Age and sex related differences in orthostatic cerebral oxygenation: Findings from 2764 older adults in the Irish Longitudinal Study on Ageing (TILDA)

Aims: Cerebral hypoperfusion is implicated in the pathogenesis of associations between orthostatic hypotension and adverse outcome such as falls, cognitive impairment, depression, and mortality. Although the blood pressure response to orthostasis has been well studied there is a lack of information on orthostatic cerebrovascular responses in older populations. Methods and results: We measured cerebral hemodynamics, utilizing near infrared spectroscopy, coupled with peripheral blood pressure during an active stand in a large population of well-phenotyped older adults (N = 2764). Multi-level mixed effect models were utilized to investigate associations with age and sex, as well as confounders including anti-hypertensive medications. Normative cerebral oxygenation responses were also modelled utilizing generalized additive models for location, scale, and shape (GAMLSS). Older age groups experienced larger initial drops in oxygenation and a slower recovery, and responses also differed by sex. The drop after standing ranged from 1.85 % (95 % confidence interval (CI): -2.02 to -1.68) in the males aged 54-59 years vs -1.15 % (95 % CI: -1.31 to 1.00) in females aged 54-59 years, to -2.67 % (95 % CI: -3.01 to -2.33) in males aged >= 80 years vs -1.97 % (95 % CI: -2.32 to -1.62) females aged >= 80 years. Reduced oxygenation levels were also evident in those taking anti-hypertensive medications. Conclusion: Cerebral autoregulation is impaired with age, particularly in older women and those taking anti-hypertensives. SBP during the stand explained some of the age gradient in the late recovery stage of the stand for the oldest age group. Reported orthostatic symptoms did not correlate with hypoperfusion. Therefore, measures of orthostatic cerebral flow should be assessed in addition to peripheral BP in older patients irrespective of symptoms. Further studies are required to investigate the relationship between NIRS measurements and clinical outcomes such as falls, cognitive impairment and depression.