A simple, organized web-based system improved the transfer efficiency and patient outcomes for endovascular thrombectomy in regional stroke network.

BACKGROUND: Endovascular thrombectomy (EVT) is a time-sensitive treatment for acute ischemic stroke with large vessel occlusion. To optimize transfer efficiency, a web-based platform was introduced in the Tainan Stroke Network (TSN). We assessed its application and effectiveness in regional stroke care. METHOD: This new web-based platform containing a questionnaire-style interface was introduced on October 1, 2021. To assess the transfer efficiency and patient outcomes, acute stroke patients transferred from PSCs to CSC for EVT from April 01, 2020, to December 30, 2022, were enrolled. The patients were classified into the traditional transferal pathway (TTP) group and the new transferal pathway (NTP) group depending on mode of transfer. Patient characteristics, time segments after stroke onset and outcome were compared between groups. RESULT: A total of 104 patients were enrolled, with 77 in the TTP group and 27 in the NTP group. Compared to the TTP group, the NTP group had a significantly shorter onset-to-CSC door time (TTP vs. NTP: 267 vs. 198 min; p = 0.041) and a higher EVT rate (TTP vs. NTP: 18.2% vs. 48.1%, p = 0.002). Among EVT patients, those in the NTP group had a significantly shorter CSC door-to-puncture time (TTP vs. NTP: 131.5 vs. 110 min; p = 0.029). The NTP group had a higher rate of good functional outcomes at 3 months (TTP vs. NTP: 21% vs. 61.5%; p = 0.034). CONCLUSION: This new web-based EVT transfer system provides notable improvements in clinical outcomes, transfer efficiency, and EVT execution for potential EVT candidates without markedly changing the regional stroke care paradigm.

Minimal amount of exercise prevents incident dementia in cognitively normal older adults with osteoarthritis: a retrospective longitudinal follow-up study.

Robust evidence suggests that regular exercise, including walking more than 6000 steps, is effective for preventing dementia; however, such activity is less feasible in older people with osteoarthritis (OA) or other motor disabilities. Therefore, we aimed to test whether the minimal amount of exercise (MAE) could help prevent dementia in older adults with OA. A retrospective longitudinal study was performed and a non-demented cohort (≥ 50-years-old) of 242 people (155 [64.0%] non-converters and 87 [36.0%] converters) from three centers in Taiwan was analyzed with a mean follow-up of 3.1 (range 0.3-5.9) and 2.9 (range 0.5-6.0) years, respectively. MAE was defined as walking for approximately 15-30 min or 1500-3000 steps. Rate of MAE (0, 1-2, or ≥ 3) within one week were defined as MAE-no, MAE-weekly, or MAE-daily, respectively. The incidence rates of dementia were compared between groups. Multivariate logistic regression and Cox proportional hazards analyses were used to study the influence of MAE on dementia occurrence. Age, education, sex, activities of daily living, neuropsychiatric symptoms, cognition, multiple vascular risk factors, and related medications were adjusted. Compared to the MAE-no group, the odds ratios for the incidents of dementia were 0.48 and 0.19 in the MAE-weekly and MAE-daily groups, respectively. In addition, older age, poorer cognition, poorer ADL performance, and congestive heart failure increased the incidence of dementia. Daily and weekly MAE prevented dementia in older adults with OA. As such, an informative public health policy may help promote adequate exercise in at-risk groups.

Cholesterol Paradox in Older People with Type 2 Diabetes Mellitus Regardless of Lipid-Lowering Drug Use: A Cross-Sectional Cohort Study.

Lipid-lowering drugs (LLDs) have protective effects against coronary artery disease (CAD) and cerebrovascular disease (CVD); however, a paradoxical association with cholesterol has been identified in several diseases, such as diabetes, dementia, and atrial fibrillation. We aimed to analyze the association between LLDs and cholesterol levels in older adults with type 2 diabetes mellitus (T2DM). This cross-sectional study enrolled consecutive patients aged ≥50 years from three centers in Taiwan. A multiple logistic regression model was used, and odds ratios (ORs) for different levels of total cholesterol (TC) or low-density-lipoprotein cholesterol (LDL-C) compared with the highest level were adjusted for age, triglyceride level, sex, comorbidities, and medications. Among the 3688 participants, 572 with and 676 without T2DM used LLDs. After adjusting for age and sex, the non-T2DM group demonstrated better medical conditions, cognition, and daily function than the T2DM group, regardless of LLD use. Compared to the highest TC level (≥240 mg/dL), ORs were significantly increased as TC levels decreased. A similar pattern of T2DM prevalence was observed in LDL-C levels. Older people with T2DM demonstrated low cognitive and daily functions. Significantly reduced TC and LDL levels were associated with a higher T2DM prevalence in older adults regardless of LLD use. T2DM was associated with impaired cognitive and daily functioning. A higher prevalence of T2DM in older people with low cholesterol levels raises doubt surrounding cognition and daily function being jeopardized when the "lower is better" strategy is applied for the secondary prevention of CAD or CVD.

Sum of boxes of the clinical dementia rating scale highly predicts conversion or reversion in predementia stages.

Background: The clinical dementia rating (CDR) scale is commonly used to diagnose dementia due to Alzheimer's disease (AD). The sum of boxes of the CDR (CDR-SB) has recently been emphasized and applied to interventional trials for tracing the progression of cognitive impairment (CI) in the early stages of AD. We aimed to study the influence of baseline CDR-SB on disease progression to dementia or reversion to normal cognition (NC). Materials and methods: The baseline CDR < 1 cohort registered from September 2015 to August 2020 with longitudinal follow-up in the History-based Artificial Intelligence Clinical Dementia Diagnostic System (HAICDDS) database was retrospectively analyzed for the rates of conversion to CDR ≥ 1. A Cox regression model was applied to study the influence of CDR-SB levels on progression, adjusting for age, education, sex, neuropsychological tests, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors. Results: A total of 1,827 participants were analyzed, including 1,258 (68.9%) non-converters, and 569 (31.1%) converters with mean follow-up of 2.1 (range 0.4-5.5) and 1.8 (range 0.3-5.0) years, respectively. Conversion rates increased with increasing CDR-SB scores. Compared to a CDR-SB score of 0, the hazard ratios (HR) for conversion to dementia were 1.51, 1.91, 2.58, 2.13, 3.46, 3.85, 3.19, 5.12, and 5.22 for CDR-SB scores of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, and ≥4.5, respectively (all p < 0.05 except for CDR-SB score = 0.5). In addition, older age, lower education, lower cognitive performance, and a history of diabetes also increased conversion rates. Furthermore, reversions to NC were 12.5, 5.6, 0.9, and 0% for CDR-SB scores of 0.5, 1.0-2.0, 2.5-3.5 and ≥4.0, respectively (p < 0.001). Conclusion: CDR-SB in predementia or very mild dementia (VMD) stages highly predicts progression to dementia or reversion to NC. Therefore, CDR-SB could be a good candidate for tracing the effectiveness of pharmacological and non-pharmacological interventions in populations without dementia.

Emergency department visits among people with predementia highly predicts conversion to dementia.

Emergency department visits (EDV) are common among older adults with and without dementia. The risk factors and demands of EDVs for people with dementia have been well studied; however, the association between EDVs and conversion to dementia among people with predementia has not been thoroughly explored. To study the predictive value of EDVs in predementia's progression to dementia. The baseline predementia cohort registered from September 2015 to August 2017, with longitudinal follow-up in the History-based Artificial Intelligent Clinical Dementia Diagnostic System database, was retrospectively analyzed. The rates of conversion among the different EDVs were compared. Multivariate logistic regression and Cox proportional hazards analyses were applied to study the influence of EDVs on progression. Age, education, sex, neuropsychological tests, activities of daily living, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors were adjusted for. A total of 512 participants were analyzed, including 339 (66.2%) non-converters and 173 (33.8%) converters with a mean follow-up of 3.3 (range 0.4-6.1) and 2.8 (range 0.5-5.9) years, respectively. Compared to people without EDV (EDV 0), the hazard ratios for conversion to dementia were 3.6, 5.9, and 6.9 in those with EDV once (EDV 1), twice (EDV 2), and more than twice (EDV >2), respectively. In addition, older age, lower education, poorer cognition, poorer ADL performance, and longer follow-up periods also increased the conversion rates. EDVs in the predementia stages highly predict progression to dementia. Therefore, a sound public health as well as primary healthcare system that provide strategies for better management of mental and physical condition might help prevention of EDVs among older people in the predementia stages.

Operational Determination of Subjective Cognitive Decline, Mild Cognitive Impairment, and Dementia Using Sum of Boxes of the Clinical Dementia Rating Scale.

Objectives: The Clinical Dementia Rating (CDR) Scale is the gold standard for the staging of dementia due to Alzheimer's disease (AD). However, the application of CDR for the staging of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in AD remains controversial. This study aimed to use the sum of boxes of the CDR (CDR-SB) plus an SCD single questionnaire to operationally determine the different stages of cognitive impairment (CI) due to AD and non-AD. Methods: This was a two-phase study, and we retrospectively analyzed the Show Chwan Dementia registry database using the data selected from 2015 to 2020. Individuals with normal cognition (NC), SCD, MCI, and mild dementia (MD) due to AD or non-AD with a CDR < 2 were included in the analysis. Results: A total of 6,946 individuals were studied, including 875, 1,009, 1,585, and 3,447 with NC, SCD, MCI, and MD, respectively. The cutoff scores of CDR-SB for NC/SCD, SCD/MCI, and MCI/dementia were 0/0.5, 0.5/1.0, and 2.5/3.0, respectively. The receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) values of the test groups were 0.85, 0.90, and 0.92 for discriminating NC from SCD, SCD from MCI, and MCI from dementia, respectively. Compared with the Cognitive Abilities Screening Instrument or the Montreal Cognitive Assessment, the use of CDR-SB is less influenced by age and education. Conclusion: Our study showed that the operational determination of SCD, MCI, and dementia using the CDR-SB is practical and can be applied in clinical settings and research on CI or dementia.

Prevalence and Effect of Cerebral Small Vessel Disease in Stroke Patients With Aspirin Treatment Failure-A Hospital-Based Stroke Secondary Prevention Registry.

Background: Breakthrough strokes during treatment with aspirin, termed clinical aspirin treatment failure (ATF), is common in clinical practice. The burden of cerebral small vessel disease (SVD) is associated with an increased recurrent ischemic stroke risk. However, the association between SVD and ATF remains unclear. This study investigated the prevalence and clinical characteristics of SVD in stroke patients with ATF. Methods: Data from a prospective, and multicenter stroke with ATF registry established in 2018 in Taiwan were used, and 300 patients who developed ischemic stroke concurrent with regular use of aspirin were enrolled. White matter lesions (WMLs) and cerebral microbleeds (CMBs) were identified using the Fazekas scale and Microbleed Anatomical Rating Scale, respectively. Demographic data, cardiovascular comorbidities, and index stroke characteristics of patients with different WML and CMB severities were compared. Logistic regression analyses were performed to explore the factors independently associated with outcomes after ATF. Results: The mean patient age was 69.5 ± 11.8 years, and 70.0% of patients were men. Among all patients, periventricular WML (PVWML), deep WML (DWML), and CMB prevalence was 93.3, 90.0, and 52.5%, respectively. Furthermore, 46.0% of the index strokes were small vessel occlusions. Severe PVWMLs and DWMLs were significantly associated with high CMB burdens. Patients with moderate-to-severe PVWMLs and DWMLs were significantly older and had higher cardiovascular comorbidity prevalence than did patients with no or mild WMLs. Moreover, patients with favorable outcomes exhibited significantly low prevalence of severe PVWMLs (p = 0.001) and DWMLs (p = 0.001). After logistic regression was applied, severe WMLs predicted less favorable outcomes independently, compared with those with no to moderate PVWMLs and DWMLs [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.25-0.87 for severe PVWMLs; OR, 0.40; 95% CI, 0.21-0.79 for severe DWMLs]. Conclusions: SVD is common in stroke patients with ATF. PVWMLs and DWMLs are independently associated with functional outcomes in stroke patients with ATF. The burden of SVD should be considered in future antiplatelet strategies for stroke patients after ATF.

Function-based dementia severity assessment for vascular cognitive impairment.

BACKGROUND/PURPOSES: Unimpaired activities of daily living (ADL) is essential for the diagnosis of normal cognition and mild cognitive impairment. However, diagnosis according to this concept is difficult to apply to patients comorbid with motor dysfunction. We aim to use a novel ADL questionnaire for operationally diagnosing unimpaired ADL in vascular cognitive impairment with no dementia (VCIND). METHODS AND PARTICIPANTS: This was a retrospective cohort study with both cross-sectional and long-term follow-up analysis. Patients with cerebrovascular disease with normal cognition (CVDNC), VCIND, and vascular dementia (VaD) were analyzed. Cutoff scores for differentiating different stages of cognitive impairment were compared between the new History-based Artificial Intelligent ADL questionnaire (HAI-ADL) and other tools. RESULTS: A total of 596 individuals were analyzed, including 40 CVDNC, 167 VCIND, 218 mild, 119 moderate, and 52 severe-dementia patients. The cutoff scores for determining unimpaired ADL in VCIND were 8.5, 3.5, 5, 100, and 60 in HAI-ADL, CDR-SB, IADL, BI, and CASI, respectively. HAI-ADL had the highest correlations with CDR-SB and the CDR staging system compared to other tools. Four models of progression rates from CVDNC/VCIND to VaD revealed it was much higher in the group with HAI-ADL > 8.5 compared to those with HAI-ADL≦8.5 with odds ratios of 3.75, 3.66, 3.31, and 2.77, respectively. CONCLUSION: Our study showed that HAI-ADL provides an operational determinates unimpaired ADL which is necessary for the diagnosis of VCIND. The predictive value for progression to dementia was proved by a long-term follow-up analysis of the research cohort.

Tremor in Vascular Cognitive Impairment Raises the Possibility of Mixed Pathology With Lewy Body Disease.

OBJECTIVES: Tremor is common in patients with Lewy body disease (LBD) and not rare in normal individuals. Prevalence of tremor in patients with vascular cognitive impairment (VCI) and its association with other comorbidities are seldom studied. The aim of this study was to investigate the patient characteristics of VCI associated with tremor and to evaluate the possibility of mixed pathology with LBD in these patients. METHODS: Retrospective analysis of a large population with VCI registered in the database of a regional healthcare system was performed. VCI patients were divided into tremor and non-tremor groups. The associated characteristics including demographics, clinical features in motor and non-motor domains, vascular risk factors, and neuroimaging features were compared between the tremor group and the non-tremor group. RESULTS: Among 1337 patients with VCI, 292 (21.8%) had tremor, while 1045 (78.2%) did not have tremor. The tremor group had significantly higher prevalence of all motor and non-motor LBD clinical features than the non-tremor group. The tremor group also demonstrated more severe neuropsychiatric symptoms. Among patients with tremor, patients having tremor onset earlier than stroke onset showed significantly higher prevalence of rapid eye movement sleep behavior disorder. All comparisons were adjusted for age and severity of dementia. CONCLUSION: Tremor is a common comorbidity of VCI. VCI patients with tremor had a higher prevalence of motor and non-motor LBD features. These findings raised the possibility of VCI patients with tremor having high possibility of mixed pathology with LBD.

Freezing of Speech Single Questionnaire as a Screening Tool for Cognitive Dysfunction in Patients With Dementia With Lewy Bodies.

INTRODUCTION: Freezing phenomenon is a striking feature of Parkinson's disease. However, it has never been studied in people with dementia with Lewy bodies (DLB). We designed a freezing of speech single questionnaire (FOSSQ) and investigated the frequency and association of freezing of speech (FOS) in patients with DLB and other types of dementia. METHODS: This is a retrospective analysis of data from the project of history-based artificial intelligent computerized dementia diagnostic system. We compared the frequencies of FOS among non-demented (ND) participants, patients with Alzheimer's disease (AD), vascular dementia (VaD), and DLB. Further, we explored the association factors of FOS in all the participants. RESULTS: We enrolled 666 individuals with the following disease distribution: 190, ND; 230, AD; 183, VaD; and 63, DLB. Compared to individuals with ND (2.1%), patients with AD (6.1%), or VaD (18.0%), DLB (54.0%) showed a significantly higher frequency of positive FOS (all p < 0.001). The association factors of FOS were older age, more severe dementia, more severe motor dysfunction, fluctuating cognition, visual hallucinations, parkinsonism, rapid eye movement sleep behavior disorder, attention, mental manipulation, and language. CONCLUSION: Our study showed that the informant-based FOSSQ may be a practical screening tool for discriminating DLB from individuals with ND or other forms of dementia. The FOSSQ can be applied in clinical practice as well as on the artificial intelligent platform.

An Informant-Based Simple Questionnaire for Visuospatial Dysfunction Assessment in Dementia.

OBJECTIVES: Visuospatial dysfunction (VSD) is one of the most important symptoms for the diagnosis of dementia with Lewy bodies (DLB). The aim of this study was to validate a novel VSD questionnaire and determine the cutoff score for the screening for VSD in DLB. METHODS: This is a retrospective analysis of data from a project of the History-based Artificial Intelligent Clinical Dementia Diagnostic System (HAICDDS). VSD of non-demented control (NDC), Alzheimer's disease (AD), and DLB participants were analyzed and compared using the visuospatial questionnaire in the HAICDDS (HAI-VSQ), the Draw subscale in the Cognitive Abilities Screening Instrument (CASI-Draw), and the visuospatial subscale in Montreal Cognitive Assessment (MoCA-VS). RESULTS: A total of 440 individuals were studied, including 154 NDC, 229 AD, and 57 DLB participants. Compared to NDC or AD participants, DLB participants showed a higher total score on HAI-VSQ after adjustment for age. Using HAI-VSQ, a cutoff score ≥ 2 was useful for the screening for VSD in DLB with a sensitivity of 0.77 and a specificity of 0.94. Compared with CASI-Draw or MoCA-VS, HAI-VSQ was least influenced by gender, age, and education and had the highest correlation with the sum of boxes of the Clinical Dementia Rating scale. After adjustment for age, education, gender, and global cognitive function, HAI-VSQ significantly discriminated DLB from AD and NDC whereas MoCA-VS or CASI-Draw did not. CONCLUSION: Our study showed that the newly designed simple questionnaire was a practical screening tool for VSD in DLB that can be applied in clinical practice as well as on a registration platform.

The Novel Direct Modulatory Effects of Perampanel, an Antagonist of AMPA Receptors, on Voltage-Gated Sodium and M-type Potassium Currents.

Perampanel (PER) is a selective blocker of AMPA receptors showing efficacy in treating various epileptic disorders including brain tumor-related epilepsy and also potential in treating motor neuron disease. However, besides its inhibition of AMPA-induced currents, whether PER has any other direct ionic effects in different types of neurons remains largely unknown. We investigated the effects of PER and related compounds on ionic currents in different types of cells, including hippocampal mHippoE-14 neurons, motor neuron-like NSC-34 cells and U87 glioma cells. We found that PER differentially and effectively suppressed the amplitude of voltage-gated Na+ currents (INa) in mHippoE-14 cells. The IC50 values required to inhibit peak and late INa were 4.12 and 0.78 µM, respectively. PER attenuated tefluthrin-induced increases in both amplitude and deactivating time constant of INa. Importantly, PER also inhibited the amplitude of M-type K+ currents (IK(M)) with an IC50 value of 0.92 µM. The suppression of IK(M) was attenuated by the addition of flupirtine or ZnCl2 but not by L-quisqualic acid or sorafenib. Meanwhile, in cell-attached configuration, PER (3 µM) decreased the activity of M-type K+ channels with no change in single-channel conductance but shifting the activation curve along the voltage axis in a rightward direction. Supportively, PER suppressed IK(M) in NSC-34 cells and INa in U87 glioma cells. The inhibitory effects of PER on both INa and IK(M), independent of its antagonistic effect on AMPA receptors, may be responsible for its wide-spectrum of effects observed in neurological clinical practice.

An Informant-Based Simple Questionnaire for Language Assessment in Neurodegenerative Disorders.

BACKGROUND/AIMS: Language dysfunction is a crucial feature of brain disorders. This study investigated language dysfunction in patients with dementia with or without parkinsonism by using an informant-based simple questionnaire. METHODS: Language dysfunction in normal controls (NCs), and patients with Parkinson disease (PD), Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), or Alzheimer disease (AD) were analyzed and compared. RESULTS: A total of 1,662 individuals were studied: 285 NCs, 157 PD patients, 161 PDD patients, 248 DLB patients, and 811 AD patients. Patients with PD displayed higher frequency of language dysfunction in several language domains than NC. Patients with PDD and DLB showed higher frequency of language dysfunction in most of the language domains than those with AD. A composite score of our simple questionnaire was comparable with the score for the language domain of the Cognitive Abilities Screening Instrument (CASI) in different stages of dementia due to Lewy body diseases or not. CONCLUSION: Our study showed that the informant-based simple questionnaire is a practical screening tool and is comparable with the language subscale of CASI. This tool can be applied in clinical practice and in the registration platform for rapid language dysfunction screening.

Delusions in Patients with Dementia with Lewy Bodies and the Associated Factors.

OBJECTIVE: Delusions are common neuropsychiatric symptoms in patients with dementia with Lewy bodies (DLB). The aim of this study was to investigate the associated factors of delusions in patients with DLB. METHOD: A retrospective study of outpatients with DLB registered in a regional hospital's database was performed. The associated factors including cognitive performance, clinical features, vascular risk factors, and neuropsychiatric symptoms between delusional and nondelusional patients with DLB were compared. RESULTS: Among 207 patients with DLB, 106 (51.2%) were delusional and 101 (48.8%) were not. Delusion of other persons are stealing was the most common symptom (35.3%). The delusional group had a significantly higher diagnostic rate of probable than possible DLB, higher disease severity, poorer cognitive performance, more severe neuropsychiatric symptoms, and higher caregiver burden (all p < 0.05). In addition, the delusional group had a significantly lower frequency of diabetes compared to the nondelusional group (odds ratio = 0.28, p < 0.001). CONCLUSION: Delusion of other persons are stealing was the most common delusional symptom. The patients with DLB who presented with delusions had poorer cognitive function and more severe neuropsychiatric symptoms. A novel finding is that the DLB patients with diabetes had a lower frequency of delusions.