Association between use of antihypertensives and cognitive decline in the elderly-A retrospective observational study.

AIM: Mild cognitive impairment (MCI) is the prodromal phase of dementia. The objective of this study was to determine whether specific antihypertensives were associated with conversion from MCI to dementia. METHODS: In this retrospective study, a chart review was conducted on 335 older adults seen at the University of Alberta Hospital, Kaye Edmonton Seniors Clinic who were diagnosed with MCI. At the point of diagnosis, data was collected on demographic and lifestyle characteristics, measures of cognitive function, blood pressure measurements, use of antihypertensives, and other known or suspected risk factors for cognitive decline. Patients were followed for 5.5 years for dementia diagnoses. A logistic regression analysis was then conducted to determine the factors associated with conversion from MCI to dementia. RESULTS: Mean age (± standard deviation) of the study participants was 76.5 ± 7.3 years. Patients who converted from MCI to dementia were significantly older and were more likely to have a family history of dementia. After controlling for potential confounders including age, sex, Mini Mental Status Exam scores and family history of dementia, patients who were on beta-blockers (BBs) had a 57% reduction in the odds of converting to dementia (OR: 0.43, 95% CI: 0.23, 0.81). CONCLUSIONS: In this study, BB use was protective against conversion from MCI to dementia. Further studies are required to confirm the findings of our study and to elucidate the effect of BBs on cognitive decline.

Predictors of Conversion to Dementia in Patients With Mild Cognitive Impairment: The Role of Low Body Temperature.

Background: Subjects with mild cognitive impairment (MCI) can progress to dementia. Studies have shown that neuropsychological tests, biological or radiological markers individually or in combination have helped to determine the risk of conversion from MCI to dementia. These techniques are complex and expensive, and clinical risk factors were not considered in these studies. This study examined demographic, lifestyle and clinical factors including low body temperature that may play a role in the conversion of MCI to dementia in elderly patients. Methods: In this retrospective study, a chart review was conducted on patients aged 61 to 103 years who were seen at the University of Alberta Hospital. Information on onset of MCI and demographic, social, and lifestyle factors, family history of dementia and clinical factors, and current medications at baseline was collected from patient charts on an electronic database. The conversion from MCI to dementia within 5.5 years was also determined. Logistic regression analysis was conducted to identify the baseline factors associated with conversion from MCI to dementia. Results: The prevalence of MCI at baseline was 25.6% (335/1,330). During the 5.5 years follow-up period, 43% (143/335) of the subjects converted to dementia from MCI. The factors that were significantly associated with conversion from MCI to dementia were family history of dementia (odds ratio (OR): 2.78, 95% confidence interval (CI): 1.56 - 4.95, P = 0.001), Montreal cognitive assessment (MoCA) score (OR: 0.91, 95% CI: 0.85 - 0.97, P = 0.01), and low body temperature (below 36 °C) (OR: 10.01, 95% CI: 3.59 - 27.88, P < 0.001). Conclusion: In addition to family history of dementia and MoCA, low body temperature was shown to be associated with the conversion from MCI to dementia. This study would help clinicians to identify patients with MCI who are at highest risk of conversion to dementia.

Dilated Cardiomyopathy Mutations and Phosphorylation disrupt the Active Orientation of Cardiac Troponin C.

Cardiac troponin (cTn) is made up of three subunits, cTnC, cTnI, and cTnT. The regulatory N-terminal domain of cTnC (cNTnC) controls cardiac muscle contraction in a calcium-dependent manner. We show that calcium-saturated cNTnC can adopt two different orientations, with the "active" orientation consistent with the 2020 cryo-EM structure of the activated cardiac thin filament by Yamada et al. Using solution NMR 15N R2 relaxation analysis, we demonstrate that the two domains of cTnC tumble independently (average R2 10 s-1), being connected by a flexible linker. However, upon addition of cTnI1-77, the complex tumbles as a rigid unit (R2 30 s-1). cTnI phosphomimetic mutants S22D/S23D, S41D/S43D and dilated cardiomyopathy- (DCM-)associated mutations cTnI K35Q, cTnC D75Y, and cTnC G159D destabilize the active orientation of cNTnC, with intermediate 15N R2 rates (R2 17-23 s-1). The active orientation of cNTnC is stabilized by the flexible tails of cTnI, cTnI1-37 and cTnI135-209. Surprisingly, when cTnC is incorporated into complexes lacking these tails (cTnC-cTnI38-134, cTnC-cTnT223-288, or cTnC-cTnI38-134-cTnT223-288), the cNTnC domain is still immobilized, revealing a new interaction between cNTnC and the IT-arm that stabilizes a "dormant" orientation. We propose that the calcium sensitivity of the cardiac troponin complex is regulated by an equilibrium between active and dormant orientations, which can be shifted through post-translational modifications or DCM-associated mutations.