Objective: To define cerebral oxygenation changes during positional cognitive testing in Parkinson’s disease (PD), comparing those with orthostatic hypotension (OH+) to those without (OH-).

Background: OH in PD is linked to short-term cognitive deficits when in the upright position [1-3] and chronic cognitive decline [4-6], but the acute impact of OH on brain function remains unclear. Functional near-infrared spectroscopy (fNIRS), a portable neuroimaging modality that measures oxygenated (HbO) and deoxygenated (HbR) hemoglobin, can provide real-time evaluation of cerebral perfusion during a cognitive task [7].

Method: Non-demented individuals with PD completed a cognitive test battery [table1] while on a tilt table in supine and upright positions [figure1A] using described methods [1]. A 16-source, 23-detector (including short channels) fNIRS system (NIRSport2, NIRx®) [figure1B, figure2] measured cerebral oxygenation changes during performance of a letter verbal fluency task (VFT) [8]. A two-way mixed ANCOVA controlling for age examined the effects of OH status (OH- vs. OH+ groups) and position (supine vs. upright) on the letter fluency score. Linear mixed-effects regression models assessed changes in HbO and HbR during the task in the dorsolateral prefrontal cortex (DLPFC), a key region for letter fluency [9-10], comparing OH groups across positions.

Results: Demographic and clinical characteristics of the 29 participants (19 OH-, 10 OH+) are shown in Table 1 [table1].  A significant two-way interaction effect was found between OH status and position for letter fluency, F(1, 26) = 4.51, p = .043, partial η2 = .533 [figure3], with the OH+ group performing worse when upright. Analysis of fNIRS data from 26 participants (16 OH- and 10 OH+) showed the OH+ group exhibited a significant decrease in HbR in left DLPFC (M = -0.20, SE = 0.08, p = .010) and right DLPFC (M = -0.31, SE = 0.12, p = .011) when upright vs. supine, indicating greater utilization of cognitive resources while upright vs. supine [figure4]. Conversely, the OH- group showed increased HbR in the right DLPFC when upright vs. supine (M = 0.27, SE = 0.09, p = .004), indicating lower cognitive resource use while upright.

Conclusion: These preliminary results suggest that persons with PD and OH have impaired cerebral hemodynamic regulation when upright which is associated with poorer cognitive performance.

Figure 1

Figure 2

Table 1

Figure 3

Figure 4

References: 1. Centi J, Freeman R, Gibbons CH, Neargarder S, Canova AO, Cronin-Golomb A. Effects of orthostatic hypotension on cognition in Parkinson disease. Neurology. 2017 Jan 3;88(1):17–24.

2. Sforza M, Assogna F, Rinaldi D, Sette G, Tagliente S, Pontieri FE. Orthostatic hypotension acutely impairs executive functions in Parkinson’s disease. Neurol Sci. 2018 Aug;39(8):1459–62.

3. Robinson L, Kimpinski K. Neurogenic orthostatic hypotension impairs information processing speed and attention. Physiol Behav. 2019 Nov 1;211:112682.

4. Loureiro D, Bilbao R, Bordet S, Grasso L, Otero-Losada M, Capani F, et al. A systematic review and meta-analysis on the association between orthostatic hypotension and mild cognitive impairment and dementia in Parkinson’s disease. Neurol Sci. 2023 Apr;44(4):1211–22.

5. Ruiz Barrio I, Miki Y, Jaunmuktane ZT, Warner T, De Pablo-Fernandez E. Association Between Orthostatic Hypotension and Dementia in Patients With Parkinson Disease and Multiple System Atrophy. Neurology. 2023 Mar 7;100(10):e998–1008.

6. Hiorth YH, Schulz J, Pedersen KF, Tysnes O, Alves G. Orthostatic Hypotension and Risk of Mild Cognitive Impairment and Dementia in Parkinson’s Disease. Movement Disord Clin Pract. 2024 Nov;11(11):1365–72.

7. Pinti P, Tachtsidis I, Hamilton A, Hirsch J, Aichelburg C, Gilbert S, et al. The present and future use of functional near-infrared spectroscopy (fNIRS) for cognitive neuroscience. Ann N Y Acad Sci. 2020 Mar;1464(1):5–29.

8. Delis DC, Kaplan E, Kramer JH. Delis-Kaplan Executive Function System [Internet]. 2012 [cited 2024 Jan 30]. Available from: http://doi.apa.org/getdoi.cfm?doi=10.1037/t15082-000

9. Herrmann MJ, Ehlis AC, Fallgatter AJ. Frontal activation during a verbal-fluency task as measured by near-infrared spectroscopy. Brain Research Bulletin. 2003 Jun;61(1):51–6.

10. Huang CJ, Chou PH, Wei HL, Sun CW. Functional Connectivity During Phonemic and Semantic Verbal Fluency Test: A Multichannel Near Infrared Spectroscopy Study. IEEE J Select Topics Quantum Electron. 2016 May;22(3):43–8.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/orthostatic-hypotension-and-acute-cognitive-dysfunction-in-parkinsons-disease-insights-from-fnirs/