Preamble

Chinese General Practice https://www.chinagp.net E-mail: zgqkyx@chinagp.net.cn

Study on the Current Status and Influencing Factors of Mild Cognitive Impairment in Elderly Patients with Type 2 Diabetes Mellitus from the Perspective of "Physical Disease-Related Adjustable Constitution": A Case Study in Sichuan Province

MA Yuping¹, QIAO Mengyuan¹, HE Yanyun¹, XU Manru¹, CHEN Chongli², WU Wenbin²*

¹Chengdu University of Chinese Medicine, Chengdu 610075, China
²Department of Elderly Cadres, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China

*Corresponding author: WU Wenbin, Professor/Chief Physician/Doctoral Supervisor; E-mail: wwb1201@vip.sina.com

[Abstract]

Background The rising prevalence of type 2 diabetes mellitus (T2DM) among the elderly has emerged as a critical global public health challenge. Diabetes exerts substantial detrimental effects on cognitive function, yet simple and effective indicators for early monitoring and identification remain lacking, underscoring an urgent need for further investigation. This study leverages real-world cross-sectional data to explore the disease from the perspective of "physical disease-related adjustable constitution," offering potential clinical value for diagnosis and treatment.

Objective To investigate the prevalence and influencing factors of mild cognitive impairment (MCI) in elderly patients with T2DM in Sichuan Province.

Methods Elderly patients aged ≥60 years with T2DM were recruited from multiple communities and three nursing homes across six cities in Sichuan Province (Chengdu, Deyang, Bazhong, Emeishan, Meishan, and Mianyang) between November 2021 and November 2023. Face-to-face surveys were conducted using paper questionnaires covering basic demographic information, the Changsha version of the Montreal Cognitive Assessment (MoCA), and Traditional Chinese Medicine (TCM) constitution assessment. Univariate analysis followed by multivariate logistic regression was performed to identify potential independent factors associated with T2DM accompanied by MCI.

Results A total of 407 questionnaires were distributed, yielding 397 valid responses (97.54% valid response rate). The sample comprised 351 community-dwelling elderly (88.4%) and 46 nursing home residents (11.6%). Eighty-four participants had MCI, resulting in a prevalence of 21.2% for T2DM with MCI. Participants were stratified into two groups: T2DM with MCI (n=84) and T2DM without MCI (n=313). Statistically significant differences between groups were observed in education level, depression, reading habits, and TCM constitution types including qi deficiency, yang deficiency, phlegm-dampness, and damp-heat (P<0.05). Multivariate logistic regression revealed that lower educational attainment (junior high school: OR=0.487, 95%CI=0.253–0.939; university and above: OR=0.149, 95%CI=0.034–0.659) and yang deficiency constitution (OR=2.284, 95%CI=1.220–4.279) were independent risk factors for MCI in elderly T2DM patients (P<0.05). At the biased constitution level, yang deficiency constitution scores were negatively correlated with delayed memory domain scores (r=-0.106, P<0.05).

Conclusion The prevalence of MCI among elderly T2DM patients in Sichuan Province is 21.2%, with low educational attainment and yang deficiency constitution constituting high-risk populations. Grounded in the TCM theory that "constitution can be differentiated, constitution is disease-related, and constitution can be adjusted," early intervention targeting yang deficiency constitution may help reduce the progression to diabetic cognitive impairment.

[Key words] Type 2 diabetes mellitus; Mild cognitive impairment; Aged; Root cause analysis; TCM constitutions

Funding: National Key R&D Program of China (2020YFC2003100; 2020YFC2003104)

Citation: MA YP, QIAO MY, HE YY, et al. Study on the current status and influencing factors of mild cognitive impairment in elderly patients with type 2 diabetes mellitus from the perspective of "physical disease-related adjustable constitution": a case study in Sichuan Province [J]. Chinese General Practice, 2025. DOI: 10.12114/j.issn.1007-9572.2025.0029. [Epub ahead of print]

Introduction

Type 2 diabetes mellitus (T2DM) is a systemic disease characterized by glucolipid metabolism disorders that affects multiple organs, with an extremely high incidence rate. According to the International Diabetes Federation (IDF), the global prevalence of diabetes has reached 10.5%, with projections indicating that the total number of affected individuals will reach 783 million by 2045. In China, the diabetic population continues to grow substantially, and the complications affecting various systems due to hyperglycemia present a serious concern. T2DM with concurrent mild cognitive impairment (MCI) is considered an early stage of dementia, clinically manifested by diminished memory, learning ability, and executive function. Research has demonstrated that both high glucose levels and long disease duration in diabetes are risk factors for cognitive impairment. Moreover, the probability of MCI in T2DM patients over 65 years old is 1.4 times higher than in non-diabetic populations, with the former being more susceptible to progression to Alzheimer's disease. This highlights that clinical management of T2DM should extend beyond glycemic control to emphasize the prevention and management of complications, thereby improving patients' quality of life and reducing societal burden.

Currently, the pathogenesis of T2DM progression to cognitive impairment remains incompletely understood from a Western medicine perspective, and even fewer studies have elucidated this from TCM indicators. TCM theory posits that biased constitution is strongly associated with the occurrence and development of chronic diseases, and constitution identification facilitates early disease recognition and prevention, making it a widely adopted monitoring approach. This study examines elderly populations in select regions of Sichuan to analyze the current status and biased constitution characteristics of MCI in T2DM, aiming to uncover valuable and easily monitorable indicators for disease prevention and treatment, thereby providing guidance for clinical practice.

Methods

Study Design and Participants

This cross-sectional survey was conducted from November 2021 to November 2023. Elderly T2DM patients aged ≥60 years were recruited from multiple communities and three nursing homes across six cities in Sichuan Province: Chengdu, Deyang, Bazhong, Emeishan, Meishan, and Mianyang. Sample size was estimated using the formula n=μ²₂/ₐπ(1-π)/δ² for population proportion estimation, with test level α=0.05 (μₐ/₂=1.96) and allowable error δ=0.05, yielding a calculated sample size of 340. Accounting for a 10% attrition rate, the minimum required sample was 378; this study ultimately included 397 participants. The study protocol was approved by the Medical Ethics Committee of Chengdu University of Traditional Chinese Medicine (Ethics No.: 2021KL-055).

Inclusion Criteria

Participants were required to: (1) meet the diagnostic criteria for diabetes in the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes Mellitus (2017 edition), specifically presenting with typical diabetic symptoms (polydipsia, polyuria, polyphagia, and unexplained weight loss) and random blood glucose ≥11.1 mmol/L or fasting blood glucose ≥7.0 mmol/L; (2) be aged ≥60 years; (3) have resided in Sichuan Province for ≥10 years; (4) be conscious and able to cooperate; and (5) provide informed consent voluntarily.

Exclusion Criteria

Participants were excluded if they had: (1) severe speech, vision, or hearing impairments preventing verbal communication; (2) diagnosed dementia or severe mental disorders; (3) cognitive dysfunction with identified alternative etiologies; or (4) refusal to participate by the individual or legal guardian.

Survey Methods

Face-to-face surveys were administered using paper-based questionnaires with one-on-one assistance from trained researchers. The questionnaire comprised three components: basic demographic information, the Changsha version of the Montreal Cognitive Assessment (MoCA), and TCM constitution assessment.

Basic Information Collection

Basic information included: (1) sociodemographic characteristics: age, gender, education level, living situation, whether living alone, and number of close friends available for support; (2) lifestyle habits: alcohol consumption history, smoking history, smartphone usage, sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI) (comprising 7 items: sleep quality, duration, efficiency, latency, disturbances, medication use, and daytime dysfunction, each scored 0–3 points for a total of 21 points, with 0–5 indicating good sleep, 6–10 fair, and ≥11 poor), recreational activities, reading habits, and physical exercise; and (3) health status: diabetes duration, diabetes medication regimen, hearing, vision, BMI (<18.5 kg/m²=underweight; 18.5–23.9 kg/m²=normal; 24.0–27.9 kg/m²=overweight; >28.0 kg/m²=obese), Barthel Index (BI) (comprising 10 items: feeding, grooming, dressing, bathing, bowel and bladder control, toilet use, ambulation, stair climbing, and bed-chair transfer; total score 0–100, with higher scores indicating better daily living ability: 100=no dependency; 75–95=mild dependency; 50–70=moderate dependency; <45=severe dependency), Instrumental Activities of Daily Living (IADL) scale (comprising 8 items: telephone use, shopping, meal preparation, housekeeping, laundry, transportation, financial management, and medication management; higher scores indicate better instrumental functioning: 8=no dependency; 6–7=mild dependency; 3–5=moderate dependency; <3=severe dependency), Generalized Anxiety Disorder scale (GAD-7) (7 items, total score 0–21, with each item scored 0–3; higher scores indicate greater anxiety: 0–4=no anxiety; 5–9=possible mild anxiety; 10–13=possible moderate anxiety; ≥14=possible severe anxiety), Patient Health Questionnaire-9 (PHQ-9) (9 items, total score 0–27; higher scores indicate greater depression: 0–4=no depression; 5–9=possible mild depression; 10–14=possible moderate depression; ≥15=possible severe depression), and number of chronic diseases.

MoCA Assessment

The Changsha version of MoCA was used to evaluate cognitive function across seven domains: visuospatial/executive function, naming, memory, attention, language, abstract thinking, and delayed memory, with a total score of 30 points. For participants with <12 years of education, one point was added to the final score to correct for educational bias. A cutoff score of 22 points was used to identify cognitive impairment, with ≥22 indicating normal cognition and <22 indicating impairment, of which 18–21 points were classified as MCI.

TCM Constitution Assessment

According to the Classification and Determination of TCM Constitution standards, constitution types include balanced constitution, qi deficiency constitution, phlegm-dampness constitution, yang deficiency constitution, yin deficiency constitution, damp-heat constitution, blood stasis constitution, and special diathesis constitution. This study utilized the Elderly TCM Constitution Scale, with each question scored on a 5-point scale. Constitution determination followed the highest score method. A biased constitution was identified when the score for any constitution type (except balanced) was ≥11 points, while balanced constitution was determined when the balanced constitution score was >17 points and all other eight constitution scores were ≤10 points.

Quality Control

All researchers underwent standardized training to ensure accurate and effective data collection and assessment. Participants were thoroughly briefed on the survey purpose, precautions, and significance before questionnaire administration. All questionnaires were distributed, completed, and collected on-site, with final data entered by two independent researchers and cross-verified. Surveys with >10% missing data or participants who withdrew mid-survey were excluded.

Statistical Analysis

Data were analyzed using SPSS 26.0 software. Quantitative data following normal or approximately normal distribution were expressed as (x̄±s) and compared between groups using independent samples t-tests. Categorical data were expressed as frequencies and percentages, with inter-group comparisons performed using χ² tests or Fisher's exact test. Pearson correlation analysis was used to examine relationships between different cognitive domains and yang deficiency constitution. Multivariate binary logistic regression was employed to explore independent influencing factors of T2DM with MCI, with MCI status as the dependent variable (0=no MCI, 1=MCI) and forward conditional method for variable selection. Model fit was assessed using Omnibus tests and Hosmer-Lemeshow tests. Statistical significance was set at P<0.05.

Results

Survey Response and Participant Characteristics

A total of 407 questionnaires were distributed, with 10 excluded due to improper completion, resulting in 397 valid questionnaires (97.54% valid response rate). The sample included 351 community-dwelling elderly (88.4%) and 46 nursing home residents (11.6%); 154 (38.79%) were male and 243 (61.21%) female, with ages ranging from 60 to 101 years and a mean age of 73.4±0.4 years. Eighty-four participants had MCI, yielding a prevalence of 21.2% for T2DM with MCI. Participants were divided into two groups based on MCI status: T2DM with MCI group (n=84) and T2DM without MCI group (n=313).

The mean MoCA score for all 397 elderly T2DM patients was 21.98±0.26. The T2DM without MCI group had a mean MoCA score of 22.53±5.77, while the T2DM with MCI group had a mean score of 19.96±1.01.

Univariate Analysis of MCI in Elderly T2DM Patients

Significant differences between groups were observed in education level, depression, reading habits, qi deficiency constitution, yang deficiency constitution, phlegm-dampness constitution, and damp-heat constitution (P<0.05). No statistically significant differences were found in age, gender, diabetes duration, diabetes medication regimen, living situation, social support, smartphone usage, vision, hearing, BMI, BI, IADL, PSQI, GAD-7, PHQ-9, smoking, alcohol consumption, number of chronic diseases, recreational activities, physical exercise, yin deficiency constitution, blood stasis constitution, qi stagnation constitution, or special diathesis constitution (P>0.05). Detailed results are presented in Table 1 [TABLE:1].

Multivariate Logistic Regression Analysis of MCI Influencing Factors

Multivariate logistic regression analysis was performed with MCI status as the dependent variable (0=no MCI, 1=MCI) and variables showing significant differences in univariate analysis as independent variables. Results indicated that lower educational attainment (junior high school: OR=0.487, 95%CI=0.253–0.939; university and above: OR=0.149, 95%CI=0.034–0.659) and yang deficiency constitution (OR=2.284, 95%CI=1.220–4.279) were independent risk factors for MCI in elderly T2DM patients (P<0.05). The Hosmer-Lemeshow test yielded χ²=1.142, P=0.992, indicating good model fit. Detailed results are presented in Table 2 [TABLE:2].

Comparison of Cognitive Domain Scores Between Groups

Significant differences between groups were observed in five cognitive domains: naming, attention, language, abstraction, and delayed memory (P<0.05). No significant differences were found in visuospatial/executive function or orientation domains (P>0.05). Detailed results are presented in Table 3 [TABLE:3].

Correlation Analysis Between Cognitive Domains and Yang Deficiency Constitution

Correlation analysis between cognitive domain scores and yang deficiency constitution scores revealed significant correlations among all seven cognitive domains (P<0.05). Yang deficiency constitution scores were negatively correlated with delayed memory domain scores (r=-0.106, P<0.05). Detailed results are presented in Table 4 [TABLE:4].

Discussion

Diabetic cognitive impairment severely impacts patients' quality of life, and its pathogenesis remains incompletely understood. Current evidence suggests that insulin resistance, endoplasmic reticulum stress, neuronal calcium homeostasis imbalance, inflammatory stress responses, and mitochondrial energy imbalance are all implicated in the disease process. As a nation with a large diabetic population and severe aging demographics, China must proactively address cognitive function in elderly diabetic patients. With no specific cure for cognitive impairment currently available, and progression to various degrees of dementia imposing enormous societal burden, early identification and prevention are more meaningful than treatment.

This study, based on data from multiple regions in Sichuan, found a 21.2% prevalence of MCI among elderly T2DM patients in select areas of the province. This aligns closely with a study showing a 21.9% prevalence among elderly communities in Wuhan, Hubei, but differs from findings by Ma et al. (39.3% prevalence in community-dwelling elderly T2DM patients) and a 10.28% prevalence among elderly communities in Weifang. These discrepancies may be attributable to differences in study populations, regional factors, and assessment tools.

Multivariate analysis identified education level and yang deficiency constitution as independent risk factors for MCI in T2DM. The educational finding is consistent with previous research establishing low education as a risk factor for MCI, showing a negative correlation. Higher education levels correlate with longer engagement in mental activities, better cognitive function, and enhanced comprehension and thinking abilities. Mental stimulation strengthens synaptic connections between neurons, thereby slowing cognitive decline associated with brain aging. At the constitution level, this study revealed that elderly T2DM patients with yang deficiency constitution had more than twice the risk of developing MCI compared to non-yang deficiency individuals (OR=2.284, 95%CI=1.220–4.279, P<0.05), a finding that differs from Wang et al., possibly due to variations in age structure and disease duration. We recommend incorporating constitution screening into health monitoring for diabetic populations, with particular emphasis on cognitive assessment in yang deficiency individuals.

Classical TCM texts have long documented yang qi nourishing the spirit: "When yang qi is vigorous, it nourishes the spirit; when gentle, it nourishes the sinews" (Suwen·Shengqi Tongtian Lun) and "Exhaustion of yang qi causes forgetfulness" (Suwen·Sishi Ci Ni Cong Lun), providing theoretical foundations for yang qi nourishing the spirit. Elderly individuals experience declining organ function and yin-yang imbalance, with yang deficiency constitution being particularly common. Biased constitution contributes to the development and progression of numerous chronic diseases. Diabetic patients, due to constitutional insufficiency and improper diet, initially present with yin deficiency and heat excess, which over time damages yang qi, resulting in mixed cold-heat patterns. As Huang Yuanyu explained in Si Sheng Xin Yuan regarding the pathogenesis of diabetes: "Drinking one dou [unit] and urinating one dou; upper body injury from dryness-heat, lower body disease from damp-cold; dryness-heat in liver and lung channels, damp-cold in spleen and kidney organs." Sichuan's basin geography exposes organs to chronic dampness, which is a yin pathogen that readily damages yang qi, predisposing individuals to yang deficiency constitution. The brain governs the marrow, which is generated from essence and blood. In yang deficiency individuals, insufficient generation of qi, blood, and fluids leads to two consequences: first, clear yang fails to ascend, inadequately nourishing brain marrow; second, yang deficiency cannot transform dampness, allowing damp evils to obstruct the clear orifices and block the spirit mechanism, manifesting as MCI. If yang deficiency progresses further, cold-dampness accumulates and generates phlegm, leading to intermingling of phlegm-turbidity, blood stasis, and toxic evils, ultimately resulting in dementia. Therefore, early intervention for biased constitution holds long-term value. Liu Wansu stated in San Xiao Lun: "For diabetes, the spleen and stomach are extremely deficient and should be warmed and supplemented; if cold medicinals are administered, they will further damage spleen and stomach, making the condition difficult to treat due to original qi deficiency," thus advocating spleen-warming methods. Chen Rui proposed treating T2DM by balancing cold-heat, eliminating turbidity, and supporting yang, with rational application of yang-warming medicinals such as Cinnamomi Ramulus, Zingiberis Rhizoma, and Astragali Radix. Additionally, Wang et al. and Zhu et al. reported significant efficacy of moxibustion on the Governor Vessel in treating MCI, demonstrating the importance of protecting yang qi in cognitive preservation. These findings suggest that applying TCM's disease prevention concepts—"constitution can be differentiated, constitution is disease-related, and constitution can be adjusted"—may improve clinical recognition of MCI development in T2DM and enable earlier prevention.

This study found that patients with comorbid MCI showed higher impairment rates in naming, attention, language, abstraction, and delayed memory domains compared to those without MCI, with delayed memory being the most significantly affected—a finding consistent with previous research. This suggests that T2DM-related cognitive impairment may initially damage these five cognitive domains. The results also demonstrated a strong association between delayed memory and yang deficiency constitution, indicating that while T2DM-related cognitive impairment is widespread, yang deficiency constitution may primarily affect delayed memory, thereby reducing overall cognitive function. Clinically, assessing delayed memory decline may enable early disease interception.

In conclusion, this study demonstrates that low education level and yang deficiency constitution are closely associated with MCI in elderly T2DM patients. For elderly T2DM patients, comprehensive geriatric assessment including cognitive function should be emphasized during regular follow-up to improve quality of life. TCM constitution theory holds significant value for monitoring and managing chronic diseases, and integrating constitution indicators may open new avenues for TCM prevention and treatment of this condition. However, this study had a relatively small sample size, necessitating future larger-scale studies for deeper exploration.

Author Contributions: MA Yuping conceptualized the study, designed the research, and drafted the manuscript; QIAO Mengyuan and HE Yanyun collected and organized data and performed statistical analysis; XU Manru and CHEN Chongli revised the manuscript; WU Wenbin supervised quality control and review and was responsible for overall manuscript supervision.

Conflicts of Interest: None declared.

Received: 2025-02-10
Revised: 2025-04-30

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