Alterations in functional connectivity (FC) have been observed in individuals with Alzheimers disease (AD) with elevated amyloid (Aβ) and tau. However, it is not yet known whether directed FC is already influenced by Aβ and tau load in cognitively healthy (CH) individuals. A 21-channel electroencephalogram (EEG) was used from 46 CHs classified based on cerebrospinal fluid (CSF) Aβ tau ratio: pathological (CH-PAT) or normal (CH-NAT). Directed FC was estimated with Partial Directed Coherence in frontal, temporal, parietal, central, and occipital regions. We also examined the correlations between directed FC and various functional metrics, including neuropsychology, cognitive reserve, MRI volumetrics, and heart rate variability between both groups. Compared to CH-NATs, the CH-PATs showed decreased FC from the temporal regions, indicating a loss of relative functional importance of the temporal regions. In addition, frontal regions showed enhanced FC in the CH-PATs compared to CH-NATs, suggesting neural compensation for the damage caused by the pathology. Moreover, CH-PATs showed greater FC in the frontal and occipital regions than CH-NATs. Our findings provide a useful and non-invasive method for EEG-based analysis to identify alterations in brain connectivity in CHs with a pathological versus normal CSF Aβ/tau.

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.

Abstract: Background: Stroop task is used to evaluate inhibition, a core executive function. Alpha Event‐Related Desynchronization (ERD) from analysis of electroencephalogram (EEG) during Stroop task reflects brain interference processing. We previously reported different relationships between heart rate variability (HRV) and alpha ERD during Stroop task. However, HRV proxied autonomic function can be confounded by increasing erratic rhythm with age, quantified by heart rate fragmentation (HRF). The knowledge of HRF is limited in a Cognitively Healthy (CH) cohort. To fill this gap, we studied these measurements in CH participants who underwent a Stroop task. Method: We studied HRF in an established EEG dataset during Stroop task from CH participants when their CSF amyloid/tau ratio were normal (≥2.71, CH‐NATs) or pathological (<2.71, CH‐PATs). Heart rate fragmentation (HRF) was analyzed from 5‐minute electrocardiogram (ECG) during resting or task. HRF was classified into three categories: hard inflection point, soft inflection point, and non‐inflection. Hard inflection point represents an acceleration‐to‐deceleration (AD) in heart rate and vice versa (DA). Soft inflection point describes heart rate transitions from acceleration or deceleration‐to‐zero acceleration (AZ or DZ) and vice versa (ZA or ZD). Non inflection means heart rates are accelerating (NA), decelerating (ND), or no change (NZ). Result: We previously reported that alpha ERD during incongruent trials were negatively correlated with heart rate (HR) in CH‐NATs but not in CH‐PATs (Figure 1). In CH‐NATs, there was a decrease in a subcategory of non‐inflection during task compared to resting (Figure 2A). We observed a significant increase in hard inflection points and a decrease in non‐inflections during Stroop task compared to resting in CH‐PATs (Figure 2B). Conclusion: These pilot results suggest: 1) from resting to task, CH‐PATs presented increase of HRF hard inflection points, which was not observed in CH‐NATs; 2) our previous analysis show that HR was negatively correlated with alpha ERD in CH‐NATs (higher HR related to more brain activation ‐ more negative alpha ERD), which was not observed in CH‐PATs. Although a larger sample size is needed, these results support a potential heart‐brain dysregulation using non‐invasive EEG and ECG in cognitively healthy individuals at higher risk of cognitive decline.