Synopsis

Keywords: Neurodegeneration, Perfusion, sleep, aging

We applied multi-echo Hadamard encoded ASL imaging to study blood flow (CBF) and trans-endothelial exchange of water (T_ex) as markers of vascular function to study two common risk factors of dementia; aging and sleep deprivation. We found that older adults had significantly lower CBF, and shorter T_ex compared to young adults. In the same young adults, we compared CBF and T_ex after a normal night of sleep and after sleep deprivation. Both CBF and T_ex were insignificantly lower when measured after sleep deprivation compared to measurements after normal sleep.

PURPOSE

The exchange of solutes as well as water transport across the endothelium are important components for maintaining vascular function and brain health¹. This is especially true in aging where vascular dysfunction increases risk of cognitive impairment and dementia. In this study, we explore application of a multi-echo Hadamard-encoded multi-delay arterial spin labeling (ASL) scheme to measure, cerebral blood flow (CBF), and endothelial exchange time (T ) under two conditions: aging and sleep deprivation^2,3. We, therefore, tested the hypothesis that older adults have lower CBF (reduced perfusion), and shorter T_ex (leakier vessels resulting in faster exchange over the endothelium) compared to young adults. Furthermore, poor sleep quality and prolonged sleep restriction adversely affect cognitive function, and it is yet unclear whether acute sleep deprivation also affects cognitive function and whether such a change would be mediated by change in vascular function. Hence, we compared CBF, and T_ex in the younger adults following a night of normal sleep and a night of sleep deprivation. Our second hypothesis is that after only one night of sleep deprivation, even young adults will have lower CBF and shorter T_ex.

METHODS

Experiment: Per institutional review board guidelines, ten older adults (66±3 years old, 4F) were scanned for this study. In addition, eleven young adults (22±3 years old, 5F) underwent a night of full sleep and a night of sleep deprivation. Of these, eight individuals completed both the full sleep and sleep deprivation scans. All individuals completed two cognitive tests in the morning prior to their MRI scan: General Practitioner’s assessment of cognition (GPCOG) and Memory Impairment Screen (MIS). The MRI protocol on a 3T Philips Ingenia Elition X scanner with a 32-channel head-coil: T1: we acquired a standard 1×1×1 mm³ anatomical protocol with TR/TE = 9.2/3.5. ASL: 4-block Hadamard encoded ASL with T2-prep pulses allowed for a multi-echo (TE = 0, 40, 80, 120 ms), multi-delay ASL acquisition with resolution = 3.75×3.75×5 mm³, slices = 18, label duration = 3.4 s, three effective post labeling delay = 0.65, 1.21, and 2.08 s, background suppression. A multi-echo acquisition for M0 images with identical resolution and TEs, but no labeling or background suppression was also acquired. Analysis: After rearranging data, the multi-delay ASL images were used to compute CBF and arterial arrival times using FSL, and the multi-echo ASL images were used to calculate T_ex based on Ohene et al⁴.

RESULTS

In the 10 older adults, GPCOG and MIS scores were 9±1 and 8±0. The eight younger adults showed a marginally significant difference on the GPCOG measures between full sleep (9±0) and sleep deprivation (8±1, p=0.08). No difference was observed on MIS (8±0) with changes in sleep. The multi-echo acquisition of the M0 images and the perfusion-weighted images at each of the three delay times are shown in Figure 1. CBF and T_ex maps for a representative old participant and a young participant with normal sleep and sleep deprivation are shown in Figure 2. Cortical CBF (including at least 75% gray matter) in older adults, young adults with normal sleep, and the same young adults after sleep deprivation was 37±3, 41±2, 41±4, ml/100g/min respectively. Similarly, T_ex values were 474±74, 609±49, 602±75 ms in the three groups respectively. The older participants had a significantly (p<0.001) lower CBF and shorter T_ex compared to the young adults after full sleep. The young adults with sleep deprivation showed similar CBF and T_ex compared to their values after a proper night of sleep. No significant association between T_ex and cognition was observed in older adults or young adults. No significant association of CBF with cognition was detected with aging or after sleep modulation. However, percent difference in T_ex values ((full sleep - sleep deprivation)/full sleep)) in the young adults was associated with corresponding percent difference in cognition (r = 0.70, p = 0.02, Figure 3).

DISCUSSION

CBF and Tex were significantly reduced in older adults. Differences in CBF and T_ex were not significant different after a night of sleep, but the observed change of T_ex was related to difference on our cognitive tests. This might point towards poorer aquaporin-4 functioning after sleep deprivation affecting cognitive abilities, although this interpretation should be considered to be highly speculative. Furthermore, cognitive tests, sensitive to sleep-related cognitive deficits should be used in the future.

CONCLUSION

Similar to many prior studies, here we confirm that CBF reduced with aging. In addition, we show that T_ex is reduced i.e., water moves across the endothelium much faster with aging. These results are similar to those observed in studies of mice⁵. Contrary to our expectations, decreases in CBF and T_ex were not observed after sleep deprivation. It is likely in acute settings of sleep deprivation, changes in vascular function are minimal and in line with observed minimal changes in cognition. Other reasons could be that our sample size was too small or that our approach is not sensitive enough to detect subtle changes such as those observed with only one night of sleep deprivation.

Acknowledgements

No acknowledgement found.