Cerebrovascular reserve differentiates cognitively normal older adults from individuals with mild cognitive impairment

Abstract Background Abnormal cerebral blood flow (CBF) is observed in early Alzheimer’s disease. Cerebrovascular reserve (CVR) represents the ability of the vasculature to maintain normal CBF. While CBF abnormalities can indicate a primary vascular dysfunction, it could also arise secondary to neurodegeneration and reduced metabolic demands. CVR, on the other hand, is a specific marker of vascular insufficiency. Our goal was to evaluate the associations between CVR, CBF, and cognition in older adults with and without MCI. Methods 70 older adults (>65 years 77.3 ± 8.32 years old, 42F, 46 controls i.e., NC and 24 MCI) were scanned in compliance with Institutional Review Board guidelines. Besides a T1 scan, we performed pCASL to quantify baseline CBF and a breath‐hold BOLD fMRI experiment to quantify CVR. We use a mixed‐effects model in FSL to test CVR and CBF differences between groups as well as association with cognitive tests, i.e., Montreal Cognitive Assessment (MoCA), Immediate and Delayed recall (CRAFTi/d) and Trails‐B, using Gaussian random field theory for a cluster‐wise threshold of p = 0.05. All comparisons were adjusted for age and gender. Results Only CVR was significantly (p<0.05) different between NC and MCI (Figure 1). While there was no group difference in CBF, the group difference between CVR was no longer significant when adjusted for baseline CBF. Investigating further, high CBF was significantly associated with lower CVR in the MCI group only. A high CBF was very weakly related to high CVR in NC (Figure 2). A high CVR was associated with a high MoCA score (Figure 3) and CRAFTi/d (Figure 4). Conclusion We demonstrated the utility of a simple breath‐hold based CVR measurement in understanding the association between vascular mechanisms and cognition. It is likely that CBF is not different between groups because MCI participants utilize their vascular reserve to maintain baseline CBF. Consequently, an additional vascular challenge results in a lower CVR measurement. Furthermore, a higher CVR in MCI subjects such as that seen in association with cognitive tests could be a result steal phenomenon to redirect perfusion from degenerating tissue to viable tissue. However, these mechanisms need to be further investigated.

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