BACKGROUND: This study aims to evaluate the add-on effects of oral Chinese herbal medicine (CHM) for mild cognitive impairment (MCI), when used in addition to donepezil compared to donepezil alone.
METHODS: Randomized controlled trials comparing these treatments across all types of MCI were identified from nine databases and three registers until August 2023. Outcome measures were Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and adverse events (AEs). Methodological quality was assessed using Cochrane risk-of-bias tool, and evidence certainty was evaluated using the GRADE method.
RESULTS: Involving 1611 participants across 20 studies, meta-analysis results indicate that oral CHM combined with donepezil significantly improved cognitive function in MCI patients compared to donepezil alone, as evidenced by MMSE (1.88 [1.52, 2.24], I2 = 41%, 12 studies, 993 participants) and MoCA (MD: 2.01 [1.57, 2.44], I2 = 52%, 11 studies, 854 participants). Eleven studies reported details of AEs, identifying gastrointestinal symptoms and insomnia as the most common symptoms. No significant difference in AEs frequency was found between the groups (RR: 0.91 [0.59, 1.39], I2 = 4%, 11 studies, 808 participants). All 20 studies were evaluated as having \"some concerns\" regarding the overall risk of bias. The certainty of evidence for MMSE was \"moderate\" and \"low\" for MoCA. From frequently utilized herbs, two classical CHM formulae were identified: Kai xin san and Si wu decoction. The observed treatment effects of commonly used herbs may be exerted through multiple pharmacological mechanisms, including anti-inflammatory, anti-oxidative stress, anti-apoptotic actions, promotion of neuronal survival and modulation of the cholinergic system.
CONCLUSIONS: The concurrent use of oral CHM and donepezil appears to be more effective than donepezil alone in improving the cognitive function of MCI, without leading to an increase in AEs. While recognizing concerns of overall methodological quality, this combined therapy should be considered as an alternative option for clinical practice.

The expression of inflamma-miRs and human leukocyte antigen (HLA) haplotypes could indicate mild cognitive impairment (MCI) and Alzheimer\'s disease (AD). We used international databases to conduct a systematic review of studies on HLA variants and a meta-analysis of research on microRNAs (miRNAs). We aimed to analyze the discriminative value of HLA variants and miRNAs in MCI, AD and controls to evaluate the protective or causative effect of HLA in cognitive decline, establish the role of miRNAs as biomarkers for the early detection of AD, and find a possible link between miRNAs and HLA. Statistical analysis was conducted using Comprehensive Meta-analysis software, version 2.2.050 (Biostat Inc., Englewood, NJ, USA). The effect sizes were estimated by the logarithm base 2 of the fold change. The systematic review revealed that some HLA variants, such as HLA-B*4402, HLA-A*33:01, HLA-A*33:01, HLA-DPB1, HLA-DR15, HLA-DQB1*03:03, HLA-DQB1*06:01, HLA-DQB1*03:01, SNPs on HLA-DRB1/DQB1, and HLA-DQA1, predisposed to cognitive decline before the occurrence of AD, while HLA-A1*01, HLA-DRB1∗13:02, HLA-DRB1*04:04, and HLA-DRB1*04:01 demonstrated a protective role. The meta-analysis identified let-7 and miR-15/16 as biomarkers for the early detection of AD. The association between these two miRNA families and the HLA variants that predispose to AD could be used for the early screening and prevention of MCI.

BACKGROUND: Multicomponent exercise has the potential to improve cognitive function in people with mild cognitive impairment. However, the effects of multicomponent exercise on specific cognitive subdomains in mild cognitive impairment and the optimal combination of exercise components remain unclear.
OBJECTIVE: This systematic review aimed to (a) investigate the effects of multicomponent exercise on different cognitive subdomains in people with mild cognitive impairment and (b) investigate the effects of different combinations of multicomponent exercise on global cognition in people with mild cognitive impairment.
METHODS: A systematic review and meta-analysis.
METHODS: Six electronic databases, including PubMed, Medline, EMBASE, Web of Science, Cochrane Library, and CINAHL were systematically searched from inception to January 1st, 2023. Randomized controlled trials assessing the effect of multicomponent exercise interventions on cognitive function in people with mild cognitive impairment were included. The risk of bias was assessed using the Cochrane collaborative bias assessment tool. A random-effects model was used to calculate standardized mean difference. Subgroup analyses, meta-regression, and sensitive analysis were performed. If a meta-analysis was not feasible, studies were synthesized narratively.
RESULTS: Twenty studies were identified for systematic review and meta-analysis. Multicomponent exercise significantly improved global cognition [SMD = 1.04; 95 % confidence interval (CI): 0.53, 1.55], cognitive flexibility (SMD = -1.04; 95 % CI: -1.81, -0.27), processing speed (SMD = 0.43; 95 % CI: 0.04, 0.82), verbal fluency (SMD = 0.38; 95 % CI: 0.13, 0.63), attention (SMD = -0.90; 95 % CI: -1.68, -0.12) and memory (SMD = 0.36; 95 % CI: 0.04, 0.69) in mild cognitive impairment. The multicomponent exercise including cardiovascular (exercise that promotes cardiovascular health, such as endurance training or aerobic exercise) and motor (exercises that improve physical abilities, such as balance, coordination, agility, flexibility, etc.) components positively affected global cognition in people with mild cognitive impairment (SMD = 1.06; 95 % CI: 0.55, 1.57).
CONCLUSIONS: The findings of this study suggest that multicomponent exercise has a positive impact on various cognitive domains, including global cognition, cognitive flexibility, processing speed, verbal fluency, attention and memory in mild cognitive impairment. Specifically, the combination of exercises including cardiovascular and motor components was found to be effective in improving global cognition. However, further research is needed to investigate the optimal frequency and intensity of the multicomponent exercise intervention, and more detail about exercise combinations of the motor component (not classified in this study) for individuals with mild cognitive impairment.
BACKGROUND: The protocol was registered on PROSPERO (CRD42023400302).

BACKGROUND: Markerless motion capture (MMC) uses video cameras or depth sensors for full body tracking and presents a promising approach for objectively and unobtrusively monitoring functional performance within community settings, to aid clinical decision-making in neurodegenerative diseases such as dementia.
OBJECTIVE: The primary objective of this systematic review was to investigate the application of MMC using full-body tracking, to quantify functional performance in people with dementia, mild cognitive impairment, and Parkinson disease.
METHODS: A systematic search of the Embase, MEDLINE, CINAHL, and Scopus databases was conducted between November 2022 and February 2023, which yielded a total of 1595 results. The inclusion criteria were MMC and full-body tracking. A total of 157 studies were included for full-text screening, out of which 26 eligible studies that met the selection criteria were included in the review. .
RESULTS: Primarily, the selected studies focused on gait analysis (n=24), while other functional tasks, such as sit to stand (n=5) and stepping in place (n=1), were also explored. However, activities of daily living were not evaluated in any of the included studies. MMC models varied across the studies, encompassing depth cameras (n=18) versus standard video cameras (n=5) or mobile phone cameras (n=2) with postprocessing using deep learning models. However, only 6 studies conducted rigorous comparisons with established gold-standard motion capture models.
CONCLUSIONS: Despite its potential as an effective tool for analyzing movement and posture in individuals with dementia, mild cognitive impairment, and Parkinson disease, further research is required to establish the clinical usefulness of MMC in quantifying mobility and functional performance in the real world.

UNASSIGNED: The rise in the aging population highlights the need to address cognitive decline and neurodegenerative diseases. Intermittent hypoxia (IH) protocols show promise in enhancing cognitive abilities and brain health.
UNASSIGNED: This review evaluates IH protocols\' benefits on cognition and brain health in older adults, regardless of cognitive status.
UNASSIGNED: A systematic search following PRISMA guidelines was conducted across four databases (PubMed, Scopus, Web of Science, and Cochrane Library) and two registers, covering records from inception to May 2024 (PROSPERO: CRD42023462177). Inclusion criteria were: 1) original research with quantitative details; 2) studies involving older adults, with or without cognitive impairment; 3) studies including IH protocols; 4) articles analyzing cognition and brain health in older adults.
UNASSIGNED: Seven studies and five registered trials met the criteria. Findings indicate that Intermittent Hypoxia Training (IHT) and Intermittent Hypoxia-Hyperoxia Training (IHHT) improved cognitive functions and brain health. Intermittent Hypoxic Exposure (IHE) improved cerebral tissue oxygen saturation, middle cerebral arterial flow velocity, and cerebral vascular conductance, particularly in cognitively impaired populations. IHT and IHHT had no significant effect on BDNF levels. There is a lack of studies on IHHE in older adults with and without cognitive impairment.
UNASSIGNED: IH protocols may benefit cognition regardless of cognitive status. IHT and IHE positively affect cerebral outcomes, with all protocols having limited effects on BDNF levels. Future research should standardize IH protocols, investigate long-term cognitive effects, and explore neuroprotective biomarkers. Combining these protocols with physical exercise across diverse populations could refine interventions and guide targeted therapeutic strategies.

OBJECTIVE: To systematically assess the effectiveness of transcranial direct current stimulation (tDCS) on global cognition in patients with mild cognitive impairment (MCI) and Alzheimer\'s disease (AD).
METHODS: Ten databases were retrieved for pertinent Chinese and English studies published up until February 2023.
METHODS: Two researchers independently selected the literature, extracted the data, evaluated using the Cochrane Collaboration\'s quality criteria, and then cross-checked. Meta-analysis was performed using RevMan 5.4.
RESULTS: 22 studies involving 1074 patients were included. Compared with the control group received the interventions such as pharmacotherapy, cognitive stimulation, et al., with/without sham-tDCS, while the experiment group received tDCS added to the interventions of the control group. The meta-analysis found that tDCS increased MMSE, MoCA, MODA scores and reduced the P300 latency scores (all P < 0.05).
CONCLUSIONS: The tDCS can ameliorate the global cognition of patients with MCI and AD, and it has a better rehabilitation effect than non-tDCS or sham-tDCS.

BACKGROUND: Alzheimer\'s disease (AD) is a progressive neurodegenerative disorder that severely affects cognitive functions and social behaviors, leading to a significant decline in an individual\'s quality of life. Auditory processing deficits often precede the clinical symptoms of AD, prompting interest in auditory-based interventions as potential treatments. This scoping review aimed to compile the existing evidence on active and passive auditory-based interventions for individuals with AD and its prodromal stages.
RESULTS: This scoping review followed Arksey and O\'Malley\'s five-step framework to identify the existing evidence on auditory-based interventions for AD. Four databases (PubMed, Web of Science, CINAHL, and Embase) were used to search for studies on auditory stimulation techniques to treat cognitive decline in AD patients. In total, 14 studies were included in the analysis. Seven studies explored active auditory stimulation techniques, such as the Brain Fitness Program (BrainHQ), aiming to improve cognitive function in individuals with Mild Cognitive Impairment (MCI). The other seven studies focused on passive auditory stimulation, often combined with other sensory stimuli such as light or tactile inputs. Passive stimulation studies have focused mainly on Gamma Entrainment Using Sensory Stimulation (GENUS). The intervention frequency and duration varied across studies, ranging from one session lasting 8 h to a year. Both active and passive auditory stimulation showed potential for enhancing cognitive function in individuals with AD.
CONCLUSIONS: The literature suggests that auditory stimulation may positively influence cortical wiring and enhance cognitive abilities. Multimodal interventions that combine auditory stimulation with other sensory or behavioural approaches could yield more substantial effects on global cognition. However, the study design, intervention characteristics and outcome measures varied across studies, underscoring the necessity for standardised reporting. Well-designed studies using standard cognitive assessment protocols are recommended.

BACKGROUND: Serious games (SGs) are nonpharmacological interventions that are widely applied among older adults. To date, no evidence has been published regarding the effect of digital SGs on cognitive ability, daily behavioral capacity, or depression in older adults with Alzheimer\'s disease (AD) and mild cognitive impairment (MCI).
OBJECTIVE: This study aimed to assess the effect of SGs on older adults with AD and MCI by summarizing and pooling the results of previous studies.
METHODS: This meta-analysis examined the effectiveness of digital SGs in improving cognitive ability, enhancing daily behavioral capacity, and alleviating depression in older adults with AD and MCI. We searched the following databases up to December 31, 2023, to identify relevant high-quality randomized controlled trials (RCTs): PubMed, Embase, Web of Science, Scopus, and Cochrane Library. Stata 15.1 and Review Manager 5.3 were used to screen the 14 studies, extract data, code the data, and perform meta-analysis. Mean differences and standardized mean differences (SMDs) with 95% CIs were used to calculate continuous variables. The Cochrane risk-of-bias assessment tool was used to evaluate the risk of bias. Eligibility criteria were developed in accordance with the Population, Intervention, Comparison, Outcomes, and Study Design framework: (1) population (older adults with AD and MCI), (2) intervention (digital SG intervention), (3) comparison (digital SG intervention vs routine health care), (4) outcomes (cognitive ability, daily behavioral capacity, and depression), and (5) study or research design (RCT). Sensitivity analysis was performed, and a funnel plot was constructed.
RESULTS: From January 2017 to December 2023, we enrolled 714 individuals across 14 RCTs, with 374 (52.4%) in the severe game group using digital SGs and 340 (47.6%) in the control group using traditional methods. The results of our meta-analysis indicated that using digital SGs in older adults with AD and MCI is more effective than traditional training methods in several key areas. Specifically, digital SG therapy significantly increased cognitive ability, as found in the Mini-Mental State Examination (SMD 2.11, 95% CI 1.42-2.80; P<.001) and the Montreal Cognitive Assessment (SMD 2.75, 95% CI 1.98-3.51; P<.001), significantly increased daily behavioral capacity (SMD 0.53, 95% CI 0.06-0.99; P=.03), and significantly reduced depression (SMD -2.08, 95% CI -2.94 to -1.22; P<.001) in older adults with AD and MCI. No publication bias was detected based on the results of Begg and Egger tests.
CONCLUSIONS: Digital SGs offer a viable and effective nonpharmacological approach for older adults with AD and MCI, yielding better results compared to traditional formats. However, caution is warranted in interpreting these findings due to limited RCTs, small sample sizes, and low-quality meta-analyzed evidence.
BACKGROUND: PROSPERO International Prospective Register of Systematic Reviews: CRDCRD42023486090; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=486090.

UNASSIGNED: Exergames are an innovative method that can promote neuroplasticity and improve the cognitive abilities of the elderly. This study aimed to compare the effects of single-task and multi-task exergames on the cognitive ability of the elderly with mild cognitive impairment (MCI).
UNASSIGNED: Computerized literature search was performed using PubMed, Web of Science, EBSCO, Elsevier, ProQuest, China National Knowledge Infrastructure (CNKI), Wanfang and VIP database to identify relevant articles from the establishment of the database from inception to April 1, 2024. The inclusion criteria were: (i) participants aged 60 or older diagnosed with mild cognitive impairment, regardless of gender; (ii) use of randomized controlled trials (RCTs); (iii) interventions involving exergames with physical activity or as the primary variable; and (iv) outcome measures using standardized neuropsychological instruments to assess cognitive function, including statistical data on sample size, mean, and standard deviation. Finally, the included study comprised a total of 526 participants. Mean difference (MD) and 95% confidence interval (CI) were used to synthesize the effect size in the data.
UNASSIGNED: 11 studies were included. Due to the differences in the intervention methods, subgroup analysis was performed on the included research. Compared with the control group assessed by the Montreal Cognitive Assessment Scale, the single-task intervention improved the cognitive ability of the elderly with MCI (MD 3.40, 95% CI 2.43-4.37), the Mini-Mental State Examination Scale (MD 2.38, 95% CI -2.03 to 2.72), the Trail Making Test (MD -3.89, 95% CI -6.45 to -1.33), and the Digit Span Forward test (MD 1.16, 95% CI 0.73-1.60).
UNASSIGNED: This meta-analysis supports that exergames could be an effective cognitive rehabilitation method for MCI patients. Our study recommends that patients implement a customized exergames program and adhere to it for a long time. It is necessary to pay attention to the exercise guidelines and provide evidence from clinicians.
UNASSIGNED: (1) This meta-analysis supports that exergames could be an effective cognitive rehabilitation method for MCI patients. Our study recommends that patients implement a customized exergames program and adhere to it for a long time. It is necessary to pay attention to the exercise guidelines and provide evidence from clinicians. (2) This research provides preliminary evidence for the clinical utility of VR tasks developed for mild cognitive impairment. (3) In this paper, only relevant studies in Chinese and English were searched, and no studies in other languages were searched.

BACKGROUND: Understanding mild behavioral impairment, a relatively recent notion in neuropsychological studies, provides significant insights into early behavioral indicators of cognitive decline and predicts the onset of dementia in older adults. Although the importance of understanding mild behavioral impairment is acknowledged, comprehensive reviews of its correlates with older adults are limited.
OBJECTIVE: This scoping review aims to identify the impact of mild behavioral impairment on health outcomes in older adults and the factors associated with mild behavioral impairment.
METHODS: The review will adhere to the Joanna Briggs Institute\'s methodological principles for scoping reviews. We will include studies focusing mainly on mild behavioral impairment in older adults, with the literature on this topic being limited to the period from 2003 to the present. Other clinical diagnoses, such as cognitive impairment, Parkinson disease, and multiple sclerosis, will not be included. We will use databases including PubMed (MEDLINE), CINAHL, Web of Science, Embase, PsycINFO, Cochrane, and Scopus for relevant articles published in English. Both gray literature and peer-reviewed articles will be considered during screening. Three independent reviewers will extract data using a predefined data extraction tool. Extracted data will be presented using tables, figures, and a narrative summary aligned with review questions, accompanied by an analysis of study characteristics and categorization of mild behavioral impairment correlates.
RESULTS: The results will be presented as a descriptive summary, structured according to the associated factors related to mild behavioral impairment, and the health outcomes. Additionally, the data on study characteristics will be presented in tabular format. An exploratory search was conducted in July 2023 to establish a comprehensive search strategy, and iterative refinements to the scoping review protocol and formalization of methods were completed. A follow-up search is planned for May 2024, with the aim of submitting the findings for publication in peer-reviewed journals.
CONCLUSIONS: To our knowledge, this would be the first study to map the literature on the health-related factors and outcomes of mild behavioral impairment. The findings will support the development of interventions to prevent the occurrence of mild behavioral impairment and mitigate the negative outcomes of mild behavioral impairment.
UNASSIGNED: DERR1-10.2196/60009.