Effect of Yang-deficiency constitution on cognitive impairment in cerebral small vessel disease and its neuroimaging mechanism

doi:10.19852/j.cnki.jtcm.2025.05.019

Abstract

Abstract:

OBJECTIVE: To explore the effect of Traditional Chinese Medicine (TCM) constitution on cognitive impairment (CI) in patients with cerebral small vessel disease (CSVD) and its underlying neuroimaging mechanism and to provide countermeasures for health management of CSVD patients.

METHODS: A total of 241 CSVD patients were recruited from the Department of Neurology. All subjects underwent head magnetic resonance imaging (MRI), Chinese Medicine Questionnaire (CCMQ) and cognitive function examination. The CSVD patients were divided according to the Montreal Cognitive Assessment (MoCA) score into a normal cognitive group (73 cases) and a CI group (168 cases). Logistic regression was used to analyse the risk constitution of CSVD-CI and to construct a risk prediction model. 3DT1 MRI images and FreeSurfer 6.0 software (Athinoula A. Martinos, Boston, MA, USA) were used to further explore the involvement of hippocampal subregion volume in patients with at-risk constitution and its correlation with cognitive function.

RESULTS: Logistic regression analysis showed that Yang-deficiency constitution (YADC) (P = 0.020), older age (P = 0.008) and hypertension (P = 0.011) were risk factors for CSVD-CI but that balanced constitution (P = 0.003) and education (P < 0.001) were protective factors. A receiver operating characteristic curve (ROC) was drawn, and the area under the curve was 0.820. Further comparison of overall hippocampal and 12 hippocampal subregion volumes between YADC and non-YADC patients revealed decreased total volume of the left and right hippocampus, bilateral subiculum, presubiculum, molecular layer and right fimbria in the YADC group (P < 0.05/13, 13 is the number of hypothesis tests). Moreover, in the YADC group, the cognitive function of CSVD patients correlated positively with the overall volume of the left hippocampus (r = 0.304, P < 0.05) and the molecular layer volume of the left hippocampus (r = 0.288, P < 0.05).

CONCLUSION: CSVD patients with YADC are more prone towards developing CI, and asymmetric atrophy of the hippocampus might be the underlying neuroimaging mechanism. In particular, the volume of the left whole hippocampus and the left hippocampal molecular layer correlated significantly with general cognitive function.

Key words: cerebral small vessel disease, cognitive dysfunction, hippocampal subregion, Yang deficiency, Traditional Chinese Medicine constitution

LIU Xin, YANG Shuning, XU Yun. Effect of Yang-deficiency constitution on cognitive impairment in cerebral small vessel disease and its neuroimaging mechanism[J]. Journal of Traditional Chinese Medicine, 2025, 45(5): 1144-1151.

Figures/Tables 6

Table 1 Baseline characteristics of the participants

Characteristic	CSVD-NC group (n = 73)	CSVD-CI group (n = 168)	Test value	P value
General clinical information
Sex [n (%)]			5.479^a	0.019
Male	45 (61.64)	76 (45.24)
Female	28 (38.36)	92 (54.76)
Age (years, $x - ± s$ )	65.11±10.19	68.36±7.87	2.688^b	0.008
BMI (kg/m2, $x - ± s$ )	24.67±3.23	24.21±3.29	-1.004^b	0.316
Years of education [years, M (Q₁, Q₃)]	12 (12, 16)	9 (6, 12)	-6.460^c	<0.001
Smoking [n (%)]	19 (26.03)	40 (23.81)	0.135^a	0.713
Alcohol consumption [n (%)]	18 (24.66)	33 (19.64)	0.767^a	0.381
Family history [n (%)]	23 (31.51)	48 (28.57)	0.211^a	0.646
Assessment of CSVD
Course of CSVD [years, M (Q₁, Q₃)]	2 (1, 5)	3 (1, 5)	-1.612^c	0.107
Presence of dementia [n (%)]	0 (0)	4 (2.38)	1.767^d	0.318
WMH [n (%)]	46 (63.01)	135 (80.36)	8.186^a	0.004
LI [n (%)]	41 (56.16)	118 (70.24)	4.490^a	0.034
CMBs [n (%)]	28 (38.36)	93 (55.36)	5.883^a	0.015
Brain atrophy [n (%)]	20 (27.40)	58 (34.52)	1.181^a	0.277
Blood indexes
TC (mmol/L)	3.92±1.09	4.15±1.08	-1.100^b	0.273
TG (mmol/L)	1.36±0.56	1.57±0.78	1.609^b	0.110
LDL-C (mmol/L)	2.40±0.90	2.35±0.86	0.295^b	0.768
HDL-C (mmol/L)	1.12±0.34	1.21±0.38	-1.176^b	0.242
Apo A1 (g/L)	1.06±0.25	1.11±0.25	-1.013^b	0.313
Apo B (g/L)	0.76±0.25	0.75±0.23	0.281^b	0.779
Hcy (μmol/L)	14.07±4.10	13.12±4.29	1.028^b	0.307
Medical history
Hypertension [n (%)]	42 (57.53)	124 (73.81)	6.288^a	0.012
Diabetes [n (%)]	20 (27.40)	47 (27.98)	0.008^a	0.927
Coronary heart disease [n (%)]	7 (9.59)	10 (5.95)	1.026^a	0.311
Hyperlipidemia [n (%)]	22 (30.14)	38 (22.62)	1.538^a	0.215
Obesity [n (%)]	12 (16.44)	23 (13.69)	0.310^a	0.578
Carotid artery plaque [n (%)]	10 (13.70)	19 (11.31)	0.274^a	0.600
Insomnia [n (%)]	26 (35.62)	54 (32.14)	0.277^a	0.599
Anxiety-depression [n (%)]	22 (30.14)	70 (41.67)	2.866^a	0.090
OSAS [n (%)]	9 (12.33)	15 (8.93)	0.656^a	0.418
Hearing loss [n (%)]	10 (13.70)	27 (16.07)	0.220^a	0.639
Abnormal smell [n (%)]	7 (9.59)	14 (8.33)	0.101^a	0.751
Long-term constipation [n (%)]	16 (21.92)	42 (25.00)	0.265^a	0.607
COPD [n (%)]	4 (5.48)	6 (3.57)	0.466^d	0.496
Hypothyroidism [n (%)]	12 (16.44)	14 (8.33)	3.473^a	0.062
Life history
Lack of nutrition [n (%)]	1 (1.37)	6 (3.57)	0.875^d	0.678
High-fat diet [n (%)]	23 (31.51)	46 (27.38)	0.424^a	0.515
Presence of reading habits [n (%)]	37 (50.64)	38 (22.62)	18.70^a	<0.001
Lack of exercise [n (%)]	46 (63.01)	117 (69.64)	1.022^a	0.312
Lack of social interaction [n (%)]	6 (8.22)	10 (5.95)	0.422^d	0.516
Do household chores [n (%)]	29 (39.73)	49 (29.17)	2.592^a	0.107
Daily life dependence [n (%)]	6 (8.22)	16 (9.52)	0.104^a	0.747

Table 1 Baseline characteristics of the participants

Characteristic	CSVD-NC group (n = 73)	CSVD-CI group (n = 168)	Test value	P value
General clinical information
Sex [n (%)]			5.479^a	0.019
Male	45 (61.64)	76 (45.24)
Female	28 (38.36)	92 (54.76)
Age (years, $x - ± s$ )	65.11±10.19	68.36±7.87	2.688^b	0.008
BMI (kg/m2, $x - ± s$ )	24.67±3.23	24.21±3.29	-1.004^b	0.316
Years of education [years, M (Q₁, Q₃)]	12 (12, 16)	9 (6, 12)	-6.460^c	<0.001
Smoking [n (%)]	19 (26.03)	40 (23.81)	0.135^a	0.713
Alcohol consumption [n (%)]	18 (24.66)	33 (19.64)	0.767^a	0.381
Family history [n (%)]	23 (31.51)	48 (28.57)	0.211^a	0.646
Assessment of CSVD
Course of CSVD [years, M (Q₁, Q₃)]	2 (1, 5)	3 (1, 5)	-1.612^c	0.107
Presence of dementia [n (%)]	0 (0)	4 (2.38)	1.767^d	0.318
WMH [n (%)]	46 (63.01)	135 (80.36)	8.186^a	0.004
LI [n (%)]	41 (56.16)	118 (70.24)	4.490^a	0.034
CMBs [n (%)]	28 (38.36)	93 (55.36)	5.883^a	0.015
Brain atrophy [n (%)]	20 (27.40)	58 (34.52)	1.181^a	0.277
Blood indexes
TC (mmol/L)	3.92±1.09	4.15±1.08	-1.100^b	0.273
TG (mmol/L)	1.36±0.56	1.57±0.78	1.609^b	0.110
LDL-C (mmol/L)	2.40±0.90	2.35±0.86	0.295^b	0.768
HDL-C (mmol/L)	1.12±0.34	1.21±0.38	-1.176^b	0.242
Apo A1 (g/L)	1.06±0.25	1.11±0.25	-1.013^b	0.313
Apo B (g/L)	0.76±0.25	0.75±0.23	0.281^b	0.779
Hcy (μmol/L)	14.07±4.10	13.12±4.29	1.028^b	0.307
Medical history
Hypertension [n (%)]	42 (57.53)	124 (73.81)	6.288^a	0.012
Diabetes [n (%)]	20 (27.40)	47 (27.98)	0.008^a	0.927
Coronary heart disease [n (%)]	7 (9.59)	10 (5.95)	1.026^a	0.311
Hyperlipidemia [n (%)]	22 (30.14)	38 (22.62)	1.538^a	0.215
Obesity [n (%)]	12 (16.44)	23 (13.69)	0.310^a	0.578
Carotid artery plaque [n (%)]	10 (13.70)	19 (11.31)	0.274^a	0.600
Insomnia [n (%)]	26 (35.62)	54 (32.14)	0.277^a	0.599
Anxiety-depression [n (%)]	22 (30.14)	70 (41.67)	2.866^a	0.090
OSAS [n (%)]	9 (12.33)	15 (8.93)	0.656^a	0.418
Hearing loss [n (%)]	10 (13.70)	27 (16.07)	0.220^a	0.639
Abnormal smell [n (%)]	7 (9.59)	14 (8.33)	0.101^a	0.751
Long-term constipation [n (%)]	16 (21.92)	42 (25.00)	0.265^a	0.607
COPD [n (%)]	4 (5.48)	6 (3.57)	0.466^d	0.496
Hypothyroidism [n (%)]	12 (16.44)	14 (8.33)	3.473^a	0.062
Life history
Lack of nutrition [n (%)]	1 (1.37)	6 (3.57)	0.875^d	0.678
High-fat diet [n (%)]	23 (31.51)	46 (27.38)	0.424^a	0.515
Presence of reading habits [n (%)]	37 (50.64)	38 (22.62)	18.70^a	<0.001
Lack of exercise [n (%)]	46 (63.01)	117 (69.64)	1.022^a	0.312
Lack of social interaction [n (%)]	6 (8.22)	10 (5.95)	0.422^d	0.516
Do household chores [n (%)]	29 (39.73)	49 (29.17)	2.592^a	0.107
Daily life dependence [n (%)]	6 (8.22)	16 (9.52)	0.104^a	0.747

Table 2 Distribution characteristics of TCM constitution [n (%)]

TCM constitutional types	Cases (n = 241)	CSVD-NC group (n = 73)	CSVD-CI group (n = 168)	Test value	P value
BC	24 (9.96)	16 (21.92)	8 (4.76)	16.703	< 0.001
YADC	49 (20.33)	6 (8.22)	43 (25.60)	9.485	0.002
YIDC	22 (9.13)	10 (13.70)	12 (7.14)	2.637	0.104
QDC	28 (11.62)	10 (13.70)	18 (10.71)	0.441	0.506
PDC	26 (10.79)	5 (6.85)	21 (12.50)	1.688	0.194
DHC	13 (5.39)	5 (6.85)	8 (4.76)	0.434	0.510
BSC	37 (15.35)	8 (10.96)	29 (17.26)	1.556	0.212
ISC	17 (7.05)	6 (8.22)	11 (6.55)	0.217	0.641
QSC	25 (10.37)	7 (9.59)	18 (10.71)	0.069	0.792

Table 3 Results of multiple logistic regression analysis of factors influencing CSVD-CI

Variable	β value	SE	Wald value	P value	OR value	95% CI
Age	0.05	0.019	6.944	0.008	1.051	1.013, 1.091
Hypertension	0.906	0.357	6.428	0.011	2.475	1.228, 4.988
YADC	1.211	0.522	5.381	0.020	3.356	1.207, 9.337
BC	－1.708	0.573	8.896	0.003	0.181	0.059, 0.557
Education	－0.294	0.054	29.984	<0.001	0.746	0.671, 0.828

Figure 1 AUC for prediction models of CSVD-CI CSVD-CI: cerebral small vessel disease with cognitive impairment; ROC curve: receiver operator characteristic curve; AUC: area under the curve. The AUC was calculated to evaluate the efficiency of the risk model. The AUC ranges from 0.5 to 1.0, whereby 0.9-1.0 indicates an excellent effect, 0.7-0.9 a good effect, and 0.5-0.7 a mediocre effect. P < 0.05 was considered statistically significant.

Table 4 Comparison of hippocampal volume between YADC and non-YADC patients (volume/mm3)

Item	Non-YADC group (n = 192)	YADC group (n = 49)	P value
Left whole hippocampus	3099±327	2935±389	0.003
Left hippocampal tail	508±70	490±80	0.088
Left subiculum	399±49	370±62	0.001
Left CA1	567±71	541±66	0.018
Left hippocampal fissure	173±29	166±27	0.158
Left presubiculum	296±42	275±43	0.002
Left parasubiculum	60±13	55±13	0.025
Left molecular layer	501±56	473±63	0.003
Left GC-ML-DG	252±30	240±35	0.015
Left CA3	168±25	165±30	0.474
Left CA4	217±25	207±28	0.014
Left fimbria	76±22	68±22	0.022
Left HATA	53±9	51±9	0.294
Right whole hippocampus	3214±346	3036±391	0.002
Right hippocampal tail	542±75	511±81	0.013
Right subiculum	404±49	378±57	0.001
Right CA1	610±80	577±80	0.009
Right hippocampal fissure	186±30	184±29	0.731
Right presubiculum	282±38	263±35	0.001
Right parasubiculum	56±12	52±10	0.055
Right molecular layer	524±60	495±67	0.003
Right GC-ML-DG	263±30	251±38	0.046
Right CA3	181±26	180±30	0.784
Right CA4	224±26	215±32	0.061
Right fimbria	71±19	61±18	0.001
Right HATA	55±9	54±9	0.489

Figure 2 Correlation between hippocampal subregion volume and cognitive function in the YADC group A: correlation between the left whole hippocampal volume and MoCA score in the YADC group; B: correlation between tthe left molecular layer volume and MoCA score in the YADC group. YADC group: Yang-deficiency constitution group. MoCA: the Montreal Cognitive Assessment. Spearman correlation analysis was used for correlation analysis. P < 0.05 was considered significant.

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