Orthostatic hypotension and acute cognitive dysfunction in Parkinson’s disease: insights from functional near-infrared spectroscopy

Fig. 1.. Schematic illustrating potential acute and chronic pathophysiological mechanisms linking orthostatic hypotension to cognitive impairment in Parkinson’s disease, with representative assessment modalities. Assessment of acute cerebral hypoperfusion and cerebral autoregulation requires concurrent cerebral hemodynamic and blood pressure monitoring during an orthostatic challenge, such as head-up tilt or, for MRI-based approaches, lower-body negative pressure. Assessment of neurovascular coupling requires a cognitive or sensory stimulus. Assessment of cerebrovascular reactivity requires a vasodilatory challenge. Abbreviations: ASL MRI: arterial spin labeling magnetic resonance imaging; BOLD: blood oxygenation level-dependent imaging; BP: blood pressure; NIRS: near-infrared spectroscopy; TCD: transcranial Doppler ultrasound; WM: white matter.

Fig. 2.. Flow diagram of participant screening, randomization, and study procedures. Participants underwent an initial orthostatic blood pressure assessment at the screening visit to provisionally classify orthostatic hypotension (OH) status before randomization. The starting posture (supine vs. upright) and test order (standard vs. alternate) were each randomized in a 1:1 ratio. Orthostatic blood pressure was reassessed during the study visit, and the presence or absence of OH at the study visit was used for the final analytic grouping.

Fig. 3.. Unadjusted Delis-Kaplan Executive Function System letter verbal fluency test total scores in Parkinson’s disease participants by orthostatic hypotension (OH) status and position. Bars represent means ± SD. The asterisk indicates a significant unadjusted comparison between the OH− and OH+ groups in the upright position [p = 0.037]. In the unadjusted two-way mixed ANOVA, a between-group simple-effects contrast was used to test the effect of OH status within the upright position. Upright letter VFT total scores were significantly higher in the OH− group than in the OH+ group (47.05 ± 2.71 vs 36.90 ± 3.74 correct words), F(1, 27) = 4.834, p = 0.037, partial η2 = 0.152. Inferential conclusions were based on the age-adjusted mixed ANCOVA; the adjusted OH− versus OH+ comparison in the upright position was not significant [p = 0.131], although the OH status × position interaction was significant [p = 0.043]. Abbreviations: M, mean; SD, standard deviation; OH, orthostatic hypotension; OH−, without OH; OH+, with OH.

Fig. 4.. Delis-Kaplan Executive Function System letter verbal fluency test total errors in Parkinson’s disease participants without orthostatic hypotension (OH−) and with orthostatic hypotension (OH+) across supine and upright positions, controlling for age. Bars indicate group means; error bars represent 95% confidence intervals. Covariates are evaluated at age = 67.28. Significance: * p < 0.05. Abbreviations: M, mean; SD, standard deviation; OH, orthostatic hypotension; OH−, without OH; OH+, with OH.

Fig. 5.. Deoxygenated hemoglobin (HbR) during the Delis-Kaplan Executive Function System letter verbal fluency test across the (A) left and (B) right dorsolateral prefrontal cortex (DLPFC) compared between Parkinson’s disease groups without orthostatic hypotension (OH−) and with orthostatic hypotension (OH+) and by position (supine vs. upright). Significance: * p < 0.05. Abbreviations: M, mean; SD, standard deviation; OH, orthostatic hypotension; OH−, without OH; OH+, with OH; HbR, deoxygenated hemoglobin; LDLPFC, left dorsolateral prefrontal cortex; RDLPFC, right dorsolateral prefrontal cortex.

Fig. 6.. Between-group and within-group comparisons of orthostatic vital sign measurements during the Delis-Kaplan Executive Function System letter verbal fluency test: (A) systolic blood pressure; (B) diastolic blood pressure; (C) mean arterial pressure; (D) heart rate. Significance: * p < 0.05. Abbreviations: M, mean; SD, standard deviation; OH, orthostatic hypotension; OH−, without OH; OH+, with OH; mmHg, millimeters mercury; bpm, beats per minute.