of DNA that cap chromosomes. They shorten over the mammalian life span, especially in the presence of oxidative stress and inflammation. Telomeres may play a direct role in cell senescence, serving as markers of premature vascular aging. Leukocyte telomere length (LTL) may be associated with premature vascular brain injury and cerebral atrophy. However, reports have been inconsistent, especially among minority populations with a heavy burden of illness related to vascular aging. We examined associations between LTL and magnetic resonance imaging in 363 American Indians aged 64-93 years from the Strong Heart Study (1989-1991) and its ancillary study, Cerebrovascular Disease and Its Consequences in American Indians (2010-2013). Our results showed significant associations of LTL with ventricular enlargement and the presence of white matter hyperintensities. Secondary models indicated that renal function may mediate these associations, although small case numbers limited inference. Hypertension and diabetes showed little evidence of effect modification. Results were most extreme among participants who evinced the largest decline in LTL. Although this study was limited to cross-sectional comparisons, it represents (to our knowledge) the first consideration of associations between telomere length and brain aging in American Indians. Findings suggest a relationship between vascular aging by cell senescence and severity of brain disease.

SUBMITTER: Suchy-Dicey AM

PROVIDER: S-EPMC5982792 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Telomere Length and Magnetic Resonance Imaging Findings of Vascular Brain Injury and Central Brain Atrophy: The Strong Heart Study.

Suchy-Dicey Astrid M AM Muller Clemma J CJ Madhyastha Tara M TM Shibata Dean D Cole Shelley A SA Zhao Jinying J Longstreth W T WT Buchwald Dedra D

American journal of epidemiology 20180601 6

Telomeres are repeating regions of DNA that cap chromosomes. They shorten over the mammalian life span, especially in the presence of oxidative stress and inflammation. Telomeres may play a direct role in cell senescence, serving as markers of premature vascular aging. Leukocyte telomere length (LTL) may be associated with premature vascular brain injury and cerebral atrophy. However, reports have been inconsistent, especially among minority populations with a heavy burden of illness related to ...[more]

PMID: 29860472

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Project description:BACKGROUND:The neuroanatomic basis for cognitive impairment in chronic kidney disease (CKD) is incompletely characterized. We performed advanced quantitative structural magnetic resonance imaging (MRI) to determine whether CKD affects brain structure and whether poorer neurocognitive performance in CKD is associated with structural brain differences. STUDY DESIGN:Cross-sectional. SETTING & PARTICIPANTS:85 individuals with CKD stages 2 to 5 and 63 healthy controls, aged 8 to 25 years PREDICTORS: CKD versus control, estimated glomerular filtration rate (eGFR), and kidney transplant status were analyzed as predictors of MRI findings. MRI volumes in 19 prespecified regions of gray matter (GM), white matter (WM), and cerebrospinal fluid were analyzed as predictors of neurocognitive performance (median z scores) in 7 prespecified domains. OUTCOMES:19 prespecified brain regions of interest (ROIs) in 7 prespecified domains. Neurocognitive performance in 7 prespecified domains. MEASUREMENTS:ROI volumes were compared in CKD versus controls using unadjusted t tests and analysis of covariance (ANCOVA). Associations of ROI volumes with eGFR and kidney transplant status in participants with CKD were analyzed using ANCOVA and linear regression. Associations of neurocognitive performance and ROI volumes were analyzed by linear regression. RESULTS:Participants with CKD had lower whole-brain, cortical, and left parietal GM volumes than controls in unadjusted analyses, but no differences were found in adjusted analysis. In participants with CKD, lower eGFR was associated with higher WM volume in whole-brain (P=0.05) and frontal (P=0.04) ROIs, but differences were not significant after multiple comparisons correction. Kidney transplant recipients had lower GM volumes in whole-brain (P=0.01; Q=0.06), frontal (P=0.02; Q=0.08), and left and right parietal (P=0.01; Q=0.06; and P=0.03; Q=0.1) ROIs and higher whole-brain WM volume (P=0.04; Q=0.1). Neurocognitive performance in the CKD group was not associated with ROI volumes. LIMITATIONS:Unable to assess changes in brain structure and kidney function over time; analysis limited to prespecified ROIs and neurocognitive domains. CONCLUSIONS:CKD in children and young adults may be associated with lower GM and higher WM volumes in some ROIs. Differences were relatively subtle in the CKD group as a whole, but were more prominent in recipients of a kidney transplant. However, neurocognitive performance was not explained by differences in brain ROI volumes, suggesting a functional rather than structural basis for neurocognitive impairment in CKD.

Project description:Essentials Plasminogen activator inhibitor-1 (PAI-1) advanced cellular senescence in experiment studies. No population study exists on the association between PAI-1 and biological aging in American Indians. We found cross-sectional and longitudinal associations between higher PAI-1 and shorter telomere length. Our findings suggest a pathway linking PAI-1 with biological aging beyond metabolic factors. SUMMARY:Background Plasminogen activator inhibitor-1 (PAI-1) promotes cellular aging both in vitro and in vivo. Telomere length is a marker of biological aging. Objectives To examine the cross-sectional and longitudinal associations between plasma PAI-1 and leukocyte telomere length in a large-scale epidemiological study of American Indians. Methods We measured leukocyte telomere length (LTL) and plasma PAI-1 in 2560 American Indians who were free of overt cardiovascular disease (CVD) and participated in the Strong Heart Family Study (SHFS) clinical examination in 2001-2003. LTL and PAI-1 were repeatedly measured in 475 participants who attended SHFS clinical visits in both 2001-2003 and 1998-1999. A generalized estimating equation model was used to examine the cross-sectional and longitudinal associations between PAI-1 and LTL, adjusting for known risk factors. Results A higher level of plasma PAI-1 was negatively associated with shorter age-adjusted LTL (? = -0.023; 95% CI, -0.034 to -0.013). This association was attenuated (? = -0.015; 95% CI, -0.029 to -0.002) after adjustments for demographics, study site, lifestyle (smoking, drinking and physical activity) and metabolic factors (obesity, blood pressure, fasting glucose, insulin, lipids and kidney function). Further adjustment for hsCRP did not change this association (? = -0.015; 95% CI, -0.029 to -0.001). Longitudinal analysis revealed that change in plasma PAI-1 was also inversely associated with change in LTL after adjusting for demographics, follow-up years, lifestyle factors, changes in metabolic factors, baseline levels of PAI-1 and LTL (? = -0.0005; 95% CI, -0.0009 to -0.0001). Conclusions A higher level of plasma PAI-1 was associated with shorter LTL in American Indians. This finding may suggest a potential role of PAI-1 in biological aging among American Indians.

Dataset Information

Telomere Length and Magnetic Resonance Imaging Findings of Vascular Brain Injury and Central Brain Atrophy: The Strong Heart Study.

Publications

Telomere Length and Magnetic Resonance Imaging Findings of Vascular Brain Injury and Central Brain Atrophy: The Strong Heart Study.

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