Effects of Blood Pressure on Cognition and Cerebral Hemodynamics in PD

NCT06252376 | Withdrawn

• 1 other identifier: 210738a
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of clinical trial is to learn about how blood pressure fluctuations affect cognitive performance (thinking abilities) and brain blood flow in persons with Parkinson's disease with and without orthostatic hypotension (low blood pressure when standing). The main questions it aims to answer are:

• Is there a certain level of blood pressure that correlates with change in cognitive performance while upright?
• Is there a certain level of change in brain blood flow that correlates with change in cognitive performance when upright?
• How does cognitive performance differ between persons with Parkinson's disease that have orthostatic hypotension and those without orthostatic hypotension?
• How does cognitive performance differ between the supine (laying down) and upright positions?
• How do blood pressure and brain blood predict changes in cognitive performance over two years? Participants in this study will undergo the following procedures:
• Complete a screening visit with questionnaires, medical history, physical exam, and head-up tilt-table test.
• Attend one baseline study visit, during which they will undergo a battery of computerized cognitive tests repeated twice: once while laying down and once while upright on a tilt table. Simultaneously, during the experiments we will measure blood pressure using a wrist-worn device and inflatable arm cuff and will measure brain blood flow using functional near-infrared spectroscopy (fNIRS), a non-invasive device that uses light sensors to detect changes in brain blood flow.
• Attend one two-year follow-up visit, during which they will repeat a battery of computerized cognitive tests repeated twice: once while laying down and once while upright on a tilt table. During this visit, like before, we will measure blood pressure using a wrist-worn device and inflatable arm cuff and will measure brain blood flow using functional near-infrared spectroscopy (fNIRS). Researchers will compare participants with Parkinson's disease with and without orthostatic hypotension in the laying down and upright positions to see if there are changes in thinking abilities between these groups.

Conditions

Parkinson Disease; Orthostatic Hypertension; Cognitive Change; Cognitive Impairment; Cognitive Decline

Keywords

Parkinson's disease; Blood pressure; Blood flow; Cognition; fNIRS

Outcome Measures

Primary Outcomes (3)

• Verbal fluency score (number of words generated in one minute)

  Participant names as many words from a prompt as possible in one minute. Minimum: 0; Maximum: N/A; higher is better

  24 months

• Blood pressure (mmHg)

  Participants' blood pressure will be measured during the visit.

  24 months

• Oxygenated hemoblobin change from baseline

  Functional near-infrared spectroscopy will measure relative changes in oxygenated hemoglobin during cognitive testing.

  24 months

Study Arms (2)

Supine cognitive testing first

EXPERIMENTAL

Participants will undergo a computerized cognitive battery in the supine position, followed by a similar battery with alternate test versions in the upright position while on a head-up tilt table.

Diagnostic Test: Head-up tilt table

Upright cognitive testing first

EXPERIMENTAL

Participants will undergo a computerized cognitive battery in the upright position, followed by a similar battery with alternate test versions in the supine position while on a head-up tilt table.

Diagnostic Test: Head-up tilt table

Interventions

Head-up tilt table DIAGNOSTIC_TEST

Different versions of cognitive assessments will be administered in the supine and upright positions while the participant is on the tilt table.

Supine cognitive testing first; Upright cognitive testing first

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of idiopathic Parkinson's disease (PD) using the Movement Disorders Society (MDS) Clinical Diagnostic Criteria (Postuma, 2015)
• Age least 50 years old
• Hoehn \& Yahr (H\&Y) stages I to III (early to moderate stage PD)
• Proficiency in the English language (native English speaker level)

You may not qualify if:

• Any involuntary movements (i.e., tremor or dyskinesia) greater than 3 cm in amplitude, since the motion artifact can interfere with BP monitor cuff
• Taking antihypertensive medications or alpha-adrenergic blocking medications since these can cause hypotension.
• Dementia (including PD dementia (Emre, 2007) characterized by either Dementia Rating Scale 2 (DRS-2) score) 124 or less or clinical evidence of impaired instrumental activities of daily living
• History of deep brain stimulation (DBS) surgery
• Any unstable, active medical problem, e.g., decompensated heart failure, liver failure, etc.
• Moderate or severe carotid artery stenosis (according to North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria (Ferguson, 1999)
• History of cerebral infarction or hemorrhage
• Uncontrolled diabetes or any other systemic disease that causes autonomic failure
• Any terminal illness with life expectancy less than 2 years
• Illiteracy
• Impairment of hearing or vision that is not corrected by devices (e.g., hearing aids or glasses)
• Currently pregnant (will be confirmed with a urine pregnancy screening test in people of child-bearing potential)
• Any other condition, which, in the opinion of the investigator, could place the participant at increased risk (e.g., substance abuse)

Sponsors & Collaborators

• University of California, San Diego: lead

Related Publications (12)

• Longardner K, Bayram E, Litvan I. Orthostatic Hypotension Is Associated With Cognitive Decline in Parkinson Disease. Front Neurol. 2020 Sep 2;11:897. doi: 10.3389/fneur.2020.00897. eCollection 2020.

  PMID: 32982926 BACKGROUND

• Freeman R, Illigens BMW, Lapusca R, Campagnolo M, Abuzinadah AR, Bonyhay I, Sinn DI, Miglis M, White J, Gibbons CH. Symptom Recognition Is Impaired in Patients With Orthostatic Hypotension. Hypertension. 2020 May;75(5):1325-1332. doi: 10.1161/HYPERTENSIONAHA.119.13619. Epub 2020 Mar 30.

  PMID: 32223377 BACKGROUND

• Gibbons CH, Schmidt P, Biaggioni I, Frazier-Mills C, Freeman R, Isaacson S, Karabin B, Kuritzky L, Lew M, Low P, Mehdirad A, Raj SR, Vernino S, Kaufmann H. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol. 2017 Aug;264(8):1567-1582. doi: 10.1007/s00415-016-8375-x. Epub 2017 Jan 3.

  PMID: 28050656 BACKGROUND

• Udow SJ, Robertson AD, MacIntosh BJ, Espay AJ, Rowe JB, Lang AE, Masellis M. 'Under pressure': is there a link between orthostatic hypotension and cognitive impairment in alpha-synucleinopathies? J Neurol Neurosurg Psychiatry. 2016 Dec;87(12):1311-1321. doi: 10.1136/jnnp-2016-314123. Epub 2016 Sep 9.

  PMID: 27613160 BACKGROUND

• McDonald C, Newton JL, Burn DJ. Orthostatic hypotension and cognitive impairment in Parkinson's disease: Causation or association? Mov Disord. 2016 Jul;31(7):937-46. doi: 10.1002/mds.26632. Epub 2016 Apr 19.

  PMID: 27091624 BACKGROUND

• Poda R, Guaraldi P, Solieri L, Calandra-Buonaura G, Marano G, Gallassi R, Cortelli P. Standing worsens cognitive functions in patients with neurogenic orthostatic hypotension. Neurol Sci. 2012 Apr;33(2):469-73. doi: 10.1007/s10072-011-0746-6. Epub 2011 Sep 6.

  PMID: 21894556 BACKGROUND

• 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. doi: 10.1212/WNL.0000000000003452. Epub 2016 Nov 30.

  PMID: 27903817 BACKGROUND

• Pinti P, Tachtsidis I, Hamilton A, Hirsch J, Aichelburg C, Gilbert S, Burgess PW. 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. doi: 10.1111/nyas.13948. Epub 2018 Aug 7.

  PMID: 30085354 BACKGROUND

• Palma JA, Gomez-Esteban JC, Norcliffe-Kaufmann L, Martinez J, Tijero B, Berganzo K, Kaufmann H. Orthostatic hypotension in Parkinson disease: how much you fall or how low you go? Mov Disord. 2015 Apr 15;30(5):639-45. doi: 10.1002/mds.26079. Epub 2015 Feb 12.

  PMID: 25678194 BACKGROUND

• Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015 Oct;30(12):1591-601. doi: 10.1002/mds.26424.

  PMID: 26474316 BACKGROUND

• Kaufmann H, Malamut R, Norcliffe-Kaufmann L, Rosa K, Freeman R. The Orthostatic Hypotension Questionnaire (OHQ): validation of a novel symptom assessment scale. Clin Auton Res. 2012 Apr;22(2):79-90. doi: 10.1007/s10286-011-0146-2. Epub 2011 Nov 2.

  PMID: 22045363 BACKGROUND

• Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008 Nov 15;23(15):2129-70. doi: 10.1002/mds.22340.

  PMID: 19025984 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Clinical Professor of Health Sciences

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 9, 2024
• Study Start: August 15, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share