Cortical thickness is associated with altered autonomic function in cognitively impaired and non‐impaired older adults

Abstract

The parasympathetic nervous system (PNS) is critical for adaptation to environment demands. PNS can reflect an individual's regulatory capacity of frontal brain regions and has been linked to cognitive capacity. Yet, the relationship of PNS function to cognitive decline and abnormal frontal function that characterize preclinical progression toward Alzheimer's disease (AD) is unclear. Here, we aimed to elucidate the relationship between PNS function and AD-associated neurodegeneration by testing two competing hypotheses involving frontal regions' activity (neurodegeneration vs. compensation). In 38 older human adults with amnestic mild cognitive impairment (aMCI) or normative cognition, we measured AD-associated neurodegeneration (AD signature cortical thickness; ADSCT), resting-state functional magnetic resonance imaging of frontal regions' spontaneous activation, and an electrocardiography measure of PNS (high frequency heart rate variability; HF-HRV). HF-HRV was assessed at rest and during a cognitive task protocol designed to capture HF-HRV reactivity. Higher HF-HRV at rest was significantly related to both more severe AD-associated neurodegeneration (lower ADSCT scores) and worse cognitive ability. Cognitive impairments were also related to greater suppression of HF-HRV reactivity. High activities of the anterior cingulate cortex significantly mediated relationships between ADSCT and both HF-HRV at rest and HF-HRV reactivity. Notably, these relationships were not affected by the clinical phenotype. We show that AD-associated neurodegeneration is associated with altered PNS regulation and that compensatory processes linked to frontal overactivation might be responsible for those alterations. This finding provides the first line of evidence in a new framework for understanding how early-stage AD-associated neurodegeneration affects autonomic regulation.

Cortical Thickness and Resting State Cardiac Function Across the Lifespan: A Cross-Sectional Pooled Mega Analysis

“…Several studies have recently shown that resting-state HRV is associated with the morphology of the brain across regions of interest [ROI], indexed by cerebral cortical thickness [CT] (Carnevali et al, 2019;Koenig et al, 2018;Lin et al, Woodward, Kaloupek, Schaer, Martinez, & Eliez, 2008;Yoo et al, 2017). CT is considered to reflect cellular aspects of the cortical organization (Lerch, 2001).…”

The mediating role of hippocampal networks on stress regulation in amnestic mild cognitive impairment

“…Abnormal HF-HRV reactivity to acute stress was observed in the middle to late stages of AD compared to healthy older adults (Femminella et al, 2014), suggesting altered acute stress regulation with more advanced neurodegeneration. For individuals with aMCI, however, there have been contradictory findings regarding the HF-HRV reactivity or recovery to acute stress (Collins et al, 2012; Zulli et al, 2005; Lin et al, 2017c). The inconsistent findings may be due to the heterogeneity in the pathophysiology in individuals with aMCI (Jacquemont et al, 2017).…”

“…The function of parasympathetic nervous system, both reactivity and recovery, reflects an individual's adaptation to stress. The ECG data was processed in HRV software (Mindware) as described previously (Berntson et al, 1997; Lin et al, 2017a). The first and last minute of each recording were excluded to avoid potential noise and intervals between R peaks were preprocessed to remove ectopic beats and artifacts.…”

Engagement in Lifestyle Activities is Associated with Increased Alzheimer’s Disease-Associated Cortical Thickness and Cognitive Performance in Older Adults

“…Automated cortical parcellation and region of interest (ROI) definition were performed using the Desikan-Killiany Atlas, which manually labelled 34 cortical ROIs in each hemisphere [54]. AD signature cortical thickness was defined by averaging cortical thickness of the entorhinal cortex, inferior temporal lobes, middle temporal lobes, and fusiform gyrus, a lower value indicating more severe AD pathology [25,55].…”