Therapeutic Potential of Combined Herbal Medicine and Electroacupuncture in Mild Cognitive Impairment Through Cytokine Modulation: An Observational Study

Figures & data

Table 1 Schedule for Enrollment, Clinical Outcomes, and Safety Assessment

Period	Screening	Treatment and Follow-Up*
Visit	Screening	1	2~11	12	13~23	24	25
Week	−1	0	1~5	6	7~11	12	24
Provided informed consent	○
Identification of inclusion and exclusion criteria	○
Demographics	○
Medical and disease history	○
Vital signs	○	○	○	○	○	○	○
Clinical laboratory examination	○					○
Pregnancy test	○
Out comes
MoCA-K	○					○	○
CDR	○
ADAS-K-Cog		○				○	○
PSS		○		○		○	○
BDI		○		○		○	○
ISI		○		○		○	○
SNAQ		○		○		○	○
EQ-5D		○		○		○	○
IMPSS				○		○	○
Blood collection for immune analysis		○				○
Treatment
HM, EA		○	Δ	Δ	Δ	Δ	Δ
Others		Δ	Δ	Δ	Δ	Δ	Δ
Identification of adverse reaction(s)			Δ	○	Δ	○	○
Medication compliance				○		○	Δ
Identification of concomitant drug change		○		○		○	○
Education on visit schedule	○	○	○	○	○	○	Δ

Notes: ΔIf applicable, record the result. *If participant’s temporary suspension of treatment or missing one follow-up, it was not a drop out.

Abbreviations: MoCA-K, the Korean version of the Montreal Cognitive Assessment; CDR, clinical dementia rating; ADAS-K-Cog, Korean version of the cognitive subscale of the Alzheimer’s Disease Assessment Scale; PSS, Perceived Stress Scale; BDI, Beck Depression Inventory; ISI, Insomnia Severity Index; SNAQ, Simplified Nutritional Appetite Questionnaire; EQ-5D, European Quality of Life-5 Dimensions; IMPSS, Integrative Medicine Patient Satisfaction Scale; HM, herbal medicine; EA, electroacupuncture.

Figure 1 Study design flowchart.

Table 2 Outcomes Changes Associated with Herbal Medicine

Outcome	Baseline		After 24 Weeks		24 Weeks-Baseline
	Mean (SD)	Median [IQR]	Mean (SD)	Median [IQR]	p-value
MoCA-K	19.00 ± 3.10	19.5 [16.0, 22.0]	24.67 ± 2.34	24.5 [24.0, 26.0]	0.0313^a
ADAS-K-Cog	15.17 ± 4.79	16.5 [11.0, 18.0]	7.33 ± 3.83	7.5 [3.0, 11.0]	0.0313^a
PSS	19.83 ± 4.96	19.5 [16.0, 20.0]	16.67 ± 2.73	17.0 [14.0, 19.0]	0.0313^a
BDI	21.83 ± 15.50	22.5 [7.0, 31.0]	15.33 ± 12.51	11.0 [10.0, 20.0]	0.0938
ISI	11.33 ± 6.50	10.5 [6.0, 16.0]	6.83 ± 2.64	8.0 [4.0, 9.0]	0.1250
SNAQ	13.50 ± 2.43	14.5 [11.0, 15.0]	13.67 ± 2.07	13.5 [12.0, 16.0]	0.7813
EQ-5D	0.78 ± 0.14	0.82 [0.77, 0.82]	0.80 ± 0.09	0.80 [0.77, 0.87]	0.7500

Notes: Values are expressed as the mean of the score change and its 95% confidence interval; ^ap < 0.05, vs baseline.

Abbreviations: SD, standard deviation; IQR, interquartile range; MoCA-K, Korean version of the Montreal Cognitive Assessment; ADAS-K-Cog, Korean version of the cognitive subscale of the Alzheimer’s Disease Assessment Scale; PSS, Perceived Stress Scale; BDI, Beck Depression Inventory; ISI, Insomnia Severity Index; SNAQ, Simplified Nutritional Appetite Questionnaire; EQ-5D, European Quality of Life-5 Dimensions.

Figure 2 Cytokine levels before and after herbal formula treatment. Graphs represent an average concentration of cytokines in six patients.

Abbreviations: IL, interleukin; FGF, fibroblast growth factor; G-CSF, granulocyte-colony-stimulating factor; IFN, interferon; IP, inducible protein; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; RANTES, regulated on activation normal T-cell expressed and presumably secreted; TNF, tumor necrosis factor.

Data Sharing Statement

Original data (crude data) from this study are available by contacting the corresponding author via email.