Converting MMSE to MoCA and MoCA 5-minute protocol in an educationally heterogeneous sample with stroke or transient ischemic attack.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA. METHODS: A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment. RESULTS: The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859. CONCLUSION: We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy.

Analysis of non-synonymous-coding variants of Parkinson's disease-related pathogenic and susceptibility genes in East Asian populations.

To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinson's disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare non-synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD cases and 9046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence interval = 1.29-1.93; P = 8.05 × 10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss of function of these genes were present in healthy controls. Overall, non-synonymous-coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis.

Evolution of intracranial atherosclerotic disease under modern medical therapy.

OBJECTIVE: Understanding how symptomatic intracranial atherosclerotic disease (ICAD) evolves with current medical therapy may inform secondary stroke prevention. METHODS: In a prospective academic-initiated study, we recruited 50 patients (mean age = 63.4 ± 9.0 years) with acute strokes attributed to high-grade (≥70%) intracranial atherosclerotic stenosis for 3-dimensional rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low-density lipoprotein ≤ 70mg/dl, glycosylated hemoglobin (HbA1c) ≤ 6.5%, and systolic blood pressure ≤ 140 mmHg. We analyzed infarct topography and monitored microembolic signal in recurrent strokes. The reference group was a published cohort of 143 ICAD patients. RESULTS: Overall, the stenoses regressed from 79% at baseline (interquartile range [IQR] = 71-87%) to 63% (IQR = 54-74%) in 1 year (p < 0.001). Specifically, the qualifying lesions (n = 49) regressed (stenosis reduced >10%) in 24 patients (49%), remained quiescent (stenosis same or ±10%) in 21 patients (43%), and progressed (stenosis increased >10%) in 4 patients (8%). There was no difference in intensity of risk factor control between groups of diverging clinical or angiographic outcomes. Higher HbA1c at baseline predicted plaque regression at 1 year (odds ratio = 4.4, 95% confidence interval = 1.4-14.5, p = 0.006). Among the 6 patients with recurrent strokes pertaining to the qualifying stenosis, 5 patients had solitary or rosarylike acute infarcts along the internal or anterior border zones, and 2 patients showed microembolic signals in transcranial Doppler ultrasound. INTERPRETATION: A majority of symptomatic high-grade intracranial plaques had regressed or remained quiescent by 12 months under intensive medical therapy. Artery-to-artery thromboembolism with impaired washout at border zones was a common mechanism in stroke recurrence.

Delayed-onset dementia after stroke or transient ischemic attack.

INTRODUCTION: Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. METHODS: Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. RESULTS: Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. DISCUSSION: Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group.

Montreal Cognitive Assessment 5-minute protocol is a brief, valid, reliable, and feasible cognitive screen for telephone administration.

BACKGROUND AND PURPOSE: The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization working group proposed a brief cognitive protocol for screening of vascular cognitive impairment. We investigated the validity, reliability, and feasibility of the Montreal Cognitive Assessment 5-minute protocol (MoCA 5-minute protocol) administered over the telephone. METHODS: Four items examining attention, verbal learning and memory, executive functions/language, and orientation were extracted from the MoCA to form the MoCA 5-minute protocol. One hundred four patients with stroke or transient ischemic attack, including 53 with normal cognition (Clinical Dementia Rating, 0) and 51 with cognitive impairment (Clinical Dementia Rating, 0.5 or 1), were administered the MoCA in clinic and a month later, the MoCA 5-minute protocol over the telephone. RESULTS: Administration of the MoCA 5-minute protocol took 5 minutes over the telephone. Total score of the MoCA 5-minute protocol correlated negatively with age (r=-0.36; P<0.001) and positively with years of education (r=0.41; P<0.001) but not with sex (ρ=0.03; P=0.773). Total scores of the MoCA and MoCA 5-minute protocol were highly correlated (r=0.87; P<0.001). The MoCA 5-minute protocol performed equally well as the MoCA in differentiating patients with cognitive impairment from those without (areas under receiver operating characteristics curve for MoCA 5-minute protocol, 0.78; MoCA=0.74; P>0.05 for difference; Cohen d for group difference, 0.80-1.13). It differentiated cognitively impaired patients with executive domain impairment from those without (areas under receiver operating characteristics curve, 0.89; P<0.001; Cohen d=1.7 for group difference). Thirty-day test-retest reliability was excellent (intraclass correlation coefficient, 0.89). CONCLUSIONS: The MoCA 5-minute protocol is a free, valid, and reliable cognitive screen for stroke and transient ischemic attack. It is brief and highly feasible for telephone administration.

A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia.

BACKGROUND: Spinocerebellar ataxias (SCAs) are a group of clinically and genetically diverse and autosomal-dominant disorders characterised by neurological deficits in the cerebellum. At present, there is no cure for SCAs. Of the different distinct subtypes of autosomal-dominant SCAs identified to date, causative genes for only a fraction of them are currently known. In this study, we investigated the cause of an autosomal-dominant SCA phenotype in a family that exhibits cerebellar ataxia and pontocerebellar atrophy along with a global reduction in brain volume. METHODS AND RESULTS: Whole-exome analysis revealed a missense mutation c.G1391A (p.R464H) in the coding region of the coiled-coil domain containing 88C (CCDC88C) gene in all affected individuals. Functional studies showed that the mutant form of CCDC88C activates the c-Jun N-terminal kinase (JNK) pathway, induces caspase 3 cleavage and triggers apoptosis. CONCLUSIONS: This study expands our understanding of the cause of autosomal-dominant SCAs, a group of heterogeneous congenital neurological conditions in humans, and unveils a link between the JNK stress pathway and cerebellar atrophy.

Risk factors for incident dementia after stroke and transient ischemic attack.

BACKGROUND: We hypothesized that chronic brain changes are important substrates for incident dementia after stroke and transient ischemic attack (TIA). METHODS: We compared clinical and imaging features between patients with consecutive stroke/TIA with (n = 88) and without (n = 925) incident dementia at 3 to 6 months after a stroke/TIA. Pittsburg compound B (PiB) positron emission tomography was performed in 50 patients, including those with (n = 37) and without (n = 13) incident dementia. RESULTS: Age, history of diabetes mellitus, severity of white matter changes (WMCs), and medial temporal lobe atrophy (MTLA) were associated with incident dementia. Alzheimer's disease (AD)--like PiB retention was found in 29.7% and 7.7% (P = .032) of patients with and without incident dementia, respectively. CONCLUSIONS: Chronic brain changes including WMCs, MTLA, and AD pathology are associated with incident dementia after stroke/TIA. Interventions targeting these chronic brain changes may reduce burden of vascular cognitive impairment.

Evaluation of carotid angioplasty and stenting for radiation-induced carotid stenosis.

BACKGROUND AND PURPOSE: We aimed to evaluate the procedural safety, clinical, and angiographic outcome of carotid angioplasty and stenting for high-grade (≥70%) radiation-induced carotid stenosis (RIS) using atherosclerotic stenosis (AS) as a control. METHODS: In this 6-year prospective nonrandomized study, we compared the carotid angioplasty and stenting outcome of 65 consecutive patients (84 vessels) with RIS with that of a control group of 129 consecutive patients (150 vessels) with AS. Study end points were 30-day periprocedural stroke or death, ipsilateral ischemic stroke, technical success, procedural characteristics, instent restenosis (ISR; ≥50%) and symptomatic ISR. RESULTS: The median follow-up was 47.3 months (95% confidence interval, 26.9-61.6). Imaging assessment was available in 74 vessels (RIS) and 120 vessels (AS) in 2 years. Comparing RIS group with AS group, the rates of periprocedural stroke or death were 1.5% (1/65) versus 1.6% (2/129; P=1); ipsilateral ischemic stroke rates were 4.6% (3/65) versus 4.7% (6/129; P=1); the annual risks of ipsilateral ischemic stroke were 1.2% (3 patient/254.7 patient year) versus 1.2% (6 patient/494.2 patient year; P=0.89); technical success rates were both 100%. Stenting of common carotid artery and the use of multiple stents was more common in the RIS group (P=0 in both cases); ISR rates were 25.7% (19/74) versus 4.2% (5/120; P<0.001); symptomatic ISR rates were 6.8% (5/74) versus 0.8% (1/120; P=0.031). CONCLUSIONS: The safety, effectiveness, and technical difficulty of carotid angioplasty and stenting for RIS are comparable with that for AS although it is associated with a higher rate of ISR. CLINICAL TRIAL REGISTRATION: This trial was not registered as enrollment started in 2006.

Validity and reliability of the neuropsychiatric inventory questionnaire version in patients with stroke or transient ischemic attack having cognitive impairment.

This study examined the validity and reliability of the Neuropsychiatric Inventory Questionnaire version (NPI-Q), a proxy-reported format of the interview-based NPI, in assessing neuropsychiatric symptoms in 173 patients with stroke or transient ischemic attack (TIA) having cognitive impairment. The NPI-Q was validated against the NPI as a gold standard. Informants took approximately 7 minutes to complete the NPI-Q. Bland-Altman analysis revealed a bias of 0.7 points, with 95% limits of agreement between -8.6 and 10.0 between the total symptom scores of the NPI and NPI-Q. The NPI-Q correlated significantly with the NPI in individual and total symptom scores and caregiver distress scores. In predicting presence of symptoms on the NPI, the NPI-Q yielded, on average, sensitivity of 74.1% and specificity of 79.5%. On the NPI-Q, informants tended to overreport symptoms in patients with less severe symptoms but underreport with increasing symptom severity. Internal consistency of the NPI-Q was acceptable (Cronbach's α = 0.756). One-week test-retest reliability of the NPI-Q was excellent (intraclass correlation coefficient = .990). The NPI-Q is a valid and reliable instrument for screening neuropsychiatric symptoms in patients with stroke and TIA.

Pallidal deep brain stimulation: an effective treatment in Chinese patients with tardive dystonia.

Tardive dystonia is an iatrogenic complication of dopamine receptor antagonist medication such as first-generation antipsychotics. It occurs in up to 2% of patients and only 10% recover after stopping medication. Deep brain stimulation for primary dystonia has proven to be effective and its application for secondary dystonias is gaining acceptance. We report our experience in treating three ethnic Chinese schizophrenia patients with severe medically refractory tardive dystonia by globus pallidus internus deep brain stimulation. Preoperatively, all required assistance with essential activities of daily living and two were bed-bound. The mean Burke-Fahn-Marsden Dystonia Rating Scale score was 61 (range, 44-80) and mean Global Dystonia Rating Scale score was 47 (range, 40-52). No procedure-related complications were encountered. By 3 months all could return to unassisted living and walk with support with a mean of 77% and 66% improvement in the Burke-Fahn-Marsden Dystonia Rating Scale and Global Dystonia Rating Scale scores, respectively. Quality-of-life assessment performed for two patients using the EuroQol-5 dimensions visual analogue scale showed a mean improvement of 86% at 3 months. On clinical follow-up, the effect was well maintained for a period of 3 to 10 years. Pallidal deep brain stimulation is a safe and highly effective form of symptomatic treatment for patients with medically refractory tardive dystonia.

Subthalamic nucleus deep brain stimulation for Parkinson's disease: evidence for effectiveness and limitations from 12 years' experience.

OBJECTIVE: To present the result and experience of subthalamic nucleus deep brain stimulation for Parkinson's disease. DESIGN: Case series. SETTING: Prince of Wales Hospital, Hong Kong. PATIENTS: A cohort of patients with Parkinson's disease received subthalamic nucleus deep brain stimulation from September 1998 to January 2010. Patient assessment data before and after the operation were collected prospectively. RESULTS: Forty-one patients (21 male and 20 female) with Parkinson's disease underwent bilateral subthalamic nucleus deep brain stimulation and were followed up for a median interval of 12 months. For the whole group, the mean improvements of Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III were 32.5% and 31.5%, respectively (P<0.001). Throughout the years, a multidisciplinary team was gradually built. The deep brain stimulation protocol evolved and was substantiated by updated patient selection criteria and outcome assessment, integrated imaging and neurophysiological targeting, refinement of surgical technique as well as the accumulation of experience in deep brain stimulation programming. Most of the structural improvement occurred before mid-2005. Patients receiving the operation before June 2005 (19 cases) and after (22 cases) were compared; the improvements in UPDRS part III were 13.2% and 55.2%, respectively (P<0.001). There were three operative complications (one lead migration, one cerebral haematoma, and one infection) in the group operated on before 2005. There was no operative mortality. CONCLUSIONS: The functional state of Parkinson's disease patients with motor disabilities refractory to best medical treatment improved significantly after subthalamic nucleus deep brain stimulation. A dedicated multidisciplinary team building, refined protocol for patient selection and assessment, improvement of targeting methods, meticulous surgical technique, and experience in programming are the key factors contributing to the improved outcome.

Angiographic features, collaterals, and infarct topography of symptomatic occlusive radiation vasculopathy: a case-referent study.

BACKGROUND AND PURPOSE: Occlusive radiation vasculopathy (ORV) predisposes head-and-neck cancer survivors to ischemic strokes. METHODS: We analyzed the digital subtraction angiography acquired in 96 patients who had first-ever transient ischemic attack or ischemic strokes attributed to ORV. Another age-matched 115 patients who had no radiotherapy but symptomatic high-grade (>70%) carotid stenoses were enrolled as referent subjects. Digital subtraction angiography was performed within 2 months from stroke onset and delineated carotid and vertebrobasilar circulations from aortic arch up to intracranial branches. Two reviewers blinded to group assignment recorded all vascular lesions, collateral status, and infarct pattern. RESULTS: ORV patients had less atherosclerotic risk factors at presentation. In referent patients, high-grade stenoses were mostly focal at the proximal internal carotid artery. In contrast, high-grade ORV lesions diffusely involved the common carotid artery and internal carotid artery and were more frequently bilateral (54% versus 22%), tandem (23% versus 10%), associated with complete occlusion in one or both carotid arteries (30% versus 9%), vertebral artery (VA) steno-occlusions (28% versus 16%), and external carotid artery stenosis (19% versus 5%) (all P<0.05). With comparable rates of vascular anomaly, ORV patients showed more established collateral circulations through leptomeningeal arteries, anterior communicating artery, posterior communicating artery, suboccipital/costocervical artery, and retrograde flow in ophthalmic artery. In terms of infarct topography, the frequencies of cortical or subcortical watershed infarcts were similar in both groups. CONCLUSIONS: ORV angiographic features and corresponding collaterals are distinct from atherosclerotic patterns at initial stroke presentation. Clinical decompensation, despite more extensive collateralization, may precipitate stroke in ORV.

Validity of balance measures in cerebellar ataxia: A prospective study with 12-month follow-up.

INTRODUCTION: Balance deficits are common in cerebellar ataxia. Determining which balance outcome measures are psychometrically strong for this population remains an unmet need. OBJECTIVE: To evaluate the validity and responsiveness of two clinic-based balance measures (Berg Balance Scale [BBS] and balance sub-component of the Scale for the Assessment and Rating of Ataxia [SARA-bal]) and two laboratory-based balance measures (Sensory Organization Test [SOT] and Limits of Stability [LOS]) in cerebellar ataxia. DESIGN: Prospective cohort study. SETTING: Institutional study assessing 40 participants with cerebellar ataxia at baseline, and 6 and 12 months. MAIN OUTCOME MEASURES: Balance was assessed using the BBS, SARA-bal, SOT, and LOS; disease severity was assessed using the SARA; and Patients' Global Impression of Change (PGIC) was used to estimate responsiveness to disease progress at 6 and 12 months. RESULTS: BBS and SARA-bal (Spearman's correlation coefficient, ρS = -0.89, p < .01) demonstrated strong criterion validity. Convergent validity was moderate to high (ρS range: -0.75 to 0.92) and external validity was low (ρS range: -0.75 to 0.11). Composite SOT scores (SOT-COM; ρS = 0.29, p < .01) and maximal excursion (MXE-LOS) in the forward (F) and right (R) directions of the LOS (ρS = 0.18, p < .01) demonstrated moderate to low criterion and convergent validity. The area under the receiver-operating characteristic curve (AUCROC ) and its effect size (standard response mean [SRM]) for categorizing "stable" and "worsened" patients at 6 and 12 months were satisfactory for the BBS (AUCROC : 0.75; SRM-Stable: 1.06; SRM-Worsened: 1.16), SARA-bal (AUCROC : 0.76; SRM-Stable: 0.86; SRM-Worsened: 0.85), and MXE-LOS(R) (AUCROC : 0.29; SRM-Stable: 0.41; SRM-Worsened: 1.39). CONCLUSION: BBS and SARA-bal have moderate to strong criterion and convergent validity and adequate responsiveness to balance changes. Both laboratory-based measures (SOT and LOS) demonstrated a high floor effect. The SOT-COM and MXE-LOS(R) demonstrated moderate to low criterion validity, with only the MXE-LOS(R) displaying adequate responsiveness to balance changes after 6 and 12 months.

Effectiveness and cost of integrated cognitive and balance training for balance and falls in cerebellar ataxia: a blinded two-arm parallel group RCT.

Background: In patients with cerebellar ataxia (CA), dual-tasking deteriorates the performance of one or both tasks. Objective: Evaluate the effects of 4 weeks of cognitive-coupled intensive balance training (CIBT) on dual-task cost, dynamic balance, disease severity, number of falls, quality of life, cognition and cost among patients with CA. Methods: This RCT compared CIBT (Group 1) to single-task training (Group 2) among 32 patients with CA. The intervention included either dual-task (CIBT) or single-task training for 4 weeks followed by 6 months of unsupervised home exercises. Dual-task timed up-and-go test (D-TUG) assessed dual-task cost of the physical and cognitive tasks. Assessment time points included baseline 1 (Week 0:T1), baseline 2 (Week 6:T2), post-intervention (Week 10:T3), and follow-up (Week 34:T4). Results: Compared to single-task training CIBT improved the dual-task cost of physical task [MD -8.36 95% CI (-14.47 to -2.36, p < 0.01), dual-tasking ability [-6.93 (-13.16 to -0.70); p = 0.03] assessed using D-TUG, balance assessed using the scale for the assessment and rating of ataxia (SARAbal) [-2.03 (-4.04 to -0.19); p = 0.04], visual scores of the SOT (SOT-VIS) [-18.53 (-25.81 to -11.24, p ≤ 0.01] and maximal excursion [13.84 (4.65 to 23.03; p ≤ 0.01] of the Limits of Stability (LOS) in the forward direction and reaction time in both forward [-1.11 (-1.42 to -0.78); p < 0.01] and right [-0.18 (0.05 to 0.31); p < 0.01] directions following 4 weeks of training. CIBT did not have any additional benefits in reducing the number of falls, or improving disease severity, quality of life and cognition. The mean cost of intervention and healthcare costs for 7 months was HKD 33,380 for CIBT group and HKD 38,571 for single-task training group. Conclusion: We found some evidence to support the use of CIBT for improving the dual-tasking ability, dual-task cost of physical task and dynamic balance in CA. Future large fully-powered studies are needed to confirm this claim. Clinical trial registration: https://clinicaltrials.gov/study/NCT04648501, identifier [Ref: NCT04648501].

Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease.

OBJECTIVES: The predisposition of intracranial atherosclerotic disease (ICAD) to East Asians over Caucasians infers a genetic basis which, however, remains largely unknown. Higher prevalence of vascular risk factors (VRFs) in Chinese over Caucasian patients who had a stroke, and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD. METHODS: Unrelated symptomatic patients with ICAD were recruited for genome sequencing (GS, 60-fold). Rare and potentially deleterious single-nucleotide variants (SNVs) and small insertions/deletions (InDels) were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes. Rare aneuploidies, copy number variants (CNVs) and chromosomal structural rearrangements were also investigated. Lastly, candidate genes were used for pathway and gene ontology enrichment analysis. RESULTS: Among 92 patients (mean age at stroke onset 61.0±9.3 years), GS identified likely ICAD-associated rare genomic variants in 54.3% (50/92) of patients. Forty-eight patients (52.2%, 48/92) had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes. None of the 59 rare variants were identified in local subjects without ICAD (n=126). 31 SNVs/InDels were related to conventional VRFs, and 28 were discovered in genes related to other stroke subtypes. Our study also showed that rare CNVs (n=7) and structural rearrangement (a balanced translocation) were potentially related to ICAD in 8.7% (8/92) of patients. Lastly, candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process. CONCLUSIONS: Our GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.

Frequency and predictors of proxy-confirmed post-stroke cognitive complaints in lacunar stroke patients without major depression.

OBJECTIVE: Many lacunar stroke patients complained of cognitive decline after stroke. This study aims to investigate the factors underlying post-stroke cognitive complaints in these patients. METHODS: Seventy-five consecutive lacunar stroke patients without major depression were recruited for the study. Stroke severity was measured using NIHSS score and MRI was performed during the acute admission period. At 3 months, objective psychometric performance and depressive symptoms were assessed. Post-stroke cognitive complaints were corroborated by a proxy. Using logistic regression we examined the contribution of demographic features, stroke severity, objective psychometric scores, depressive symptoms, and imaging features (white matter lesion volume and infarct measures) to post-stroke cognitive complaints. RESULTS: Thirty-two (42.7%) patients had post-stroke cognitive complaints. Patients with post-stroke cognitive complaints had more depressive symptoms and worse psychometric performance than those without. In the multivariate logistic regression model, only the severity of depressive symptoms was independently associated with post-stroke cognitive complaints. CONCLUSIONS: This study suggests that post-stroke cognitive complaints are frequent among lacunar stroke patients without major depression and are prominently determined by the subclinical depressive symptomatology.

Executive dysfunction and left frontal white matter hyperintensities are correlated with neuropsychiatric symptoms in stroke patients with confluent white matter hyperintensities.

BACKGROUND/AIMS: This study aimed to determine the clinical and neuroimaging correlates of the presence of neuropsychiatric symptoms in stroke patients with age-related confluent white matter hyperintensities (WMH). METHODS: The Neuropsychiatric Inventory was utilized to detect the presence of 12 symptoms. Multivariate logistic regression models were used to identify clinical and neuroimaging correlates of the presence of symptoms. RESULTS: Seventy-seven stroke patients (mean WMH volume: 39.5 cm(3)) were recruited. Thirty patients (39%) had ≥ 1 neuropsychiatric symptom. Poor executive function was associated with the presence of any symptoms and symptoms other than depression. More severe left frontal WMH was associated with depression. CONCLUSION: Executive dysfunction and left frontal WMH are correlated with neuropsychiatric symptoms in these patients.

Identification of Risk Loci for Parkinson Disease in Asians and Comparison of Risk Between Asians and Europeans: A Genome-Wide Association Study.

Importance: Large-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the largest population worldwide (ie, Asian). Objectives: To identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts. Design Setting, and Participants: Genome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson's Disease Society Brain Bank Criteria. Main Outcomes and Measures: Genotypes of common variants, association with disease status, and polygenic risk scores. Results: Of 31 575 samples identified, 6724 PD cases (mean [SD] age, 64.3 [10] years; age at onset, 58.8 [10.6] years; 3472 [53.2%] men) and 24 851 controls (age, 59.4 [11.4] years; 11 030 [45.0%] men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2C and WBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association for SV2C (rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21; P = 1.17 × 10-10 in meta-analysis of discovery and replication samples) but showed potential genetic heterogeneity at WBSCR17 (rs9638616; I2=67.1%; P = 3.40 × 10-3 for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%; P = 6.81 × 10-12). Conclusions and Relevance: This study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta-genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia.

Would self-expanding stent occlude middle cerebral artery perforators?

BACKGROUND AND PURPOSE: A major concern of intracranial stenting is perforator infarction. It is unclear whether the sustained radial force of a self-expanding stent or subsequent stent restenosis would cause late occlusion of perforators. METHODS: We compared the baseline and poststent (>or=4 months) MRI scans of patients who underwent self-expanding stenting for recurrent ischemic symptoms attributed to a MCA stenosis >or=60%. New infarcts in the ipsilateral striatocapsular region were recorded. RESULTS: MCA stenting was technically successful in 23 of 24 recruited patients. No new perforator territory infarct was found in follow-up MRI scans of all recruited patients. Postoperatively, all patients reported no further TIA or stroke over a median follow-up of 15 months. CONCLUSIONS: The use of a self-expanding stent in patients with high-grade MCA stenosis may not pose a major risk to the perforators.

The validity, reliability and clinical utility of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in patients with cerebral small vessel disease.

BACKGROUND/AIMS: To evaluate the psychometric properties of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in patients with cerebral small vessel disease (SVD). METHODS: 40 SVD patients and 40 matched controls were recruited. Concurrent and criterion validity, inter-rater and test-retest reliability, internal consistency of the HK-MoCA were examined and clinical observations were made. RESULTS: Performance on the HK-MoCA was significantly predicted by both executive (beta = 0.23, p = 0.013) and non-executive (beta = 0.64, p < 0.001) composite scores. It differentiated SVD patients from controls (area under the curve = 0.81, p < 0.001) with an optimal cutoff at 21/22. Reliability, internal consistency and clinical utility were good. CONCLUSION: The HK-MoCA is a useful cognitive screening instrument for use in SVD patients.