Cognitive impairment generally refers to various degrees of compromised cognitive function due to diverse factors, ranging from mild cognitive impairment to dementia. Along with global aging, the incidence of cognitive impairment is increasing [
During human life, Traditional Chinese Medicine (TCM) constitution is a comprehensive and relative stable trait based on the congenital and acquired morphological structure, physiological function, and psychological status [
Blood stasis (BS) constitution is a common TCM constitution in the elderly population with cognitive impairment [
Inclusion criteria include patients
Flowchart of data processing and screening.
Sociodemographic data are sex, age, education level, smoking (in the past 12 months), alcohol consumption (none, occasionally, often, or alcoholic), and exercise (none, occasionally, or often).
History of chronic illnesses: the diagnostic criteria of hypertension referred to China’s Guidelines for Prevention and Control of Hypertension (2010 edition) [
Red blood cells (RBC) and hemoglobin (HB) [
Blood lipids and glucose: blood lipid and glucose levels were examined by a Mindray BS420 automatic biochemical analyzer (Shenzhen, China). Related reagents were purchased from Purebio Biotechnology Co., Ltd. (Ningbo, China). Fasting venous blood (5 ml) was drawn from all subjects. Total cholesterol and triglyceride levels were measured by an enzyme-coupled assay. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) were measured by an enzyme-multiplied immune assay.
ABI and BaPWV: limb bilateral ABI and BaPWV were determined using an AS-1000 PWV Measurement System (Heath Digit, Hong Kong, China). The reference value of BaPWV was set at 14.00 m/s; a higher value indicated a stiffer arterial wall. Diagnostic criteria of lower extremity arteriosclerosis include arteriosclerosis, ABI
MMSE, created by Folstein
According to the 33-item questionnaire in the TCM Service Log for the Elderly issued by China TCM Administration in 2013 [
Statistical analysis of the data was performed using SPSS 24.0 software (SPSS Inc., Chicago, IL, USA). Quantitative data with a normal distribution were presented as the mean ± standard deviation, whereas quantitative data that did not meet a normal distribution were presented as the median and interquartile range. Enumeration data were presented as absolute number and rate. Group-wise comparisons of quantitative data with normal distribution were conducted by t-test. Quantitative data that did not meet a normal distribution were compared using Rank-sum test. Group-wise comparisons of enumeration data were performed using the Chi-square test. Ranked data were compared with the Rank-sum test. For categorical variables, the group with the lowest risk was used as the reference, and the odds ratio (OR) and 95% confidence interval (CI) of each stratum were obtained by setting dummy variables in a binary logistic regression model. The interaction effects of sociodemographic and atherosclerotic factors on MMSE score were analyzed using multivariate linear regression [
After sending an invitation letter to older adults, n=3,201 individuals registered for the physical examination. Subjects who were < 65 years old (n=1,394) or who had incomplete data for diagnostic purposes (n=27+743) were excluded from the study. Finally, a total of 1,037 eligible subjects were included into the analysis. The 1,037 subjects scored 0-30 in MMSE and the average MMSE score was 25.06±4.42. A total of 135 subjects (13.0%) were characterized with cognitive impairment.
As shown in Table
Distribution of general factors in aged subjects with and without cognitive impairment (n=1,037).
Item | Cognitive impairment | P-value | |||
---|---|---|---|---|---|
Normal | Presence | ||||
| Male | 502 (90.0) | 56 (10.0) | 9.490 | 0.002 |
Female | 400 (83.5) | 79 (16.5) | |||
| <70 | 491 (89.9) | 55 (10.1) | 8.833 | 0.003 |
≥70 | 411 (83.7) | 80 (16.3) | |||
| No | 777 (86.1) | 125 (13.9) | 4.498 | 0.034 |
Yes | 109 (93.2) | 8 (6.80) | |||
| None | 786 (86.2) | 126 (13.8) | 2.720 | 0.099 |
Occasionally | 72 (94.7) | 4 (5.30) | |||
Often | 44 (89.8) | 5 (10.2) | |||
| Illiteracy | 118 (65.2) | 63 (34.8) | 45.863 | <0.001 |
Primary | 318 (93.0) | 24 (7.0) | |||
Secondary | 286 (88.5) | 37 (11.5) | |||
High school and above | 180 (94.2) | 11 (5.8) | |||
| Often | 38 (82.6) | 8 (17.4) | 11.755 | 0.008 |
Everyday | 677 (88.7) | 86 (11.3) | |||
Occasionally | 110 (85.9) | 18 (14.1) | |||
None | 77 (77.0) | 23 (23.0) | |||
| Normal | 446 (87.8) | 62 (12.2) | 2.551 | 0.110 |
Overweight | 361 (87.8) | 50 (12.2) | |||
Obesity | 95 (80.5) | 23 (19.5) | |||
| Absence | 362 (88.3) | 48 (11.7) | 1.029 | 0.310 |
Presence | 540 (86.1) | 87 (13.9) | |||
| Absence | 683 (87.5) | 98 (12.5) | 0.618 | 0.432 |
Presence | 219 (85.5) | 37 (14.5) |
Note: the data are presented as number of subjects (rate, %).
Compared with individuals in the group with normal cognitive function, individuals in the cognitive impairment group had a higher BaPWV level (P < 0.05) and reduced levels of RBC, HB, and ABI (P < 0.05) (Table
Distribution of atherosclerotic factors in the elderly population with or without cognitive impairment (n=1037).
Item (reference range) | Cognitive impairment | Z value | P-value | |
---|---|---|---|---|
Normal | Presence | |||
| 4.30 (0.54) | 4.18 (0.54) | -2.518 | |
| 136.0 (23.0) | 132.5 (16.0) | -2.802 | |
FBS (3.89-6.11mmol/L) | 5.47 (1.21) | 5.53 (1.53) | -0.451 | 0.652 |
TC (0-5.2 mmol/L) | 5.09 (1.31) | 5.09 (1.67) | -0.387 | 0.699 |
TG (0-1.7 mmol/L) | 1.40 (0.90) | 1.36 (0.81) | -0.333 | 0.739 |
LDL-C (0-3.12 mmol/L) | 2.83 (1.01) | 2.89 (1.06) | -0.083 | 0.934 |
HDL-C (0.91-2.59 mmol/L) | 1.42 (0.43) | 1.43 (0.44) | -0.266 | 0.790 |
| 14.64 (3.98) | 15.36 (3.87) | -2.077 | |
| 1.08 (0.17) | 1.02 (0.14) | -3.933 | |
Note: the data are presented as median (interquartile range).
Univariate analyses showed that the BS constitution variable was associated with cognitive function significantly (P<0.05, Table
Distribution of cognitive impairment in various TCM constitutions of aged population (n=1037)
TCM constitution | Cognitive impairment | P-value | |||
---|---|---|---|---|---|
Normal | Presence | ||||
Balanced | No | 727(86.2) | 116(13.8) | 2.191 | 0.139 |
Yes | 175(90.2) | 19(9.8) | |||
Qi-deficiency | No | 821 (87.3) | 119 (12.7) | 1.142 | 0.285 |
Yes | 81 (83.5) | 16 (16.5) | |||
Yang-deficiency | No | 738 (87.9) | 102 (12.1) | 2.993 | 0.084 |
Yes | 164 (83.2) | 33 (16.8) | |||
Yin-deficiency | No | 656 (88.1) | 89 (11.9) | 2.685 | 0.101 |
Yes | 246 (84.2) | 46 (15.8) | |||
Phlegm | No | 627 (87.2) | 92 (12.8) | 0.103 | 0.749 |
Yes | 275 (86.5) | 43 (13.5) | |||
Damp-heat | No | 865 (86.9) | 130 (13.1) | 0.048 | 0.827 |
Yes | 37 (88.1) | 5 (11.9) | |||
| No | 835 (87.6) | 118 (12.4) | 4.208 | 0.040 |
Yes | 67 (79.8) | 17 (20.2) | |||
Qi-stagnation | No | 872 (87.4) | 126 (12.6) | 3.621 | 0.057 |
Yes | 39(76.9) | 9(23.1) | |||
Inherited Special | No | 897(87.1) | 133(12.9) | 0.228 | |
Yes | 5 (71.4) | 2 (13.0) |
Distribution of MMSE scores in various TCM constitutions of aged population with cognitive impairment (n=135)
TCM constitution | MMSE score | P-value | |||
---|---|---|---|---|---|
Normal | Tendency | Presence | |||
Balanced | 16.61±5.74 | 17.77±5.32 | 18.74±4.19 | 3.076 | 0.215 |
Qi-deficiency | 17.50±5.06 | 18.11±4.32 | 14.13±7.99 | 2.222 | 0.329 |
Yang-deficiency | 17.16±5.37 | 18.10±5.76 | 16.94±5.79 | 0.407 | 0.816 |
Yin-deficiency | 17.40±5.60 | 17.62±6.11 | 16.59±4.86 | 2.047 | 0.359 |
Phlegm | 17.23±4.63 | 16.44±7.06 | 17.65±5.29 | 0.208 | 0.901 |
Damp-heat | 17.14±5.45 | 17.50±6.14 | 17.20±5.17 | 0.254 | 0.881 |
| | | | | |
Qi-stagnation | 17.53±5.02 | 13.83±9.09 | 14.78±7.61 | 1.567 | 0.457 |
Inherited Special | 17.24±5.38 | 13.67±10.5 | 18.50±3.54 | 0.428 | 0.807 |
Note: as some subjects presented several TCM constitutions, i.e., they met the criteria of two or more TCM constitutions, they were included in the table as two TCM constitutions. For example, if a subject was identified as both Qi-deficiency constitution and phlegm constitution, the patient was included in the Qi-deficiency group as well as the phlegm group. If the subject did not meet the criteria of “Yes” for that constitution type, they were not included in the statistical analysis.
After controlling for sociodemographic factors, such as sex, age, smoking, education level, and exercise habit, logistic regression analysis indicated that RBC (OR=0.503, P=0.004), HB (OR=0.980, P=0.003), ABI ⩽0.90 (OR=2.199, P=0.023), and BS constitution (OR=1.808, P=0.042) correlated with cognitive impairment (Table
Logistic regression analysis of cognitive impairment as a function of atherosclerotic factors and blood-stasis.
Items | OR (95% CI) | P-value |
---|---|---|
RBC | 0.530 (0.343-0.817) | 0.004 |
HB | 0.980 (0.967-0.993) | 0.003 |
BaPWV | ||
<14 Normal | 1.00 | |
≥14 Atherosclerosis | 1.441 (0.982-2.115) | 0.062 |
ABI | ||
1.0~1.3 Normal | 1.00 | |
0.9~1.0 Critical | 1.747 (1.160-2.629) | 0.008 |
≤0.9 Arteriostenosis | 2.199 (1.112-4.347) | 0.023 |
≥1.3 Atherosclerosis | 1.132 (0.495-2.587) | 0.769 |
Blood stasis | ||
Absence | 1.00 | |
Tendency | 1.056 (0.600-1.857) | 0.850 |
| | |
Note: data after adjustment for sociodemographic factors including sex, age, smoking, education level, and exercise habit.
Hierarchical regression was employed to study the interaction effect between BS constitution and atherosclerotic factors on MMSE score. In order to avoid the influence of collinearity, variables were decentralized to obtain the corresponding standard scores. Subsequently, BS constitution was multiplied by standard scores of the atherosclerotic factors that displayed statistical significance in Table
The interaction effect between BS constitution and atherosclerotic factors on MMSE score.
Variables | R2 | ΔR2 | ΔF | ||
---|---|---|---|---|---|
Step 1 | 0.377 | 0.002 | 3.622 | ||
RBC | 0.126 | ||||
HB | 0.102 | ||||
ABI | 0.343 | ||||
BaPWV | -0.053 | ||||
BS constitution | -0.207 | ||||
Step 2 | 0.392 | 0.016 | 6.604 | ||
RBC | 0.165 | ||||
HB | 0.058 | ||||
ABI | 0.390 | ||||
BaPWV | -0.066 | ||||
BS constitution | -0.202 | ||||
BS × RBC | -0.028 | ||||
BS × HB | 0.362 | ||||
BS × ABI | 0.348 | ||||
BS × BaPWV | 0.317 |
Note:
In order to better present the interactions with blood stasis constitution, all subjects were assigned to two groups: BS constitution group and non-BS group (Normal + Tendency). The fitting curves of regression equations for atherosclerotic factors and MMSE score were plotted for each group. As shown in Figure
Interaction effect between blood stasis and atherosclerotic factors on MMSE score.
Different TCM constitutions may be encountered in patients diagnosed according to Western practices as having a similar disease. In the present study, a total of 135 subjects (13.0%) were characterized with cognitive impairment, and 17 of those (12.6%) involved BS constitution. This was consistent with the TCM etiology of cognitive impairment originates from deficiency in viscera and presents as blood stasis and phlegm obstruction [
Individuals with BS constitution tend to express blood high viscosity syndrome (BHVS), which is the pathological state of blood stagnation and associated with increased atherosclerosis [
The interaction between BS constitution and atherosclerotic factors was further investigated. The results showed that there were interactions of BS with HB, RBC, and ABI on cognitive impairment (P<0.05). These findings demonstrated that the MMSE score in HB, ABI, and BaPWV level decreased even further in the presence of concurrent BS constitution. The possible reason is that a relatively stable constitution has formed in adults and blood stasis exists throughout the whole process of disease development. Thus, blood stasis is a product of disease development, and it in turn causes further damage in the target organ(s). On the other hand, the nature of hemorheology changes with age [
Serum lipid and glucose levels have frequently been reported as risk factors for cognitive impairment [
In this study, we have shown that the elderly population with BS constitution have a higher risk of arterial stenosis and sclerosis, leading to susceptibility to cognitive impairment. Hence, it is important that community health service institutes shall not only provide basic medical treatment for chronic diseases in the elderly with a high risk of cognitive impairment, but also offer TCM intervention to promote blood circulation and remove BS according to the TCM constitution under the TCM principle of preventive treatment, for the best control of risk factors of cognitive impairment.
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that they have no conflicts of interest.
This study was supported by the Research Project for Traditional Chinese Medicine of Fujian Province (no. 2017FJZYZC101), Fujian Province Natural Science Foundation (nos. 2016J01665 and 2018J01880), and the University Distinguished Young Research Talent Training Program of Fujian Province.
Two short descriptions for appendixes are as follows. Appendix 1-MMSE-Form. The MMSE is a brief, quantitative measure of cognitive status in adults. It can be used to screen for cognitive impairment, to estimate the severity of cognitive impairment at a given point in time, to follow the course of cognitive changes in an individual over time, and to document an individual's response to treatment. Appendix 2-Constitution in TCM Questionnaire(33). The “English version Constitution in Traditional Chinese Medicine Questionnaire” is an effective research tool to carry out a large-scale research. It also can be used as a physical fitness assessment tool on foreigners.