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BackgroundSubclinical cardiovascular disease (CVD) measures may reflect biological pathways that contribute to increased risk for coronary heart disease (CHD) events, stroke, and dementia beyond conventional risk scores.MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) followed 6,814 participants (45-84 years of age) from baseline in 2000-2002 to 2018 over 6 clinical examinations and annual follow-up interviews. MESA baseline subclinical CVD procedures included: seated and supine blood pressure, coronary calcium scan, radial artery tonometry, and carotid ultrasound. Baseline subclinical CVD measures were transformed into z-scores before factor analysis to derive composite factor scores. Time to clinical event for all CVD, CHD, stroke and ICD code-based dementia events were modeled using Cox proportional hazards models reported as area under the curve (AUC) with 95% Confidence Intervals (95%CI) at 10 and 15 years of follow-up. All models included all factor scores together and adjustment for conventional risk scores for global CVD, stroke, and dementia.ResultsAfter factor selection, 24 subclinical measures aggregated into four distinct factors representing: blood pressure, arteriosclerosis, atherosclerosis, and cardiac factors. Each factor significantly predicted time to CVD events and dementia at 10 and 15 years independent of each other and conventional risk scores. Subclinical vascular composites of arteriosclerosis and atherosclerosis best predicted time to clinical events of CVD, CHD, stroke, and dementia. These results were consistent across sex and racial and ethnic groups.ConclusionsSubclinical vascular composites of arteriosclerosis and atherosclerosis may be useful biomarkers to inform the vascular pathways contributing to events of CVD, CHD, stroke, and dementia.

ObjectivesEvaluate neurocognitive health and its response to interventions in older, obese patients with heart failure with preserved ejection fraction (HFpEF).BackgroundNeurocognitive dysfunction may be an underrecognized feature of HFpEF that responds to weight-loss interventions.MethodsWe first compared detailed baseline cognitive testing (Uniform Data Set version 3 and Rey Auditory Verbal Learning Test [RAVLT]), and brain volumes and cerebral blood flow (CBF) from 3T magnetic resonance imaging between older patients with HFpEF (n=46) and healthy age-matched controls (HC; n=22). The HFpEF patients were then randomized to a 20-week caloric restriction (CR) intervention with either aerobic-only (CR+AT; n=23) or aerobic+resistance exercise training (CR+AT+RT; n=23), and repeated cognitive testing and neuroimaging post-intervention. Cognitive scores were normalized to national data and transformed toz-scores for global, memory, attention, executive function, visuospatial, and language fluency domains.ResultsCompared to HC, participants with HFpEF had significantly lower baseline global cognitive performance, and lower global, visuospatial processing and language fluency domainz-scores than normative means. Following the diet and exercise intervention, there were significant improvements in global (+0.6 [95% CI: 0.3, 0.8]) and category fluency (+0.2 [95% CI: −0.004, 0.3])z-scores, and in RAVLT immediate (+0.6 [95% CI: 0.1, 1.0] points) and delayed (0.9 [95% CI: 0.2, 1.6] points) recall. Only CR+AT+RT was associated with improved phonemic fluency z-score (+0.4 [95% CI: 0.1, 0.7]). There were no significant intervention effects on brain volumes or CBF.ConclusionsOlder, obese patients with chronic HFpEF have significant cognitive deficits that are ameliorated by diet and exercise interventions.

Strategies to prevent or delay Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) are urgently needed. Blood pressure (BP) management is a promising strategy for AD/ADRD prevention and the key element in the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet the effects of different population level BP control strategies across the life course on AD/ADRD are not known.Large-scale randomized controlled trials are the least biased approach to identifying the effect of BP control on AD/ADRD, yet trials may be infeasible due to the need for prolonged follow-up and very large sample sizes. Thus, simulation analyses leveraging the best available observational data may be the best and most practical approach to answering these questions.In this manuscript, we describe the design principles, implementation details, and population-level validation of a novel population health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP COG) study of the effect of BP levels over the life course on cognitive decline and dementia.MICROSIM was designed by applying computer programming best practices to create a novel simulation model. The initial purpose of this extensible, open-source framework is to explore a series of questions related to the impact of different blood pressure management strategies on late-life cognition and all-cause dementia, as well as the effects on race differences in all-cause dementia incidence. Ultimately, though, the framework is designed to be extensible such that a variety of different clinical conditions could be added to the framework.