Effetti di modulazione dell'esercizio di Baduanjin sul declino cognitivo soggettivo (BDJ)

This group will participate in the Baduanjin exercise intervention for 24 weeks (three times/week for the first three months and two times/week for the last three months).

Subjects will participate in Baduanjin, a simple mind-body exercise, for 24 weeks.

This group will participate in the Cognitive Fitness Program intervention for 24 weeks (three times/week for the first three months and two times/week for the last three months).

Subjects will complete paper puzzles (Sudoku, crosswords, etc.) for 24 weeks.

The ADCS-PACC is a composite of well-validated neuropsychological tests selected for their sensitivity to detect the earliest cognitive decline from normal to subtly abnormal performance. In this study, the ADCS-PACC will be reported as a z-transformed composite score, where a z-score of 0 represents the reference population mean and each 1.0 z-score unit corresponds to one standard deviation (SD) from that mean. Higher (more positive) z-scores indicate better cognitive performance, whereas lower (more negative) z-scores indicate worse cognitive performance. We will interpret changes over time as standardized change in global cognition. We reported the change from baseline to 6 months because this is the study's primary timepoint (end of intervention).

Resting-state functional connectivity (rsFC) between the hippocampus and the dorsolateral prefrontal cortex (DLPFC) will be quantified from resting-state functional magnetic resonance imaging (rs-fMRI) data. Specifically, we will compute the correlation between the hippocampal seed time series and the time series from a right DLPFC region of interest (ROI), and report connectivity as a Fisher r-to-z-transformed correlation coefficient (zFC) to support statistical inference. Higher (more positive) zFC values indicate stronger positive coupling, values near 0 indicate little to no coupling, and negative values indicate anticorrelation between regions. In typical rs-fMRI data, Fisher z-transformed connectivity values generally fall within an interpretable range of approximately -0.5 to +0.5. We reported the change from baseline to 6 months because this is the study's primary timepoint (end of intervention) and the prespecified primary endpoint.

The Everyday Cognition - Participant Report Form (ECog) - Everyday Memory domain is an 8-item self-report measure of perceived changes in everyday memory functioning compared with the participant's functioning approximately 10 years earlier. Each item is rated on a 4-point scale ranging from 1 (better or no change) to 4 (consistently much worse). The Everyday Memory domain score is calculated as the average of the completed item scores and ranges from 1 to 4. Higher scores indicate greater perceived decline in everyday memory functioning and represent a worse outcome, while lower scores indicate less perceived decline and represent a better outcome. Here we report the change in this score from baseline to the post-treatment assessment (post-treatment (6 month) - baseline).

PROMIS-29 domain subscore is used to assess Physical Function (includes 4 items). Physical Function score ranges from 4-20 (higher = better function). We report the change in Physical Function from baseline to 6 months as the pre-specified primary time point.

We will quantify bilateral hippocampal volume at baseline and Month 6 (end of intervention) and report the change (Month 6 - baseline). Volumes will be reported in mm³ (and, if applicable, normalized to total intracranial volume). Higher volume indicates greater structural integrity; decreases indicate atrophy. Values are non-negative and typically ~2,000-5,000 mm³ per hemisphere in adults (method- and age-dependent). We will report the observed mean change scores (Δmm³).

p-tau217 (Tau 217) is a blood/CSF biomarker closely linked to Alzheimer's pathology, rising early with amyloid and increasing further with tau tangle burden. "Normal range" is assay-specific; amyloid-negative values are often ~0.2 pg/mL, with rule-in/abnormal cutoffs commonly ~0.33 pg/mL (plus a gray zone).

Secondary autonomic endpoints from a 5-min ECG included RMSSD. We report change from baseline to 6 months (6-month minus baseline) because 6 months was the prespecified primary time point (end of the intervention), intended to capture more sustained effects while reducing short-term variability/attrition. RMSSD (ms) is non-negative (0 to unbounded) and is commonly used as an index of parasympathetic/vagal modulation.

The Beck Anxiety Inventory (BAI) is a 21-item self-report measure of anxiety symptom severity over the past week. Total scores range from 0 to 63 (higher scores indicate greater anxiety). We evaluated change from baseline to month 6, the end of the intervention.

The Symbol Digit Modalities Test (SDMT) is a brief, well-validated measure of processing speed, attention, and visual scanning. Performance is typically the number of correct symbol-digit pairings completed within the time limit (commonly 90 seconds), with scores ranging from 0 to 110 (higher is better). We evaluated change from baseline to month 6, the end of the intervention.

The Stroop Color and Word Test (SCWT) is a widely used measure of selective attention, processing speed, and inhibitory control. Specifically, it measures the ability to suppress the automatic tendency to read a word rather than name the ink color. The slowing in performance caused by this conflict is called Stroop interference. The interference score is often calculated as the additional time required to complete the incongruent color-word condition relative to a baseline (neutral or congruent) condition, with lower time indicating better performance. Scores range from approximately 0 seconds (no interference) to an unbounded upper limit constrained by test duration. We report the change in interference score from post-treatment to baseline.

The Trail Making Test (TMT) Parts A and B measure processing speed, attention, and executive function. Part A assesses visual scanning and speeded sequencing, while Part B additionally requires set-shifting between numbers and letters. Performance on each part is measured as completion time in seconds, with shorter completion times indicating better performance. The outcome reported is the set-shifting cost, calculated as (TMT Part B completion time - TMT Part A completion time)/(TMT Part B completion time + TMT Part A completion time). This is intended to quantify the additional time required for the executive set-shifting demands of Part B while accounting for individual differences in overall processing speed. Lower values indicate better executive performance, whereas higher values indicate worse executive performance. The measure has no established clinical cutoff or threshold values. We report the change in set-shifting cost from baseline to post-treatment.

The Controlled Oral Word Association Test (COWAT), Category Fluency, and Category Switching assess verbal fluency and executive control (letter-based word generation, semantic word generation, and switching between categories). Participants are asked to alternately generate words belonging to two semantic categories during a timed trial. Scores are typically the number of correct, non-repeated words produced within the timed trial(s) (practical range 0 to >40, with higher scores indicating better performance). There are no established clinical threshold or cutoff values for this measure. We evaluated change from baseline to month 6.

The PROMIS® Cognitive Function and Cognitive Function-Abilities item banks assess patient-reported cognitive concerns and perceived cognitive abilities (e.g., memory, attention, mental clarity). Scores are typically reported as T-scores standardized to the U.S. general population (mean 50, SD 10), with higher scores indicating better perceived cognitive function/abilities. We evaluated change from baseline to month 6, the end of the intervention.

The California Verbal Learning Test-II (CVLT-II) is a standardized measure of verbal learning and episodic memory for adolescents and adults. The Short-Delay Free Recall trial assesses the ability to recall a word list approximately 2 minutes after completion of the learning phase. Results are reported as age-adjusted Z-scores based on published normative data. A Z-score of 0 represents the normative population mean, positive Z-scores indicate performance above the population mean (better memory performance), and negative Z-scores indicate performance below the population mean (worse memory performance). There are no universally accepted clinical cutoff values for this outcome. We report the change in Short-Delay Free Recall Z-score from baseline to month 6 (end of the intervention).

The Brief Pain Inventory (BPI) is a 15-item questionnaire that assesses pain location, intensity, relief, quality, and pain-related interference with daily functioning and quality of life. Here, we report average pain over the past week on a 0-10 numeric rating scale. Lower scores indicate less pain (better outcome) and higher scores indicate more pain (worse outcome). We analyzed change from baseline to month 6, which is the end of the study, and included only participants reporting pain (i.e., BPI average pain ≥ 1).

Quantitative sensory testing (QST) will be assessed from baseline to month 6, which represents the end of the intervention. QST will include mechanical and heat pain measures, specifically pain threshold and pain tolerance. Expected values can vary by test location/body site (e.g., face vs forearm), as well as participant and contextual factors such as age, sex, skin characteristics, and testing conditions.