Meta-analysis links Chinese herbal therapy to short-term cognitive gains in vascular dementia

A systematic review and meta-analysis of 38 randomized controlled trials involving 3,357 adults with vascular dementia found that traditional Chinese medicine kidney-tonifying and blood-activating therapy, used alone or alongside conventional Western medicines, was associated with better clinical responses and cognitive-test scores than Western medicine alone. The reported effects occurred during treatment periods of one to six months. However, the review identified substantial weaknesses in trial reporting, possible publication bias and insufficient safety data to establish that the herbal approach is risk-free or changes the underlying disease.

The analysis, published in Frontiers in Neurology, examined interventions selected for a traditional Chinese medicine principle described as “kidney deficiency and blood stasis.” Within that framework, kidney-tonifying herbs are intended to restore what is described as deficient kidney essence, while blood-activating herbs are intended to improve circulation. The researchers operationally included decoctions, granules, capsules, tablets and patent medicines containing both types of components. Twenty studies used decoctions and 15 used capsules, while granules, tablets and mixtures each appeared in one study.

Frequently used ingredients included Chuanxiong rhizome, prepared Rehmannia root, Polygonum multiflorum and Cornus fruit, but formulas, ingredient combinations and dosages differed substantially among the trials. In 22 trials comparing kidney-tonifying and blood-activating therapy plus Western medicine with Western medicine alone, the pooled risk ratio was 1.25, with a 95% confidence interval of 1.20 to 1.31. Thirteen trials comparing the herbal approach as monotherapy with Western medicine produced a similar pooled risk ratio of 1.26, with a 95% confidence interval of 1.19 to 1.34.

These estimates indicate a higher probability of meeting each study’s own definition of clinical effectiveness, rather than a standardized improvement measured on one validated scale. Standardized cognitive measures showed the same general pattern. Thirty-two trials reported Mini-Mental State Examination results.

Among 17 studies evaluating herbal therapy as an add-on to Western medicine, participants receiving the combination had an average MMSE advantage of 3.71 points, with a 95% confidence interval of 2.96 to 4.47. In 13 monotherapy comparisons, the corresponding difference was 3.59 points, with a 95% confidence interval of 2.60 to 4.58. The Hasegawa Dementia Scale results pointed in the same direction: adjunctive therapy was associated with a mean difference of 4.07 points, with a 95% confidence interval of 2.63 to 5.52, while monotherapy produced a mean difference of 3.94 points, with a 95% confidence interval of 0.83 to 7.05.

The Clinical Dementia Rating Scale was assessed in only three trials, which also reported lower scores with the herbal interventions, but the evidence base was much smaller. Subgroup analyses suggested that several treatment characteristics might influence the observed cognitive differences, although comparisons between subgroups remain observational rather than randomized. In adjunctive-treatment trials, capsules and decoctions were associated with larger MMSE gains, while a small granule subgroup did not reach statistical significance.

Benefits were reported across treatment durations ranging from one to six months, with the largest mean difference appearing in a one-month subgroup. Six-month studies provided more extensive evidence for sustained effects, including a pooled MMSE difference of 4.85 points, with a 95% confidence interval of 2.52 to 7.19, in the monotherapy group. Baseline dementia severity, individualized herb dosages, formulation differences and inconsistent administration of cognitive scales may help explain why results varied more widely across some analyses.

Several laboratory markers also shifted in the direction of a potential neurobiological effect. Combining the herbal therapy with Western medicine was associated with higher circulating brain-derived neurotrophic factor, or BDNF, with a standardized mean difference of 1.02 and a 95% confidence interval of 0.13 to 1.90. When one influential trial was removed, the estimate became 0.55, with a 95% confidence interval of 0.23 to 0.86.

Nerve growth factor, or NGF, was also higher overall, with a standardized mean difference of 0.69 and a 95% confidence interval of 0.27 to 1.12. Glial cell line-derived neurotrophic factor was reported in just one trial involving 108 participants and was higher with the combination treatment. These are intermediate biomarkers, however, and the reviewers stressed that changes in their blood concentrations do not demonstrate clinical benefit, neuronal protection or disease modification.

Preclinical research offers possible explanations without proving that the treatments work in people through those pathways. Blood-activating ingredients such as Chuanxiong rhizome, red sage root, safflower and red peony root have been investigated for effects on blood flow, thrombosis, endothelial integrity, mitochondrial function, oxidative stress and inflammation in laboratory models. Kidney-tonifying herbs such as prepared Polygonum multiflorum, polygonatum rhizome, Schisandra fruit, desert cistanche and epimedium have shown antioxidant, anti-inflammatory and anti-apoptotic activity in experimental systems.

Some preparations also influence cholinergic signaling or neurotrophic-factor expression. The authors described these findings as hypotheses for future research rather than clinical evidence of a mechanism or a demonstration that the therapy alters vascular dementia’s course. Safety results appeared reassuring at first glance.

Across the six trials included in the quantitative adverse-event synthesis, 48 participants experienced adverse events: 22 in the herbal groups and 26 in the control groups. Pooled analysis found no statistically significant difference for monotherapy, with a risk ratio of 0.71, a 95% confidence interval of 0.32 to 1.57 and a p value of 0.40. The corresponding estimate for combination therapy was 0.85, with a 95% confidence interval of 0.43 to 1.68 and a p value of 0.64.

Reported events included insomnia, diarrhea, abdominal pain, dizziness, nausea, rash and a mild reduction in blood pressure. No serious adverse events, treatment-related deaths or discontinuations because of adverse events were reported in the included trials. The safety conclusion is nevertheless much less secure than the efficacy estimates imply.

Only nine of the 38 studies reported adverse events at all, and three crossover trials could not be pooled because their safety data were not in a compatible form. Eight studies explicitly stated that no adverse events occurred, three reported events without contributing to the pooled analysis, and 21 did not mention safety. Placebo-controlled evidence was also scarce.

The review therefore found no evidence of an increased adverse-event rate in the available comparisons, but it could not exclude uncommon or delayed harms that shorter trials and incomplete reporting would fail to detect. All 38 included studies were conducted in China, published in Chinese and generally small and single-center, while treatment lasted no more than six months. None of the trials provided sufficient details on allocation concealment, and only three were judged to have clearly described blinding.

The investigators also detected asymmetric funnel plots for clinical effectiveness and MMSE outcomes, raising the possibility of small-study effects or selective publication. Given these limitations, the findings support further investigation rather than a definitive treatment claim.

Subject of Research: Efficacy and safety of Chinese herbal therapy for cognitive outcomes in vascular dementia

Article Title: Efficacy and safety of traditional Chinese medicine kidney-tonifying and blood-activating therapy in the treatment of vascular dementia: a systematic review and meta-analysis

Article References: Zhou, M., Che, M., Zhang, C., Yang, X., Liu, X., Liu, Z., Huang, J., & He, H. (2026). Efficacy and safety of traditional Chinese medicine kidney-tonifying and blood-activating therapy in the treatment of vascular dementia: a systematic review and meta-analysis. Frontiers in Neurology, 17, Article 1901245. https://doi.org/10.3389/fneur.2026.1901245

Image Credits: AI Generated

DOI: 10.3389/fneur.2026.1901245

Keywords: vascular dementia, traditional Chinese medicine, systematic review, meta-analysis, randomized controlled trials, cognitive function, herbal medicine, safety, neurotrophic factors, MMSE, Efficacy, traditional