BackgroundAmyloid-β (Aβ) deposition in mild cognitive impairment (MCI) disrupts interhemispheric homotopic connectivity, yet its longitudinal course is unclear.ObjectiveWe aim to characterize the longitudinal decay of voxel-mirrored homotopic connectivity (VMHC) in MCI patients, elucidate underlying Aβ-associated mechanisms, and link these processes to cognitive decline.MethodsEighty-three ADNI participants (60 MCI, 23 cognitively normal [CN]) underwent baseline and two-year follow-up. MCI cases were stratified by 18F-AV45 PET into Aβ-positive (MCI-Aβ+, n = 44) and Aβ-negative (MCI-Aβ-, n = 16) subgroups. VMHC and corpus-callosum volume were compared across groups (ANOVA). Spearman correlations linked regional VMHC to cognition, cerebrospinal fluid (CSF) biomarkers, and callosal volume. Linear mixed-effects models tested group-by-time interactions; two-year VMHC change was related to parallel cognitive decline.ResultsAt baseline, MCI-Aβ- patients showed lower VMHC in the fusiform and postcentral gyri, whereas MCI-Aβ+ patients exhibited additional reductions in the precuneus, superior frontal gyrus, cerebellum, and superior occipital gyrus. Lower VMHC correlated with poorer cognition, corpus-callosum atrophy, and abnormal CSF profiles; callosal volume itself did not differ between groups. Longitudinally, MCI-Aβ+ participants exhibited a slower VMHC decline across the posterior cingulate, cerebellum and thalamus. Two-year cumulative change in VMHC inversely correlated with change in cognitive performance.ConclusionsAβ burden shapes distinct trajectories of interhemispheric connectivity loss in MCI. VMHC decline tracks multi-domain cognitive deterioration and may serve as a biomarker of progression toward Alzheimer's disease.

Repetitive transcranial magnetic stimulation (rTMS) has emerged as a research focus in the treatment of Alzheimer’s disease (AD). However, the optimal stimulation target remains controversial and requires urgent resolution. To evaluate the cognitive effects of 5 Hz rTMS targeting the cerebellar Crus II region in patients with AD and to explore the underlying neural mechanisms using functional near-infrared spectroscopy (fNIRS). A total of 35 patients with AD diagnosed at the mild cognitive impairment or mild dementia stage based on cerebrospinal fluid biomarkers were initially enrolled and randomly assigned to a real rTMS group (n = 18) or a sham stimulation group (n = 17), with 33 patients (17 and 16, respectively) completing the full intervention and being included in the final analysis. All patients received two weeks of bilateral 5 Hz rTMS or sham stimulation over the cerebellar Crus II region. Neuropsychological assessments were performed at baseline, immediately post-treatment, and at week 12. Resting-state fNIRS data were collected at baseline and post-treatment. Between-group differences in cognitive scores, cerebral functional activity, and brain network topology after intervention were analyzed. Compared with the sham group, the real rTMS group showed significant improvement in global cognition post-treatment, and this effect persisted until week 12. fNIRS analysis revealed that after treatment, the real rTMS group exhibited significantly increased fractional amplitude of low-frequency fluctuations (fALFF) in the left frontal pole and left dorsolateral prefrontal cortex (DLPFC), along with enhanced functional connectivity across the cerebral cortex. Graph theory analysis showed significant increases in global efficiency, local efficiency, and clustering coefficient, and significant decreases in characteristic path length and normalized characteristic path length in the real rTMS group post-treatment. Correlation analysis indicated that the increase in fALFF in the DLPFC was positively correlated with improvements in MMSE and Digit Span Test scores, while improvement in delayed recall score of the Auditory Verbal Learning Test was correlated with decreased normalized characteristic path length. Five Hz rTMS applied to the cerebellar Crus II region effectively improves cognitive function in patients with mild AD, with benefits persisting for at least three months. fNIRS-based mechanistic analyses suggest that the therapeutic effects may involve cerebellar-cortical loop modulation of hemodynamic activity in key frontal regions, accompanied by enhanced whole-brain functional connectivity and optimized network topology. However, given that fNIRS measures hemodynamic responses rather than direct neuronal activity, these findings should be interpreted as network-level hemodynamic changes rather than as direct evidence of neuronal reorganization. The study was registered at chictr.org.cn website (ID: ChiCTR2200061754) on 02–07-2022.

Objective: The long‐term prognosis of anti‐neuronal antibody‐positive autoimmune encephalitis (AE) remains unclear. Conventional scales such as the modified Rankin Scale (mRS) may not fully capture residual deficits. This study evaluated long‐term outcomes in AE patients (≥5 years after treatment) using three AE‐specific scales combined with patient‐reported outcomes. Methods: AE patients hospitalized from 2013‐2019 were enrolled and followed until 2024. Outcomes were assessed using mRS, the Clinical Assessment Scale for Autoimmune Encephalitis (CASE), and the Liverpool Outcome Score (LOS). Self‐reported data included seizures, return to work/school, memory, sleep, and psychiatric symptoms. Results: A total of 105 patients (mean onset age 36.15±17.53 years; 54.3% female) were followed for a median of 8.31 years. Anti‐NMDAR was the predominant antibody (83.8%). At ≥5 years, self‐reported sequelae were common: sleep disorders (76.2%), cognitive impairment (68.6%), seizure recurrence (57.1%), psychiatric disorders (45.7%), and inability to return to work/school (61.9%). Among those who returned, 56.9% felt incompetent. In contrast, mRS indicated mild disability in 74.3% (mRS ≤2), with mean CASE 4.96±3.02 and mean LOS 66.38±7.53, suggesting a seemingly favorable prognosis by conventional scales. Conclusions: Despite conventional scales suggesting good recovery, AE patients commonly experience persistent neuropsychiatric dysfunction, including sleep, cognitive, seizure, and psychiatric disorders, with most unable to resume work or school. Current assessment tools inadequately capture long‐term functional recovery, highlighting the need for multidimensional, patient‐centered follow‐up.

Background: The present study was to investigate the hospitalization costs and length of hospital stay of patients with first-episode psychosis (FEP) following emergency department visits. Methods: Patients hospitalized for the first time with a diagnosis of psychotic disorder via the emergency department were retrospectively assessed through clinical records in a mental health center in East China from Jan 1 st 2018, to Dec 12 th 2023. The total annual hospitalization cost, per capita cost of the first hospitalization, and length of hospital stay for such FEP patients were calculated separately. The related influencing factors were subsequently analyzed. Results: During the six-year observation period, a total of 737 individuals were enrolled, with a mean age of 42.30±19.54 years. There were 382 female patients (51.8%) predominantly. Among them, 399 cases (54.1%) were nonorganic mental disorders, with the 2 highest prevalences being mood (affective) disorders and schizophrenia. A total of 338 patients (45.8%) had organic mental disorders, with the 2 highest prevalences of infectious and immune-related diseases. The per capita direct cost per hospitalization for FEP patients was a median of 2,876.04 US dollars, with the highest cost associated with immune-related diseases (7431.43±8877.06). The per capita length of stay per hospitalization varied from 1 to 182 days, with a mean of 21.31±19.40 days and a median of 16 days. The average length of the first hospitalization was 16.87±12.38 days, with the longest duration of (43.83±43.83 days). A disease duration exceeding two weeks prior to consultation was associated with an increased length of hospital stay, and the time required for diagnosis more than one week after admission also prolonged the hospital stay and increased hospitalization costs. Conclusions Among all the FEP patients, the number of nonorganic mental disorders was greater than that of organic mental disorders, but the per capita hospitalization cost was significantly greater for organic disorders than for nonorganic disorders. The initial onset of psychiatric and behavioral symptoms caused by immune-related diseases should receive particular attention, given the higher hospitalization costs and longer hospital stays. When visits and diagnoses are delayed, the economic burden becomes even more pronounced for these organic mental disorders.

Purpose:To investigate the correlation between inflammatory markers and neurological deficit severity in young ischemic stroke (YIS) patients, and to evaluate their predictive value for short‑term prognosis. Methods:We retrospectively collected clinical data from 196 YIS patients at Nanjing Brain Hospital between January 2022 and December 2025. Patients were divided into mild stroke (MIS) and moderate‑to‑severe stroke (MSS) groups based on the National Institutes of Health Stroke Scale (NIHSS) scores assessed within 24 hours of admission. Short-term prognosis at 3 months was evaluated using the modified Rankin Scale (mRS), and patients were classified into good and poor outcome groups. Correlation analysis was used to evaluate the relationships between inflammatory markers and NIHSS scores. LASSO regression was conducted to screen variables, followed by Firth's penalized logistic regression to correct for small-sample bias. Receiver operating characteristic curves were generated to evaluate predictive performance. Results:The systemic inflammatory response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were markedly elevated in the MSS group and positively correlated with NIHSS scores. SIRI, PLR, and MLR were significantly higher in the poor outcome group. LASSO identified D‑dimer (D-D), low-density lipoprotein cholesterol (LDL‑C), and NLR as independent predictors of poor outcomes. The area under the curve (AUC) for NLR was 0.592, whereas the combined model (D-D + LDL-C + NLR) yielded an AUC of 0.734. Conclusion:PLR exhibited the strongest correlation with neurological deficit severity. The combined model may provide a more accurate laboratory‑based tool for risk stratification in YIS patients.

BACKGROUND:Developing effective neuromodulatory therapies for Alzheimer's disease (AD) is a critical unmet need. While repetitive transcranial magnetic stimulation (rTMS) shows promise, its optimal targets and mechanisms remain incompletely understood. The cerebellum, a key modulator of large-scale brain network dynamics, represents a novel therapeutic target for addressing the distributed cognitive network dysfunction in AD. OBJECTIVE:This study aimed to evaluate the cognitive efficacy and safety of cerebellar rTMS in AD and to elucidate its potential mechanism of action through the lens of structural network topology. METHODS:In this randomized, double-blind, sham-controlled trial, patients with AD were assigned to receive active or sham rTMS targeting the bilateral cerebellar Crus II region. Cognitive assessments were conducted at baseline, post-treatment (4 weeks), and at a 12-week follow-up. Diffusion tensor imaging (DTI) was employed to analyze changes in whole-brain structural network topology. RESULTS:Compared to the sham group, the active rTMS group demonstrated significantly greater improvement in global and domain-specific cognitive function at 4 weeks, with benefits sustained at the 12-week follow-up. Response rates on the MMSE and MoCA were also significantly higher in the active group. Neuroimaging revealed that active rTMS enhanced global network efficiency, indicated by significant increases in global/local efficiency and clustering coefficient, alongside a decreased characteristic path length, signifying an optimization toward small-world topology. Furthermore, treatment selectively enhanced nodal efficiency within core hubs of the default mode, frontoparietal, and salience networks. Critically, these structural improvements correlated with cognitive gains; increased nodal efficiency in the precuneus and posterior cingulate cortex was associated with improved episodic memory and visuospatial function. CONCLUSION:Cerebellar rTMS is a safe and effective intervention that confers sustained cognitive benefits in AD. Its therapeutic mechanism likely involves the reinforcement of structural connectivity and enhanced integrative capacity within supraordinate cognitive networks, particularly the default mode network, via cerebello-cortical pathways.

Neuronal ceroid lipofuscinosis is a rare lysosomal storage disorder that is difficult to distinguish from other diseases with similar clinical symptoms in its early stages. This article analyzes and summarizes the diagnostic process of a family affected by adult neuronal ceroid lipofuscinosis caused by CLN6 gene mutation. We collected clinical data from a 48-year-old female patient with neuronal ceroid lipofuscinosis who visited Nanjing Brain Hospital in March 2024. She has presented with corresponding symptoms since 2020. The patient underwent whole exome sequencing (WES) and other examinations. WES showed that both the patient and her elder brother, who exhibited similar symptoms of walking instability, were homozygous for a mutation in the CLN6 gene. This variant (c.856C > T: p.Leu286Phe) has not been previously reported and is classified as a Variant of Uncertain Significance (VUS) based on current American College of Medical Genetics and Genomics/Association for Molecular Pathology(ACMG/AMP) guidelines. Both of the patient’s parents displayed normal phenotypes but were found to have heterozygous mutations in the CLN6 gene. Additionally, no nuclear inclusion bodies were found in the patient’s skin tissue.

BackgroundThe apolipoprotein E ε4 allele (APOE ε4) and inflammation are associated with Alzheimer's disease (AD) pathology. Mild cognitive impairment (MCI) is considered the preclinical and early stage of AD. However, the comprehensive effects of APOE ε4 and inflammatory mediators on MCI patients with specific APOE ε4 genotypes remain poorly understood.ObjectiveOur study aimed to explore how different numbers of the APOE ε4 alleles affect plasma C-reactive protein (CRP) and interleukin-3 (IL-3) levels and their associations with brain structure.MethodsA total of 339 MCI patients from the Alzheimer's Disease Neuroimaging Initiative study were enrolled. We compared their plasma concentrations of CRP and IL-3, cognitive performance, and cerebrospinal fluid (CSF) AD biomarkers levels across different APOE ε4 genotypes. Structural magnetic resonance imaging was utilized to measure gray matter volume outcomes. Pearson correlation analysis was used to explore the associations between the above indicators.ResultsPlasma CRP levels increased in the APOE ε4 carriers, but IL-3 expression notably decreased, and the homozygous state is the most significant. A negative correlation between CRP and several cognitive abilities was observed only in APOE ε4 homozygotes. Additionally, a positive correlation between IL-3, cognitive scores, and CSF biomarker levels was confirmed only in APOE ε4 homozygotes. Imaging data demonstrated that the gray matter volume of the right middle frontal gyrus was associated with CRP only in APOE ε4 non-carriers.ConclusionsOur study demonstrated that peripheral inflammatory mediators' effect on cognitive function and brain structure in MCI patients differs based on their APOE ε4 allele carrier status.

BACKGROUND:The link between thyroid autoimmunity and Alzheimer's disease (AD) biomarkers in euthyroid individuals is poorly understood. We investigated the independent and interactive effects of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) on core cerebrospinal fluid (CSF) biomarkers of AD pathology. METHODS:We analyzed CSF biomarkers (Aβ1-42, Aβ1-40, T-tau, and P-tau181) measured using validated ELISA assays (Fujirebio) in 114 euthyroid, amyloid-positive participants stratified by antibody status. Associations were assessed using multiple linear regression and four-group cross-classification analyses, adjusting for age and gender. RESULTS:TPOAb positivity was independently associated with a significantly lower CSF Aβ1-42/Aβ1-40 ratio (mean ± SD: 0.04 ± 0.01 vs. 0.05 ± 0.02; adjusted p=0.022; Cohen's d = -0.65), indicating more advanced amyloid pathology. Importantly, we identified a novel interaction modulating tau pathology: isolated positivity for either TPOAb or TgAb was linked to elevated P-tau181, but this effect was significantly attenuated in subjects positive for both antibodies (interaction p=0.037). CONCLUSION:Thyroid autoimmunity is associated with AD neuropathological changes independent of thyroid hormone status. The specific association of TPOAb with amyloid pathology and the complex interplay between antibodies on tau pathology highlight previously unrecognized mechanisms. These findings, pending validation in longitudinal studies, suggest thyroid antibody screening in elderly euthyroid individuals may aid in identifying those at higher risk for Alzheimer's pathology, potentially facilitating earlier detection and intervention.

Fatal familial insomnia (FFI) is a rare autosomal dominant inherited disease and a type of prion diseases. We report a case of fatal familial insomnia (FFI) in a 52-year-old man who was initially misdiagnosed as Alzheimer’s disease. The patient presented with persistent insomnia as the initial symptom, accompanied by cognitive impairment, autonomic dysfunction, and disorders of voluntary movement. Cerebrospinal fluid analysis revealed a decrease in Aβ1−40 levels and an increase in total tau protein. Cranial imaging demonstrated bilateral hippocampal atrophy, while long-term video electroencephalography indicated focal abnormalities. The patient’s prion protein gene was D178N/129MM type, confirmed the diagnosis of FFI. The key characteristics of FFI include insomnia and rapidly progressive dementia, its differential diagnosis with AD has been extensively discussed in clinical practice. This is the first report of FFI concerning Aβ and tau protein, raises the awareness that the ratio of p-tau/t-tau in cerebrospinal fluid can provide valuable diagnostic clues for FFI.

OBJECTIVES:Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are known as the preclinical and early stage of Alzheimer's disease (AD). The dorsal attention network (DAN) is mainly responsible for the "top-down" attention process. However, previous studies mainly focused on single functional modality and limited structure. This study aimed to investigate the multimodal alterations of DAN in SCD and aMCI to assess their diagnostic value in preclinical and early-stage AD.METHODS:Resting-state functional magnetic resonance imaging (MRI) was carried out to measure the fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC). Structural MRI was used to calculate the gray matter volume (GMV) and cortical thickness. Moreover, receiver-operating characteristic (ROC) analysis was used to distinguish these alterations in SCD and aMCI.RESULTS:The SCD and aMCI groups showed both decreased ReHo in the right middle temporal gyrus (MTG) and decreased GMV compared to healthy controls (HCs). Especially in the SCD group, there were increased fALFF and increased ReHo in the left inferior occipital gyrus (IOG), decreased fALFF and increased FC in the left inferior parietal lobule (IPL), and reduced cortical thickness in the right inferior temporal gyrus (ITG). Furthermore, functional and structural alterations in the SCD and aMCI groups were closely related to episodic memory (EM), executive function (EF), and information processing speed (IPS). The combination of multiple indicators of DAN had a high accuracy in differentiating clinical stages.CONCLUSIONS:Our current study demonstrated functional and structural alterations of DAN in SCD and aMCI, especially in the MTG, IPL, and SPL. Furthermore, cognitive performance was closely related to these significant alterations. Our study further suggested that the combined multiple indicators of DAN could be acted as the latent neuroimaging markers of preclinical and early-stage AD for their high diagnostic value.

BACKGROUND:In Parkinson's disease (PD), inflammation may lead to the degeneration of dopaminergic (DAergic) neurons. Previous studies showed that inflammatory mediators mainly contributed to this phenomenon. On the other hand, invasive neuromodulation methods such as deep brain stimulation (DBS) have better therapeutic effects for PD. One possibility is that DBS improves PD by influencing inflammation. Therefore, we further explored the mechanisms underlying inflammatory mediators and DBS in the pathogenesis of PD.METHODS:We measured serum levels of two inflammatory markers, namely RANTES (regulated on activation, normal T cell expressed and secreted) and tumor necrosis factor-alpha (TNF-α), using Luminex assays in 109 preoperative DBS PD patients, 49 postoperative DBS PD patients, and 113 age- and sex-matched controls. The plasma protein data of the different groups were then statistically analyzed.RESULTS:RANTES (p < 0.001) and TNF-α (p = 0.005) levels differed significantly between the three groups. A strong and significant correlation between RANTES levels and Hoehn-Yahr (H-Y) stage was observed in preoperative PD patients (rs  = 0.567, p < 0.001). Significant correlations between RANTES levels and Unified Parkinson's Disease Rating Scale III (UPDRS III) score (rs1  = 0.644, p = 0.033 and rs2  = 0.620, p = 0.042) were observed in matched patients. No correlation was observed for TNF-α levels.CONCLUSION:The results of this study indicate that PD patients have a persistent inflammatory profile, possibly via recruitment of activated monocytes, macrophages, and T lymphocytes to the central nervous system (CNS). DBS was shown to have a significant therapeutic effect on PD, which may arise by improving the inflammatory environment of the central nervous system.

Objective:To explore the characteristics of self-referential network (SRN) functional connectivity in subjective cognitive decline (SCD) patients with normal and impaired metacognition.Methods:Seventy-one subjects were selected from Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with 25 cognitively normal controls and 46 SCD patients. The metacognitive level of SCD patients was assessed by Everyday Cognition Scale (ECog), and then, they were divided into a metacognitively normal group ( n=25, metacognitive scores>-0.074) and a metacognitively impaired group ( n=21, metacognitive scores≤-0.074). Results of Geriatric Depression Scale (GDS), Montreal Cognitive Scale (MoCA), Mini‐Mental State Examination (MMSE), Rey Auditory Word Learning Test (RAVLT), Logical Memory Scale, expressions of pathological markers (cerebrospinal fluid β-amyloid protein [Aβ], total tau protein [t-tau] and phosphorylated tau protein [p-tau]), brain glucose metabolism, and functional magnetic resonance imaging (fMRI) were collected and compared among the 3 groups. Independent component analysis (ICA) was used to extract SRN and analyze the different brain regions among the 3 groups; Pearson correlation was used to analyze the correlations of SRN functional connectivity changes with cognitive scales and pathological markers. Results:No significant differences in demographic characteristics (age and gender), scores of GDS, MoCA and MMSE, or levels of Aβ, t-tau, p-tau and brain glucose metabolism were noted among the 3 groups ( P>0.05). The metacognitive scores in metacognitively impaired group were significantly lower than those in metacognitively normal group and cognitively normal controls ( P<0.05). Significant difference in the functional connectivity of bilateral anterior cingulate gyrus and bilateral orbitofrontal cortex was noted among the 3 groups (TFCE-FWE correction, P<0.01, voxel>100); compared with the cognitively normal controls, the metacognitively impaired group showed significantly decreased functional connectivity of bilateral orbitofrontal cortex, while the metacognitively normal group showed enhanced functional connectivity of bilateral orbitofrontal cortex (TFCE-FWE correction, P<0.01, voxel>100); compared with the metacognitively normal group, the metacognitively impaired group had statistically decreased functional connectivity of bilateral orbitofrontal cortex (TFCE-FWE correction, P<0.01, voxel>100). Further correlation analysis showed that difference value of functional connectivity of bilateral orbitofrontal cortex between metacognitively impaired group and cognitively normal controls was negatively correlated with RAVLT-immediate scores ( r=-0.445, P=0.043); difference value of functional connectivity of bilateral orbitofrontal cortex between metacognitively impaired group and metacognitively normal group was negatively correlated with RAVLT-immediate scores ( r=-0.463, P=0.034). Conclusion:SCD patients with different metacognitive levels have characteristic SRN functional connectivity changes; impaired metacognition may be an early feature of Alzheimer's disease.

Background: Early identification of degenerative processes in Alzheimer’s disease (AD) is essential. Cerebello-cerebral network changes can be used for early diagnosis of dementia and its stages, namely mild cognitive impairment (MCI) and AD. Methods: Features of cortical thickness (CT) and cerebello-cerebral functional connectivity (FC) extracted from MRI data were used to analyze structural and functional changes, and machine learning for the disease progression classification. Results: CT features have an accuracy of 92.05% for AD vs. HC, 88.64% for MCI vs. HC, and 83.13% for MCI vs. AD. Additionally, combined with convolutional CT and cerebello-cerebral FC features, the accuracy of the classifier reached 94.12% for MCI vs. HC, 90.91% for AD vs. HC, and 89.16% for MCI vs. AD, evaluated using support vector machines. Conclusions: The proposed pipeline offers a promising low-cost alternative for the diagnosis of preclinical AD and can be useful for other degenerative brain disorders.

Background:Mild cognitive impairment (MCI) depicts a transitory phase between healthy elderly and the onset of Alzheimer's disease (AD) with worsening cognitive impairment. Some functional MRI (fMRI) research indicated that the frontoparietal network (FPN) could be an essential part of the pathophysiological mechanism of MCI. However, damaged FPN regions were not consistently reported, especially their interactions with other brain networks. We assessed the fMRI-specific anomalies of the FPN in MCI by analyzing brain regions with functional alterations. Methods:PubMed, Embase, and Web of Science were searched to screen neuroimaging studies exploring brain function alterations in the FPN in MCI using fMRI-related indexes, including the amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity. We integrated distinctive coordinates by activating likelihood estimation, visualizing abnormal functional regions, and concluding functional alterations of the FPN. Results:We selected 29 studies and found specific changes in some brain regions of the FPN. These included the bilateral dorsolateral prefrontal cortex, insula, precuneus cortex, anterior cingulate cortex, inferior parietal lobule, middle temporal gyrus, superior frontal gyrus, and parahippocampal gyrus. Any abnormal alterations in these regions depicted interactions between the FPN and other networks. Conclusion:The study demonstrates specific fMRI neuroimaging alterations in brain regions of the FPN in MCI patients. This could provide a new perspective on identifying early-stage patients with targeted treatment programs. Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432042, identifier: CRD42023432042.

ObjectiveImpaired interhemispheric connectivity and corpus callosum atrophy have been linked to cognitive impairment in Alzheimer's disease (AD). Existing evidence indicates that repetitive transcranial magnetic stimulation (rTMS) targeting the bilateral precuneus may enhance cognitive function in AD. This study aims to investigate the effects of precuneus rTMS on cognitive function, as well as alterations in interhemispheric functional connectivity (FC) and its structural basis in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI).MethodsA total of 14 patients with SCD and 16 patients with MCI were enrolled in this study and received 10 Hz rTMS intervention on the bilateral precuneus for 2 weeks. Neurocognitive scales, structural and functional magnetic resonance imaging were collected at enrollment and after the rTMS intervention. Interhemispheric FC was assessed using mirror homotopic functional connectivity (VMHC), while the structural equation modeling (SEM) was employed to analyze the relationship between corpus callosum volume, interhemispheric connectivity, and cognitive function after rTMS intervention.ResultsThe precuneus rTMS not only enhanced episodic memory in SCD, but also improved multiple cognitive domains in MCI. Post-rTMS intervention, decreased VMHC values in the lingual cortex, middle occipital gyrus, putamen, and fusiform gyrus were observed in SCD, and an increased VMHC value in the postcentral gyrus along with reduced VMHC value in the cerebellum and putamen in MCI. After intervention, more brain regions show decreased FC in SCD and MCI patients, suggesting that precuneus rTMS may protect cerebral cortical plasticity by reducing excessive functional compensation, and thus improve cognitive function. The SEM indicated that the corpus callosum serves as the structural foundation for rTMS regulation of interhemispheric FC to further improve cognitive function.Conclusion10 Hz rTMS in the bilateral precuneus could be a promising strategy to improve cognitive function in patients with SCD and MCI. Our study implies that improvements in cognition brought about by precuneus rTMS may result from the remodeling of interhemispheric FC, with the corpus callosum possibly acting as the anatomical basis for functional modulation.

1病例报告 病例1 :患者女 ,49岁. 因"记忆力逐渐减退2年,加重1周"于2020-03-16入院.患者2年前出现记忆功能减退,近记忆损害明显,偶有迷路,反应迟钝,伴语言表达能力、计算能力下降,无明显幻觉.症状逐步加重,性格由外向变得沉默,日常生活需要他人协助.

Evidence suggests that the cerebellum is involved in cognitive processing. Effects and specific mechanisms by which the cerebellum repetitive transcranial magnetic stimulation (rTMS) contributes to the perception of the cognitive state are not well-known.In the current randomized, double-blind, sham-controlled trial, twenty-seven patients with Alzheimer’s disease (AD) were randomly assigned to one of two groups: rTMS-real or rTMS-sham. We investigated the efficacy and specific cerebello-cerebral functional connectivity alteration of a 4-weeks treatment of cerebellum rTMS in promoting cognitive recovery.The cerebellum rTMS significantly enhances intrinsic functional connectivity between the cerebellum nodes and the dorsolateral prefrontal cortex (DLPFC), medial frontal cortex as well as cingulate cortex in the real rTMS group, which may be directly related to the observed multi-domain cognitive improvements. While sham stimulation showed no effect on the cognitive cerebello-cerebral connectivity. Our results show that high-frequency rTMS of the cerebellum is a promising, non-invasive treatment for cognitive dysfunction in patients with AD. This clinical improvement is accompanied by modulation of brain connectivity, consistently with the pathophysiological model of brain disconnection in AD.

目的 探讨眼震电图结合个案分析教学法在住院医师规范化培训带教中的应用,并为眩晕相关疾病的临床带教建立系统的、专业的眼震电图结合个案分析教学法.方法 选择2019年8月—2021年3月期间在南京脑科医院神经内科参加住院医师规范化培训的临床医学本科毕业生进行眩晕章节的教学,分为传统教学组或实验教学组:其中2019级采用传统床边教学查房法,2020级采用眼震电图结合个案分析教学,两组学生均在授课结束后立即进行课堂教学效果的学生反馈评价,在授课结束后1周内完成理论考试(包括单项选择题40分和病例分析题60分),并进行统计分析.结果 眼震电图结合个案分析教学组的学生对教学效果的满意度高于传统教学组(Wilcoxon检验,P<0.05),在病例分析题上的客观得分眼震电图结合个案分析教学组的学生成绩平均分数为(48.89±5.08)分,高于传统教学组的(43.14±5.58)分,两组差异有统计学意义(t=3.379,P<0.05).结论 眼震电图结合个案分析教学法应用于住院医师规范化培训的临床带教中,可以提高学员的学习动力和效率,提升临床思维和学习成绩.

Background Both subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) have a high risk of progression to Alzheimer's disease (AD). While most of the available evidence described changes in functional connectivity (FC) in SCD and aMCI, there was no confirmation of changes in functional connectivity density (FCD) that have not been confirmed. Therefore, the purpose of this study was to investigate the specific alterations in resting-state FCD in SCD and aMCI and further assess the extent to which these changes can distinguish the preclinical and early-stage AD. Methods A total of 57 patients with SCD, 59 patients with aMCI, and 78 healthy controls (HC) were included. The global FCD, local FCD, and long-range FCD were calculated for each voxel to identify brain regions with significant FCD alterations. The brain regions with abnormal FCD were then used as regions of interest for FC analysis. In addition, we calculated correlations between neuroimaging alterations and cognitive function and performed receiver-operating characteristic analyses to assess the diagnostic effect of the FCD and FC alterations on SCD and aMCI. Results FCD mapping revealed significantly increased global FCD in the left parahippocampal gyrus (PHG.L) and increased long-range FCD in the left hippocampus for patients with SCD when compared to HCs. However, when compared to SCD, patients with aMCI showed significantly decreased global FCD and long-range FCD in the PHG.L. The follow-up FC analysis further revealed significant variations between the PHG.L and the occipital lobe in patients with SCD and aMCI. In addition, patients with SCD also presented significant changes in FC between the left hippocampus, the left cerebellum anterior lobe, and the inferior temporal gyrus. Moreover, changes in abnormal indicators in the SCD and aMCI groups were significantly associated with cognitive function. Finally, combining FCD and FC abnormalities allowed for a more precise differentiation of the clinical stages. Conclusion To our knowledge, this study is the first to investigate specific alterations in FCD and FC for both patients with SCD and aMCI and confirms differential abnormalities that can serve as potential imaging markers for preclinical and early-stage Alzheimer's disease (AD). Also, it adds a new dimension of understanding to the diagnosis of SCD and aMCI as well as the evaluation of disease progression.