Functional magnetic resonance imaging (fMRI) has been used to infer age-differences in neural activity from the hemodynamic response function (HRF) that characterizes the blood-oxygen-level-dependent (BOLD) signal over time. BOLD literature in healthy aging lacks consensus in age-related HRF changes, the nature of those changes, and their implications for measurement of age differences in brain function. Between-study discrepancies could be due to small sample sizes, analysis techniques, and/or physiologic mechanisms. We hypothesize that, with large sample sizes and minimal analysis assumptions, age-related changes in HRF parameters could reflect alterations in one or more components of the neural-vascular coupling system. To assess HRF changes in healthy aging, we analyzed the large population-derived dataset from the Cambridge Center for Aging and Neuroscience (CamCAN) study (Shafto et al., 2014). During scanning, 74 younger (18–30 years of age) and 173 older participants (54–74 years of age) viewed two checkerboards to the left and right of a central fixation point, simultaneously heard a binaural tone, and responded via right index finger button-press. To assess differences in the shape of the HRF between younger and older groups, HRFs were estimated using FMRIB’s Linear Optimal Basis Sets (FLOBS) to minimize a priori shape assumptions. Group mean HRFs were different between younger and older groups in auditory, visual, and motor cortices. Specifically, we observed increased time-to-peak and decreased peak amplitude in older compared to younger adults in auditory, visual, and motor cortices. Changes in the shape and timing of the HRF in healthy aging, in the absence of performance differences, support our hypothesis of age-related changes in the neural-vascular coupling system beyond neural activity alone. More precise interpretations of HRF age-differences can be formulated once these physiologic factors are disentangled and measured separately.

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Background: Cognitive slowing occurs in ~70% of multiple sclerosis (MS) patients. The pathophysiology of this slowing is unknown. Neurovascular coupling, acute localized blood flow increases following neural activity, is essential for efficient cognition. Loss of vascular compliance along the cerebrovascular tree would result in suboptimal vasodilation, neurovascular uncoupling, and cognitive slowing. Objective: To assess vascular compliance along the cerebrovascular tree and its relationship to MS-related cognition. Methods: We tested vascular compliance along the cerebrovascular tree by dividing cerebral cortex into nested layers. MS patients and healthy controls were scanned using a dual-echo functional magnetic resonance imaging (fMRI) sequence while they periodically inhaled room air and hypercapnic gas mixture. Cerebrovascular reactivity was calculated from both cerebral blood flow (arterial) and blood-oxygen-level-dependent signal (venous) increases per unit increase in end-tidal CO2. Results: Arterial cerebrovascular reactivity changes along the cerebrovascular tree were reduced in cognitively slow MS compared to cognitively normal MS and healthy controls. These changes were fit to exponential functions, the decay constant (arterial compliance index; ACI) of which was associated with individual subjects’ reaction time and predicted reaction time after controlling for disease processes. Conclusion: Such associations suggest prospects for utility of ACI in predicting future cognitive disturbances, monitoring cognitive deficiencies and therapeutic responses, and implicates neurovascular uncoupling as a mechanism of cognitive slowing in MS.

Purpose: Cerebrovascular reactivity (CVR) is an index of the dilatory function of cerebral blood vessels and has shown great promise in the diagnosis of risk factors in cerebrovascular disease. Aging is one such risk factor; thus, it is important to characterize age-related differences in CVR. CVR can be measured by BOLD MRI but few studies have measured quantitative cerebral blood flow (CBF)-based CVR in the context of aging. This study aims to determine the age effect on CVR using two quantitative CBF techniques, phase-contrast (PC), and arterial spin labeling (ASL) MRI. Methods: In 49 participants (32 younger and 17 older), CVR was measured with PC, ASL, and BOLD MRI. These CVR methods were compared across young and older groups to determine their dependence on age. PC and ASL CVR were also studied for inter-correlation and mean differences. Gray and white matter CVR values were also studied. Results: PC CVR was higher in younger participants than older participants (by 17%, p = 0.046). However, there were no age differences in ASL or BOLD CVR. ASL CVR was significantly correlated with PC CVR (p = 0.042) and BOLD CVR (p = 0.016), but its values were underestimated compared to PC CVR (p = 0.045). ASL CVR map revealed no difference between gray matter and white matter tissue types, whereas gray matter was significantly higher than white matter in the BOLD CVR map. Conclusion: This study compared two quantitative CVR techniques in the context of brain aging and revealed that PC CVR is a more sensitive method for detection of age differences, despite the absence of spatial information. The ASL method showed a significant correlation with PC and BOLD, but it tends to underestimate CVR due to confounding factors associated with this technique. Importantly, our data suggest that there is not a difference in CBF-based CVR between the gray and white matter, in contrast to previous observation using BOLD MRI.