ABSTRACT
Background: Cognitive impairment is an irreversible, aging-associated condition that robs people of their independence. The purpose of this study was to investigate possible causes of this condition and propose preventive options. Methods: We assessed cognitive status in long-living adults aged 90+ (n = 2,559) and performed a genome wide association study using two sets of variables: Mini-Mental State Examination scores as a continuous variable (linear regression) and cognitive status as a binary variable (> 24, no cognitive impairment; <10, impairment) (logistic regression). Results: Both variations yielded the same polymorphisms, including a well-known marker of dementia, rs429358in the APOE gene. Molecular dynamics simulations showed that this polymorphism leads to changes in the structure of alpha helices and the mobility of the lipid-binding domain in the APOE protein. Conclusion: These changes, along with higher LDL and total cholesterol levels, could be the mechanism underlying the development of cognitive impairment in older adults. However, this polymorphism is not the only determining factor in cognitive impairment. The polygenic risk score model included 45 polymorphisms (ROC AUC 69%), further confirming the multifactorial nature of this condition. Our findings, particularly the results of PRS modeling, could contribute to the development of early detection strategies for predisposition to cognitive impairment in older adults.
ABSTRACT
It is known that glucose disturbances contribute to micro- and macrovascular complications and vascular aging. Telomere length is considered to be a cellular aging biomarker. It is important to determine the telomere length role in vascular structural and functional changes in patients with diabetes mellitus. We conducted a cross-sectional observational study in a high-risk population from Moscow, Russia. The study included 50 patients with diabetes and without clinical cardiovascular disease and 49 control group participants. Glucose metabolism assessment tests, measuring intima-media complex thickness and determining the presence of atherosclerotic plaques, pulse wave velocity measurement, and telomere length measurement were administered to all participants. Vascular changes were more dramatic in patients with diabetes than in the control group, and the telomeres were shorter in patients with diabetes. Significant differences were found in the vascular wall condition among diabetes patients, and there were no substantial differences in the arterial structure between patients with 'long' telomeres; however, there were statistically significant differences in the vascular wall condition between patients with 'short' telomeres. Vascular ageing signs were more prominent in patients with diabetes. However, despite diabetes, vascular changes in patients with long telomeres were very modest and were similar to the vascular walls in healthy individuals. Thus, long lymphocyte telomeres may have a protective effect on the vascular wall and may prevent vascular wall deterioration caused by glucose metabolism disorders.
