Cerebrovascular Reactivity, Brain Structure, and Cognition in Aging: Heart and Brain Study

1199 

Abstract Submission 

Congxiyu Wang^1,2, Raihaan Patel^1,2, Lucy Jobbins³, Clare Mackay^1,2, Graham Reid¹, Georgina Hobden⁴, Klaus P. Ebmeier^1,5, Daniel Bulte⁶, Sana Suri^1,2

¹Department of Psychiatry, University of Oxford, Oxford, United Kingdom, ²Oxford Centre for Human Brain Activity (OHBA), Wellcome Centre for Integrative Neuroimaging (WIN), Oxford, United Kingdom, ³Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom, ⁴Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom, ⁵Wellcome Centre for Integrative Neuroimaging (WIN), Oxford, United Kingdom, ⁶Department of Engineering Science, University of Oxford, Oxford, United Kingdom

Congxiyu Wang  
Department of Psychiatry, University of Oxford|Oxford Centre for Human Brain Activity (OHBA), Wellcome Centre for Integrative Neuroimaging (WIN)
Oxford, United Kingdom|Oxford, United Kingdom

Raihaan Patel  
Department of Psychiatry, University of Oxford|Oxford Centre for Human Brain Activity (OHBA), Wellcome Centre for Integrative Neuroimaging (WIN)
Oxford, United Kingdom|Oxford, United Kingdom

Lucy Jobbins  
Nuffield Department of Clinical Neuroscience, University of Oxford
Oxford, United Kingdom

Clare Mackay  
Department of Psychiatry, University of Oxford|Oxford Centre for Human Brain Activity (OHBA), Wellcome Centre for Integrative Neuroimaging (WIN)
Oxford, United Kingdom|Oxford, United Kingdom

Graham Reid  
Department of Psychiatry, University of Oxford
Oxford, United Kingdom

Georgina Hobden  
Department of Experimental Psychology, University of Oxford
Oxford, United Kingdom

Klaus P. Ebmeier  
Department of Psychiatry, University of Oxford|Wellcome Centre for Integrative Neuroimaging (WIN)
Oxford, United Kingdom|Oxford, United Kingdom

Daniel Bulte, Associate Professor  
Department of Engineering Science, University of Oxford
Oxford, United Kingdom

Sana Suri  
Department of Psychiatry, University of Oxford|Oxford Centre for Human Brain Activity (OHBA), Wellcome Centre for Integrative Neuroimaging (WIN)
Oxford, United Kingdom|Oxford, United Kingdom

Cerebrovascular reactivity (CVR) refers to a vasodilation response of brain blood vessels to vasoactive stimuli. Impaired CVR is related to neurodegenerative diseases including dementia (Hayes et al., 2022). However, the mechanisms underlying the relationship between CVR and age-related cognitive impairments remain unclear. As brain atrophy is a biomarker for Alzheimer's Disease and aging (Pini et al., 2016), our study aims to explore the relationships between CVR, grey matter volume, white matter hyperintensities, white matter integrity, and cognitive function in aging. Additionally, we examined the moderating effect of dementia risk, computed using an established score, on these relationships, aiming to inform the potential interventions of the modifiable dementia risk factors in midlife.

We recruited 163 participants (mean age=76.9±4.5) for the Heart and Brain Study (Suri et al., 2021). Participants underwent functional magnetic resonance imaging (MRI) to measure CVR under a 5% carbon dioxide respiratory challenge, structural MRI for grey matter volume (GMV), fluid attenuated inversion recovery for white matter hyperintensities (WMH), and diffusion tensor imaging for assessing white matter integrity (WMI). Cognition was evaluated using a battery of cognitive tests. Participants were stratified into high- or low-risk groups using the UK Biobank Dementia Risk Score (UKBDR) (Anatürk et al., 2023), which estimates midlife (mean age=52.5±4.4) dementia risk using retrospective records. Linear regression was performed to analyse associations between CVR (whole brain and lobe), and the MRI and cognitive outcomes while adjusting for age, sex, and total GMV. We also examined these associations separately for the high- and low-risk groups. Figure1 shows the details about the explanatory and outcome variables.

In all participants, lower whole brain CVR significantly associated with smaller left nucleus accumbens (NAc) (p<0.01) and left thalamus volumes (p<0.05). Lobar analysis showed significant positive associations: parietal CVR with left hippocampus volume (p<0.05); temporal CVR with thalamus volume (p<0.05); frontal CVR with left thalamus and right NAc volumes (p<0.05); occipital CVR with right putamen (p=0.05). When stratifying by risk group, temporal CVR was positively related to left thalamus volume (p<0.05) exclusively in the high-risk group. In the low-risk group, whole brain CVR positively associated with temporoparietal junction volume (p<0.01). Left hippocampus volume positively associated with whole brain, frontal, parietal, and temporal CVR (p<0.05); frontal CVR positively related to right NAc volume (p<0.05). Regarding cognition, lower whole brain CVR was associated with worse fluency (p<0.01, primarily influenced by parietal CVR) and lower intelligence (p<0.05, primarily influenced by temporal CVR) only in the high-risk group. We found no associations between CVR with WMH or WMI in all participants or in either risk group.

This study demonstrates how global and lobar CVR relates to brain structure and cognitive functions, and how these relationships are moderated by dementia risk, contributing to a more comprehensive understanding of cognitive aging. Impaired CVR associates with smaller NAc (reward processing) and smaller thalamus (sensory perception and memory). Significant positive associations between the hippocampus (cognitive processes), temporoparietal junction (social cognition and theory of mind), and CVR were only shown in the low dementia risk group. Conversely, positive associations between fluency and intelligence were evident only in the high dementia risk group. There could potentially be a cerebrovascular-brain structure reserve for individuals with high midlife dementia risk. However, they may exhibit diminished CVR and cognitive function in later life. Future research could explore mediating relationships among midlife dementia risk, vascular health, brain structure, and cognition.

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)

Aging ¹

Anatomy and Functional Systems

Subcortical Structures

Cerebral Metabolism and Hemodynamics ²

Aging

Cognition

MRI

STRUCTURAL MRI

Sub-Cortical

Other - Cerebrovascular reactivity