Blood Pressure Effects on Cognition and Brain Blood Flow in PD

NCT05400174 | Recruiting FDA Device

• 1 other identifier: 210738
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Besides causing symptoms that impair movement, PD also causes non-motor symptoms, such as problems thinking and orthostatic hypotension (OH), i.e., low blood pressure (BP) when standing. About one-third of people with PD have OH, which can cause sudden, temporary symptoms while upright, including lightheadedness, dizziness, and fainting. People with PD and OH can also experience problems thinking that happen only while upright and not while sitting - this can occur without other symptoms, such as feeling dizzy or faint. However, the level of low BP that can affect thinking remains unknown, and no guidelines exist for treating OH when it happens without symptoms. This is significant because OH could be a treatable risk factor for thinking problems in PD, but OH is often not treated if people do not report obvious symptoms. This project's goal is to determine how BP affects brain function in PD. The proposed experiments will measure BP and brain blood flow continuously in real-time using innovative wearable technology. Persons with PD with OH and without OH will undergo repeated cognitive tests while supine (lying down) and while upright. I will study the associations between BP, thinking abilities, and brain blood flow, and will compare groups with and without OH. These findings could be important because if a certain level of BP correlates with thinking abilities, then treating OH in PD may prevent thinking problems, which would improve health-related quality of life and reduce disability and healthcare costs.

Conditions

Parkinson Disease; Orthostatic Hypotension; Dysautonomia

Outcome Measures

Primary Outcomes (2)

• Delis-Kaplan Executive Function System Verbal Fluency Test score (number of words per minute). Minimum: 0; Maximum: N/A; higher is better

  Participant says as many words in 1 minute as possible each of several letter or category prompts.

  up to 30 months

• Oxygenated and deoxygenated hemoglobin change from baseline

  Functional near-infrared spectroscopy will measure relative changes in oxygenated and deoxygenated hemoglobin variables

  up to 30 months

Study Arms (2)

Supine cognitive testing first

OTHER

The cognitive testing sessions will be alternated between supine and upright positions. This group will perform cognitive testing sessions in the following order: 1) supine, 2) upright, 3) supine, 4) upright.

Diagnostic Test: Tilt table (upright position)

Upright cognitive testing first

OTHER

The cognitive testing sessions will be alternated between supine and upright positions. This group will perform cognitive testing sessions in the following order: 1) upright, 2) supine, 3) upright, 4) supine.

Diagnostic Test: Tilt table (upright position)

Interventions

Tilt table (upright position) DIAGNOSTIC_TEST

Different versions of cognitive assessments will be administered in the supine and upright positions.

Also known as: Cognitive testing battery

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:

• Diagnosis of idiopathic Parkinson Disease using the Movement Disorders Society (MDS) Clinical Diagnostic Criteria
• Age at least 50 years old
• Hoehn \& Yahr (H\&Y) stages I-III (early to moderate-stage PD; able to walk without assistance
• Proficiency in the English language (native English speaker level)

You may not qualify if:

• Any involuntary movements (i.e., tremor or dyskinesia) \> 3 cm in amplitude (ok if movements are treated with medication), since the motion artifact could interfere with blood pressure monitor data collection
• Dementia (including PD dementia)
• History of deep brain stimulation (DBS) surgery
• Any current unstable, active medical problem, e.g. decompensated heart failure, liver failure, pneumonia, etc.
• Moderate or severe carotid artery stenosis (according to North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria
• History of cerebral infarction or hemorrhage
• Uncontrolled diabetes or any other systemic disease causing autonomic failure
• Syncope (fainting) within the past week
• Illiteracy (unable to read)
• Taking antihypertensive medications or alpha-adrenergic blocking medications, since these can cause hypotension (see \* below)
• Impairment of hearing or vision that is not corrected by devices (e.g., hearing aids or glasses)
• Currently pregnant (will be confirmed by women of child-bearing potential with a urine pregnancy test)
• Any other condition, which, in the opinion of the investigator, could place the participant at increased risk.
• Please note that persons may not participate if they are taking any of the following:
• medications to treat high blood pressure (called "antihypertensives") such as clonidine (Catapres), hydralazine, verapamil, diltiazem (Cartia), or medications ending in "-olol", "-artan", or "-pril")

Sponsors & Collaborators

• University of California, San Diego: lead
• Beth Israel Deaconess Medical Center: collaborator
• Drexel University: collaborator

Study Sites (1)

University of California San Diego

San Diego, California, 92093, United States

RECRUITING

Related Publications (15)

• 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

• Riley DE, Espay AJ. Cognitive fluctuations in Parkinson's disease dementia: blood pressure lability as an underlying mechanism. J Clin Mov Disord. 2018 Feb 13;5:1. doi: 10.1186/s40734-018-0068-4. eCollection 2018.

  PMID: 29456869 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

• 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

• 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):1459-1462. doi: 10.1007/s10072-018-3394-2. Epub 2018 Apr 7.

  PMID: 29627942 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

• 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

• Udina C, Avtzi S, Durduran T, Holtzer R, Rosso AL, Castellano-Tejedor C, Perez LM, Soto-Bagaria L, Inzitari M. Functional Near-Infrared Spectroscopy to Study Cerebral Hemodynamics in Older Adults During Cognitive and Motor Tasks: A Review. Front Aging Neurosci. 2020 Jan 21;11:367. doi: 10.3389/fnagi.2019.00367. eCollection 2019.

  PMID: 32038224 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; Hypotension, Orthostatic; Autonomic Nervous System Diseases

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Orthostatic Intolerance; Primary Dysautonomias; Hypotension; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Katherine Longardner, MD

CONTACT

8588225751; klongardner@health.ucsd.edu

Michael Skipworth, BS

CONTACT

8588225751; mskipworth@health.ucsd.edu

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: May 23, 2022
• First Posted: June 1, 2022
• Study Start: December 14, 2021
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): August 15, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)