Age-related changes in cerebrovascular reactivity and their relationship to cognition: A four-year longitudinal study

Abstract

Although cerebrovascular factors are the second leading cause of cognitive impairment and dementia in elderly, the precise spatial and temporal trajectories of vascular decline in aging have not been fully characterized. With an advanced cerebrovascular reactivity (CVR) MRI technique that specifically informs vascular stiffness and dilatory ability of cerebral vessels, we present four-year longitudinal CVR data measured in 116 healthy individuals (20-88 years of age). Our data revealed a spatial heterogeneity in vascular decline in aging (p = 0.003), in that temporal lobe showed the fastest rate of longitudinal CVR decline, followed by parietal and frontal lobes. The rate of CVR decline was also age-dependent. Middle age, not older age, manifested the fastest rate of longitudinal CVR decline (p < 0.05). Longitudinal changes in CVR were associated with changes in processing speed (p = 0.031) and episodic memory (p = 0.022), but not with working memory or reasoning. The rate of longitudinal CVR change was not different between hypertensive and normotensive participants. However, cross-sectionally, individuals with hypertension revealed in a lower CVR compared to normotensive participants (p = 0.016). These findings help elucidate age-related decline in brain hemodynamics and support CVR as a non-invasive biomarker in evaluating cerebrovascular conditions in elderly individuals.

Keywords: Age; BOLD; Cerebrovascular reactivity; Cognition; Hypercapnia; Hypertension.

Figure 1

CVR at Wave 1 and Wave 2. (a) Decade-by-decade averaged maps of CVR for Wave 1 and Wave 2. (b) Scatter plot between whole brain gray matter (GM) Wave 1 and Wave 2 CVR values. Each dot represents data from one subject (N=116). Pearson’s correlation coefficient = 0.67 (p<0.001).

Figure 2

The rate of CVR change in major brain lobes. The error bars indicate standard errors. **: p<0.001.

Figure 3

Bar plots of longitudinal CVR decline rate stratified by age groups. The total of 116 participants were divided into three age ranges, 20–40 years old (N=36), 41–60 years old (N=41), and 61 and above (N=39). The CVR decline rate showed a quadratic dependence on age in temporal lobe (left panel, p=0.027) and (b) occipital lobe (right panel, p=0.015). The error bars indicate standard errors.

Figure 4

Association between longitudinal changes (over a four-year period) in cognition and whole brain GM CVR. (a): processing speed. (b): episodic memory.

Figure 5

Comparison of whole brain GM CVR among normotensive subjects (N=58), subjects who are currently hypertensive (HTN_current) (N=21), and subjects who have a past history of hypertension (HTN_past) (N=14). The error bars indicate standard errors. *: p<0.05.