Chinese Classics Recitation Training in Subjective Cognitive Decline

The Effect of Memory Training by Chinese Classics Recitation on Individuals With Subjective Cognitive Decline

Subjective cognitive decline (SCD) is considered a preclinical condition associated with an increased risk of dementia and Alzheimer's disease. Effective early behavioral interventions remain limited, and the neurobiological mechanisms underlying cognitive training effects are not fully understood, particularly in culturally specific educational contexts.

This randomized, assessor-blinded, controlled clinical trial will enroll 60 individuals with SCD to evaluate the effects of a six-month structured Chinese Classics recitation training program. Participants will be randomly assigned to either an intervention group or a non-active control group. Assessments will be conducted at baseline, immediately post-intervention, and during annual follow-up.

Multimodal evaluations will include neuropsychological testing, functional magnetic resonance imaging (fMRI), electroencephalography (EEG), blood biomarker profiling, gut microbiota analysis, and fecal metabolomics. The study aims to examine clinical outcomes and explore potential neurobiological and systemic correlates associated with culturally adapted cognitive training.

Study Overview

• Status: Not yet recruiting
• Conditions: Subjective Cognitive Decline; Subjective Cognitive Decline (SCD)
• Intervention / Treatment: Behavioral: Memory training by Chinese Classics recitation

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sheng-Ta Tsai, M.D., Ph.D.; Phone Number: 886-928262460; Email: tshengdar@gmail.com

Study Locations

• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital
    • Contact: Sheng-Ta Tsai, M.D., Ph.D.; Phone Number: 886-928262460; Email: 027056@tool.caaumed.org.tw
    • Principal Investigator: Sheng-Ta Tsai, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 60 years old

• At least two "yes" responses to the following questions are required:

  1. Forgetting where things are placed?
  2. Unable to recall the names of good friends?
  3. Unable to follow and recall conversation?
  4. Subjective memory problems?
  5. Consider own memory to be worse than others of a similar age?

Exclusion Criteria:

• Objective cognitive impairment defined as ≥ 1.5 standard deviations below standardized cognitive testing (e.g., MMSE)
• Diagnosis of MCI
• Clinical Dementia Rating (CDR) ≥ 0.5
• Diagnosis of major depressive disorder
• Beck Anxiety Inventory score ≥ 16
• Other medical or neurological conditions that could explain cognitive decline (e.g., vascular dementia, traumatic brain injury)
• Claustrophobia
• Contraindications of MRI (e.g., non-MRI-compatible cardiac pacemaker or devices implanted within the past three months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Chinese Classics Recitation for six months	Behavioral: Memory training by Chinese Classics recitation; At least five minutes memory training per day, for six months
No Intervention: non-active control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in task-related brain activation measured by functional MRI	Unit of measure: Whole-brain blood-oxygen-level-dependent (BOLD) signal change (%) Detail Functional magnetic resonance imaging (fMRI) will be used to evaluate changes in task-related brain activation associated with the intervention. Whole-brain blood-oxygen-level-dependent (BOLD) signals will be analyzed using voxel-wise general linear modeling to identify activation patterns during task performance compared with resting baseline. First-level analyses will generate subject-specific contrast maps reflecting task-related neural activation. Group-level random-effects analyses will then be conducted to compare activation patterns between study groups and across time points. Statistical significance will be determined using a voxel-level threshold corrected for multiple comparisons using the false discovery rate (FDR). Effect sizes extracted from significant brain regions will be used for group-level comparisons.	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting-state electroencephalogram (EEG) spectral activity	Unit of Measure µV²/Hz (power spectral density) Detail Resting electroencephalogram (EEG) recordings will be acquired using a standard 21-electrode montage positioned according to the International 10-20 system. Electrode impedance will be maintained below 10 kΩ, with a minimum sampling rate of 256 Hz. Recordings will be performed in a quiet, dimly lit environment with participants seated comfortably and instructed to remain awake with their eyes closed. EEG preprocessing and analysis will be conducted using MNE-Python implemented in Python. The preprocessing pipeline will include re-referencing, resampling to 250 Hz, and band-pass filtering between 0.1 and 41 Hz. Artifact-free EEG signals will be segmented into non-overlapping 2-second epochs for subsequent spectral analysis. Quantitative EEG measures will be derived from the processed signals to characterize resting-state brain activity.	Baseline and 6 months
Global Cognitive Function - MMSE	Outcome Measure Total score on the Mini-Mental State Examination (MMSE) Unit of Measure points Detail The MMSE is a widely used cognitive screening instrument assessing orientation, attention, memory, language, and visuospatial ability. Total score ranges from 0-30, with higher scores indicating better cognitive function.	Baseline and 6 months
Global Cognitive Function - MoCA	Outcome Measure Total score on the Montreal Cognitive Assessment (MoCA) Unit of Measure points Detail The MoCA evaluates multiple cognitive domains including executive function, memory, attention, language, abstraction, and orientation. Total score ranges from 0-30, with higher scores indicating better cognitive performance.	Baseline and 6 months
Verbal Episodic Memory - RAVLT	Outcome Measure Total recall score on the Rey Auditory Verbal Learning Test (RAVLT) Unit of Measure points Detail The RAVLT assesses verbal learning and episodic memory through repeated recall of word lists across trials. Total recall score reflects the number of correctly recalled words, with higher scores indicating better memory performance.	Baseline and 6 months
Executive Function - Stroop Test	Outcome Measure Interference completion time on the Stroop Color and Word Test Unit of Measure seconds Detail The Stroop test measures selective attention and cognitive control. The interference condition requires participants to name the ink color of incongruent color words. Lower completion time indicates better executive function.	Baseline and 6 months
Working Memory - Digit Span	Outcome Measure Total span score on the Digit Span Test Unit of Measure points Detail Digit Span evaluates auditory attention and working memory through forward and backward recall of number sequences. Higher scores indicate better working memory capacity.	Baseline and 6 months
Language Function - Boston Naming Test	Outcome Measure Total score on the Short Form (15 items) of the Boston Naming Test Unit of Measure points Detail The Boston Naming Test assesses confrontational naming ability. The short form contains 15 items, with total score ranging from 0-15, and higher scores indicating better language function.	Baseline and 6 months
Dementia Severity - CDR	Outcome Measure Global score on the Clinical Dementia Rating (CDR) Unit of Measure scale score Detail The CDR is a clinician-rated scale evaluating cognitive and functional performance in dementia. Global score ranges from 0 (no impairment) to 3 (severe dementia).	Baseline and 6 months
Vascular Cognitive Risk - Hachinski Score	Outcome Measure Total score on the Hachinski Ischemic Score Unit of Measure points Detail The Hachinski Ischemic Score differentiates vascular from degenerative causes of cognitive impairment. Scores range from 0-18, with higher scores suggesting greater vascular contribution.	Baseline
Depressive Symptoms - GDS	Outcome Measure Total score on the Geriatric Depression Scale (GDS) Unit of Measure points Detail The GDS evaluates depressive symptoms in older adults. Higher scores indicate more severe depressive symptoms.	Baseline and 6 months
Anxiety Symptoms - BAI	Outcome Measure Total score on the Beck Anxiety Inventory (BAI) Unit of Measure points Detail The BAI measures the severity of anxiety symptoms. Total score ranges from 0-63, with higher scores indicating greater anxiety.	Baseline and 6 months
Cognitive Reserve - CRI-q	Outcome Measure Cognitive reserve index score on the Cognitive Reserve Index questionnaire Unit of Measure index score Detail The CRI-q quantifies lifetime cognitive reserve based on education, occupational complexity, and leisure activities. Higher index scores indicate greater cognitive reserve.	Baseline
APOE genotype distribution	Unit of Measure genotype category Detail Genomic DNA will be extracted from peripheral blood samples to determine the genotype of the APOE, a major genetic risk factor associated with cognitive decline and Alzheimer's disease. Participants will be categorized according to APOE genotype (e.g., ε2/ε2, ε2/ε3, ε3/ε3, ε3/ε4, ε4/ε4).	Baseline
Circulating inflammatory and stress biomarkers (IL-6, TNF-α, hsCRP, and cortisol)	Unit of Measure IL-6: pg/mL TNF-α: pg/mL hsCRP: mg/dL Cortisol: µg/dL Detail Peripheral venous blood samples will be collected after overnight fasting to quantify circulating inflammatory and stress-related biomarkers, including Interleukin-6, Tumor necrosis factor alpha, High-sensitivity C-reactive protein, and Cortisol. Blood samples will be collected in EDTA anticoagulant tubes and processed within 30 minutes by centrifugation at 2,000 × g for 10 minutes at 4 °C. Plasma will be aliquoted and stored at -80 °C until analysis. Cytokine concentration HsCRP concentrations will be measured using high-sensitivity immunoassays to evaluate systemic low-grade inflammation. Plasma cortisol levels will be measured using validated immunoassay methods to assess hypothalamic-pituitary-adrenal (HPA) axis activity and physiological stress responses. Changes in these biomarkers will be analyzed to explore potential inflammatory and neuroendocrine mechanisms associated with the intervention.	Baseline and 6 months
Gut microbiota diversity (Shannon index)	Unit of Measure Shannon diversity index Detail Fecal samples will be collected to evaluate changes in gut microbial diversity associated with the intervention. Microbial community composition will be characterized using full-length 16S rRNA gene sequencing, enabling species-level taxonomic identification of intestinal microorganisms. Alpha diversity will be quantified using the Shannon diversity index, which reflects both species richness and evenness within the microbial community. Changes in Shannon diversity between baseline and follow-up will be analyzed to assess intervention-related alterations in gut microbiota diversity.	Baseline and 6 months
Gut microbiota taxonomic composition	Unit of Measure Relative abundance (%) Detail Fecal microbiota composition will be analyzed using full-length 16S rRNA gene sequencing to determine the relative abundance of bacterial taxa at different taxonomic levels (e.g., phylum, genus, and species). Differential abundance analyses will be conducted to identify microbial taxa whose relative abundance changes over time or differs between study groups.	Baseline and 6 months
Fecal metabolomic profiles related to the gut-brain axis	Unit of Measure Metabolite concentrations (µmol/g feces or relative abundance) Detail Fecal metabolomic profiling will be performed using Liquid chromatography-tandem mass spectrometry to quantify metabolites associated with gut microbiota-host interactions. Metabolites of interest include short-chain fatty acids, bile acids, tryptophan pathway metabolites, neurotransmitter precursors, and inflammation-related metabolites. These analyses will be used to investigate potential metabolic pathways linking gut microbial activity with cognitive and neurophysiological outcomes.	Baseline and 6 months

Collaborators and Investigators

• Sponsor: China Medical University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: March 1, 2026
• First Submitted That Met QC Criteria: March 5, 2026
• First Posted (Actual): March 11, 2026

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: randomized controlled trial; memory training; subjective cognitive decline; Chinese Classics; recitation
• Other Study ID Numbers: CMUH115-REC2-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data will be made available upon reasonable request after publication.

Drug and device information, study documents

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