Chinese Herbal Medicine for Mild Cognitive Impairment: Current State of Evidence and Perspectives of Patients, Caregivers and Clinicians

Background Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal ageing and the more serious decline of dementia. Individuals with MCI have an increased risk of developing dementia. As a recognised precursor to dementia, MCI presents a critical window for early intervention, offering the potential to delay or prevent further cognitive decline. However, current therapeutic strategies for MCI remain limited. Conventional pharmacological treatments have shown limited clinical benefits in MCI individuals and adverse effects are common. Given the multifactorial pathophysiology of MCI, therapeutic strategies that target isolated mechanisms may provide only limited clinical benefit. In contrast, multi-targeted interventions, such as Chinese herbal medicine (CHM), hold potential for modulating multiple pathological mechanisms while supporting intrinsic compensatory processes. While cognitive symptoms are the hallmark of MCI, neuropsychiatric symptoms, like sleep disturbances are also clinically significant. Hypnotics are commonly prescribed for sleep disturbances but are associated with adverse effects, particularly in older adults, and may negatively impact cognitive function. Moreover, evidence specifically for managing sleep disturbances in MCI remains limited. Consequently, there is a critical need for safe and accessible therapeutic options that not only address the complex and heterogeneous pathophysiology of MCI but also meet the diverse clinical needs of affected individuals. CHM, characterised by holistic principles and personalised treatment approaches, has historically been employed in the management of symptoms and signs related to cognitive disorders. Preliminary evidence suggests that CHM may benefit MCI by modulating multiple pathological processes. Nevertheless, robust evidence regarding the efficacy, effectiveness, safety and clinical applicability of CHM in MCI remains limited. Further, little is known about the perspectives of patients, caregivers and clinicians on the use of CHM in this population. Therefore, this research seeks to address these gaps through an integrated investigation of clinical evidence, real-world practice patterns and stakeholder experiences. Research questions, aims and objectives The research questions for this project are: • What is the current clinical research evidence of CHM for MCI? • What are the clinical characteristics of MCI patients and the CHM prescription patterns observed in real-world clinical practice? • What are the experiences, attitudes, and perspectives of patients, caregivers and clinicians on using CHM to manage MCI with coexisting sleep disturbances? The research aims of this project are to: • synthesise the evidence of CHM for MCI from clinical research, real-world clinical practice and the perspectives of patients, caregivers and clinicians • gain a deeper insight into the role of CHM in the management of MCI, with a specific focus on addressing coexisting sleep disturbances. The specific objectives of this project are to: • conduct a systematic review to evaluate the efficacy and safety of oral CHM for MCI compared to placebo • conduct a systematic review to evaluate the add-on effects of oral CHM when used in combination with donepezil for managing MCI compared to donepezil alone • conduct a retrospective analysis of electronic medical records (EMRs) from a major tertiary public hospital in China to investigate the clinical characteristics of MCI patients and the CHM prescriptions they received for MCI • conduct a qualitative study to understand the experiences, attitudes, and perspectives of patients, caregivers and clinicians regarding the use of CHM in managing MCI with coexisting sleep disturbances. Methods and results This project consists of three components: 1) two systematic reviews of clinical research evidence; 2) a retrospective study of the EMRs of MCI patients; and 3) a qualitative study exploring the perspectives of MCI patients with sleep disturbance, their caregivers and clinicians. Systematic review of clinical evidence The two systematic reviews were conducted according to the guidelines provided in the Cochrane handbook for systematic reviews of interventions. Results of the first systematic review indicated that CHM significantly improved cognitive function compared to placebo in terms of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The second systematic review revealed that combining CHM with donepezil significantly enhanced cognitive function in MCI patients, as evidenced by improvements in MMSE and MoCA scores. Both reviews, found no significant difference in the reported number of adverse events (AEs) between groups. Retrospective analysis of medical records The retrospective study examined the EMRs of MCI patients from Guangdong Provincial Hospital of Chinese Medicine (GPHCM), China. Memory decline was identified as the predominant concern, with sleep disturbances also being a significant neuropsychiatric symptom. Coexisting sleep disturbances were associated with a higher average number of medical visits, suggesting that neuropsychiatric symptoms may influence their healthcare engagement, although a direct correlation was not confirmed. CHM use was common, particularly among those with sleep disturbances. A subset of patients received both CHM and anti-dementia drugs, suggesting that a tailored approach to oral pharmacological therapy is being adopted in this hospital to address the need for individualised treatment plans. The findings highlight the importance of considering sleep issues in the clinical management of MCI. Qualitative study of stakeholders’ perspectives The qualitative study was aimed at understanding the experiences, attitudes, and perspectives of patients, caregivers and clinicians regarding the use of CHM in managing MCI and coexisting sleep disturbances. An interpretive phenomenological design was used, with semi-structured interviews analysed through inductive thematic analysis. The findings indicated that the key stakeholders generally perceived CHM, particularly decoctions, as a safer, individualised and more holistic treatment option for MCI and coexisting sleep disturbances, contributing to its broad acceptance in clinical practice. However, barriers to clinical implementation of CHM, such as the complexity of preparation, unpleasant taste and concerns regarding CHM quality and treatment costs, presented ongoing challenges. Interviews also revealed patients’ and caregivers’ limited knowledge of MCI and sleep disturbances, the considerable caregiver burden and inadequate healthcare service support. Conclusion This project integrated evidence from clinical research, real-world clinical practice and stakeholder perspectives to comprehensively understand the role of CHM in managing MCI, particularly among patients experiencing concurrent sleep disturbance. Through this approach, the study identified potential clinical applications of CHM therapies to help address key challenges in MCI management and priorities for further investigation to support the development of evidence-based health care.<p></p>