The Association Between Primary Aldosteronism and Cognitive Dysfunction (PACD)

The goal of this observational study is to learn about the prevalence, progression, and influencing factors of cognitive impairment in patients with primary aldosteronism (PA). The main questions it aims to answer are:

1. What is the prevalence of baseline cognitive impairment in PA patients and what factors are associated with it?
2. What is the incidence of cognitive progression in PA patients within 1 and 5 years of follow-up and what factors influence this progression? Participants who are already diagnosed with PA as part of their regular medical care will be invited to join this long-term study. They will complete regular cognitive tests, medical check-ups, and questionnaires for up to 5 years. Some participants will also have optional blood tests and brain scans to help researchers understand the causes behind any cognitive changes.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Dysfunction; Dementia; Mild Cognitive Impairment (MCI); Primary Aldosteronism

Detailed Description

This is a prospective observational cohort study conducted in two tertiary hospitals. The main purposes are to investigate the prevalence and influencing factors of mild cognitive impairment (MCI) and dementia at baseline in patients with primary aldosteronism (PA), assess the incidence and influencing factors of cognitive progression within 1 and 5 years of follow-up, and compare exploratory biomarkers, such as plasma neurofilament light chain (NfL) and brain magnetic resonance imaging (MRI) measures, between PA patients with and without baseline cognitive impairment. Eligible patients will be followed up for 5 years, with regular cognitive function assessment, clinical indicator monitoring, and detection of relevant biomarkers and imaging indicators. The study aims to delineate the cognitive trajectory in PA and identify associated clinical and biological predictors.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Xiang Xie, PhD; Phone Number: +86-991-4366892; Email: xiangxie999@sina.com
• Study Contact Backup: Name: Kaige Feng; Phone Number: +86-17828098050; Email: fengkaigedoc@163.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • The First Affiliated Hospital of Chengdu Medical College
      • Contact: peijian wang, PhD; Phone Number: +86-18272558112; Email: wpjmed@aliyun.com
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830000
      • Recruiting
      • The First Affiliated Hospital of Xinjiang Medical University
      • Contact: Xiang Xie, PhD; Phone Number: +86-991-4366892; Email: xiangxie999@sina.com
      • Contact: Kaige Feng; Phone Number: +86-17828098050; Email: fengkaigedoc@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will establish a prospective, two-center cohort of primary aldosteronism (PA). Designed to capture the full baseline spectrum of cognitive function, the cohort aims to systematically determine the incidence and progression of cognitive impairment and identify its clinical and biochemical predictors.

Description

Inclusion Criteria:

• 1. Aged ≥ 40 years.
• 2. Biochemically confirmed diagnosis of Primary Aldosteronism (PA) according to contemporary guidelines (e.g., confirmed positive case detection test and confirmatory test).
• 3. Ability to understand and cooperate with comprehensive neuropsychological assessment.
• 4. Voluntary participation and provision of written informed consent.

Exclusion Criteria:

• 1. Significant visual, hearing, or motor impairment that prevents completion of cognitive testing.
• 2. History of major neurological disorders (e.g., stroke, Parkinson's disease, intracranial tumor, severe traumatic brain injury).
• 3. History of major psychiatric illness, intellectual disability, or current use of antipsychotic medications.
• 4. Diagnosis of secondary hypertension other than PA.
• 5. Unwillingness to participate by the patient or their legal representative.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-Year Early Cognitive Progression in Patients with PA	Defined as the proportion of PA patients who experience cognitive progression within 1 year of follow-up. Cognitive progression includes three transitions: 1) Normal cognition → MCI; 2) Normal cognition → Dementia; 3) MCI → Dementia.The diagnostic criteria for MCI and dementia are based on the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria (for MCI and dementia). All events are adjudicated by an independent endpoint committee.	Baseline and 12 months.
5-Year Cumulative Incidence of Cognitive Progression in Patients with PA	Defined as the proportion of PA patients who experience cognitive progression within 5 years of follow-up. Cognitive progression follows the same transitions and diagnostic criteria as the 1-year primary outcome (NIA-AA criteria). All events are adjudicated by an independent endpoint committee.	Baseline, 12, 24, 36, 48, and 60 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Prevalence of Cognitive Impairment (MCI or Dementia) in Patients with PA	The proportion of patients with PA who have MCI or dementia at study baseline, as adjudicated by an independent endpoint committee using the NIA-AA criteria.	Baseline
3-year cumulative incidence of cognitive progression in patients with PA	The proportion of patients who experience cognitive progression within 3 years of follow-up. Cognitive progression is defined as the same transitions and diagnostic criteria (NIA-AA) as the primary outcomes.	Baseline, 12, 24, and 36 months.
Longitudinal Change in Global Cognitive Function	Change in global cognitive function as measured by the validated Chinese version of the Montreal Cognitive Assessment (MoCA, Beijing version). The total score ranges from 0 to 30 (higher scores indicate better cognitive function).	Baseline, 12, 24, 36, 48, and 60 months
Change in Neuropsychiatric Inventory (NPI) Total Score	Change in the validated Chinese version of the NPI total score (range: 0-144; higher scores indicate greater neuropsychiatric symptom burden), assessing 12 behavioral domains.	Baseline, 12, 24, 36, 48, and 60 months.
Plasma Aldosterone Concentration (PAC)	Absolute plasma aldosterone concentration, measured in pg/mL.	Baseline, 12, 24, 36, 48, and 60 months.
Plasma Renin Concentration (PRC)	The absolute concentration of renin in plasma, measured in pg/mL. This outcome, along with aldosterone, is used to calculate the aldosterone-to-renin ratio (ARR), a key screening and diagnostic biomarker for PA.	Baseline, 12, 24, 36, 48, and 60 months.
Serum Potassium (K+) Level	Absolute serum potassium concentration, measured in mmol/L.	Baseline, 12, 24, 36, 48, and 60 months.
Serum Sodium (Na+) Level	Absolute serum sodium concentration, measured in mmol/L.	Baseline, 12, 24, 36, 48, and 60 months.
Low-Density Lipoprotein Cholesterol (LDL-C) Level	Fasting serum concentration of LDL-C, measured in mmol/L.	Baseline, 12, 24, 36, 48, and 60 months.
Lipoprotein(a) (Lp(a)) Level	Fasting serum concentration of Lp(a), measured in nmol/L, an independent risk factor for cardiovascular disease.	Baseline, 12, 24, 36, 48, and 60 months.
Fasting Plasma Glucose Level	Concentration of glucose in plasma after ≥8 hours of fasting, measured in mmol/L.	Baseline, 12, 24, 36, 48, and 60 months.
Urinary Albumin-to-Creatinine Ratio (UACR)	The UACR measured from a spot urine sample and reported in mg/g, a marker of kidney damage.	Baseline, 12, 24, 36, 48, and 60 months.
Left Ventricular Mass Index (LVMI)	Left ventricular mass indexed to body surface area (g/m²), calculated from echocardiographic measurements. The key criterion for diagnosing left ventricular hypertrophy.	Baseline, 12, 24, 36, 48, and 60 months.
Left Ventricular Ejection Fraction (LVEF)	The percentage of blood ejected from the left ventricle during each contraction, measured by echocardiography.	Baseline, 12, 24, 36, 48, and 60 months.
Carotid Intima-Media Thickness (CIMT)	The mean far-wall intima-media thickness of the common carotid artery (mm), measured bilaterally by ultrasound. A marker of subclinical atherosclerosis.	Baseline, 12, 24, 36, 48, and 60 months.
Cerebral Blood Flow (Sub-study)	Quantitative measurement of regional and global cerebral blood flow, obtained via arterial spin labeling (ASL) magnetic resonance imaging, and reported in milliliters per 100 grams of tissue per minute (mL/100g/min).	Baseline, 12, 36, and 60 months.
Incidence of Major Adverse Cardiovascular Events (MACE)	The proportion of patients who experience an adjudicated MACE, a composite of non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, or cardiovascular death.	Baseline, 12, 24, 36, 48, and 60 months.
All-cause mortality	Record of deaths from any cause during follow-up. Confirmed by medical records, family follow-up, or national death registration systems.	Baseline, 12, 24, 36, 48, and 60 months.
Change in Functional Activities Questionnaire (FAQ) total score	Change in the total score of the validated Chinese version of the FAQ (range 0-30; higher scores indicate greater impairment). This scale assesses instrumental activities of daily living.	Baseline, 12, 24, 36, 48, and 60 months.
Office Blood Pressure Control Rate	The proportion of patients achieving controlled office blood pressure at each post-baseline follow-up visit. Control is defined as an average of triplicate seated measurements with systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg.	12, 24, 36, 48, and 60 months.
24-Hour Ambulatory Blood Pressure Control Rate	The proportion of patients achieving controlled 24-hour ambulatory blood pressure. Control is defined as a mean 24-hour SBP < 130 mmHg and DBP < 80 mmHg.	12, 24, 36, 48, and 60 months.
Glycated Hemoglobin (HbA1c) Level	The percentage of HbA1c in blood, reflecting average blood glucose over the preceding 2-3 months.	Baseline, 12, 24, 36, 48, and 60 months.
Estimated Glomerular Filtration Rate (eGFR)	Renal function assessed by the eGFR, calculated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (units: mL/min/1.73m²).	Baseline, 12, 24, 36, 48, and 60 months.
Plasma NfL Concentration (Sub-study)	Concentration of plasma NfL (pg/mL), a biomarker of neuroaxonal injury, measured in a pre-defined sub-cohort.	Baseline, 12, 36, and 60 months.
White Matter Hyperintensity (WMH) Volume (Sub-study)	Total volume of white matter hyperintensities, quantified in cubic millimeters (mm³) from T2-fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging sequences. WMH volume is a quantitative marker of cerebral small vessel disease burden.	Baseline, 12, 36, and 60 months.

Collaborators and Investigators

• Sponsor: Xinjiang Medical University
• Investigators: Study Chair: Xiang Xie, PhD, First Affiliated Hospital of Xinjiang Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: December 13, 2025
• First Submitted That Met QC Criteria: December 13, 2025
• First Posted (Estimated): December 26, 2025

Study Record Updates

• Last Update Posted (Actual): January 5, 2026
• Last Update Submitted That Met QC Criteria: January 1, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Adrenal Gland Diseases; Adrenocortical Hyperfunction; Cognitive Dysfunction; Dementia; Hyperaldosteronism
• Other Study ID Numbers: K202511-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No