How measurement artifacts affect cerebral autoregulation outcomes: A technical note on transfer function analysis.

Cerebral autoregulation (CA) is the mechanism that aims to maintain adequate cerebral perfusion during changes in blood pressure (BP). Transfer function analysis (TFA), the most reported method in literature to quantify CA, shows large between-study variability in outcomes. The aim of this study is to investigate the role of measurement artifacts in this variation. Specifically, the role of distortion in the BP and/or CBFV measurementon TFA outcomes was investigated. The influence of three types of artifacts on TFA outcomes was studied: loss of signal, motion artifacts, and baseline drifts. TFA metrics of signals without the simulated artifacts were compared with those of signals with artifacts. TFA outcomes scattered highly when more than 10% of BP signal or over 8% of the CBFV signal was lost, or when measurements contained one or more artifacts resulting from head movement. Furthermore, baseline drift affected interpretation of TFA outcomes when the power in the BP signal was 5 times the power in the LF band. In conclusion, loss of signal in BP and loss in CBFV, affects interpretation of TFA outcomes. Therefore, it is vital to validate signal quality to the defined standards before interpreting TFA outcomes.

Transfer function analysis of dynamic cerebral autoregulation: A white paper from the International Cerebral Autoregulation Research Network.

Cerebral autoregulation is the intrinsic ability of the brain to maintain adequate cerebral perfusion in the presence of blood pressure changes. A large number of methods to assess the quality of cerebral autoregulation have been proposed over the last 30 years. However, no single method has been universally accepted as a gold standard. Therefore, the choice of which method to employ to quantify cerebral autoregulation remains a matter of personal choice. Nevertheless, given the concept that cerebral autoregulation represents the dynamic relationship between blood pressure (stimulus or input) and cerebral blood flow (response or output), transfer function analysis became the most popular approach adopted in studies based on spontaneous fluctuations of blood pressure. Despite its sound theoretical background, the literature shows considerable variation in implementation of transfer function analysis in practice, which has limited comparisons between studies and hindered progress towards clinical application. Therefore, the purpose of the present white paper is to improve standardisation of parameters and settings adopted for application of transfer function analysis in studies of dynamic cerebral autoregulation. The development of these recommendations was initiated by (but not confined to) theCerebral Autoregulation Research Network(CARNet -www.car-net.org).

Between-centre variability in transfer function analysis, a widely used method for linear quantification of the dynamic pressure-flow relation: the CARNet study.

Transfer function analysis (TFA) is a frequently used method to assess dynamic cerebral autoregulation (CA) using spontaneous oscillations in blood pressure (BP) and cerebral blood flow velocity (CBFV). However, controversies and variations exist in how research groups utilise TFA, causing high variability in interpretation. The objective of this study was to evaluate between-centre variability in TFA outcome metrics. 15 centres analysed the same 70 BP and CBFV datasets from healthy subjects (n=50 rest; n=20 during hypercapnia); 10 additional datasets were computer-generated. Each centre used their in-house TFA methods; however, certain parameters were specified to reduce a priori between-centre variability. Hypercapnia was used to assess discriminatory performance and synthetic data to evaluate effects of parameter settings. Results were analysed using the Mann-Whitney test and logistic regression. A large non-homogeneous variation was found in TFA outcome metrics between the centres. Logistic regression demonstrated that 11 centres were able to distinguish between normal and impaired CA with an AUC>0.85. Further analysis identified TFA settings that are associated with large variation in outcome measures. These results indicate the need for standardisation of TFA settings in order to reduce between-centre variability and to allow accurate comparison between studies. Suggestions on optimal signal processing methods are proposed.

Transfer function analysis for the assessment of cerebral autoregulation using spontaneous oscillations in blood pressure and cerebral blood flow.

Cerebral autoregulation (CA) is a key mechanism to protect the brain against excessive fluctuations in blood pressure (BP) and maintain cerebral blood flow. Analyzing the relationship between spontaneous BP and cerebral blood flow velocity (CBFV) using transfer function analysis is a widely used technique to quantify CA in a non-invasive way. The objective of this review was to provide an overview of transfer function techniques used in the assessment of CA. 113 publications were included. This literature showed that there is no gold standard for the execution and implementation of the transfer function. There is a high diversity in settings and criteria used for transfer function analysis. Notable is also the high number of studies which report little on the settings. This disparity makes it difficult to replicate or compare the results of the different studies and further hinders the opportunity to make a distinction between intact and impaired CA in different patient groups. More research on the effects of different implementation techniques on CA results and optimization of the transfer function analysis is urgently needed. Furthermore, international guidelines should be created to inform the minimal description of the applied technique and the interpretation of transfer function outcomes in scientific research.

Impaired systolic blood pressure recovery directly after standing predicts mortality in older falls clinic patients.

BACKGROUND: Normally, standing up causes a blood pressure (BP) drop within 15 seconds, followed by recovery to baseline driven by BP control mechanisms. The prognostic value of this initial BP drop, but also of the recovery hereafter, is unknown. The aim of this study was to examine the prognostic value of these BP characteristics in response to standing. METHODS: In a retrospective cohort study of 238 consecutive patients visiting our falls outpatient clinic, we examined the relation between all-cause mortality and BP decline and recovery directly after active standing up with Cox proportional hazards analyses. RESULTS: Of 238 patients (mean age 78.4 ± 7.8 years), during a median follow-up of 21.0 months, 36 (15%) patients died. Neither absolute nor relative (%) initial BP drop after standing predicted mortality. In contrast, the magnitude of BP recovery 40-60 seconds after standing was associated with mortality, even after adjustment for age, comorbidity, and other baseline characteristics. When systolic BP had recovered to less than 80% of prestanding baseline after 60 seconds of standing, this was a powerful independent predictor of mortality (hazard ratio: 3.00; 95% confidence interval 1.17-7.68). CONCLUSIONS: Failure to recover from BP decline in the first minute after active standing up is associated with excess mortality in falls clinic patients. A recovery of systolic BP to less than 80% of baseline after 60 seconds may be used as an easily available cardiovascular marker for increased mortality risk in older falls clinic patients.

Very-low-frequency oscillations of cerebral hemodynamics and blood pressure are affected by aging and cognitive load.

Spontaneous slow oscillations occur in cerebral hemodynamics and blood pressure (BP), and may reflect neurogenic, metabolic or myogenic control of the cerebral vasculature. Aging is accompanied by a degeneration of the vascular system, which may have consequences for regional cerebral blood flow and cognitive performance. This degeneration may be reflected in a reduction of spontaneous slow oscillations of cerebral hemodynamics and BP. Therefore, we aimed to establish the dependency of slow oscillations of cerebral hemodynamics and BP on the factors age and cognitive load, by using functional near-infrared spectroscopy (fNIRS). Fourteen healthy young (23-32 years) and 14 healthy older adults (64-78 years) performed a verbal n-back working-memory task. Oxygenated and deoxygenated hemoglobin concentration changes were registered by two fNIRS channels located over left and right prefrontal cortex. BP was measured in the finger by photoplethysmography. We found that very-low-frequency oscillations (0.02-0.07 Hz) and low-frequency oscillations (0.07-0.2 Hz) of cerebral hemodynamics and BP were reduced in the older adults compared to the young during task performance. In young adults, very-low-frequency oscillations of cerebral hemodynamics and BP reduced with increased cognitive load. Cognitive load did not affect low-frequency oscillations of the cerebral hemodynamics and BP. Transfer function analysis indicated that the relationship between BP and cerebral hemodynamic oscillations does not change under influence of age and cognitive load. Our results suggest aging-related changes in the microvasculature such as declined spontaneous activity in microvascular smooth muscle cells and vessel stiffness. Moreover, our results indicate that in addition to local vasoregulatory processes, systemic processes also influence cerebral hemodynamic signals. It is therefore crucial to take the factors age and BP into consideration for the analysis and interpretation of hemodynamic neuroimaging data.

Geriatric hypotensive syndromes are not explained by cardiovascular autonomic dysfunction alone.

BACKGROUND: Though highly prevalent, the pathophysiology of orthostatic hypotension (OH), postprandial hypotension (PPH), and carotid sinus hypersensitivity (CSH) are rarely studied together. Therefore, we conducted such a comprehensive study focusing on the common role of the cardiovascular autonomic system. We hypothesized that in geriatric patients, OH, PPH, and CSH are manifestations of cardiovascular autonomic dysfunction and investigated state-of-the-art cardiovascular autonomic function indices in a group of geriatric falls or syncope patients. METHODS: In a cross-sectional study of 203 consecutive eligible falls clinic patients, we compared heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) as potential autonomic function determinants of the three different hypotensive syndromes. RESULTS: OH, PPH, and CSH were diagnosed in 53%, 57%, and 50% of the patients, respectively. In a population relevant for geriatric practice, we found no differences in HRV, BPV, and BRS between patients with and without OH, with and without PPH, and with and without CSH, respectively, nor between patients with and without falls, dizziness, or syncope as presenting symptom, respectively. CONCLUSIONS: In geriatric patients with hypotensive syndromes, cardiovascular autonomic function as measured by HRV, BPV, and BRS is comparable to patients without such syndromes. These findings argue against a single or dominant etiological factor, that is, cardiac autonomic dysfunction and underline the structured, broad, and multifactorial approach to elderly patients with falls and/or syncope as proposed in the current evidence-based syncope guidelines.

Baroreflex function is reduced in Alzheimer's disease: a candidate biomarker?

The baroreflex (BR) reflects autonomic blood pressure control. Alzheimer's disease (AD) affects the autonomic system. Detailed properties of BR in AD are unknown. We hypothesized that BR is reduced in AD, and is influenced by autonomic effects of cholinesterase inhibitors (ChEI). BR was determined in 18 AD patients, 11 patients with mild cognitive impairment (MCI) and 19 healthy control subjects. In AD, BR was measured again after ChEI treatment. Receiver operating characteristic analysis was used to define a BR cutoff value, which was then tested in an independent validation sample of 16 AD, 18 MCI, and 18 control subjects. BR was lower in AD compared with MCI (p < 0.05) and in MCI compared with healthy control subjects (p < 0.01). Receiver operating characteristic analysis between AD and healthy control subjects yielded a sensitivity of 89% and a specificity of 94%. ChEI treatment increased BR with 66% (p < 0.01). BR was reduced in AD and increased after treatment with ChEI. BR might be a good biomarker to further explore the link between cardiovascular disease and AD.