Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. METHODS: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. RESULTS: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02-0.89]). CONCLUSIONS: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01932203.

Subtle Cognitive Deficits Are Associated with Amyloid-ß Positivity, but Not Severity of Self-Reported Decline: Results from the CoSCo Study.

INTRODUCTION: Subjective cognitive decline (SCD) can be considered as the preclinical manifestation of Alzheimer's disease (AD). The National Institute on Aging and the Alzheimer's Association criteria for preclinical AD proposed that subtle cognitive changes appear along with AD biomarkers in the late stage of preclinical AD. The objective of this study was to explore whether subtle cognitive impairment (SCI) in individuals with SCD is associated with brain amyloid-ß (Aß) status and SCD severity. METHODS: One hundred twenty individuals with SCD (mean age: 70.87 ± 6.10 years) were included in this study. SCI was defined as performance ≤ -1.0 SD on at least two neuropsychological tests. Participants underwent an amyloid positron emission tomography, which was assessed visually and quantitatively using standardized uptake value ratio (SUVR). The severity of SCD was assessed using two self-reported questionnaires: the SCD questionnaire based on the SCD-plus features and the Korean-Everyday Cognition (K-ECog) scale. RESULTS: SCD individuals with SCI (n = 25) had more Aß positivity than the SCD only group (n = 95) (44% vs. 15.79%; p = 0.002). In addition, the SCI group had a higher global SUVR than the SCD only group (p = 0.048). For self-reported questionnaires, there were no differences in SCD questionnaire total scores and K-ECog global and cognitive domain-specific scores between two groups. CONCLUSIONS: In SCD individuals, SCI was associated with higher Aß positivity, but not with the severity of self-reported cognitive decline, compared to the SCD only group. These results suggest that the recognition of objectively defined subtle cognitive deficits may contribute to the early identification of AD in SCD.

The Effect of Hearing Loss on Cognitive Function in Subjective Cognitive Decline.

INTRODUCTION: Subjective cognitive decline (SCD) is a self-reported cognitive decline without objective cognitive impairment. The relationship between audiometric hearing loss (HL) and cognitive function has not been reported in SCD. The purpose of this study was to investigate whether HL affects cognition-related indexes in SCD individuals. METHODS: This is a cross-sectional study that used the baseline data of a multicenter cohort study that monitors clinical progression from SCD to dementia. Individuals aged ≥60 years who reported cognitive decline but had no objective cognitive impairment on comprehensive neuropsychological tests were recruited. Participants were grouped into the normal-hearing (NH) and bilateral HL groups. The demographics, clinical characteristics, dementia biomarkers, global cognition, questionnaire scores, neuropsychological test scores, and segmental brain volumes from MRI were compared between the groups. RESULTS: Of a total of 120 participants, one hundred and two had NH (n = 57) or bilateral HL (n = 45). There were no group differences in the demographic and clinical data except the age. The biomarkers, global cognition, and questionnaire scores were not different between the groups. The HL group performed worse (the z-score of -0.06) in the Stroop Color Word Test than the NH group (0.27) (p = 0.025). Brain volumetric analysis revealed that the HL group had reduced gray matter volumes in four brain subregions: left temporal pole, left caudal middle frontal gyrus, left hippocampus, and right isthmus of the cingulate gyrus. CONCLUSION: In SCD, HL exerted an adverse effect on cognitive function, primarily frontal executive function tested in the Stroop task. HL was also related to gray matter volume reductions in brain subregions, although causality needs further investigation. This study may provide evidence for a potential link between hearing and cognition in SCD, an emerging clinical entity.

Caregiving, care burden and awareness of caregivers and patients with dementia in Asian locations: a secondary analysis.

BACKGROUND: This study investigated the differences in caregiver activity, caregiver burden, and awareness of both caregivers and patients with Alzheimer's disease (AD) across different Asian locations. METHODS: This was a secondary analysis of a multi-national cohort study that aimed to assess caregiver activity and caregiver burden using the Caregiver Activity Scale (CAS) and Zarit Burden Interview (ZBI), respectively. Patients' awareness of their dementia diagnosis was assessed by asking the following yes/no question: "Do you have dementia?" Caregivers' awareness of the patient's dementia diagnosis was assessed by asking the following yes/no question: "Does your patient have dementia?" RESULTS: In total, 524 caregivers of patients with AD from China, Hong Kong, South Korea, the Philippines, Singapore, Thailand, and Taiwan participated. The CAS and ZBI score were significantly different across most locations (p < 0.001 and p = 0.033, respectively). Overall, 56.6% of caregivers and 37.5% of patients had awareness of the dementia diagnosis, and the proportion of patients and caregivers with awareness were also different between each location (all, p < 0.001). CONCLUSIONS: Caregiving, caregiver burden, and the awareness of caregivers and patients were different across many Asian locations. With understanding of cultural differences, further public education on dementia could help increase the awareness of patients and caregivers and reduce caregiver burden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02262975 . Registered 13 October 2014.

Self- and informant-reported cognitive functioning and awareness in subjective cognitive decline, mild cognitive impairment, and very mild Alzheimer disease.

OBJECTIVES: The present study examined self-reports and informant reports of cognitive function and discrepancies between the two reporting methods in healthy controls (HC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and very mild Alzheimer disease (AD) using three questionnaires. METHODS: The study included a total of 300 individuals (mean age: 74.4 ± 5.7 y), including 130 HC, 70 SCD, 51 MCI, and 49 very mild AD patients. Self-ratings and informant ratings of cognitive function were assessed using the Korean Dementia Screening Questionnaire-Cognition (KDSQ-C), AD8, and Subjective Memory Complaints Questionnaire (SMCQ). Awareness of cognitive functioning was measured on the basis of the discrepancy scores between self-reports and informant reports. RESULTS: Group comparisons on questionnaire scores adjusting for age, education, and depressive symptoms showed that self-reports were lowest in HC than other groups, with no differences between SCD and MCI groups. Informant reports were lower in SCD than in MCI, while discrepancy scores were higher in SCD than in MCI (P < .001 for KDSQ-C and SMCQ; P = .076 for AD8). There were no differences in self-reports, informant reports, and discrepancy scores between MCI and AD groups. CONCLUSIONS: These results support the usefulness of informant-reported cognitive functioning to classify MCI among elderly with subjective cognitive complaints. In addition, discrepancies between self-reports and informant reports demonstrate that overestimation and underestimation of cognitive function may serve as a clinical indicator of SCD and MCI across the cognitive continuum, respectively.

A Comparative Evaluation of the KDSQ-C, AD8, and SMCQ as a Cognitive Screening Test to Be Used in National Medical Check-ups in Korea.

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.

Prediction of cognitive impairment via deep learning trained with multi-center neuropsychological test data.

BACKGROUND: Neuropsychological tests (NPTs) are important tools for informing diagnoses of cognitive impairment (CI). However, interpreting NPTs requires specialists and is thus time-consuming. To streamline the application of NPTs in clinical settings, we developed and evaluated the accuracy of a machine learning algorithm using multi-center NPT data. METHODS: Multi-center data were obtained from 14,926 formal neuropsychological assessments (Seoul Neuropsychological Screening Battery), which were classified into normal cognition (NC), mild cognitive impairment (MCI) and Alzheimer's disease dementia (ADD). We trained a machine learning model with artificial neural network algorithm using TensorFlow (https://www.tensorflow.org) to distinguish cognitive state with the 46-variable data and measured prediction accuracies from 10 randomly selected datasets. The features of the NPT were listed in order of their contribution to the outcome using Recursive Feature Elimination. RESULTS: The ten times mean accuracies of identifying CI (MCI and ADD) achieved by 96.66 ± 0.52% of the balanced dataset and 97.23 ± 0.32% of the clinic-based dataset, and the accuracies for predicting cognitive states (NC, MCI or ADD) were 95.49 ± 0.53 and 96.34 ± 1.03%. The sensitivity to the detection CI and MCI in the balanced dataset were 96.0 and 96.0%, and the specificity were 96.8 and 97.4%, respectively. The 'time orientation' and '3-word recall' score of MMSE were highly ranked features in predicting CI and cognitive state. The twelve features reduced from 46 variable of NPTs with age and education had contributed to more than 90% accuracy in predicting cognitive impairment. CONCLUSIONS: The machine learning algorithm for NPTs has suggested potential use as a reference in differentiating cognitive impairment in the clinical setting.

Comparison of Psychiatric Symptoms in Patients With Obstructive Sleep Apnea, Simple Snoring, and Normal Controls.

OBJECTIVE: Patients with sleep-related breathing disorders are known to have more severe psychiatric symptoms than good sleepers. The aim of this study was to compare the psychiatric symptoms of participants with obstructive sleep apnea (OSA), those with simple snoring (SS), and normal controls (NC). METHODS: A total of 386 participants (260 with OSA, 75 with SS, and 51 NC) completed self-report questionnaires including the Symptoms Checklist 90-Revised and underwent nocturnal polysomnography. The scores of nine primary symptom dimensions and three global distress indices of the Symptoms Checklist 90-Revised were compared among the three groups, adjusting for age, sex, and body mass index. RESULTS: Participants with suspected OSA (OSA + SS) reported more severe psychiatric symptoms than the NC group. Compared with the participants with OSA, those with SS manifested more severe obsessive-compulsive (1.4 (1.0) versus 1.1 (0.7), p = .008) and depressive (1.2 (1.2) versus 0.8 (0.8), p = .031) symptoms and higher Global Severity Index (1.0 (0.9) versus 0.7 (0.6), p = .039) and Positive Symptom Distress Index (2.0 (0.8) versus 1.7 (0.6), p = .009). Only higher Pittsburgh Sleep Quality Index values predicted higher Global Severity Index (B = 0.11, p = .041) and Positive Symptom Distress Index (B = 0.46, p = .007) in suspected OSA participants. CONCLUSIONS: This study found that individuals with suspected OSA experienced more severe psychiatric symptoms than NCs and that psychiatric symptoms were more severe in the SS group than in the OSA group. The psychiatric symptoms of suspected OSA patients were associated with subjective sleep quality rather than with the apnea-hypopnea index.

[18F]-THK5351 PET Imaging in Patients With Semantic Variant Primary Progressive Aphasia.

BACKGROUND: Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and ß-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients. MATERIALS AND METHODS: Five svPPA patients, 14 Alzheimer's disease patients, and 15 age-matched normal controls underwent [F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest-based and voxel-based statistical analyses. RESULTS: In svPPA patients, [F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer's disease patients. [F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [F]-flutemetamol scans were negative for ß-amyloid. CONCLUSIONS: These findings show that [F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.

The moderating effect of religiosity on caregiving burden and depressive symptoms in caregivers of patients with dementia.

OBJECTIVES: This study explored whether religiosity/spirituality has a protective role against negative caregiving outcomes, in a large multicenter nationwide sample of caregivers of patients with dementia in South Korea. Additionally, this study was the first to examine whether religiosity/spirituality could affect caregiving outcomes according to the various religious affiliations of caregivers. METHODS: The study was conducted on a sample of 476 caregivers of patients with dementia participated in the Clinical Research Center for Dementia of South Korea (CREDOS). We examined the moderating effect of each of the three dimensions of religiosity/spirituality (organizational religious activity, ORA; non-organizational religious activity, NORA; intrinsic religiosity, IR) on the relationship between activities of daily living (ADL) of patients with dementia and caregiving burden and depressive symptoms of caregivers, using a series of hierarchical regression analyses. In addition, these analyses were conducted according to the religious affiliations of the caregivers. RESULTS: ORA, NORA, and IR of religiosity/spirituality alleviated the effect of ADL of patients on caregiving burden. ORA and IR moderated the relationship between ADL of patients and depressive symptoms of caregivers. These moderating effects of religiosity on caregiving outcomes were different according to various religious groups. CONCLUSION: We have identified religiosity/spirituality as a protective factor for caregivers of patients with dementia. The sub-dimensions of religiosity as moderators were different by religious affiliations of caregivers. Further studies are needed to investigate the specific religiosity-related factors which could positively impact the mental health of the caregivers of patients with dementia by religions.

Influence of personality on depression, burden, and health-related quality of life in family caregivers of persons with dementia.

BACKGROUND: Personality may predispose family caregivers to experience caregiving differently in similar situations and influence the outcomes of caregiving. A limited body of research has examined the role of some personality traits for health-related quality of life (HRQoL) among family caregivers of persons with dementia (PWD) in relation to burden and depression. METHODS: Data from a large clinic-based national study in South Korea, the Caregivers of Alzheimer's Disease Research (CARE), were analyzed (N = 476). Path analysis was performed to explore the association between family caregivers' personality traits and HRQoL. With depression and burden as mediating factors, direct and indirect associations between five personality traits and HRQoL of family caregivers were examined. RESULTS: Results demonstrated the mediating role of caregiver burden and depression in linking two personality traits (neuroticism and extraversion) and HRQoL. Neuroticism and extraversion directly and indirectly influenced the mental HRQoL of caregivers. Neuroticism and extraversion only indirectly influenced their physical HRQoL. Neuroticism increased the caregiver's depression, whereas extraversion decreased it. Neuroticism only was mediated by burden to influence depression and mental and physical HRQoL. CONCLUSIONS: Personality traits can influence caregiving outcomes and be viewed as an individual resource of the caregiver. A family caregiver's personality characteristics need to be assessed for tailoring support programs to get the optimal benefits from caregiver interventions.

Formula for predicting OSA and the Apnea-Hypopnea Index in Koreans with suspected OSA using clinical, anthropometric, and cephalometric variables.

PURPOSE: This study developed formulas to predict obstructive sleep apnea (OSA) and the Apnea-Hypopnea Index (AHI) in Korean patients with suspected OSA using clinical, anthropometric, and cephalometric variables. METHODS: We evaluated relevant variables in 285 subjects with suspected OSA. These included demographic characteristics, sleep-related symptoms, medical history, clinical scales, anthropometric measurements including facial surface measurements, and cephalometric measurements. All participants underwent full-night laboratory polysomnography. The prediction formula for the probability of OSA was created by logistic regression analysis and confirmed by the bootstrap resampling technique. The formula for predicting the AHI was developed using multiple linear regression analysis. RESULTS: The probability of having OSA was as follows: p = 1 / (1 + exponential (exp)-f ), where f = -16.508 + 1.445 × loudness of snoring 4 + 0.485 × loudness of snoring 3 + 0.078 × waist circumference + 0.209 × subnasale-to-stomion distance + 0.183 × thickness of the uvula (UTH) supine + 0.041 × age. The AHI prediction formula was as follows: -112.606 + 3.516 × body mass index + 0.683 × mandibular plane-hyoid supine + 10.915 × loudness of snoring 4 + 6.933 × loudness of snoring 3 + 1.297 × UTH supine + 0.272 × age. CONCLUSION: This is the first study to establish formulas to predict OSA and the AHI in Koreans with suspected OSA using cephalometric and other variables. These results will contribute to prioritizing the order in which patients with suspected OSA are referred for polysomnography.

The quality of life of suspected obstructive sleep apnea patients is related to their subjective sleep quality rather than the apnea-hypopnea index.

PURPOSE: The relationship between the severity of the apnea-hypopnea index (AHI) and the quality of life (QOL) in patients with obstructive sleep apnea (OSA) has been inconsistent in previous studies. This study aimed to identify the core factor associated with the QOL of suspected OSA patients and to compare the QOL of subjects with OSA and simple snoring (SS). METHODS: Two hundred eighty-five subjects who were clinically suspected to have OSA underwent nocturnal polysomnography (PSG) and completed self-report questionnaires including the World Health Organization Quality of Life Short Form (WHOQOL-BREF) and the Pittsburgh Sleep Quality Index (PSQI). The effects of the clinical and PSG variables on the QOL score were analyzed using multiple stepwise regression analyses, and the QOL of OSA and SS groups was compared. RESULTS: In correlation analyses, the most significant factor that correlated with the QOL of the subjects was the PSQI total score (p < 0.001), while the AHI was not related to the WHOQOL-BREF total score. In multiple linear regression analysis, the PSQI total score was the most significant factor associated with the QOL of participants (p < 0.001). The mean score of the WHOQOL-BREF did not differ significantly between the OSA group and the SS group. CONCLUSION: This study suggests that the main factor affecting the QOL of suspected OSA subjects is their subjective sleep quality. We therefore conclude that patients with OSA symptoms estimate their QOL based on their subjective sleep perception rather than AHI.

Effect of rivastigmine or memantine add-on therapy is affected by butyrylcholinesterase genotype in patients with probable Alzheimer's disease.

BACKGROUND: The K variant of butyrylcholinesterase (BCHE-K) exhibits a reduced acetylcholine-hydrolyzing capacity; so the clinical response to rivastigmine may differ in Alzheimer's disease (AD) patients with the BCHE-K gene. OBJECTIVE: To investigate the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine transdermal patch therapy in AD patients based on the BCHE-K gene. METHODS: A total of 146 probable AD patients consented to genetic testing for butyrylcholinesterase and underwent the final efficacy evaluations. Responders were defined as patients with an equal or better score on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) at 16 weeks compared to their baseline score. RESULTS: BCHE-K carriers showed a lower responder rate on the ADAS-cog than non-carriers (38.2 vs. 61.7%, p = 0.02), and this trend was evident in AD patients with apolipoprotein E ε 4 (35 vs. 60.7%, p = 0.001). The presence of the BCHE-K allele predicted a worse response on the ADAS-cog (odds ratio 0.35, 95% confidence interval 0.14-0.87), after adjusting for demographic and baseline cognitive and functional variables. CONCLUSION: The BCHE-K genotype may be related to a poor cognitive response to rivastigmine patch or memantine add-on therapy, especially in the presence of apolipoprotein E ε 4.

Predicting stroke outcome using clinical- versus imaging-based scoring system.

BACKGROUND: Several models to predict outcome in ischemic stroke patients receiving intravenous (i.v.) alteplase can be divided into clinical-based and imaging-based systems. Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) and Dense cerebral artery sign/early infarct signs on admission CT scan, prestroke modified Rankin Scale (mRS) score, Age, Glucose level at baseline, Onset-to-treatment time, and baseline National Institutes of Health Stroke Scale score (DRAGON) are typical imaging- and clinical-based scoring systems, respectively. Therefore, we compared predictability of stroke outcome of clinical (DRAGON)- and imaging (ASPECTS)-based scoring systems. METHODS: We analyzed patients who were diagnosed with middle cerebral artery territory stroke and treated with i.v. alteplase at Gachon University Gil Hospital over 5 years and compared performance of 2 scoring systems for prediction of good functional outcome (mRS, 0-2) with Pearson correlation and area under the curve-receiver operating characteristic (AUC-ROC). In addition, we analyzed predicting power of several clinical factors and 2 scoring systems by multiple regression analysis. RESULTS: Study population (N = 120) had mean age of 66.2 ± 13.2 years. ASPECTS (r = -.841, P < .0001) and DRAGON (r = .657, P < .0001) were significantly correlated with good functional outcome. In addition, statistical comparisons suggested that ASPECTS (AUC-ROC, .972; 95% confidence interval [CI], .947-.996) is significantly superior to DRAGON (AUC-ROC, .854; 95% CI, .786-.922) in predicting functional outcome (difference between areas, .118 ± .0332; 95% CI, .0559-.180, P = .0002). Multiple regression analysis revealed that ASPECTS was the independent predictor of good prognosis (OR, 6.59 per 1-point increase; 95% CI, 2.35-18.49; P < .0001 and OR, 77.67 for ASPECTS ≥ 8; 95% CI, 14.30-421.79; P < .0001). CONCLUSIONS: ASPECTS is superior method for predicting functional outcome in acute ischemic stroke patients receiving i.v. alteplase compared with DRAGON and integration of ASPECTS score into clinical care pathway as decision-making tool can be reasonable.

White matter hyperintensities in mild cognitive impairment: clinical impact of location and interaction with lacunes and medial temporal atrophy.

This study was to evaluate the influence on cognition and activities of daily living (ADL) by white matter hyperintensities (WMHs) based on the severity and location, as well as the interactions among WMHs, lacunes, and medial temporal atrophy (MTA). In 150 patients with amnestic mild cognitive impairment, WMHs were quantified with the use of a semiautomated volumetric method. Lacune counting and MTA assessment were performed by visual rating. The severer WMHs were, the more executive functions decreased. The influence on executive functions such as verbal fluency test and Stroop color reading test were greater in periventricular (PV) WMHs than deep WMHs, as well as bigger in anterior, middle, and posterior areas in order. The instrumental (I) ADL was strongly associated with the anterior (P = .028) and middle area (P = .014) of PVWMHs only. WMHs had synergistic interactions with lacunes in Controlled Oral Word Association Task-semantic (ß = -1.12; R(2) = .24; P = .039), Stroop color (ß = -2.07; R(2) = .15; P = .049), and IADL (ß = .23; R(2) = .20; P = .009). Anterior PVWMHs demonstrated the most powerful impact on frontal executive dysfunction and poor performance of IADL. WMHs had synergistic effects with the number of lacunes on them. Therefore, it is desirable to consider WMHs and lacunes simultaneously as potential imaging biomarkers for predicting cognition and IADL in aMCI.

A new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities.

The Clinical Research Center for Dementia of South Korea (CREDOS) group developed a new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities (WMHs). In this study, we aimed to evaluate the validity of the CREDOS ischemia classification system. A total of 352 patients with cognitive impairments were included. Their WMH scores were rated using the CREDOS WMH visual rating scale. These patients were divided into 3 groups according to the CREDOS ischemia classification system. The volume of WMH was also automatically measured. The number of lacunes and microbleeds (MBs) were counted. The CREDOS ischemia classification system was revised with factor analysis using vascular risk factors and cerebrovascular disease (CVD) markers (WMH volume, lacunes, and MBs). External validation was performed in another group of patients with cognitive impairment using multinomial logistic regression analysis. The CREDOS WMH visual rating scale showed excellent correlation with the automatically measured volume of WMH. The factor analysis showed that the severe group was expanded to D3P1 and D3P2 in the revised CREDOS ischemia classification system. In the validation group, the presence of vascular risk factors and the severity of CVD markers could be distinguished according to the revised CREDOS ischemia classification. We validated a newly developed classification system for ischemia. This simple visual classification system was capable of providing information on vascular risk factors and CVD markers by simply rating WMH on magnetic resonance imaging.

A Longitudinal Study on Memory Enhancement in Subjective Cognitive Decline Patients: Clinical and Neuroimaging Perspectives.

BACKGROUND: Subjective cognitive decline (SCD) refers to the self-reported persistent cognitive decline despite normal objective testing, increasing the risk of dementia compared to cognitively normal individuals. OBJECTIVE: This study aims to investigate the attributes of SCD patients who demonstrated memory function improvement. METHODS: In this prospective study of SCD, a total of 120 subjects were enrolled as part of a multicenter cohort study aimed at identifying predictors for the clinical progression to mild cognitive impairment or dementia (CoSCo study). All subjects underwent 18F-florbetaben PET and brain MRI scans at baseline and annual neuropsychological tests. At the 24-month follow-up, we classified SCD patients based on changes in memory function, the z-score of the Seoul verbal learning test delayed recall. RESULTS: Of the 120 enrolled patients, 107 successfully completed the 24-month follow-up assessment. Among these, 80 patients (74.8%) with SCD exhibited memory function improvements. SCD patients with improved memory function had a lower prevalence of coronary artery disease at baseline and performed better in the trail-making test part B compared to those without improvement. Anatomical and biomarker analysis showed a lower frequency of amyloid PET positivity and larger volumes in the left and right superior parietal lobes in subjects with improved memory function. CONCLUSIONS: Our prospective study indicates that SCD patients experiencing memory improvement over a 24-month period had a lower amyloid burden, fewer cardiovascular risk factors, and superior executive cognitive function. Identifying these key factors associated with cognitive improvement may assist clinicians in predicting future memory function improvements in SCD patients.

Relationship Between Amyloid Positivity and Sleep Characteristics in the Elderly With Subjective Cognitive Decline.

Background and Purpose: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognition and performance of daily activities. Recent studies have attempted to establish the relationship between AD and sleep. It is believed that patients with AD pathology show altered sleep characteristics years before clinical symptoms appear. This study evaluated the differences in sleep characteristics between cognitively asymptomatic patients with and without some amyloid burden. Methods: Sleep characteristics of 76 subjects aged 60 years or older who were diagnosed with subjective cognitive decline (SCD) but not mild cognitive impairment (MCI) or AD were measured using Fitbit® Alta HR, a wristwatch-shaped wearable device. Amyloid deposition was evaluated using brain amyloid plaque load (BAPL) and global standardized uptake value ratio (SUVR) from fluorine-18 florbetaben positron emission tomography. Each component of measured sleep characteristics was analyzed for statistically significant differences between the amyloid-positive group and the amyloid-negative group. Results: Of the 76 subjects included in this study, 49 (64.5%) were female. The average age of the subjects was 70.72±6.09 years when the study started. 15 subjects were classified as amyloid-positive based on BAPL. The average global SUVR was 1.598±0.263 in the amyloid-positive group and 1.187±0.100 in the amyloid-negative group. Time spent in slow-wave sleep (SWS) was significantly lower in the amyloid-positive group (39.4±13.1 minutes) than in the amyloid-negative group (49.5±13.1 minutes) (p=0.009). Conclusions: This study showed that SWS is different between the elderly SCD population with and without amyloid positivity. How SWS affects AD pathology requires further research.

A Two-Year Observational Study to Evaluate Conversion Rates from High- and Low-Risk Patients with Amnestic Mild Cognitive Impairment to Probable Alzheimer's Disease in a Real-World Setting.

Background: Predicting conversion to probable Alzheimer&s disease (AD) from amnestic mild cognitive impairment (aMCI) is difficult but important. A nomogram was developed previously for determining the risk of 3-year probable AD conversion in aMCI. Objective: To compare the probable AD conversion rates with cognitive and neurodegenerative changes for 2 years from high- and low risk aMCI groups classified using the nomogram. Methods: This prospective, multicenter, observational study was conducted in Korea. A total of patients were classified as high- or low-risk aMCI according to the nomogram and followed-up for 2 years to compare the annual conversion rate to probable AD and brain structure changes between the two groups. Results: In total, 176 (high-risk, 85; low-risk, 91) and 160 (high-risk, 77; low-risk, 83) patients completed the 1-year and 2-year follow-up, respectively. The probable AD conversion rate was significantly higher in the high-risk (Year 1, 28.9%; Year 2, 46.1%) versus low-risk group (Year 1, 0.0%; Year 2, 4.9%, both p < 0.0001). Mean changes from baseline in Seoul Neuropsychological Screening Battery-Dementia Version, Clinical Dementia Rating-Sum of Box, and Korean version of the Instrumental Activities of Daily Living scores and cortical atrophy index at Years 1 and 2 were significantly greater in the high-risk group (p < 0.0001). Conclusions: The high-risk aMCI group, as determined by the nomogram, had a higher conversion rate to probable AD and faster cognitive decline and neurodegeneration change than the low-risk group. These real-world results have clinical implications that help clinicians in accurately predicting patient outcomes and facilitating early decision-making.Trial Registration: ClinicalTrials.gov (NCT03448445).