| dc.description.abstract | Sufficient cerebral blood flow (CBF) is critical for brain health and normal cognitive function, and cerebral hypoperfusion is implicated as a pathway to cognitive decline, as well as other adverse outcomes such as falls, and syncope. Age-related changes in cardiovascular physiology, including autonomic function, may contribute to disrupted CBF and CBF regulation via impaired blood pressure (BP) regulation. However, the relationship between impaired BP regulation and cerebral haemodynamics remains unclear, especially in older age. In particular, orthostatic hypotension (OH) and hypertension, two clinical manifestations of cardiovascular ageing and impaired BP regulation may modify cerebral haemodynamics in older adults and impact brain health. Hypertension and OH can also co-exist and there is evidence of greater cognitive dysfunction in individuals with the two conditions, where cerebral hypoperfusion may be a possible pathway. With a rapidly growing ageing population, identifying those at risk of cerebral hypoperfusion is critical for early intervention, as well as for health-related planning and policy decisions. It is also crucial to understand this relationship between cerebral haemodynamics and BP in the context of the promotion of intensive BP lowering, particularly given that older adults and those with comorbidities are often excluded from relevant random control trials.
Technological advancements, such as non-invasive continuous BP monitors, have allowed for the improved assessment of orthostatic BP. Current evidence has demonstrated that impaired BP stabilization after standing is common, and the prevalence increases significantly with age. However, whether this translates to cerebral hypoperfusion is yet to be elucidated, not least due to the non-linear nature of cerebral autoregulation. Many large trials and current studies of orthostatic BP rely on discrete BP measurements as opposed to continuous measurements, and many lack objective measures of cerebral haemodynamics. Other studies which employed continuous measurements have lacked statistical power, had limited age ranges, low numbers of females or excluded other cohorts of interest. Transcranial Doppler ultrasound is the predominant method for assessing cerebral haemodynamics, with a small number of studies utilizing near infrared spectroscopy (NIRS). However, there is a lack of comprehensive population data for NIRS, hampering its widespread use, despite it being more accessible and easier to use.
The primary aim of this study was to examine cerebral haemodynamics across a continuum of ages in large cohort sufficiently powered to detect sex differences. It was hypothesized that cerebral haemodynamics are modified by cardiovascular risk factors, and the influence of hypertension and OH as manifestations of impaired BP regulation were investigated. The relationship with cognitive performance was also examined. Data from the Irish Longitudinal Study on Ageing was utilized. Two experimental paradigms were employed: (i) five minutes of supine rest and (ii) an active stand challenge, during which NIRS measured cerebral oxygenation at the frontal lobe and non-invasive continuous BP was recorded simultaneously. Study 1 estimated normative values of cerebral oxygenation for the older adult population whilst Study 2 characterized the cerebrovascular response to orthostasis. Study 3 evaluated the influence of supine hypertension on the orthostatic cerebral response. Study 4 probed the effect of co-existing supine hypertension and OH on the orthostatic cerebral response. Finally, in Study 5, the relationship between resting-state cerebral oxygenation and cognitive performance was examined, both cross-sectionally and longitudinally.
The main findings demonstrated the presence of a clear age gradient and sex differences in both resting-state and orthostatic cerebral haemodynamics. Cerebral oxygenation at rest declined with increasing age. During the active stand challenge older age groups had a larger initial drop in cerebral oxygenation, a slower recovery and impaired stabilization. Oxygenation levels at rest were significantly lower in males than females, across all ages. Females experienced a smaller drop in oxygenation compared to males. However, impaired stabilization was more marked in women. As hypothesized, decreased resting-state cerebral oxygenation was associated with a higher cardiovascular disease burden, behavioural risk factors, and poorer cognitive performance.
An impaired orthostatic cerebrovascular recovery was associated with the use of antihypertensive medications. However, orthostatic symptoms did not correlate with an impaired cerebral response, highlighting the requirement for objective measures of cerebral haemodynamics to identify individuals experiencing transient cerebral hypoperfusion episodes.
Participants with supine hypertension experienced a larger drop in BP upon standing and impaired stabilization, graded by severity of supine hypertension. Of great clinical significance, the absolute BP value was found to be a predictor of cerebral oxygenation levels (as opposed to the relative size of the BP drop), suggesting that those with OH risk cerebral hypoperfusion, but that the cerebral autoregulatory systems adapts to the higher BP in those with hypertension. These findings are relevant and topical in the context of aggressive BP lowering targets and will be of interest to clinicians implementing the BP lowering guidelines, managing hypertension, as well as orthostatic hypotension, and identifying those at risk for falls.
In addition, we have provided normative reference values and characterization of the NIRS responses, allowing for the comparison of individual data to population data for the same age range and sex, advancing the use of NIRS as a clinical and research tool.
In summary, sufficient CBF is vital for brain health and early identification of those at risk of cerebral hypoperfusion is critical. This research highlights the need for objective measures of cerebral haemodynamics in the clinic and in future therapeutic studies or trials, to identify individuals at risk and to fully understand the relationship between cerebral oxygenation, medications, supine BP, OH and symptoms. | en |
