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Background@#and Purpose Physical frailty is known to be closely associated with cognitive impairment and to be an early sign of Alzheimer’s disease. We aimed to understand the characteristics of physical frailty and define factors associated with physical frailty in subjects with subjective cognitive decline (SCD) by analyzing amyloid data. @*Methods@#We prospectively enrolled subjects with SCD from a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from SCD (CoSCo). All of the subjects underwent brain magnetic resonance imaging, and brain amyloid positron-emission tomography (PET) to detect amyloid beta plaques. Self-reported exhaustion, handgrip strength, and gait speed were used to measure physical frailty. @*Results@#Of 120 subjects with SCD, 26 (21.7%) were amyloid-positive in PET. Female (odds ratio [OR]=3.79, p=0.002) and amyloid-PET-positive (OR=3.80, p=0.008) subjects with SCD were at high risks of self-reported exhaustion. Amyloid PET positivity (OR=3.22, p=0.047) and high burden from periventricular white-matter hyperintensity (OR=3.34, 95% confidence interval=1.18–9.46, p=0.023) were significantly associated with a weaker handgrip. The subjects with SCD with self-reported exhaustion and weaker handgrip presented with lower cognitive performance in neuropsychological tests, especially for information processing speed and executive function. Subjects with a slower gait performed worse in visual memory function tests. @*Conclusions@#Amyloid PET positivity was associated with a higher risk of self-reported exhaustion and weaker handgrip in subjects with SCD. The subjects with SCD and physical frailty also performed worse in neuropsychological tests.
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Background@#and Purpose Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer’s disease (AD). @*Methods@#This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio. @*Results@#The difference between the control group and the IPI-301 group, quantified as the Hodges–Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer’s Disease Cooperative Study– Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (f0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups. @*Conclusions@#IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.
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Background@#and Purpose: In this study we aimed to find the association between neuropsychological performance and body mass index (BMI) in patients with mild cognitive impairment (MCI). In addition, we investigated the effects of the apolipoprotein E (APOE) genotype in the relationship between the BMI and cognition in MCI. @*Methods@#We enrolled a cohort of 3,038 subjects with MCI aged 65–90 from the Clinical Research Center for Dementia of South Korea and a dementia cohort of the Ewha Womans University Mokdong Hospital. MCI patients were classified into three subgroups according to the Asian standard of BMI. We compared cognitive performances between groups by one-way analysis of variance. To investigate the effects of the APOE genotype, we used multivariate linear regression models after adjusting for possible confounders. @*Results@#Even though normal BMI groups were younger, had more females, and had less comorbidities, the higher BMI groups had better cognitive functions. Among subjects with APOE ε4 carriers, there was a positive relationship between the BMI and the memory task alone. @*Conclusions@#Our findings suggested that higher BMI in patients with MCI were associated with better cognitive performance. The effects of the APOE ε4 genotype in the associations between BMI and cognition were distinguishing. Therefore, according to physical status, APOE ε4 genotype-specific strategies in the assessments and treatments may be necessary in elderly patients with MCI.
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Objective@#We aimed to present the study design and baseline cross-sectional participant characteristics of biobank innovations for chronic cerebrovascular disease with Alzheimer’s disease study (BICWALZS) participants. @*Methods@#A total of 1,013 participants were enrolled in BICWALZS from October 2016 to December 2020. All participants underwent clinical assessments, basic blood tests, and standardized neuropsychological tests (n=1,013). We performed brain magnetic resonance imaging (MRI, n=817), brain amyloid positron emission tomography (PET, n=713), single nucleotide polymorphism microarray chip (K-Chip, n=949), locomotor activity assessment (actigraphy, n=200), and patient-derived dermal fibroblast sampling (n=175) on a subset of participants. @*Results@#The mean age was 72.8 years, and 658 (65.0%) were females. Based on clinical assessments, total of 168, 534, 211, 80, and 20 had subjective cognitive decline, mild cognitive impairment (MCI), Alzheimer’s dementia, vascular dementia, and other types of dementia or not otherwise specified, respectively. Based on neuroimaging biomarkers and cognition, 199, 159, 78, and 204 were cognitively normal (CN), Alzheimer’s disease (AD)-related cognitive impairment, vascular cognitive impairment, and not otherwise specified due to mixed pathology (NOS). Each group exhibited many differences in various clinical, neuropsychological, and neuroimaging results at baseline. Baseline characteristics of BICWALZS participants in the MCI, AD, and vascular dementia groups were generally acceptable and consistent with 26 worldwide dementia cohorts and another independent AD cohort in Korea. @*Conclusion@#The BICWALZS is a prospective and longitudinal study assessing various clinical and biomarker characteristics in older adults with cognitive complaints. Details of the recruitment process, methodology, and baseline assessment results are described in this paper.
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This study examined the effect of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet of the Korean multi-domain dementia prevention program on the cognitive functions of the elderly with dementia risk factors. We developed the program including nutrition, exercise, cognitive training, vascular disease prevention, and motivation. One- hundred and fifty-three participants aged 60∼79 years with at least 1 dementia risk factor were randomly assigned in a 1:1:1 ratio to the facility-based intervention (FMI), home-based intervention (HMI), and the control group. The nutrition education program consisted of 10 classes over 24 weeks: the FMI received 7 group sessions and three 1:1 sessions, the HMI received 4 group sessions and three 1:1 sessions with 3 homework sessions. The Nutrition Quotient for Elderly (NQ-E) and the Mini Nutritional Assessment (MNA) were used to evaluate nutritional status. The Repeatable Battery for the Assessment Neuropsychological Status (RBANS), Korean Mini-Mental State Examination (K-MMSE), and the Cognitive Complaint Interview (CCI) were used to evaluate cognitive functions. A total of 136 people completed the program with an 11.1% dropout rate. The NQ-E (P=0.009) and RBANS (P=0.001) scores significantly increased in the FMI (N=45) and HMI (N=49) groups compared to the control group (N=42) after the study. The changes in the score of MNA and CCI did not differ significantly between groups. In conclusion, the nutritional intervention which focused on the MIND diet as a part of a multi-domain intervention program had a positive effect on the improvement of healthy eating habits and cognitive function scores in the high-risk dementia group.
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Background@#and Purpose: Reportedly 30–50% of patients being treated for chronic illnesses do not adhere to their medication regimen. We assessed the impact of a nurse-led education program for caregivers of Korean de novo Alzheimer’s disease patients who had newly been prescribed donepezil. @*Methods@#This multicenter study analyzed 93 participants in a caregiver education group and 92 participants in a caregiver no-education group. At every visit up to the end of the study (1 year), caregivers in the education group were given educational brochures regarding Alzheimer’s disease and the efficacy and adverse events of donepezil treatment. The primary endpoint was the discontinuation rate of donepezil treatment during the 1-year observation period. The secondary endpoints included the effect of education on compliance with donepezil treatment assessed at each visit using a clinician rating scale (CRS) and visual analog scale (VAS), and changes from baseline in cognitive assessment tests. @*Results@#The donepezil discontinuation rates at 1 year were 5.38% (5/93) and 6.52% (6/92) in the caregiver education and no-education groups, respectively (p=0.742). No significant between-group differences in donepezil compliance rates on the CRS and VAS were observed, but significant changes were observed in some cognitive tests from baseline to the end of the study. @*Conclusions@#Caregiver education had no significant effect on treatment discontinuation, but this may have been due to the low severity of cognitive impairment among the included population at baseline. In addition, the low discontinuation rates meant that no significant difference in treatment compliance was observed.
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Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.
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This study was conducted as a pilot project to evaluate the feasibility of building an integrate dementia platform converging preexisting dementia cohorts from several variable levels. The following four cohorts were used to develop this pilot platform: 1) Clinical Research Center for Dementia of South Korea (CREDOS), 2) Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s disease (K-BASE), 3) Environmental Pollution-induced Neurological Effects (EPINEF) study, and 4) a prospective registry in Dementia Platform Korea project (DPKR). A total of 29916 patients were included in the platform with 348 integrated variables. Among participants, 13.9%, 31.5%, and 44.2% of patients had normal cognition, mild cognitive impairment, and dementia, respectively. The mean age was 72.4 years. Females accounted for 65.7% of all patients. Those with college or higher education and those without problems in reading or writing accounted for 12.3% and 46.8%, respectively. Marital status, cohabitation, family history of Parkinson’s disease, smoking and drinking status, physical activity, sleep status, and nutrition status had rates of missing information of 50% or more. Although individual cohorts were of the same domain and of high quality, we found there were several barriers to integrating individual cohorts, including variability in study variables and measurements. Although many researchers are trying to combine pre-existing cohorts, the process of integrating past data has not been easy. Therefore, it is necessary to establish a protocol with considerations for data integration at the cohort establishment stage.
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Background@#and Purpose: Reportedly 30–50% of patients being treated for chronic illnesses do not adhere to their medication regimen. We assessed the impact of a nurse-led education program for caregivers of Korean de novo Alzheimer’s disease patients who had newly been prescribed donepezil. @*Methods@#This multicenter study analyzed 93 participants in a caregiver education group and 92 participants in a caregiver no-education group. At every visit up to the end of the study (1 year), caregivers in the education group were given educational brochures regarding Alzheimer’s disease and the efficacy and adverse events of donepezil treatment. The primary endpoint was the discontinuation rate of donepezil treatment during the 1-year observation period. The secondary endpoints included the effect of education on compliance with donepezil treatment assessed at each visit using a clinician rating scale (CRS) and visual analog scale (VAS), and changes from baseline in cognitive assessment tests. @*Results@#The donepezil discontinuation rates at 1 year were 5.38% (5/93) and 6.52% (6/92) in the caregiver education and no-education groups, respectively (p=0.742). No significant between-group differences in donepezil compliance rates on the CRS and VAS were observed, but significant changes were observed in some cognitive tests from baseline to the end of the study. @*Conclusions@#Caregiver education had no significant effect on treatment discontinuation, but this may have been due to the low severity of cognitive impairment among the included population at baseline. In addition, the low discontinuation rates meant that no significant difference in treatment compliance was observed.
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Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.
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This study was conducted as a pilot project to evaluate the feasibility of building an integrate dementia platform converging preexisting dementia cohorts from several variable levels. The following four cohorts were used to develop this pilot platform: 1) Clinical Research Center for Dementia of South Korea (CREDOS), 2) Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s disease (K-BASE), 3) Environmental Pollution-induced Neurological Effects (EPINEF) study, and 4) a prospective registry in Dementia Platform Korea project (DPKR). A total of 29916 patients were included in the platform with 348 integrated variables. Among participants, 13.9%, 31.5%, and 44.2% of patients had normal cognition, mild cognitive impairment, and dementia, respectively. The mean age was 72.4 years. Females accounted for 65.7% of all patients. Those with college or higher education and those without problems in reading or writing accounted for 12.3% and 46.8%, respectively. Marital status, cohabitation, family history of Parkinson’s disease, smoking and drinking status, physical activity, sleep status, and nutrition status had rates of missing information of 50% or more. Although individual cohorts were of the same domain and of high quality, we found there were several barriers to integrating individual cohorts, including variability in study variables and measurements. Although many researchers are trying to combine pre-existing cohorts, the process of integrating past data has not been easy. Therefore, it is necessary to establish a protocol with considerations for data integration at the cohort establishment stage.
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Background@#and PurposeThe prevalence of dementia is increasing in South Korea. Multidomain interventions may be useful for preventing dementia. Such programs need to be disseminated to elderly Koreans throughout the country. We have developed programs of the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), which consists of a facility-based multidomain intervention (FMI) program and a home-based multidomain intervention (HMI) program suitable for elderly Koreans. We aim to determine the feasibility of the SUPERBRAIN programs before a large-scale randomized controlled trial. @*Methods@#We will recruit 150 participants among those without dementia aged 60–79 years with at least 1 modifiable dementia risk factor. They will be randomly assigned in a 1:1:1 ratio to the FMI, HMI, and the waiting-list control arm. The 6-month multidomain intervention consists of management of metabolic and vascular risk factors, cognitive training and social activity, physical exercise, nutritional guidance, and motivational enhancement programs. The primary outcomes are adherence and retention rates and changes in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to the study end. The main secondary outcomes are disability, depressive symptoms, quality of life, vascular risk factors, physical performance, nutritional assessment, and motivation questionnaire. There will be an exploratory evaluation of neurotrophic, neurodegeneration, and neuroinflammation factors, microbiome, telomere length, electroencephalography, and neuroimaging measures. @*Conclusions@#The results obtained will provide information on the applicability of these multidomain intervention programs to at-risk elderly people.
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Humanos , Área Bajo la Curva , Cognición , Demencia , Tamizaje Masivo , Memoria , Disfunción Cognitiva , Reproducibilidad de los Resultados , Curva ROC , Autoinforme , Autoevaluación (Psicología)RESUMEN
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BACKGROUND: Korea has a periodic general health check-up program that uses the Korean Dementia Screening Questionnaire-Cognition (KDSQ-C) as a cognitive dysfunction screening tool. The Alzheimer Disease 8 (AD8) and Subjective Memory Complaints Questionnaire (SMCQ) are also used in clinical practice. We compared the diagnostic ability of these screening questionnaires for cognitive impairment when completed by participants and their caregivers. Hence, we aimed to evaluate whether the SMCQ or AD8 is superior to the KDSQ-C and can be used as its replacement. METHODS: A total of 420 participants over 65 years and their informants were recruited from 11 hospitals for this study. The patients were grouped into normal cognition, mild cognitive impairment, and dementia subgroups. The KDSQ-C, AD8, and SMCQ were completed separately by participants and their informants. RESULTS: A receiver operating characteristic analysis of questionnaire scores completed by participants showed that the areas under the curve (AUCs) for the KDSQ-C, AD8, and SMCQ for diagnosing dementia were 0.75, 0.8, and 0.73, respectively. Regarding informant-completed questionnaires, the AD8 (AUC of 0.93), KDSQ-C (AUC of 0.92), and SMCQ (AUC of 0.92) showed good discriminability for dementia, with no differences in discriminability between the questionnaires. CONCLUSION: When an informant-report is possible, we recommend that the KDSQ-C continues to be used in national medical check-ups as its discriminability for dementia is not different from that of the AD8 or SMCQ. Moreover, consistent data collection using the same questionnaire is important. When an informant is not available, either the KDSQ-C or AD8 may be used. However, in the cases of patient-reports, discriminability is lower than that for informant-completed questionnaires.
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Humanos , Enfermedad de Alzheimer , Cuidadores , Cognición , Trastornos del Conocimiento , Recolección de Datos , Demencia , Corea (Geográfico) , Tamizaje Masivo , Memoria , Disfunción Cognitiva , Curva ROC , Autoevaluación (Psicología)RESUMEN
BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹⁸F]-THK5351 retention across all three subtypes and determine the topography of [¹⁸F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹⁸F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹⁸F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹⁸F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹⁸F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹⁸F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹⁸F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹⁸F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹⁸F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹⁸F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.
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Humanos , Afasia Progresiva Primaria , Cognición , Comprensión , Imagen por Resonancia Magnética , Ovillos Neurofibrilares , Pruebas Neuropsicológicas , Lóbulo Parietal , Tomografía de Emisión de Positrones , Corteza Prefrontal , Rabeprazol , Semántica , Lóbulo TemporalRESUMEN
BACKGROUND AND PURPOSE: Epidemiological studies have suggested the presence of strong correlations among diet, lifestyle, and dementia onset. However, these studies have unfortunately had major limitations due to their inability to fully control the various potential confounders affecting the nutritional status. The purpose of the current study was to determine the nutritional status of participants in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) and to identify clinical risk factors for being at risk of malnutrition or being malnourished. METHODS: Baseline data from 212 participants [119 cognitively unimpaired (CU), 56 with mild cognitive impairment (MCI), and 37 with dementia] included in the KBASE database were analyzed. All participants underwent a comprehensive cognitive test and MRI at baseline. The presence of malnutrition at baseline was measured by the Mini Nutritional Assessment score. We examined the cross-sectional relationships of clinical findings with nutritional status using multiple logistic regression applied to variables for which p<0.2 in the univariate analysis. Differences in cortical thickness according to the nutritional status were also investigated. RESULTS: After adjustment for demographic, nutritional, and neuropsychological factors, participants with dementia had a significantly higher odds ratio (OR) for being at risk of malnutrition or being malnourished than CU participants [OR=5.98, 95% CI=1.20–32.97] whereas participants with MCI did not (OR=0.62, 95% CI=0.20–1.83). Cortical thinning in the at-risk/malnutrition group was observed in the left temporal area. CONCLUSIONS: Dementia was found to be an independent predictor for the risk of malnutrition compared with CU participants. Our findings further suggest that cortical thinning in left temporal regions is related to the nutritional status.
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Anciano , Humanos , Envejecimiento , Enfermedad de Alzheimer , Encéfalo , Corteza Cerebral , Demencia , Dieta , Diagnóstico Precoz , Estudios Epidemiológicos , Estilo de Vida , Modelos Logísticos , Imagen por Resonancia Magnética , Desnutrición , Disfunción Cognitiva , Evaluación Nutricional , Estado Nutricional , Oportunidad Relativa , Factores de Riesgo , Lóbulo TemporalRESUMEN
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BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is the most common cause of vascular dementia and a major contributor to mixed dementia. CSVD is characterized by progressive cerebral white matter changes (WMC) due to chronic low perfusion and loss of autoregulation. In addition to its antiplatelet effect, cilostazol exerts a vasodilating effect and improves endothelial function. This study aims to compare the effects of cilostazol and aspirin on changes in WMC volume in CSVD.METHODS: The comparison study of Cilostazol and aspirin on cHAnges in volume of cerebral smaLL vEssel disease white matter chaNGEs (CHALLENGE) is a double blind, randomized trial involving 19 hospitals across South Korea. Patients with moderate or severe WMC and ≥ 1 lacunar infarction detected on brain magnetic resonance imaging (MRI) are eligible; the projected sample size is 254. Participants are randomly assigned to a cilostazol or aspirin group at a 1:1 ratio. Cilostazol slow release 200 mg or aspirin 100 mg are taken once daily for 2 years. The primary outcome measure is the change in WMC volume on MRI from baseline to 104 weeks. Secondary imaging outcomes include changes in the number of lacunes and cerebral microbleeds, fractional anisotropy and mean diffusivity on diffusion tensor imaging, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability.CONCLUSIONS: CHALLENGE will provide evidence to support the selection of long-term antiplatelet therapy in CSVD.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01932203