Background: Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. Methods: The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz­heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. Results and Conclusions: The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor.

Background: Cognitive and physical impairment frequently co-occur in older people. The aim of this study was to assess the temporal order of these age-related changes in cognitive and physical performance and to assess whether a relationship was different across specific cognitive and physical domains and age groups. Methods: Cognitive domains included global, executive, and memory function; physical domains included gait speed and handgrip strength. These domains were assessed in two population-based longitudinal cohorts covering the age ranges of 55-64, 65-74, 75-85, and 85-90 years with a follow-up of 5-12 years. Cross-lagged panel models were applied to assess the temporal relationships between the different cognitive and physical domains adjusting for age, sex, education, comorbidity, depressive symptoms, and physical activity. Results: Over all age groups, poorer executive function was associated with a steeper decline in gait speed (p < .05). From the age of 85 years, this relationship was found across all cognitive and physical domains (p < .02). From the age of 65 years, slower gait speed and/or weaker handgrip strength were associated with steeper declines in global cognitive function (p < .02), with statistically significant results across all cognitive domains in the age group of 75-85 years (p < .04). Conclusions: The temporal relationship between cognitive and physical performance differs across domains and age, suggesting a specific rather than a general relationship. This emphasizes the importance of repeated measurements on different domains and encourages future research to the development of domain-and age-specific interventions.

Background: The positive relationship between cognitive and physical performance has been widely established. The influence of brain structure on both domains has been shown as well. Objective: We studied whether the relationship between brain structure and physical performance is independent of cognitive performance. Methods: This was a cross-sectional analysis of 297 middle-aged to older adults (mean age ± SD 65.4 ± 6.8 years). Memory function, executive function and physical performance measured by the Tandem Stance Test, Chair Stand Test, 4-meter walk and 25-meter walk were assessed. Magnetic resonance imaging was available in 237 participants and used to determine the (sub)cortical gray matter, white matter, hippocampal and basal ganglia volumes and the presence of cerebral small-vessel disease, i.e. white matter hyperintensities, cerebral microbleeds (CMBs) and lacunar infarcts (LIs). Regression analysis was used adjusting for age, gender, education and whole-brain volume. A Bonferroni correction was applied considering p values <0.017 as statistically significant. Results: Poor memory function was associated with a slower 4-meter walking speed (p < 0.01). No association was found between brain structure and cognitive performance. The presence of CMBs and LIs was associated with a slower 25-meter walking speed (p < 0.001). This result did not change after additional adjustment for cognitive performance. Conclusions: In middle-aged to older adults, CMBs and LIs are associated with walking speed independent of cognitive performance. This emphasizes the clinical relevance of identifying each of the possible underlying mechanisms of physical performance, which is required for the development of timely and targeted therapies.