This study demonstrates that a decrease in the magnitude of nighttime dipping in systolic and pulse pressures is associated with greater brain atrophy. This atrophy preferentially affects the fronto-parietal region and is independent of stroke. Both, dipping of lesser magnitude and brain atrophy are associated with slower gait speed, worse IADL, and worse functional outcome post stroke. In contrast, higher blood pressure is associated with lower brain perfusion without affecting brain atrophy and with executive cognitive function.
Our study suggests that nighttime dipping in blood pressure rather than the overall blood pressure averages is associated with brain atrophy. Similar to our finding, Nagai et al has also shown that nighttime dipping is correlated with overall brain atrophy in elderly hypertensives27
. Goldstein et al demonstrated that greater 24-hour SBP variability is associated with greater brain atrophy independent of age. 3
Although we have found that this association is significant in stroke and non-stroke individuals, prior stroke modulated this relationship in the affected hemisphere. In those with prior hemispheric stroke, the association was related to gray matter loss rather than white matter.
Prior evidence has suggested that casual elevation in blood pressure is associated with lower cerebral blood flow28
. This study adds evidence that higher 24-hour SBP and PP, but not DBP, averages are associated with lower brain perfusion measured by CASL-MRI. Since no association was noted with brain volume, the observed association is more likely to be related to vascular changes in the cerebral circulation that lead to decreased brain perfusion.
Both hypertension and brain atrophy are associated with overall loss of physical and cognitive function29–31
. Our study suggests that blood pressure dipping of lesser magnitude is also associated with slower gait speed. Conceptually, nighttime dipping which is commonly seen in hypertensives32
is associated with brain tissue atrophy which leads to poor physical function. In contrast, the elevated blood pressure-poor executive function noted in our study and others31, 33
could be related to lower cerebral perfusion. Because of the cross sectional nature of our study, these pathways cannot be fully confirmed and warrant further exploration.
PP is closely correlated with arterial stiffness34
and nighttime PP is associated with increased stroke risk.35
In this study, we provide new evidence that dipping of lesser magnitude in PP is associated with greater atrophy and elevated PP is associated with reduced perfusion. These PP associations are particularly significant in those with prior stroke. PP hence may be a particularly important factor to address in managing those with stroke.
The possible mechanisms of these associations are not clear. It is possible that, lack of adequate nocturnal dipping leads to pathological vascular changes which eventually lead to neuronal death and hence white matter atrophy. It is also possible that in those with stroke, hormonal or structural changes predispose the gray matter to the lower nocturnal dipping in blood pressure.
The clinical implication of this study is that nocturnal dipping may be as important if not more important than the absolute elevation of blood pressure in the evaluation of high risk individuals. Circadian blood pressure changes may provide additional risk stratification for this population.
The advantage of this study is the simultaneous measurements of brain volumes and perfusion using CASL-MRI. Including both stroke and non-stroke participants allowed us to explore the role of stroke in the blood pressure-brain relation. One limitation of our study is its cross sectional design. We cannot describe the temporal relationship between ABPM, brain atrophy and perfusion, and functional measures. The temporal lag between the 24h ABPM and performing the MRI (3 hours) may have affected our results. There were no significant differences between ABPM measurements and blood pressures during the MRI procedures. Another concern in this study, as in most studies that involve hypertensives, is the short and longterm effects of hypertension treatment on the outcome measures. This may have also lead to a misclassification of participants with respect to their hypertension status. In our study, we attempted at addressing the short-term effect by stopping antihypertensives, albeit for a short time for safety reasons. We also did not see any association between use of antihypertensives and brain volume or perfusion, suggesting that this effect is not critical for our brain outcomes. Finally, our sample size might have precluded us from identifying existing associations between ABPM, MRI and function measures.