Virtual Multidisciplinary Stroke Care Clinic for Community-Dwelling Stroke Survivors: A Randomized Controlled Trial.

BACKGROUND: Stroke survivors constantly feel helpless and unprepared after discharge from hospitals. More flexible and pragmatic support are needed for their optimized recovery. We examined the effects of a virtual multidisciplinary stroke care clinic on survivors' health and self-management outcomes. METHODS: A randomized controlled trial was conducted. Survivors were recruited from 10 hospitals and randomized at 1:1 ratio into the intervention or the control groups. Intervention group participants received the Virtual Multidisciplinary Stroke Care Clinic service (monthly online consultations with a nurse, follow-up phone calls, and access to an online platform). Control group participants received the usual care. Outcomes of self-efficacy (stroke self-efficacy questionnaire; primary), self-management behaviors (Stroke Self-Management Behaviors Performance Scale), social participation (reintegration to normal living index), and depression (Geriatric Depression Scale; secondary) were measured at baseline, and 3 and 6 months after commencing the intervention (post-randomization). A generalized estimating equations model was used to compare the differential changes in outcomes at 3 and 6 months with respect to baseline between 2 groups. RESULTS: Between July 2019 and June 2022, 335 eligible participants were enrolled in the study. Participants (intervention group; n=166) showed significantly greater improvements in outcomes of self-efficacy (group-by-time interaction regression coefficient, B=4.60 [95% CI, 0.16 to 9.05]), social participation (B=5.07 [95% CI, 0.61 to 9.53]), and depression (B=-2.33 [95% CI, -4.06 to -0.61]), and no significant improvement in performance of self-management behaviors (B=3.45, [95% CI, -0.87 to 7.77]), compared with the control group (n=169) right after the intervention (6 months after its commencement). Hedges' g effect sizes of the intervention on outcomes: 0.19 to 0.36. CONCLUSIONS: The results provide some positive evidence on the usefulness of the Virtual Multidisciplinary Stroke Care Clinic service. The effect sizes are regarded as small to medium, which may not be of clinical relevance. The baseline levels in outcomes were in favor of the control group, the intervention effects might be overestimated. The service must be tested further to determine its effectiveness. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800016101.

Messenger RNA Coronavirus Disease 2019 (COVID-19) Vaccination With BNT162b2 Increased Risk of Bell's Palsy: A Nested Case-Control and Self-Controlled Case Series Study.

BACKGROUND: Observable symptoms of Bell's palsy following vaccinations arouse concern over the safety profiles of novel coronavirus disease 2019 (COVID-19) vaccines. However, there are only inconclusive findings on Bell's palsy following messenger (mRNA) COVID-19 vaccination. This study aims to update the previous analyses on the risk of Bell's palsy following mRNA (BNT162b2) COVID-19 vaccination. METHODS: This study included cases aged ≥16 years with a new diagnosis of Bell's palsy within 28 days after BNT162b2 vaccinations from the population-based electronic health records in Hong Kong. Nested case-control and self-controlled case series (SCCS) analyses were used, where the association between Bell's palsy and BNT162b2 was evaluated using conditional logistic and Poisson regression, respectively. RESULTS: Totally 54 individuals were newly diagnosed with Bell's palsy after BNT162b2 vaccinations. The incidence of Bell's palsy was 1.58 (95% confidence interval [CI], 1.19-2.07) per 100 000 doses administered. The nested case-control analysis showed significant association between BNT162b2 vaccinations and Bell's palsy (adjusted odds ratio [aOR], 1.543; 95% CI, 1.123-2.121), with up to 1.112 excess events per 100 000 people who received 2 doses of BNT162b2. An increased risk of Bell's palsy was observed during the first 14 days after the second dose of BNT162b2 in both nested case-control (aOR, 2.325; 95% CI, 1.414-3.821) and SCCS analysis (adjusted incidence rate ratio, 2.44; 95% CI, 1.32-4.50). CONCLUSIONS: There was an overall increased risk of Bell's palsy following BNT162b2 vaccination, particularly within the first 14 days after the second dose, but the absolute risk was very low.

Comparing machine learning-derived MRI-based and blood-based neurodegeneration biomarkers in predicting syndromal conversion in early AD.

INTRODUCTION: We compared the machine learning-derived, MRI-based Alzheimer's disease (AD) resemblance atrophy index (AD-RAI) with plasma neurofilament light chain (NfL) level in predicting conversion of early AD among cognitively unimpaired (CU) and mild cognitive impairment (MCI) subjects. METHODS: We recruited participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who had the following data: clinical features (age, gender, education, Montreal Cognitive Assessment [MoCA]), structural MRI, plasma biomarkers (p-tau181 , NfL), cerebrospinal fluid biomarkers (CSF) (Aß42, p-tau181 ), and apolipoprotein E (APOE) ε4 genotype. We defined AD using CSF Aß42 (A+) and p-tau181 (T+). We defined conversion (C+) if a subject progressed to the next syndromal stage within 4 years. RESULTS: Of 589 participants, 96 (16.3%) were A+T+C+. AD-RAI performed better than plasma NfL when added on top of clinical features, plasma p-tau181 , and APOE ε4 genotype (area under the curve [AUC] = 0.832 vs. AUC = 0.650 among CU, AUC = 0.853 vs. AUC = 0.805 among MCI) in predicting A+T+C+. DISCUSSION: AD-RAI outperformed plasma NfL in predicting syndromal conversion of early AD. HIGHLIGHTS: AD-RAI outperformed plasma NfL in predicting syndromal conversion among early AD. AD-RAI showed better metrics than volumetric hippocampal measures in predicting syndromal conversion. Combining clinical features, plasma p-tau181 and apolipoprotein E (APOE) with AD-RAI is the best model for predicting syndromal conversion.

Clinical and radiomic features for predicting the treatment response of repetitive transcranial magnetic stimulation in major neurocognitive disorder: Results from a randomized controlled trial.

Image-guided repetitive transcranial magnetic stimulation (rTMS) has shown clinical effectiveness in senior adults with co-occurring depression and cognitive impairment, yet the imaging markers for predicting the treatment response are less investigated. In this clinical trial, we examined the efficacy and sustainability of 10 Hz rTMS for the treatment of depression and cognitive impairment in major neurocognitive disorder (NCD) patients and tested the predictive values of imaging-informed radiomic features in response to rTMS treatment. Fifty-five major NCD patients with depression were randomly assigned to receive a 3-week rTMS treatment of either active 10 Hz rTMS (n = 27) or sham rTMS (n = 28). Left dorsolateral prefrontal cortex (DLPFC) was the predefined treatment target. Based on individual structural magnetic resonance imaging scans, surface-based analysis was conducted to quantitatively measure the baseline radiomic features of left DLPFC. Severity of depression, global cognition and the serum brain-derived neurotrophic factor (BDNF) level were evaluated at baseline, 3-, 6- and 12-week follow-ups. Logistic regression analysis revealed that advanced age, higher baseline cognition and randomized group were associated with the remission of depression. Increased cortical thickness and gyrification in left DLPFC were the significant predictors of clinical remission and cognitive enhancement. A 3-week course of 10 Hz rTMS is an effective adjuvant treatment for rapid ameliorating depressive symptoms and enhancing cognitive function. Pre-treatment radiomic features of the stimulation target can predict the response to rTMS treatment in major NCD. Cortical thickness and folding of treatment target may serve as imaging markers to detect the responders. ChiCTR-IOR-16008191, registered on March 30, 2016.

Effects of Mindfulness Yoga Versus Conventional Physical Exercises on Symptom Experiences and Health-related Quality of Life in People with Parkinson's Disease: The Potential Mediating Roles of Anxiety and Depression.

BACKGROUND: Although several studies have reported positive effects of mind-body exercises on symptom management and health-related quality of life (HRQOL) of people living with Parkinson's disease (PD), it is not known whether these effects are attributable to a change in anxiety and depression. PURPOSE: To compare the effects of mindfulness yoga to conventional stretching exercises in a randomized controlled trial while examining potentially mediating effects of anxiety and depression. METHODS: 138 adults with PD were randomized to eight weekly yoga (n = 71) or stretching (n = 67) sessions. Symptom experiences, anxiety and depression, and HRQOL outcomes were assessed at baseline, immediate post-intervention, and 3-month post-intervention. RESULTS: Generalized estimating equation analyses revealed that, compared to stretching, yoga significantly improved patients' nonmotor (time-by-group interaction, T1:ß = -1.99, p = .008; T2:ß = -2.86, p < .001) and motor (time-by-group interaction, T1:ß = -1.77, p = .03) symptom experiences. The mediation analysis found that the changes in anxiety and depression were the mediators in the associations between non-motor experience and HRQOL; while only the changes in depression were found to be the mediator in the relationship between motor experience and HRQOL. CONCLUSIONS: Yoga is superior to conventional stretching exercises in improving nonmotor and motor symptoms in daily living. Reduced anxiety and depression play a role in mediating the positive effects of the mindfulness yoga intervention. To optimize HRQOL, rehabilitation should reinforce psychological care in addition to pharmacological treatments and physical relief of PD symptoms. Future studies are needed to identify strategies for facilitating the implementation and sustainability of mind-body rehabilitation to enhance the quality of care for PD.

Rest-Activity Pattern Alterations in Idiopathic REM Sleep Behavior Disorder.

OBJECTIVE: The purpose of this study was to investigate the differences in actigraphy-measured rest-activity patterns (eg, sleep-wake cycle, circadian rest-activity rhythm, and physical activity) across different stages of α-synucleinopathy. METHODS: We compared alterations in 7-day actigraphy-measured rest-activity patterns among patients with clinically diagnosed α-synucleinopathies (n = 44), and their age-, sex-, and body mass index (BMI)-matched patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD, n = 88), and non-rapid eye movement (REM) sleep behavior disorder (RBD) controls (n = 44) in a case-control study (study 1) and between convertors (n = 22) and their age-, sex-, BMI-, iRBD-duration, and follow-up duration-matched non-convertors (n = 66) in a prospective nested case-control study (study 2). RESULTS: In study 1, there were significant increases (all p values were adjusted by false discovery rate < 0.01) in probable napping behaviors (percentage, duration, and episodes), activity fragmentation (estimated by kAR ), and physical inactivity during active periods across controls, and iRBD, to clinically diagnosed α-synucleinopathies. In study 2, higher levels (all p values were adjusted by false discovery rate < 0.05) of baseline objective probable napping, activity fragmentation, and physical inactivity during active periods were associated with the conversion of patients with iRBD into clinically diagnosed α-synucleinopathies at 2 years of follow-up with medium to large effect sizes (Cohen's d: 0.56 to 0.80). These findings were further supported by functional linear modeling analyses. INTERPRETATION: Rest-activity pattern alterations, mainly objective probable napping behaviors, activity fragmentation, and physical inactivity during active period, emerge as early as at the stage of iRBD, which serves as early and robust prodromal markers of the conversion of iRBD into clinically diagnosed α-synucleinopathies. ANN NEUROL 2020;88:817-829.

Quantitative Susceptibility Mapping of the Hippocampal Fimbria in Alzheimer's Disease.

BACKGROUND: The fimbria is a small white matter bundle that connects the hippocampus to the rest of the brain. Damage to the hippocampal gray matter is established in Alzheimer's disease (AD), but the hippocampal fimbrial status in the pathogenesis of AD is unclear. AD-related demyelination and iron deposition alter the diamagnetic and paramagnetic composition of tissues, which can be measured by quantitative susceptibility mapping (QSM). HYPOTHESIS: AD is associated with microstructural changes in the fimbria that might be detected by QSM. STUDY TYPE: Retrospective cross-sectional study. SUBJECTS: In all, 53 adults comprised of controls (n = 30), subjects with early stage AD (n = 13), and late stage AD (n = 10) who were classified according to their amyloid and tau status and presence of hippocampal atrophy. FIELD STRENGTH / SEQUENCE: 3T; 3D fast-field echo sequence for QSM analysis and 3D T1 -weighted MP-RAGE sequence for anatomical analysis. ASSESSMENT: Segmentation of the left hippocampal fimbria subfield was performed on T1 -weighted images and was applied to the coregistered QSM map for extraction of the mean, median, minimum, and maximum values of QSM. STATISTICAL TESTS: Group comparison of QSM values using analysis of variance (ANOVA) with post-hoc Tukey's test, accuracy of binary differentiation using receiver operating characteristic (ROC), and individual classification using discriminant analysis. RESULTS: QSMmean and QSMmedian values were significantly different among the three groups (P < 0.05) and showed a shifting from negative in the control group to positive in the AD group. The control and early AD subjects, who have normal hippocampal volumes, were differentiated by the QSMmean value (area under the curve [AUC] 0.744, P < 0.05) and the QSMmedian value (AUC 0.782, P < 0.05). Up to 76% of subjects (inclusive of 26 controls and six with early AD) were correctly classified using a model incorporating clinical and radiologic data. DATA CONCLUSION: The fimbria showed higher magnetic susceptibility in AD compared with controls. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

A case-control-family study of idiopathic rapid eye movement sleep behavior disorder.

OBJECTIVE: To determine the familial aggregation of idiopathic rapid eye movement sleep behavior disorder (iRBD), neurodegenerative diseases, and related biomarkers. METHODS: A total of 404 and 387 first-degree relatives of 102 patients with iRBD and of 89 controls were recruited, respectively. Among them, 204 and 208 relatives of patients and controls underwent face-to-face clinical assessment, whereas 97 and 75 relatives underwent further video-polysomnographic assessment, respectively. RESULTS: Compared with relatives of controls, relatives of patients demonstrated higher levels of RBD features, including chin tonic electromyography activity (mean = 1.5 ± 7.5 vs 0.3 ± 1.0, p = 0.04) and behavioral events (n [weighted %] = 12 [11.3] vs 2 [1.9], adjusted hazard ratio [aHR] = 7.69, 95% confidence interval [CI] = 1.54-33.33, p = 0.009) during rapid eye movement sleep, probable diagnosis (n [%] = 57 [14.9] vs 20 [4.9], aHR = 3.45, 95% CI = 1.96-6.25, p < 0.001), and definite diagnosis (n [weighted %] = 10 [8.4] vs 2 [1.4], aHR = 5.56, 95% CI = 1.16-25.00, p = 0.03). They also had higher risks of Parkinson disease (3.1% vs 0.5%, aHR = 5.88, 95% CI = 1.37-25.00, p = 0.02), dementia (6.9% vs 2.6%, aHR = 2.44, 95% CI = 1.15-5.26, p = 0.02), constipation (8.3% vs 2.4%, adjusted odds ratio = 4.21, 95% CI = 1.34-13.17, p = 0.01), and motor dysfunction (Movement Disorders Society Unified Parkinson's Disease Rating Scale part III motor score, mean = 1.9 ± 3.2 vs 0.9 ± 2.3, p = 0.002). The unaffected relatives of patients demonstrated a higher likelihood ratio of prodromal Parkinson disease (median [interquartile range] = 0.27 [1.19] vs 0.22 [0.51], p = 0.03). INTERPRETATION: iRBD is familially aggregated from isolated features to full-blown sleep disorder. Relatives of patients carry a higher risk of alpha-synucleinopathy in terms of neurodegenerative diseases and prodromal markers, suggesting a familial aggregation and staging pathology of alpha-synucleinopathy. Ann Neurol 2019;85:582-592.

Development of a Delayed Cerebral Infarction Load Scoring System (DCI Score).

Delayed cerebral infarction (DCI) is related to unfavorable outcome after aneurysmal subarachnoid hemorrhage (SAH). There lacks a clear understanding how the DCI load affects cognitive function after SAH. We conducted a literature review on the clinical classification systems on brain hemorrhages and cerebral infarction and devised a Delayed Cerebral Infarction Load Scoring System (DCI Score). DCI Score significantly correlated with Symbol Digit Modalities Test (-0.334, p = 0.032), Color Trail Test (-0.310, p = 0.032), Hong Kong List Learning Test (-0.318, p = 0.036), Verbal Digit Span Forward (-0.382, p = 0.017), and Visual Digit Span Backward (-0.425, p = 0.012). In conclusion, higher DCI load impacted significantly on memory and executive function. DCI Score is a useful system for clinical quantification of DCI load and clinical research.

Standardization of hippocampus volumetry using automated brain structure volumetry tool for an initial Alzheimer's disease imaging biomarker.

BACKGROUND: One significant barrier to incorporate Alzheimer's disease (AD) imaging biomarkers into diagnostic criteria is the lack of standardized methods for biomarker quantification. The European Alzheimer's Disease Consortium-Alzheimer's Disease Neuroimaging Initiative (EADC-ADNI) Harmonization Protocol project provides the most authoritative guideline for hippocampal definition and has produced a manually segmented reference dataset for validation of automated methods. PURPOSE: To validate automated hippocampal volumetry using AccuBrain™, against the EADC-ADNI dataset, and assess its diagnostic performance for differentiating AD and normal aging in an independent cohort. MATERIAL AND METHODS: The EADC-ADNI reference dataset comprise of manually segmented hippocampal labels from 135 volumetric T1-weighted scans from various scanners. Dice similarity coefficient (DSC), intraclass correlation coefficient (ICC), and Pearson's r were obtained for AccuBrain™ and FreeSurfer. The magnetic resonance imaging (MRI) of a separate cohort of 299 individuals (150 normal controls, 149 with AD) were obtained from the ADNI database and processed with AccuBrain™ to assess its diagnostic accuracy. Area under the curve (AUC) for total hippocampal volumes (HV) and hippocampal fraction (HF) were determined. RESULTS: Compared with EADC-ADNI dataset ground truths, AccuBrain™ had a mean DSC of 0.89/0.89/0.89, ICC of 0.94/0.96/0.95, and r of 0.95/0.96/0.95 for right/left/total HV. AccuBrain™ HV and HF had AUC of 0.76 and 0.80, respectively. Thresholds of ≤ 5.71 mL and ≤ 0.38% afforded 80% sensitivity for AD detection. CONCLUSION: AccuBrain™ provides accurate automated hippocampus segmentation in accordance with the EADC-ADNI standard, with great potential value in assisting clinical diagnosis of AD.

Location of Acute Infarcts and Agitation and Aggression in Stroke.

The role of the infarct location in the development of poststroke agitation (PSA) is largely unknown. This study examined the association between the locations of infarcts and PSA at 9 months following the index stroke in 213 patients with the Chinese version of the Neuropsychiatric Inventory. Compared with the non-PSA group, PSA patients had a higher number and volume of acute pontine infarcts. Ventral pontine and lateral cerebellar infarcts were independent predictors of PSA in the multivariate analysis.

Location, Infarct Load, and 3-Month Outcomes of Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage is a serious disease with high case fatality and morbidity. Delayed cerebral infarction (DCI) is an important surrogate marker. How location and infarct load affected outcomes was unclear. We aimed to assess the effects of load and location of DCI on outcomes of aneurysmal subarachnoid hemorrhage at 3 months. METHODS: We prospectively enrolled patients with subarachnoid hemorrhage presenting to an academic neurosurgical unit in Hong Kong during a 3-year period. DCI was defined by new hypoattenuation on computed tomography at 4 to 6 weeks, which was not present in the postaneurysm-treatment computed tomography at 24 to 48 hours. DCI was assessed for location according to cerebral artery territories and load semiquantitatively. Cognitive and functional outcome assessments were carried out 3 months after ictus. RESULTS: One hundred twenty-six patients with subarachnoid hemorrhage consented for this study. DCI occurred in 56 (44%) patients and was associated with poorer cognitive and functional outcomes (Montreal Cognitive Assessment, Mini-Mental State Examination, modified Rankin Scale, and Lawton Instrumental Activity of Daily Living) at 3 months. In patients with DCI, the presence of perforator zone infarct was associated with poorer cognitive and functional outcomes, and cortical middle cerebral artery infarct was associated with poorer modified Rankin Scale. After adjustment for age, admission World Federation of Neurosurgical Societies Grade and mode of aneurysm treatment, both middle cerebral artery cortical infarct load and perforator infarct load were independently associated with poor cognitive outcomes (Montreal Cognitive Assessment and Mini-Mental State Examination) and modified Rankin Scale. CONCLUSIONS: Middle cerebral artery cortical and perforator zone infarct loads are potential surrogate marker to assess the severity of delayed cerebral ischemia.

Cerebral microbleeds as a predictor of 1-year outcome of poststroke depression.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are common in stroke survivors and community-dwelling elderly. The clinical significance of CMBs in the outcome of poststroke depression (PSD) is unknown. This study examined the association between the 1-year outcome of PSD and CMBs. METHODS: The study population comprised 774 Chinese patients with acute ischemic stroke who were admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong. Three and 15 months after the onset of the index stroke, a research assistant administered the locally validated 15-item Geriatric Depression Scale. PSD was defined as a Geriatric Depression Scale score of ≥7. Of the 213 patients with PSD at the 3-month follow-up, 135 (63.4%) attended the 15-month follow-up, at which time 89 (65.9%) patients remained depressed (nonremitters), and 46 (34.1%) had recovered (remitters). The presence and location of CMBs were evaluated with magnetic resonance imaging. RESULTS: In comparison with the remitters, nonremitters were more likely to have lobar CMBs (18.4% versus 4.3%; P=0.024). Lobar CMBs remained an independent predictor of PSD in the multivariate analysis, with an odds ratio of 4.96 (P=0.039). CONCLUSIONS: The results suggest that lobar CMBs may influence the outcome of PSD. The importance of CMBs in the clinical course of depression in stroke survivors warrants further investigation.

Cerebral microbleeds and fatigue in stroke.

BACKGROUND AND PURPOSE: Poststroke fatigue (PSF) is a frequent and persistent problem in stroke survivors. The neuroanatomical model of PSF remains unclear. This study examined the association between PSF and cerebral microbleeds (CMBs). METHODS: The sample comprised 199 patients with acute ischemic stroke. A psychiatrist who was blind to the subjects' radiological data administered the Chinese version of the Fatigue Severity Scale. PSF was defined as a Fatigue Severity Scale score of 4.0 or more. The locations of CMBs were evaluated with magnetic resonance imaging within 7 days of admission. RESULTS: Of the 199 patients screened, 47 (23.6%) had PSF. The PSF group had a higher Geriatric Depression Scale score (p < 0.001) and a trend for a higher age (p = 0.074). The proportion of patients with deep CMBs was significantly higher in the PSF group (66.0 vs. 48.7%; p = 0.038). The presence of deep CMBs was a significant independent predictor of PSF with an odds ratio of 2.68 (p = 0.016). CONCLUSION: The results suggest that deep CMBs are associated with a higher risk of PSF. Further studies are needed to clarify whether CMBs affect the clinical presentation, treatment response and outcome of PSF.

Diagnostic Accuracy and Field for Improvement of Frameless Stereotactic Brain Biopsy: A Focus on Nondiagnostic Cases.

BACKGROUND: The diagnostic accuracy of frameless stereotactic brain biopsy has been reported, but there is limited literature focusing on the reasons for nondiagnostic cases. In this study, we evaluate the diagnostic accuracy of frameless stereotactic brain biopsy, compare it with the current international standard, and review the field for improvement. METHODS: This is a retrospective analysis of consecutive, prospectively collected frameless stereotactic brain biopsies from 2007 to 2020. We evaluated the diagnostic accuracy of the frameless stereotactic brain biopsies using defined criteria. The biopsy result was classified as conclusive, inconclusive, or negative, based on the pathologic, radiologic, and clinical diagnosis concordance. For inconclusive or negative results, we further evaluated the preoperative planning and postoperative imaging to review the errors. A literature review for the diagnostic accuracy of frameless stereotactic biopsy was performed for the validity of our results. RESULTS: There were 106 patients with 109 biopsies performed from 2007 to 2020. The conclusive diagnosis was reached in 103 (94.5%) procedures. An inconclusive diagnosis was noted in four (3.7%) procedures and the biopsy was negative in two (1.9%) procedures. Symptomatic hemorrhage occurred in one patient (0.9%). There was no mortality in our series. Registration error (RE) and inaccurate targeting occurred in three trigonal lesions (2.8%), sampling of the nonrepresentative part of the lesion occurred in two cases (1.8%), and one biopsy (0.9%) for lymphoma was negative due to steroid treatment. The literature review suggested that our diagnostic accuracy was comparable with the published literature. CONCLUSION: The frameless stereotactic biopsy is a safe procedure with high diagnostic accuracy only if meticulous preoperative planning and careful intraoperative registration is performed. The common pitfalls precluding a conclusive diagnosis are RE and biopsies at nonrepresentative sites.

Predictive values of pre-treatment brain age models to rTMS effects in neurocognitive disorder with depression: Secondary analysis of a randomised sham-controlled clinical trial.

INTRODUCTION: One major challenge in developing personalised repetitive transcranial magnetic stimulation (rTMS) is that the treatment responses exhibited high inter-individual variations. Brain morphometry might contribute to these variations. This study sought to determine whether individual's brain morphometry could predict the rTMS responders and remitters. METHODS: This was a secondary analysis of data from a randomised clinical trial that included fifty-five patients over the age of 60 with both comorbid depression and neurocognitive disorder. Based on magnetic resonance imaging scans, estimated brain age was calculated with morphometric features using a support vector machine. Brain-predicted age difference (brain-PAD) was computed as the difference between brain age and chronological age. RESULTS: The rTMS responders and remitters had younger brain age. Every additional year of brain-PAD decreased the odds of relieving depressive symptoms by ∼25.7% in responders (Odd ratio [OR] = 0.743, p = .045) and by ∼39.5% in remitters (OR = 0.605, p = .022) in active rTMS group. Using brain-PAD score as a feature, responder-nonresponder classification accuracies of 85% (3rd week) and 84% (12th week), respectively were achieved. CONCLUSION: In elderly patients, younger brain age appears to be associated with better treatment responses to active rTMS. Pre-treatment brain age models informed by morphometry might be used as an indicator to stratify suitable patients for rTMS treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR-IOR-16008191.

Machine Learning-Derived MRI-Based Neurodegeneration Biomarker for Alzheimer's Disease: A Multi-Database Validation Study.

BACKGROUND: Pilot study showed that Alzheimer's disease resemblance atrophy index (AD-RAI), a machine learning-derived MRI-based neurodegeneration biomarker of AD, achieved excellent diagnostic performance in diagnosing AD with moderate to severe dementia. OBJECTIVE: The primary objective was to validate and compare the performance of AD-RAI with conventional volumetric hippocampal measures in diagnosing AD with mild dementia. The secondary objectives were 1) to investigate the association between imaging biomarkers with age and gender among cognitively unimpaired (CU) participants; 2) to analyze whether the performance of differentiating AD with mild dementia from CU will improve after adjustment for age/gender. METHODS: AD with mild dementia (n = 218) and CU (n = 1,060) participants from 4 databases were included. We investigated the area under curve (AUC), sensitivity, specificity, and balanced accuracy of AD-RAI, hippocampal volume (HV), and hippocampal fraction (HF) in differentiating between AD and CU participants. Among amyloid-negative CU participants, we further analyzed correlation between the biomarkers with age/gender. We also investigated whether adjustment for age/gender will affect performance. RESULTS: The AUC of AD-RAI (0.93) was significantly higher than that of HV (0.89) and HF (0.89). Subgroup analysis among A + AD and A- CU showed that AUC of AD-RAI (0.97) was also higher than HV (0.94) and HF (0.93). Diagnostic performance of AD-RAI and HF was not affected by age/gender while that of HV improved after age adjustment. CONCLUSIONS: AD-RAI achieves excellent clinical validity and outperforms conventional volumetric hippocampal measures in aiding the diagnosis of AD mild dementia without the need for age adjustment.

Evaluation of Cost-Effectiveness of a Virtual Multidisciplinary Stroke Care Clinic for Community-Dwelling Survivors of Stroke.

BACKGROUND: A technologically integrated, multidisciplinary approach to stroke rehabilitation service was delivered and embedded into conventional health care practice. This article reports an evaluation of cost-effectiveness analysis of a new Virtual Multidisciplinary Stroke Care Clinic (VMSCC) service for community-dwelling survivors of stroke. METHODS AND RESULTS: A randomized controlled trial was conducted. Adults with a first/recurrent ischemic/hemorrhagic stroke were recruited from 10 hospitals. Eligible participants were randomly assigned to receive the VMSCC service (individual virtual consultations with a registered nurse, home blood pressure telemonitoring, and unlimited access to an online resource platform) plus usual care or usual care alone. Cost-effectiveness analyses were performed based on incremental cost-effectiveness ratios expressed as incremental cost per emergency admission reduced, and day of hospitalization reduced over the study period. A total of 256 participants (intervention group n=141 versus control group n=115) with complete cost and health care use data were included in the cost-effectiveness analyses. The VMSCC service, on average, resulted in a greater reduction in the number of emergency admission (-0.06 [95% bootstrapped CI, -0.14 to 0.01]) and fewer days of hospitalization (-0.08, [95% bootstrapped CI -0.40 to 0.24]) but incurred a higher total cost of HK$375 (95% bootstrapped CI, -2103 to 2743) compared with the usual care. The incremental cost-effectiveness ratios of the VMSCC service compared with the usual care were HK$6070 and HK$4826 per an emergency admission and a day of hospital stay reduced respectively. CONCLUSIONS: The study provides preliminary but not confirmative evidence that the VMSCC service could be more effective but more costly than usual care in reducing health service use. REGISTRATION: URL: https://www.chictr.org.cn. Unique identifier: ChiCTR1800016101.

Effects of Acupuncture upon cerebral hemodynamics in cerebral small vessel disease: A pilot study.

Background and aims: Recent preclinical studies and meta-analysis of clinical trials suggested that acupuncture may improve cognition in cerebral small vessel disease (CSVD). We investigated the cerebral hemodynamics of acupuncture in subjects with CSVD and compared its impact upon the cerebral hemodynamics in normal elderly subjects. Methods: 10 subjects with CSVD (CSVD group) and 10 aged-matched control subjects who had no or insignificant CSVD (control group) were recruited. A single session of acupuncture was applied for 30 min in both groups. We assessed the effect of our acupuncture intervention on cerebral hemodynamics by transcranial Doppler ultrasound (TCD). Peak systolic velocity (PSV) and pulsatility index (PI) of the middle cerebral artery (MCA) were assessed. Results: We observed that PSV increased by a maximum of 39% at 20 min (p<0.05), while there was no significant change in PI in the CSVD group during the acupuncture session. In the control group, although we observed no significant change in PSV during the acupuncture session, there was a significant decrease in PI by a maximum of 22% at 20 min (p<0.05). No adverse events were reported during or after the procedure. Conclusion: This study suggested that our acupuncture prescription was associated with an increase in cerebral blood flow in subjects with established moderate to severe CSVD yet without apparent impact on distal vascular resistance. While, in subjects with no or insignificant CSVD, it may reduce cerebral small vessel distal vascular resistance. A larger study is needed to confirm our findings.