Zhongwei Guo

Objectives: Long-term or inappropriate use of benzodiazepine receptor agonists (BZRAs) in older adults is a medication-safety concern. This study mapped trends, contributors, knowledge structures, and research hotspots of BZRA deprescribing using a comparative dual-database bibliometric framework. Methods: English-language articles and reviews from 1 January 2008 to 21 May 2026 were retrieved from the Web of Science Core Collection (WoSCC) and Scopus. Of the 377 WoSCC and 558 Scopus records entering topical relevance screening, 306 and 418, respectively, met the final eligibility criteria. Among the final datasets, 225 publications were shared, yielding 499 unique publications. The BIBLIO framework guided reporting. Analyses used R, bibliometrix, and VOSviewer, whereas CiteSpace-based analyses were restricted to WoSCC. Data for 2026 were partial; trend models used complete years through 2025. Results: Publication output showed an overall upward trend, with output during 2021–2025 generally higher than in earlier years. Quadratic models based on 2008–2025 data showed good fit for WoSCC (R² = 0.8890) and Scopus (R² = 0.9104). The United States, Canada, and Australia were leading contributors, and the University of Montreal was the leading institution (WoSCC, n = 19; Scopus, n = 18). Across both databases, themes evolved from withdrawal, discontinuation, and potentially inappropriate prescribing toward medication safety, prescription optimization, medication review, patient education, and implementation in primary care and long-term care settings. Conclusions: BZRA deprescribing research has broadened from drug discontinuation toward a patient-centered medication-safety and prescription-optimization framework. Future research should evaluate individualized tapering, nonpharmacological support, multidisciplinary care models, and standardized long-term patient-centered and safety outcomes.

Apathy in AD stems from prefrontal-basal ganglia circuit dysfunction. Multimodal imaging biomarkers may enable early detection and targeted interventions.

Background: Although donepezil alleviates Alzheimer’s disease (AD) symptoms by raising acetylcholine levels, its impact on cholinergic pathways remains unclear. In this longitudinal, resting-state functional magnetic resonance imaging (rs-fMRI) study, we investigated donepezil-induced changes in cholinergic pathway networks in AD. Methods: AD patients and healthy controls (HCs) were enrolled. AD patients received 24 weeks of donepezil treatment. Cognitive and emotional symptoms were assessed using the Mini-Mental State Examination (MMSE), Cornell Scale for Depression in Dementia (CSDD), and Neuropsychiatric Inventory (NPI) pre- and post-treatment. rs-fMRI was used to examine basal forebrain (BF) functional connectivity. Results: Sixteen AD patients and 16 HCs completed the study. Post-treatment MMSE scores improved, and NPI and CSDD scores decreased. Reduced BF functional connectivity in the left cerebellar lobule VI, post-treatment, was revealed by rs-fMRI. Compared with HCs, post-treatment AD patients showed lower BF functional connectivity in the right postcentral gyrus (PoG); pre-treatment patients exhibited higher BF functional connectivity in the left cerebellar lobule VI. Right PoG functional connectivity was negatively correlated with disease duration pre-treatment and positively correlated with MMSE post-treatment. Conclusions: Donepezil improved clinical symptoms in AD by modulating the BF–PoG cholinergic pathway.

Background/Objective: Major depressive disorder (MDD) exhibits significant heterogeneity, and identifying these distinct biological subtypes aids clinical intervention. In this study, we employed functional gradient and Hydra clustering methods to distinguish subtypes of depression. Method: Imaging data were derived from a large‐scale, multicenter MDD imaging database, comprising 1067 patients with MDD and 907 healthy controls (HCs). Based on the principal functional gradient, the Hydra method was employed to distinguish subtypes of MDD. We employed the Mann–Whitney U ‐test to compare functional gradient abnormalities across different subtypes of MDD while simultaneously conducting imaging transcriptomics analysis. Results: Using principal functional gradients, we identified two subtypes of MDD. Compared with HCs, subtype 1 exhibited abnormal functional gradient values in the dorsal attention network (DAN), ventral attention network (VAN), limbic network (LIB), frontoparietal network (FTP), and default mode network (DMN); subtype 2 exhibited abnormal functional gradient values in the visual network (VIS), somatosensory network (SMT), DAN, VAN, and DMN. Transcriptomics revealed that subtype 1 functional gradient abnormalities were significantly correlated with theory mind, 5‐hydroxytryptamine (5‐HT) 1B; subtype 2 functional gradient abnormalities were significantly correlated with motor function, dopamine D2 receptor, and norepinephrine transporter (NET). Conclusions: Our research deepens the understanding of the biological diversity of MDD, providing a biologically grounded framework for stratifying patients, which may inform the future design of hypothesis‐driven clinical trials targeting specific cognitive or sensorimotor circuits.

Background: Acupuncture has been proposed as a therapeutic intervention for stroke recovery, yet the underlying molecular mechanisms remain poorly understood. Method: In this study, we used a mouse model of hemorrhagic stroke induced by autologous blood injection to investigate the effects of acupuncture on post‐stroke recovery at the cellular and molecular levels, utilizing single‐cell RNA sequencing. Results: Our findings revealed that acupuncture modulates the gene expression of microglia, astrocytes, and oligodendrocytes, three major glial cell types, which may contribute to the improvement of stroke‐induced phenotypes. Notably, we identified a potential role of the APOE‐TREM2 signaling axis, with ligand‐binding interactions enhancing microglia activation and promoting their neuroprotective functions. These findings also suggested that acupuncture may promote microglia–astrocyte interactions, leading to enhanced neuroinflammation resolution and tissue repair. Conclusions: Our study provided new insights into the cellular mechanisms underlying acupuncture's therapeutic effects in stroke recovery and highlighted the potential of targeting glial cell‐mediated pathways, including APOE‐TREM2, as a strategy for improving post‐stroke rehabilitation.

Objective: This study aimed to explore the changes in brain functional activity before and after acceptance and commitment therapy (ACT) treatment in patients with major depressive disorder (MDD) and the correlation between brain functional changes and clinical symptoms. Methods: We recruited 12 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for MDD. Patients underwent clinical assessments and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after ACT intervention. The amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) maps were obtained after data preprocessing, and the ALFF/fALFF values of patients were extracted and compared. Pearson correlation analysis was used to analyze the correlation between fALFF/ALFF values and clinical symptoms. Results: A total of nine MDD patients completed the study. The results showed that, following treatment, there was an improvement in psychological flexibility, along with a reduction in depressive symptoms. Additionally, MDD patients exhibited increased ALFF in the left inferior frontal gyrus and triangle, as well as increased fALFF in the left medial superior frontal gyrus following symptom remission. Pearson correlation analysis showed that fALFF of the left medial superior frontal gyrus at baseline was negatively correlated with the rate of Acceptance and Action Questionnaire, Second Edition (AAQ-II), change (r = −0.76, P < 0.05). Conclusions: We observed alterations in spontaneous activity in regions of the prefrontal cortex in MDD patients following ACT, providing preliminary relevant insights into understanding the neural mechanisms underlying the treatment of MDD by ACT.

Background: Both depressive symptoms and neurotransmitter changes affect the characteristics of functional brain networks in clinical patients. We sought to explore how brain functional grading is organized among patients with mild cognitive impairment and depressive symptoms (D-MCI) and whether changes in brain organization are related to neurotransmitter distribution. Methods: Using 3 T magnetic resonance imaging (MRI) we acquired functional MRI (fMRI) data from patients with D-MCI, patients with mild cognitive impairment without depression (nD-MCI), and healthy controls. We used resting-state fMRI and diffusion embedding to examine the pattern of functional connectivity gradients. We used analysis of covariance and post hoc t tests to compare the difference in functional connectivity gradients among the 3 groups. We examined the correlation between variations in functional connectivity gradients and neurotransmitter maps using the JuSpace toolbox. Results: We included 105 participants, including 31 patients with D-MCI, 40 patients with nD-MCI, and 34 healthy controls. Compared with healthy controls, both the nD-MCI and D-MCI groups showed abnormalities in the principal unimodal–transmodal gradient pattern. Compared with controls, the D-MCI group showed an increased secondary gradient in the default mode network. Differences in the functional connectivity gradients between the D-MCI and nD-MCI groups were significantly correlated with the distribution of 5-hydroxytryptamine receptor subtype 1A. Limitations: The small sample size affects the generalizability of the results, and the neurotransmitter template is based on healthy participants, not patients. Conclusion: Our results suggest that depressive symptoms cause abnormalities in the hierarchical segregation of functional brain organization among patients with MCI. Such abnormal changes may be related to the distribution of neurotransmitters.

Introduction: Donepezil enhances the function of cholinergic nerves by increasing the concentration of acetylcholine, thereby improving clinical symptoms in patients with Alzheimer’s disease (AD). However, the neural mechanisms of how donepezil modulates the effective connectivity (EC) network of cholinergic system in AD patients remain unknown. We speculated that the effective network of the cholinergic system changes in AD patients after donepezil intervention.Methods: We employed resting-state functional magnetic resonance imaging and Granger causality analysis approach to explore changes in the effective connectivity network of the basal forebrain in AD patients before and after donepezil intervention. This study included 32 participants, including 16 healthy controls (HCs) and 16 AD patients. In a 3T MRI scanner, the 16 AD patients were scanned before and after the donepezil intervention. To compare EC differences between the three groups of participants, ANOVA and post-hoc t-tests analysis were employed.Results: Compared to baseline status, AD patients after donepezil intervention had an increased EC from left middle occipital gyrus to right medial septum/diagonal bands. Compared to HCs, AD patients after donepezil intervention had an increased EC from right inferior frontal gyrus/orbit part to right medial septum/diagonal bands, AD patients before donepezil intervention had a reduced EC from right precuneus to right medial septum/diagonal bands. A significant positive correlation was found between EC values in right precuneus and Mini-Mental State Examination in pre-intervention AD patients (r = 0.7338, p = 0.0012).Discussion: Our study showed that effective connectivity of brain regions associated with the default mode network in the cholinergic pathway was enhanced after donepezil intervention. The results of this study will help us to better understand the neural mechanisms of donepezil intervention in AD and to find clinical targets for intervention.

Background: Depression is one of the most common neuropsychiatric symptoms of Alzheimer’s disease (AD) which decreases the life quality of both patients and caregivers. There are currently no effective drugs. It is therefore important to explore the pathogenesis of depression in AD patients. Objective: The present study aimed to investigate the characteristics of the entorhinal cortex (EC) functional connectivity (FC) in the whole brain neural network of AD patients with depression (DAD). Methods: Twenty-four D-AD patients, 14 AD patients without depression (nD-AD), and 20 healthy controls underwent resting-state functional magnetic resonance imaging. We set the EC as the seed and used FC analysis. One-way analysis of variance was used to examine FC differences among the three groups. Results: Using the left EC as the seed point, there were FC differences among the three groups in the left EC-inferior occipital gyrus. Using the right EC as the seed point, there were FC differences among the three groups in the right EC-middle frontal gyrus, -superior parietal gyrus, -superior medial frontal gyrus, and -precentral gyrus. Compared with the nD-AD group, the D-AD group had increased FC between the right EC and right postcentral gyrus. Conclusion: Asymmetry of FC in the EC and increased FC between the EC and right postcentral gyrus may be important in the pathogenesis of depression in AD.