Dynamic Regulation of Cerebral Blood Flow in Patients With Alzheimer Disease

Abstract

Cerebral autoregulation and baroreflex sensitivity are key mechanisms that maintain cerebral blood flow. This study assessed whether these control mechanisms are affected in patients with dementia and mild cognitive impairment due to Alzheimer disease, as this would increase the risks of antihypertensive treatment. We studied 53 patients with dementia (73.1 years [95% confidence interval (CI), 71.4-74.8]), 37 patients with mild cognitive impairment (69.2 years [95% CI, 66.4-72.0]), and 47 controls (69.4 years [95% CI, 68.3-70.5]). Beat-to-beat blood pressure (photoplethysmography), heart rate, and cerebral blood flow velocity (transcranial Doppler) were measured during 5-minute rest (sitting) and 5 minutes of orthostatic challenges, using repeated sit-to-stand maneuvers. Cerebral autoregulation was assessed using transfer function analysis and the autoregulatory index. Baroreflex sensitivity was estimated with transfer function analysis and by calculating the heart rate response to blood pressure changes during the orthostatic challenges. Dementia patients had the lowest cerebral blood flow velocity (=0.004). During rest, neither transfer function analysis nor the autoregulatory index indicated impairments in cerebral autoregulation. During the orthostatic challenges, higher autoregulatory index (=0.011) and lower transfer function gain (=0.017), indicating better cerebral autoregulation, were found in dementia (4.56 arb. unit [95% CI, 4.14-4.97]; 0.59 cm/s per mm Hg [95% CI, 0.51-0.66]) and mild cognitive impairment (4.59 arb. unit [95% CI, 4.04-5.13]; 0.51 cm/s per mm Hg [95% CI, 0.44-0.59]) compared with controls (3.71 arb. unit [95% CI, 3.35-4.07]; 0.67 cm/s per mm Hg [95% CI, 0.59-0.74]). Baroreflex sensitivity measures did not differ between groups. In conclusion, the key mechanisms to control blood pressure and cerebral blood flow are not reduced in 2 stages of Alzheimer disease compared with controls, both in rest and during orthostatic changes that reflect daily life challenges.

Impaired cerebral autoregulation is associated with poststroke cognitive impairment

“…32,33 The possible mechanism behind this phenomenon is neurovascular unit dysfunction in small vessel disease, 34 which is consistent with the finding that VLF phase shift is the optimal CA index for predicting poststroke cognitive impairment. Patients with AD were found to have normal CA, 35 which is consistent with the lack of association between CA and lobar microbleeds observed in the current study. Therefore, CA is likely independent of AD-related pathology.…”

Autonomic function in amnestic and non-amnestic mild cognitive impairment: spectral heart rate variability analysis provides evidence for a brain–heart axis

“…In fact, despite substantive evidence of bottom-up modulation of cortical activity by the central nervous branch of the baroreceptor as well as of top-down influences of rostral brain units on the baroreflex loop, studies on baroreflex sensitivity in cognitive impairment are scarce 99 . Also, findings are inconsistent, with both decreased 100 and unchanged 21,87 baroreflex sensitivity reported in AD-related MCI and dementia.…”

“…Indeed, there are numerous reports of no difference in the HR response to an orthostatic challenge in subjects with MCI or even AD dementia (e.g. 21,86,87 ). Second, in our study the standing HR (and HRV) was determined from an ECG segment between the 5th and 10th minute of active standing.…”

The Assessment of Cerebrovascular Response to a Language Task from the Addenbrooke’s Cognitive Examination in Cognitive Impairment: A Feasibility Functional Transcranial Doppler Ultrasonography Study

“…Despite these findings at a microvascular level, studies of vessel function in dementia and MCI remain mixed [ 6, 7, 9 ]. In a recent study, despite lower resting CBFv in dementia, cerebral autoregulation was better in dementia compared to healthy controls [ 34 ]. However, while dynamic cerebral autoregulation appears to remain intact, a number of meta-analyses have consistently shown lower resting flow velocities, higher vessel resistance, and lower vasoreactivity in cognitive impairment [ 6, 7, 9 ].…”