The Association Between Primary Aldosteronism and Cognitive Dysfunction

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.

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.

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.

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.

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).

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.

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.

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.

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.

Absolute plasma aldosterone concentration, measured in pg/mL.

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.

Absolute serum potassium concentration, measured in mmol/L.

Absolute serum sodium concentration, measured in mmol/L.

Fasting serum concentration of LDL-C, measured in mmol/L.

Fasting serum concentration of Lp(a), measured in nmol/L, an independent risk factor for cardiovascular disease.

Concentration of glucose in plasma after ≥8 hours of fasting, measured in mmol/L.

The percentage of HbA1c in blood, reflecting average blood glucose over the preceding 2-3 months.

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).

The UACR measured from a spot urine sample and reported in mg/g, a marker of kidney damage.

Left ventricular mass indexed to body surface area (g/m²), calculated from echocardiographic measurements. The key criterion for diagnosing left ventricular hypertrophy.

The percentage of blood ejected from the left ventricle during each contraction, measured by echocardiography.

The mean far-wall intima-media thickness of the common carotid artery (mm), measured bilaterally by ultrasound. A marker of subclinical atherosclerosis.

Concentration of plasma NfL (pg/mL), a biomarker of neuroaxonal injury, measured in a pre-defined sub-cohort.

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.

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).

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.

Record of deaths from any cause during follow-up. Confirmed by medical records, family follow-up, or national death registration systems.