Vascular cognitive impairment and dementia: Mechanisms, treatment, and future directions.

Worldwide, around 50 million people live with dementia, and this number is projected to triple by 2050. It has been estimated that 20% of all dementia cases have a predominant cerebrovascular pathology, while perhaps another 20% of vascular diseases contribute to a mixed dementia picture. Therefore, the vascular contribution to dementia affects 20 million people currently and will increase markedly in the next few decades, particularly in lower- and middle-income countries.In this review, we discuss the mechanisms of vascular cognitive impairment (VCI) and review management. VCI refers to the spectrum of cerebrovascular pathologies that contribute to any degree of cognitive impairment, ranging from subjective cognitive decline, to mild cognitive impairment, to dementia. While acute cognitive decline occurring soon after a stroke is the most recognized form of VCI, chronic cerebrovascular disease, in particular cerebral small-vessel disease, can cause insidious cognitive decline in the absence of stroke. Moreover, cerebrovascular disease not only commonly co-occurs with Alzheimer's disease (AD) and increases the probability that AD pathology will result in clinical dementia, but may also contribute etiologically to the development of AD pathologies.Despite its enormous health and economic impact, VCI has been a neglected research area, with few adequately powered trials of therapies, resulting in few proven treatments. Current management of VCI emphasizes prevention and treatment of stroke and vascular risk factors, with most evidence for intensive hypertension control. Reperfusion therapies in acute stroke may attenuate the risk of VCI. Associated behavioral symptoms such as apathy and poststroke emotionalism are common. We also highlight novel treatment strategies that will hopefully lead to new disease course-modifying therapies. Finally, we highlight the importance of including cognitive endpoints in large cardiovascular prevention trials and the need for an increased research focus and funding for this important area.

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.

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.

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.

Prevalence of post-stroke cognitive impairment and associated risk factors in Chinese stroke survivors.

BACKGROUND: Post-stroke cognitive impairment (PSCI) adversely affects survivors' recovery trajectory and overall health outcomes. This study aimed to investigate the prevalence of PCSI and its associated risk factors. METHODS: A cross-sectional study was conducted with stroke survivors recruited from the neurology units of three hospitals in Yunnan, China. Measures included the Frenchay Aphasia Screening Test (FAST), Apathy Evaluation Scale (AES), Fatigue Severity Scale (FSS), Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE), Montreal Cognitive Assessment (MoCA), and Charlson Comorbidity Index (CCI). Logistic regression analysis was carried out to identify risk factors significantly and independently associated with PSCI. RESULTS: Of 389 stroke participants studied, 139 (36%) were found to have PSCI. Every 10-year increase in age [odds ratio (OR) =1.69, 95% confidence interval (CI): 1.27-2.24, p < 0.001], and 1-point increase in the AES (OR = 1.13, 95% CI: 1.07-1.18, p < 0.001) and FSS scores (OR = 1.06, 95% CI: 1.03-1.10, p < 0.001) were significantly associated with higher odds of PSCI. Conversely, a 1-point increase in the MoCA score (OR = 0.91, 95% CI: 0.87-0.95, p < 0.001) and having an undergraduate education (OR = 0.45, 95% CI: 0.24-0.84, p = 0.013) or postgraduate education (OR = 0.18, 95% CI: 0.06-0.50, p = 0.001) were associated with reduced odds of PSCI. CONCLUSIONS: PSCI is prevalent in the Chinese population, with advanced age, lower education levels, lower MoCA scores, and higher fatigue and apathy scores identified as strong risk factors. It is recommended that psychological and cognitive assessment be routinely incorporated into post-stroke rehabilitation pathways to mitigate cognitive decline.

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.

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.

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.

The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed. AIM: This study aims to systematically review the prevalence of cSVD in LMICs. RESULTS: Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study sample size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old; range: 36.3-80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes, while the type of study was a significant predictor of the prevalence of CMB. The heterogeneity of studies was high (>95%). Male participants were overrepresented. CONCLUSIONS: This systematic review and meta-analysis provide data on cSVD prevalence in LMICs and demonstrated the high prevalence of the condition. cSVD research in LMICs is being published at an increasing rate, especially between 2010 and 2022. More data are particularly needed from Sub-Saharan Africa and Central Europe, Eastern Europe, and Central Asia.

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.

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.

Personality profile and its association with conversion to neurodegenerative disorders in idiopathic REM sleep behavior disorder.

Patients with Parkinson's disease (PD) were described less extraverted and more neurotic. It remained unclear whether similar personality traits could be found in idiopathic rapid eye movement sleep behavior disorder (iRBD), a prodromal stage of PD, and could predict phenoconversion to neurodegenerative disorders. We aimed to investigate the personality profile and its association with future neurodegenerative phenoconversion in iRBD patients. One hundred and eighty-five video-polysomnography confirmed iRBD patients and 91 age- and sex-matched controls underwent personality assessment using the NEO five-factor inventory, and 171 iRBD patients were followed up. Our results showed that iRBD was marginally negatively associated with extraverted personality trait (B = -0.28, 95% confidence interval (CI) = -0.55, -0.001). During a median follow-up of 5.9 years, 47 iRBD patients (27.5%) had phenoconversion. More neurotic (adjusted hazard ratio (HR) = 2.0, 95% CI = 1.3, 3.1) and less extraverted personality traits (adjusted HR = 0.53, 95% CI = 0.36, 0.77) were associated with an increased risk of phenoconversion in iRBD patients. Our findings suggest that personality profile may be a potential prodromal marker of iRBD.

Lower Posterior Cingulate N-Acetylaspartate to Creatine Level in Early Detection of Biologically Defined Alzheimer's Disease.

Alzheimer's disease (AD) was recently defined as a biological construct to reflect neuropathologic status, and both abnormal amyloid and tau are required for a diagnosis of AD. We aimed to determine the proton MR spectroscopic (1H-MRS) patterns of the posterior cingulate in biologically defined AD. A total of 68 participants were included in this study, comprising 37 controls, 16 early AD, and 15 late AD, who were classified according to their amyloid and tau status and presence of hippocampal atrophy. Compared with controls, early AD showed lower N-acetylaspartate (NAA)/creatine (Cr) (p = 0.003), whereas late AD showed lower NAA/Cr and higher myoInositol (mI)/Cr (all with p < 0.05). Lower NAA/Cr correlated with a greater global amyloid load (r = −0.47, p < 0.001) and tau load (r = −0.51, p < 0.001) and allowed a discrimination of early AD from controls (p < 0.001). Subgroup analysis showed that NAA/Cr also allowed a differentiation of early AD from controls in the cognitively unimpaired subjects, with an area under the receiver operating characteristics curve, sensitivity, and specificity of 0.96, 100%, and 83.8%, respectively. Lower posterior cingulate NAA levels may help to inform underlying neuropathologic changes in the early stage of AD.

Thromboembolic events and hemorrhagic stroke after mRNA (BNT162b2) and inactivated (CoronaVac) covid-19 vaccination: A self-controlled case series study.

Background: This study aims to evaluate the association between thromboembolic events and hemorrhagic stroke following BNT162b2 and CoronaVac vaccination. Methods: Patients with incident thromboembolic events or hemorrhagic stroke within 28 days of covid-19 vaccination or SARS-CoV-2 positive test during 23 February to 30 September 2021 were included. The incidence per 100,000 covid-19 vaccine doses administered and SARS-CoV-2 test positive cases were estimated. A modified self-controlled case series (SCCS) analysis using the data from the Hong Kong territory-wide electronic health and vaccination records. Seasonal effect was adjusted by month. Findings: A total of 5,526,547 doses of BNT162b2 and 3,146,741 doses of CoronaVac were administered. A total of 334 and 402 thromboembolic events, and 57 and 49 hemorrhagic stroke cases occurred within 28 days after BNT162b2 and CoronaVac vaccination, respectively. The crude incidence of thromboembolic events and hemorrhagic stroke per 100,000 doses administered for both covid-19 vaccines were smaller than that per 100,000 SARS-CoV-2 test positive cases. The modified SCCS detected an increased risk of hemorrhagic stroke in BNT162b2 14-27 days after first dose with adjusted IRR of 2.53 (95% CI 1.48-4.34), and 0-13 days after second dose with adjusted IRR 2.69 (95% CI 1.54-4.69). No statistically significant risk was observed for thromboembolic events for both vaccines. Interpretation: We detected a possible safety signal for hemorrhagic stroke following BNT162b2 vaccination. The incidence of thromboembolic event or hemorrhagic stroke following vaccination is lower than that among SARS-CoV-2 test positive cases; therefore, vaccination against covid-19 remains an important public health intervention. Funding: This study was funded by a research grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (reference COVID19F01).

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.

Bell's palsy following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines: a case series and nested case-control study.

BACKGROUND: Bell's palsy is a rare adverse event reported in clinical trials of COVID-19 vaccines. However, to our knowledge no population-based study has assessed the association between the inactivated SARS-CoV-2 vaccines and Bell's palsy. The aim of this study was to evaluate the risk of Bell's palsy after BNT162b2 and CoronaVac vaccination. METHODS: In this case series and nested case-control study done in Hong Kong, we assessed the risk of Bell's palsy within 42 days following vaccination with BNT162b2 (Fosun-BioNTech [equivalent to Pfizer-BioNTech]) or CoronaVac (from Sinovac Biotech, Hong Kong) using data from voluntary surveillance reporting with the Hospital Authority, the COVID-19 Vaccine Adverse Event Online Reporting system for all health-care professionals, and the Hospital Authority's territory-wide electronic health records from the Clinical Data Analysis and Reporting System. We described reported cases of Bell's palsy among vaccine recipients (aged 18-110 years for CoronaVac and aged 16-110 years for BNT162b2). We compared the estimated age-standardised incidence of clinically confirmed cases among individuals who had received the CoronaVac or BNT162b2 vaccination (up to 42 days before presentation) with the background incidence in the population. A nested case-control study was also done using conditional logistic regression to estimate the odds ratio (OR) for risk of Bell's palsy and vaccination. Cases and controls were matched (1:4) by age, sex, admission setting, and admission date. FINDINGS: Between February 23 and May 4, 2021, 451 939 individuals received the first dose of CoronaVac and 537 205 individuals received the first dose of BNT162b2. 28 clinically confirmed cases of Bell's palsy were reported following CoronaVac and 16 cases were reported following BNT162b2. The age-standardised incidence of clinically confirmed Bell's palsy was 66·9 cases per 100 000 person-years (95% CI 37·2 to 96·6) following CoronaVac vaccination and 42·8 per 100 000 person-years (19·4 to 66·1) for BNT162b2 vaccination. The age-standardised difference for the incidence compared with the background population was 41·5 (95% CI 11·7 to 71·4) for CoronaVac and 17·0 (-6·6 to 40·6) for BNT162b2, equivalent to an additional 4·8 cases per 100 000 people vaccinated for CoronaVac and 2·0 cases per 100 000 people vaccinated for BNT162b2. In the nested case-control analysis, 298 cases were matched to 1181 controls, and the adjusted ORs were 2·385 (95% CI 1·415 to 4·022) for CoronaVac and 1·755 (0·886 to 3·477) for BNT162b2. INTERPRETATION: Our findings suggest an overall increased risk of Bell's palsy after CoronaVac vaccination. However, the beneficial and protective effects of the inactivated COVID-19 vaccine far outweigh the risk of this generally self-limiting adverse event. Additional studies are needed in other regions to confirm our findings. FUNDING: The Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

High burden of cerebral white matter lesion in 9 Asian cities.

Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5701) and classified into (i) stroke/transient ischemic attack (TIA), (ii) Alzheimer's disease (AD)/mild cognitive impairment (MCI), or (iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. The prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3%). Bandung Indonesia showed the highest prevalence of WML, adjusted for age, sex, education, disease groups, and imaging modality. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. WML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia, and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.

MRI-based Alzheimer's disease-resemblance atrophy index in the detection of preclinical and prodromal Alzheimer's disease.

Alzheimer's Disease-resemblance atrophy index (AD-RAI) is an MRI-based machine learning derived biomarker that was developed to reflect the characteristic brain atrophy associated with AD. Recent study showed that AD-RAI (≥0.5) had the best performance in predicting conversion from mild cognitive impairment (MCI) to dementia and from cognitively unimpaired (CU) to MCI. We aimed to validate the performance of AD-RAI in detecting preclinical and prodromal AD. We recruited 128 subjects (MCI=50, CU=78) from two cohorts: CU-SEEDS and ADNI. Amyloid (A+) and tau (T+) status were confirmed by PET (11C-PIB, 18F-T807) or CSF analysis. We investigated the performance of AD-RAI in detecting preclinical and prodromal AD (i.e. A+T+) among MCI and CU subjects and compared its performance with that of hippocampal measures. AD-RAI achieved the best metrics among all subjects (sensitivity 0.74, specificity 0.91, accuracy 85.94%) and among MCI subjects (sensitivity 0.92, specificity 0.81, accuracy 86.00%) in detecting A+T+ subjects over other measures. Among CU subjects, AD-RAI yielded the best specificity (0.95) and accuracy (85.90%) over other measures, while hippocampal volume achieved a higher sensitivity (0.73) than AD-RAI (0.47) in detecting preclinical AD. These results showed the potential of AD-RAI in the detection of early AD, in particular at the prodromal stage.