Cognitive Alterations in Pulmonary Arterial Hypertension (PAH)

NCT07391228 | Active Not Recruiting

• 1 other identifier: COG-PAH - CTSM180-25
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Pulmonary Arterial Hypertension (PAH) is a rare chronic disease marked by a pathological and sustained increase in pulmonary artery pressure as a result of structural and functional changes within the pulmonary vasculature. Beyond its cardiopulmonary manifestations, a growing body of evidence suggests that PAH may also affect cerebral hemodynamics and cognitive functioning as a consequence of prolonged reductions in cerebrovascular oxygenation potentially underlying the frontal-executive, attentional, and mnestic impairments reported in this population. Despite these preliminary findings, the few studies currently available have significant methodological limitations, such as the lack of appropriate control groups or the inclusion of other pulmonary hypertension subtypes in the cohort. In addition, they tend to rely on global cognitive screening tests that are unsuitable for the precise characterization of domain-specific alterations, such as those observed in PAH. This study aims to address these limitations by employing a battery of computerized neuropsychological tests to detect the presence of selective cognitive alterations in individuals diagnosed with PAH, through comparison with a control group matched for age, sex, handedness and schooling. The project is designed as a cross-sectional observational study conducted at a single center, with the primary aim to assess the presence of selective cognitive alterations in patients diagnosed with PAH, comparing their performance with that of a healthy control group matched for age, sex, handedness, and level of education. The secondary objective is to explore the relationship between cognitive variables and clinical variables in patients with PAH, such as disease duration, age at diagnosis, oxygen therapy, and reported comorbidities. Participants will be assessed in a single in-person session at the IRCCS Maugeri Milano, using a computerised battery of tests that will last approximately 50 minutes. Recruitment will take place consecutively among patients hospitalised at the U.O. Rehabilitative Cardiology of the IRCCS Maugeri- Milano Via Camaldoli. Healthy controls will be identified on a voluntary basis among IRCCS Maugeri staff, healthy family members of patients, or through other authorised internal channels.The total duration of the study is expected to be 24 months, with an estimated start date of 15/11/2025 and end date of 31/07/2027. Participants will undergo an initial collection of medical history data to verify their eligibility for the study. The information collected will include sociodemographic data (sex, age, marital status, number of children, employment status, level of education, years of schooling) and clinical data (past and recent medical history, current drug therapies, behavioural habits such as smoking and/or alcohol consumption, handedness). Data relating to performance in neuropsychological tests will be collected using the Inquisit 7.0 by Millisecond platform (https://www.millisecond.com/). Cognitive tasks will be performed individually and in person on an HP Envy x360 PC running Windows 11. Assessment tools Neuropsychological tests were chosen to investigate selective alterations in cognitive functions related to brain areas whose activation was found to be altered in PAH patients in the aforementioned studies, such as the selective and sustained attention, working memory, processing speed and cognitive flexibility, inhibitory control, interference contrast, categorical abstraction, as well as learning and long-term verbal memory. Selected test are listed below:

• Iowa Gambling Task (IGT): developed by Bechara and colleagues (1994);
• Emotional Stroop Task (EST): a variant of the classic Stroop Test, developed by Smith and Waterman (2003);
• The Rey Auditory Verbal Learning Test (RAVLT): validated in the Italian version by Carlesimo et al., (1995); The Visual Simon Task (VST): a variant of the Simon Task (2004); The Wisconsin Card Sorting Test (WCST): by Heaton et al., (1993);

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension; Cognitive Functions; Neuropsychological Assessment; Cross-sectional Study

Outcome Measures

Primary Outcomes (5)

• Comparison of the performance of patients with PAH versus the control group in IGT scores

  To compare the performance of the two groups on the Iowa Gambling Task (IGT), the following variables of interest will be collected and compared: * subjective ranking of the decks according to perceived convenience (ordinal ranking; e.g., 1-2-3-4); * number of advantageous choices (count); * number of disadvantageous choices (count); * Risk Index, calculated as the difference between the number of disadvantageous and advantageous choices (count).

  Baseline

• Comparison of the performance of patients with PAH versus the control group in EST scores

  To compare the performance of the two groups in EST scores, the following variables of interest will be collected and compared: * percentage of correct answers (%) * average reaction time for each category (ms) * interference bias, calculated as the difference between the average response times to each category and neutral words (ms).

  Baseline

• Comparison of the performance of patients with PAH versus the control group in RAVLT scores

  To compare the performance of the two groups in RAVLT scores the following variables of interest will be collected and compared: * number of words recalled in learning series (count) * number of words recalled in delayed recall series (count).

  Baseline

• Comparison of the performance of patients with PAH versus the control group in VST scores

  To compare the performance of the two groups in VST scores, the following variables of interest will be collected and compared: * accuracy of responses (%) * average reaction times by trial type (ms) * the 'Simon effect', calculated as the difference between the reaction times of incongruent and congruent trials (ms)

  Baseline

• Comparison of the performance of patients with PAH versus the control group in WCST scores

  To compare the performance of the two groups in WCST scores, the following variables of interest will be collected and compared: * number and percentage of perseverative responses, non-responses, and errors (count; %); * failures to maintain set (count); * Global Score, calculated as "number of cards used - (categories completed × 10)" (score).

  Baseline

Secondary Outcomes (1)

• Explore the relationship between cognitive and clinical variables (disease duration, age at diagnosis, oxygen therapy, and reported comorbidities) in patients with PAH

  Baseline

Study Arms (2)

PAH patients

The first group is composed by patients over 18 years with a confirmed diagnosis of PAH, which are clinically stable (according to the treating physician's judgement) and have no neurological and psychiatric comorbidities

Healthy subjects

Healthy controls matched for age (± 3 years), gender, handedness and educational level, with no current or past organic and/or psychiatric disorders

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited consecutively from among those with a confirmed diagnosis of PAH admitted to the U.O. Cardiologia Riabilitativa of the IRCCS Maugeri - Milano. Healthy controls will be identified on a voluntary basis among IRCCS Maugeri staff, healthy family members of patients, or through other authorised internal channels. Participation in the study will be voluntary and subject to the signing of an informed consent form.

You may qualify if:

• Confirmed diagnosis of Pulmonary Arterial Hypertension
• Age ≥ 18 years;
• Ability to understand instructions and give informed consent;
• Absence of neurological and psychiatric comorbidities;
• Stable clinical condition, according to the treating physician's judgement;
• Willingness to participate in the study for the entire duration of the tests.
• Matching for age (± 3 years), gender, manual laterality and level of education:
• No current or past organic and/or psychiatric disorders.

You may not qualify if:

• Presence of medical, neurological or psychiatric comorbidities that could interfere with cognitive performance;
• Use of drugs known to affect cognitive function; Presence of sensory and/or motor deficits that could compromise test performance; Insufficient understanding of spoken and/or written Italian; Inability to give free and/or informed consent.

Sponsors & Collaborators

• Alessandra Gorini: lead

Study Sites (1)

IRCCS Maugeri - Milano

Milan, Italy, 20138, Italy

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor Alessandra Gorini, PhD, Psychologist, Neuropsichology, Psychotherapist

Study Record Dates

• First Submitted: November 28, 2025
• First Posted: February 5, 2026
• Study Start: November 15, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: February 5, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)