Objective:

2

To evaluate the efficacy and safety of Tonifying Kidney-Yang Decoction (TKYD) in treating patients with vascular cognitive impairment (VCI) characterized by Shen (Kidney)-yang deficiency (SYD) syndrome.

Methods:

2

This multicenter

double-blind

randomized

and placebo-controlled clinical trial was conducted in 4 hospitals of China from September 2020 to December 2021. Eligible patients were enrolled and randomly assigned in a 1:1 ratio to receive either TKYD granules or placebo twice daily for 12 weeks. The primary outcomes were changes in scores of the Beijing Version of the Montreal Cognitive Assessment (MoCA-BJ) and Shen-Yang Deficiency Syndrome Scale (SYDSS) from baseline to week 12. The secondary outcomes included scores of the Mini-Mental State Examination (MMSE)

Color Trails Test interference index

Stroop Color and Word Test-Stroop interference effect

Neuropsychiatric Inventory (NPI)

Apathy Evaluation Scale-Clinician Version

and Activities of Daily Living scales. Safety was monitored throughout the trial.

Results:

2

A total of 120 patients completed the trial

including 63 and 57 in the TKYD and placebo groups

respectively. After 12 weeks of treatment

the TKYD group exhibited a significantly greater increase in MoCA-BJ (chang

e: 1.40

vs

. 0.11) and reduction in SYDSS scores (change: –12.17

vs

. –7.46) than the placebo group (

P

<

0.05 or

P

<

0.01). Regarding specific domains of MoCA-BJ

TKYD exhibited significantly greater improvements in visuospatial/executive function

orientation and delayed recall (

P

<

0.05 or

P

<

0.01). In terms of change scores in SYDSS

TKYD also showed greater reductions in diarrhea before dawn

lumbago

and weakness of knees (

P

<

0.05 or

P

<

0.01). For the secondary outcomes

the TKYD group exhibited significantly higher MMSE scores and lower NPI scores compared with the placebo group (

P

<

0.05 or

P

<

0.01). No treatment-related adverse events were reported.

Conclusion:

2

TKYD is effective and safe for improving cognitive function and alleviating SYD symptoms in VCI patients with SYD syndrome. (Registration No. ChiCTR1900025713)