Regional Cerebrovascular Reactivity and Cognitive Performance in Healthy Aging

Sarah J Catchlove, Todd B Parrish, Yufen Chen, Helen Macpherson, Matthew E Hughes, Andrew Pipingas, Sarah J Catchlove, Todd B Parrish, Yufen Chen, Helen Macpherson, Matthew E Hughes, Andrew Pipingas

Abstract

Cerebrovascular reactivity (CVR) reflects the response of brain blood vessels to vasoactive stimuli, such as neural activity. The current research assessed age-related changes in regional CVR to 5% CO2 inhalation in younger (n = 30, range: 21-45 years) and older (n = 29, range: 55-75 years) adults, and the contribution of regional CVR to cognitive performance using blood-oxygen-level dependent contrast imaging (BOLD) functional magnetic resonance imaging (fMRI) at 3T field strength. CVR was measured by inducing hypercapnia using a block-design paradigm under physiological monitoring. Memory and attention were assessed with a comprehensive computerized aging battery. MRI data analysis was conducted using MATLAB® and SPM12. Memory and attention performance was positively associated with CVR in the temporal cortices. Temporal lobe CVR influenced memory performance independently of age, gender, and education level. When analyzing age groups separately, CVR in the hippocampus contributed significantly to memory score in the older group and was also related to subjective memory complaints. No associations between CVR and cognition were observed in younger adults. Vascular responsiveness in the brain has consequences for cognition in cognitively healthy people. These findings may inform other areas of research concerned with vaso-protective approaches for prevention or treatment of neurocognitive decline.

Keywords: Cerebrovascular reactivity; cognition; healthy aging; magnetic resonance imaging (MRI); memory.

Conflict of interest statement

Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Percentage change in etCO2 and BOLD signal in the temporal lobe ROI in response to the hypercapnic challenge. Each marker on the x-axis represents 3 seconds (1 TR). BOLD traces have been shifted to the right-young by 9 seconds (3 TR), and older by 18 seconds (6 TR), which yielded the maximum cross-correlation between etCO2 and BOLD signals for this ROI. Lines representing younger and older adults are displayed in different colors. Shaded area indicates the hypercapnia period. The etCO2 data points extracted for CVR analysis are indicated by the black lines below the x-axis. To calculate CVR, BOLD data points were extracted and averaged across a 30 second period during hypercapnia and final 30 seconds of the baseline period preceding gas-inhalation separately by group (66-96 seconds after the CO2-inhalation began in the younger group and 72-102 seconds in the older group). After aligning the signals at the maximum cross-correlation, the time from the gas-inhalation onset to 50% of the maximum BOLD signal change was calculated for each group for the temporal lobe ROI, younger 47 seconds, and older 51 seconds, though an independent-samples t-test showed that these differences were not significant (P = .52).
Figure 2.
Figure 2.
Regional CVR values for younger and older adults. Mean cerebrovascular reactivity values for ROIs averaged across groups. GM grey matter. All ROIS were bilateral, masked with a grey matter mask with a 50% probability threshold. **P < .01.
Figure 3.
Figure 3.
Scatterplot showing the relationship between CVR in the temporal lobes and memory reaction times for the entire sample. Data for younger and older groups are shown in different colors. Black line indicates trend for whole sample data. An adjusted linear regression analysis showed the temporal lobe CVR predicted memory score independent of age, gender and education (P < .01).
Figure 4.
Figure 4.
Experimental design of the hypercapnia scans. 5% CO2 inhalation was used to induce hypercapnia. Blue line indicates the period where baseline etCO2 data were collected, orange line indicates the period where hypercapnia etCO2 data was collected. The BOLD data points were extracted from the average point of maximum signal change across all ROIs to the 30 seconds preceding. This equated to the sampled BOLD data points during the hypercapnia period being selected from 66 to 96 seconds after CO2 switched on in the younger group, and 72-102 seconds after CO2 switched on in the older group.
Figure 5.
Figure 5.
Breathing apparatus (a) 100 L Douglas bag, (b) 3-way valve, (c) 2-way non-rebreathing valve, (d) nose-clip, (e) filter (gas-sampling tube attaches here, not shown), and (f) mouth-piece.
Figure 6.
Figure 6.
MRI slice positioning and brain regions of interest (ROIs) (A) sagittal view, (B) coronal view, and (C) ROIs included the bilateral parietal, occipital, frontal, temporal, insula, hippocampus and cingulum.

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