Search

Background: Observational studies link high midlife systolic blood pressure to increased dementia risk. However, the synthesis of evidence from randomized controlled trials has not definitively demonstrated that antihypertensive medication use reduces dementia risk. Here, we emulate target trials of antihypertensive medication initiation on incident dementia using three cohort studies, with attention to potential violations of necessary assumptions. Methods: We emulated trials of antihypertensive medication initiation on incident dementia using data from the Atherosclerosis Risk in Communities study, Cardiovascular Health Study, and Health and Retirement Study. We used data-driven methods to restrict participants to initiators and noninitiators with overlap in propensity scores and positive control outcomes to look for violations of positivity and exchangeability assumptions. Results: Analyses were limited by the small number of cohort participants who met eligibility criteria. Associations between antihypertensive medication initiation and incident dementia were inconsistent and imprecise (Atherosclerosis Risk in Communities: HR = 0.30 [0.05, 1.93]; Cardiovascular Health Study: HR = 0.66 [0.27, 1.64]; Health and Retirement Study: HR = 1.09 [0.75, 1.59]). More stringent propensity score restrictions had little effect on findings. Sensitivity analyses using a positive control outcome unexpectedly suggested antihypertensive medication initiation increased the risk of coronary heart disease in all three samples. Conclusions: Positive control outcome analyses suggested substantial residual confounding in effect estimates from our target trials, precluding conclusions about the impact of antihypertensive medication initiation on dementia risk through target trial emulation. Formalized processes for identifying violations of necessary assumptions will strengthen confidence in target trial emulation and avoid inappropriate confidence in emulated trial results. [ABSTRACT FROM AUTHOR]

PURPOSE: Our previous work using real time monitoring has shown that motor activity is associated with a decrease in sad mood. Here we examine whether there is a dose effect of activity intensity with mood, and whether this association is moderated by pain, or sleep quality. Further, we examine whether these associations differ among those with a history of Mood Disorder subtypes. METHODS: 80 adults (mean age 42), a subset from a community-based family study enriched for mood disorders. Motor activity (MA) was assessed via actigraphy, and subjective mood, pain, and sleep quality were reported via ecological momentary assessment 4 times per day for 2 weeks. Lifetime history of mood disorder subtypes (bipolar I, bipolar II, major depressive disorder) were determined by a semi-structured clinical interview and best estimate consensus. Generalized estimating equations with granger modeling of prior states of the outcome variables were used to analyze the lagged associations among mood, pain, sleep quality, and MA/exercise. RESULTS: Intensity of MA and subjectively rated pain were not associated with changes in sad mood. However, sad mood was associated with a subsequent increase in subjective pain (Est. 0.0553, S.E. 0.025, p=0.0268) . Although mood ratings did differ by lifetime history of mood disorder subtypes, there were no differences in subjectively rated pain or MA between these subgroups. CONCLUSION: Findings suggest that intensity of MA does not explain the unidirectional association between MA with sad mood, nor was this association moderated by pain or sleep quality that were not related to sad mood. Future analyses will exploit the multilevel intensive longitudinal data using dynamic structural equation modeling and cross replicate these findings in parallel samples. [ABSTRACT FROM AUTHOR]