INTRODUCTION: Resting heart rate (HR) and heart rate variability (HRV) have been linked with cognition in the general population and in older individuals. The knowledge of this aspect of heart-brain relationship is relatively absent in older individuals with early Alzheimers disease (AD) pathology. This study explores relationships of the HR, HRV, and cognition in cognitively healthy individuals with pathological amyloid/tau ratio (CH-PATs) in cerebral spinal fluid (CSF) compared to those with normal ratio (CH-NATs). METHODS: We examined therelationshipsbetween1) resting HR and Mini-Mental State Examination (MMSE); 2) resting HR and brain processing during Stroop interference; and 3) resting vagally mediated HRV (vmHRV) and task switching performance. RESULTS: Our studies showed that compared to CH-NATs, those CH-PATs with higher resting HR presented with lower MMSE, and less brain activation during interference processing. In addition, resting vmHRV was significantly correlated with task switching accuracy in CH-NATs, but not in CH-PATs. DISCUSSION: Thesethreedifferenttestsindicatedysfunctionalheart-brainconnections in CH-PATs, suggesting a potential cardio-cerebral dysfunctional integration.

The heart and brain have bi-directional influences on each other, including autonomic regulation and hemodynamic connections. Heart rate variability (HRV) measures variation in beat-to-beat intervals. New findings about disorganized sinus rhythm (erratic rhythm, quantified as heart rate fragmentation, HRF) are discussed and suggest overestimation of autonomic activities in HRV changes, especially during aging or cardiovascular events. When excluding HRF, HRV is regulated via the central autonomic network (CAN). HRV acts as a proxy of autonomic activity and is associated with executive functions, decision-making, and emotional regulation in our health and wellbeing. Abnormal changes of HRV (e.g., decreased vagal functioning) are observed in various neurological conditions including mild cognitive impairments, dementia, mild traumatic brain injury, migraine, COVID-19, stroke, epilepsy, and psychological conditions (e.g., anxiety, stress, and schizophrenia). Efforts are needed to improve the dynamic and intriguing heart-brain interactions.

Insulin resistance (IR) and metabolic disorders are non-pulmonary adverse effects induced by fine particulate matter (PM_2.5) exposure. The worldwide pandemic of high fructose sweeteners and fat rich modern diets, also contribute to IR development. We investigated some of the underlying effects of IR, altered biochemical insulin action and Insulin/AKT pathway biomarkers. Male Sprague Dawley rats were subchronically exposed to filtered air, PM_2.5, a fructose rich diet (FRD), or PM_2.5 + FRD. Exposure to PM_2.5 or FRD alone did not induce metabolic changes. However, PM_2.5 + FRD induced leptin release, systemic hyperinsulinemia, and Insulin/AKT dysregulation in insulin-sensitive tissues preceded by altered AT₁R levels. Histological damage and increased HOMA-IR were also observed from PM_2.5 + FRD co-exposure. Our results indicate that the concomitant exposure to a ubiquitous environmental pollutant, such as PM_2.5, and a metabolic disease risk factor, a FRD, can contribute to the metabolic disorder pandemic occurring in highly polluted locations.