Optimal dose and type of non-pharmacological treatments to improve cognitive function in people with Alzheimer’s disease: a systematic review and network meta-analysis

Abstract

Objectives

To evaluate and rank the effectiveness of specific non-pharmacological treatments (NPTs) in improving the global cognitive function in individuals with Alzheimer’s disease (AD) and to examine the dose-response relationship.

Method

We conducted a systematic search in PubMed, MEDLINE, Embase, PsycINFO, CENTRAL, WOS, and CNKI from their inception to 15 February 2023. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models.

Results

We included 68 studies involving 5053 participants in this meta-analysis. The treatments with the highest cumulative probabilities for improving global cognitive function were transcranial direct current stimulation (tDCS), followed by physical exercise (PE), and repetitive transcranial magnetic stimulation (rTMS). Additionally, cognitive stimulation (CS), cognitive training CT), multidisciplinary program (MD), and reminiscence treatment (RT) also significantly improve the global cognitive function of people with AD. A non-linear dose-response association was observed for tDCS, PE, rTMS, CS, and CT with global cognitive improvement. Notably, no minimal threshold was identified for the beneficial effects of PE on cognition. The estimated minimal doses for clinically relevant changes in cognition were 33 min per week for tDCS, 330 MET-min per week for PE, and 8000 pulses per week for rTMS.

Conclusion

tDCS, PE, and rTMS are the better effective NPTs for enhancing global cognitive function in individuals with AD. Properly dosing these treatments can yield significant clinical benefits. Our findings support the clinical utility of low-dose exercise in improving cognition in people with AD.

Keywords:

• Dose-response
• minimal clinically important difference
• non-invasive brain stimulation
• exercise
• cognitive function

Acknowledgments

We thank Ph.D. Wensheng Zhou for his technical assistance in the study and contributions to amending the language of the manuscript.

Ethical approval

There are no ethical issues involved in this study.

Author contributions

JJD and XQG conceived and designed the protocol. HYZ and XYF developed and drafted the initial protocol with input from YY. HYZ and XYF tested and mapped the data variables. JJD conducted the analyses with guidance from XQG. YY provided related technology support. JJD drafted the initial manuscript. XQG revised the manuscript critically for important intellectual content. All authors read and approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data supporting the results of the study can be made available by emailing the first author or corresponding author.

Equity, diversity, and inclusion statement

Our research and author team consists of two women and two men, senior and less experienced researchers from various disciplines in China. The research population includes people with Alzheimer’s disease over the age of 50. We have no restrictions on the language and gender of the included research, so we strive to include original research of all races and genders. However, due to the limited number of included studies, we were unable to conduct subgroup analysis for race and sex, which was also a major limitation of our study.

Additional information

Funding

The authors have no financial relationships relevant to this article to disclose.