What is the impact of one's chronic illness on his or her spouse's future chronic illness: a community-based prospective cohort study.

BACKGROUND: Integrating a joint approach to chronic disease management within the context of a couple has immense potential as a valuable strategy for both prevention and treatment. Although spousal concordance has been reported in specific chronic illnesses, the impact they cumulatively exert on a spouse in a longitudinal setting has not been investigated. We aimed to determine whether one's cumulative illness burden has a longitudinal impact on that of their spouse. METHODS: Data was acquired from a community-based prospective cohort that included Koreans aged 60 years and over, randomly sampled from 13 districts nationwide. Data from the baseline assessment (conducted from November 2010 to October 2012) up to the 8-year follow-up assessment was analyzed from October 2021 to November 2022. At the last assessment, partners of the index participants were invited, and we included 814 couples in the analysis after excluding 51 with incomplete variables. Chronic illness burden of the participants was measured by the Cumulative Illness Rating Scale (CIRS). Multivariable linear regression and causal mediation analysis were used to examine the longitudinal effects of index chronic illness burden at baseline and its change during follow-up on future index and spouse CIRS scores. RESULTS: Index participants were divided based on baseline CIRS scores (CIRS < 6 points, n = 555, mean [SD] age 66.3 [4.79] years, 43% women; CIRS ≥ 6 points, n = 259, mean [SD] age 67.7 [4.76] years, 36% women). The baseline index CIRS scores and change in index CIRS scores during follow-up were associated with the spouse CIRS scores (ß = 0.154 [SE: 0.039], p < 0.001 for baseline index CIRS; ß = 0.126 [SE: 0.041], p = 0.002 for change in index CIRS) at the 8-year follow-up assessment. Subgroup analysis found similar results only in the high CIRS group. The baseline index CIRS scores and change in index CIRS scores during follow-up had both direct and indirect effects on the spouse CIRS scores at the 8-year follow-up assessment. CONCLUSIONS: The severity and course of one's chronic illnesses had a significant effect on their spouse's future chronic illness particularly when it was severe. Management strategies for chronic diseases that are centered on couples may be more effective.

The impact of the COVID-19 pandemic on depression in community-dwelling older adults: a prospective cohort study.

BACKGROUND: There are growing concerns about the impact of the COVID-19 pandemic on the mental health of older adults. We examined the effect of the pandemic on the risk of depression in older adults. METHODS: We analyzed data from the prospective cohort study of Korean older adults, which has been followed every 2 years. Among the 2308 participants who completed both the third and the fourth follow-up assessments, 58.4% completed their fourth follow-up before the outbreak of COVID-19 and the rest completed it during the pandemic. We conducted face-to-face diagnostic interviews using Mini International Neuropsychiatric Interview and used Geriatric Depression Scale. We performed generalized estimating equations and logistic regression analyses. RESULTS: The COVID-19 pandemic was associated with increased depressive symptoms in older adults [b (standard error) = 0.42 (0.20), p = 0.040] and a doubling of the risk for incident depressive disorder even in euthymic older adults without a history of depression (odds ratio = 2.44, 95% confidence interval 1.18-5.02, p = 0.016). Less social activities, which was associated with the risk of depressive disorder before the pandemic, was not associated with the risk of depressive disorder during the pandemic. However, less family gatherings, which was not associated with the risk of depressive disorder before the pandemic, was associated with the doubled risk of depressive disorder during the pandemic. CONCLUSIONS: The COVID-19 pandemic significantly influences the risk of late-life depression in the community. Older adults with a lack of family gatherings may be particularly vulnerable.

Mood disorders increase mortality mainly through dementia: A community-based prospective cohort study.

OBJECTIVE: The effects of mood disorders on mortality may be mediated by their effects on the risk of dementia, and interventions to reduce the occurrence of dementia may reduce their overall mortality. This study aimed to investigate the direct effects of depressive and bipolar disorders on the 6-year risk of mortality and also their indirect effects on mortality due to their effect on the risk of dementia. METHODS: A total of 5101 Koreans were selected from a community-based prospective cohort study, and 6-year risks of mortality and dementia in participants with depressive and bipolar disorders were estimated by Cox proportional hazard analysis. The direct and indirect effects of depressive and bipolar disorders on the risk of mortality were estimated using structural equation modeling. RESULTS: The depressive and bipolar disorder groups showed 51% and 85% higher 6-year mortality, and 82% and 127% higher risk of dementia, respectively, compared to euthymic controls. The effects of depressive and bipolar disorders on mortality were mainly mediated by their effects on the risk of dementia in a structural equation model. The direct effects of each mood disorder on mortality were not significant. CONCLUSION: Both depressive and bipolar disorders increased the risks of mortality and dementia, and the effects of mood disorders on mortality were mainly mediated through dementia. As dementia occurs later in life than mood disorders, measures to prevent it may effectively reduce mortality in individuals with a history of mood disorders, as well as being more feasible than attempting to control other causes of death.

A Clinical Decision Support System for Sleep Staging Tasks With Explanations From Artificial Intelligence: User-Centered Design and Evaluation Study.

BACKGROUND: Despite the unprecedented performance of deep learning algorithms in clinical domains, full reviews of algorithmic predictions by human experts remain mandatory. Under these circumstances, artificial intelligence (AI) models are primarily designed as clinical decision support systems (CDSSs). However, from the perspective of clinical practitioners, the lack of clinical interpretability and user-centered interfaces hinders the adoption of these AI systems in practice. OBJECTIVE: This study aims to develop an AI-based CDSS for assisting polysomnographic technicians in reviewing AI-predicted sleep staging results. This study proposed and evaluated a CDSS that provides clinically sound explanations for AI predictions in a user-centered manner. METHODS: Our study is based on a user-centered design framework for developing explanations in a CDSS that identifies why explanations are needed, what information should be contained in explanations, and how explanations can be provided in the CDSS. We conducted user interviews, user observation sessions, and an iterative design process to identify three key aspects for designing explanations in the CDSS. After constructing the CDSS, the tool was evaluated to investigate how the CDSS explanations helped technicians. We measured the accuracy of sleep staging and interrater reliability with macro-F1 and Cohen κ scores to assess quantitative improvements after our tool was adopted. We assessed qualitative improvements through participant interviews that established how participants perceived and used the tool. RESULTS: The user study revealed that technicians desire explanations that are relevant to key electroencephalogram (EEG) patterns for sleep staging when assessing the correctness of AI predictions. Here, technicians wanted explanations that could be used to evaluate whether the AI models properly locate and use these patterns during prediction. On the basis of this, information that is closely related to sleep EEG patterns was formulated for the AI models. In the iterative design phase, we developed a different visualization strategy for each pattern based on how technicians interpreted the EEG recordings with these patterns during their workflows. Our evaluation study on 9 polysomnographic technicians quantitatively and qualitatively investigated the helpfulness of the tool. For technicians with <5 years of work experience, their quantitative sleep staging performance improved significantly from 56.75 to 60.59 with a P value of .05. Qualitatively, participants reported that the information provided effectively supported them, and they could develop notable adoption strategies for the tool. CONCLUSIONS: Our findings indicate that formulating clinical explanations for automated predictions using the information in the AI with a user-centered design process is an effective strategy for developing a CDSS for sleep staging.

How COVID-19 Affected Healthcare Workers in the Hospital Locked Down due to Early COVID-19 Cases in Korea.

BACKGROUND: The healthcare workers (HCWs) were exposed to never-experienced psychological distress during the early stage of the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to investigate how the COVID-19 pandemic affected the mental health of HCWs during the hospital lockdown period due to mass healthcare-associated infection during the early spread of COVID-19. METHODS: A real-time online survey was conducted between April 14-18, 2020 among HCWs who worked at the university hospital where COVID-19 was confirmed in a patient, and the hospital was shut down for 3 weeks. Along with demographic variables and work-related information, psychological distress was measured using the Generalized Anxiety Disorder-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), the Maslach Burnout Inventory-General Survey scale, and the Stress and Anxiety to Viral Epidemics-9. RESULTS: The HCWs working in the cohort ward and those who have experienced social discrimination had significantly higher level of depression (PHQ-9 score; 5.24 ± 4.48 vs. 4.15 ± 4.38; P < 0.01 and 5.89 ± 4.78 vs. 3.25 ± 3.77; P < 0.001, respectively) and anxiety (GAD-7 score; 3.69 ± 3.68 vs. 2.87 ± 3.73; P < 0.05 and 4.20 ± 4.22 vs. 2.17 ± 3.06; P < 0.001, respectively) compared to other HCWs. Worries regarding the peer relationship and the skepticism about job were associated with depression (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.07-1.79; P < 0.05 and OR, 1.69; 95% CI, 1.31-2.17; P < 0.001, respectively) and anxiety (OR, 1.73; 95% CI, 1.21-2.49; P < 0.01 and OR, 1.54; 95% CI, 1.09-2.17; P < 0.05, respectively), while fear of infection or worsening of health was not. Path analysis showed that work-related stress associated with the viral epidemic rather than anxiety about the viral epidemic mainly contributed to depression. CONCLUSION: The present observational study indicates that mental health problems of HCWs exposed to COVID-19 are associated with distress in work and social relationship. Early intervention programs focusing on these factors are necessary.

Magnetic Resonance Imaging Texture of Medial Pulvinar in Dementia with Lewy Bodies.

INTRODUCTION: Executive dysfunction is common in dementia with Lewy bodies (DLB). The pulvinar nucleus plays a role in executive control and synchronizes with cortical regions in the salience network that are vulnerable to Lewy pathology. OBJECTIVE: We investigated the pulvinar subregions in patients with mild DLB and their associations with executive function. METHODS: The sample consisted of 38 DLB patients and 38 age- and sex-matched normal controls. We evaluated cognitive function using the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet. We obtained four pulvinar nuclei using preprocessed T1-weighted magnetic resonance images. We compared volumes and textures of the DLB patients and the normal controls for each nucleus. We used a linear regression to determine the association of textures and neuropsychological test scores. RESULTS: The DLB patients showed comparable volumes to the normal controls in all pulvinar nuclei. However, the DLB patients showed different texture of the left medial pulvinar (PuM) from the normal controls. The entropy, contrast, and cluster shade were lower but autocorrelation of left PuM was higher in the DLB patients compared to the normal controls. These texture features of the left PuM were associated with the set-shifting performance measured by the Trail Making Test. CONCLUSIONS: In DLB, the left PuM may be altered from early stage, which may contribute to the development of executive dysfunction.

Sleep and cognitive decline: A prospective nondemented elderly cohort study.

OBJECTIVE: To investigate sleep disturbances that induce cognitive changes over 4 years in nondemented elderlies. METHODS: Data were acquired from a nationwide, population-based, prospective cohort of Korean elderlies (2,238 normal cognition [NC] and 655 mild cognitive impairment [MCI]). At baseline and 4-year follow-up assessments, sleep-related parameters (midsleep time, sleep duration, sleep latency, subjective sleep quality, sleep efficiency, and daytime dysfunction) and cognitive status were measured using the Pittsburgh Sleep Quality Index and Consortium to Establish a Registry for Alzheimer's Disease Assessment, respectively. We used logistic regression models adjusted for covariates including age, sex, education, apolipoprotein E genotype, Geriatric Depression Scale, Cumulative Illness Rating Scale, and physical activity. RESULTS: In participants with NC, long sleep latency (>30 minutes), long sleep duration (≥7.95 hours), and late midsleep time (after 3:00 am) at baseline were related to the risk of cognitive decline at 4-year follow-up assessment; odds ratio (OR) was 1.40 for long sleep latency, 1.67 for long sleep duration, and 0.61 for late midsleep time. These relationships remained significant when these variables maintained their status throughout the follow-up period. Newly developed long sleep latency also doubled the risk of cognitive decline. In those with MCI, however, only long sleep latency reduced the chance of reversion to NC (OR = 0.69). INTERPRETATION: As early markers of cognitive decline, long sleep latency can be used for elderlies with NC or MCI, whereas long sleep duration and relatively early sleep time might be used for cognitively normal elderlies only. Ann Neurol 2018;83:472-482.

Gait Variability Can Predict the Risk of Cognitive Decline in Cognitively Normal Older People.

BACKGROUND: The aim of this study was to investigate the association of gait speed and gait variability, an index of how much gait parameters, such as step time, fluctuate step-to-step, with risk of cognitive decline in cognitively normal elderly individuals. While high gait variability is emerging as an early indicator of dementing illnesses, there is little research on whether high gait variability predicts cognitive decline in cognitively normal elderly who have no evidence of cognitive impairment. METHODS: In this 4-year prospective cohort study on 91 community-dwelling cognitively normal elderly individuals without cerebral ischemic burden or Parkinsonism, we evaluated gait speed and step time variability using a tri-axial accelerometer placed on the center of body mass, and diagnosed mild cognitive impairment (MCI) according to the International Working Group on MCI. We performed Kaplan-Meier analysis with consecutive log-rank testing for MCI-free survival by cohort-specific tertiles of gait speed; hazard ratios (HR) of incident MCI were estimated using Cox proportional hazards regression analysis adjusted for age, sex, education level, Cumulative Illness Rating Scale score, GDS score, and presence of the apolipoprotein E ε4 allele. RESULTS: Out of the 91 participants in the baseline assessment, 87 completed one or more 2-year follow-up assessments, and the median duration of follow-up was 47.1 months. Kaplan-Meier curves of incident MCI show evident differences in risk by gait variability group (χ2 = 9.64, p = 0.002, log-rank test). Mean MCI-free survival in the high variability group was 12% shorter than in the mid-to-low tertile group (47.4 ± 1.74 [SD] vs. 54.04 ± 0.52 months), while it was comparable between gait speed groups (51.59 ± 0.70 vs. 50.64 ± 1.77 months; χ2 = 1.16, p = 0.281). In multivariate analysis, subjects with high gait variability showed about 12-fold higher risk of MCI (HR = 11.97, 95% CI = 1.29-111.37) than those with mid-to-low variability. However, those with slow gait speed showed comparable MCI risk to those with mid-to-high speed (HR = 5.04, 95% CI = 0.53-48.18). CONCLUSIONS: Gait variability may be a better predictor of cognitive decline than gait speed in cognitively normal elderly individuals without cerebral ischemic burden or Parkinsonism.

Behavioral Variant Frontotemporal Dementia With the Dominantly Affected Caudate Nucleus in 18 F-FP-CIT PET/CT.

ABSTRACT: Frontotemporal dementia is a clinical syndrome that is characterized by a progressive deterioration in behavior, personality, and/or language, with relative preservation of memory, and its phenotype and molecular basis are heterogeneous. We present a case of a 62-year-old female patient who underwent 18 F-FDG PET/CT and 18 F-FP-CIT PET/CT for differential diagnosis of psychiatric disease and types of dementia. 18 F-FDG PET/CT image showed a compatible finding for frontotemporal dementia, and 18 F-FP-CIT PET/CT image showed dominantly decreased dopamine transporter activity in the bilateral caudate nucleus.

Angiotensin Receptor Blockers and the Risk of Suspected Drug-Induced Liver Injury: A Retrospective Cohort Study Using Electronic Health Record-Based Common Data Model in South Korea.

INTRODUCTION: Angiotensin receptor blockers are widely used antihypertensive drugs in South Korea. In 2021, the Korea Ministry of Food and Drug Safety acknowledged the need for national compensation for a drug-induced liver injury (DILI) after azilsartan use. However, little is known regarding the association between angiotensin receptor blockers and DILI. OBJECTIVE: We conducted a retrospective cohort study in incident users of angiotensin receptor blockers from a common data model database (1 January, 2017-31 December, 2021) to compare the risk of DILI among specific angiotensin receptor blockers against valsartan. METHODS: Patients were assigned to treatment groups at cohort entry based on prescribed angiotensin receptor blockers. Drug-induced liver injury was operationally defined using the International DILI Expert Working Group criteria. Cox regression analyses were conducted to derive hazard ratios and the inverse probability of treatment weighting method was applied. All analyses were performed using R. RESULTS: In total, 229,881 angiotensin receptor blocker users from 20 university hospitals were included. Crude DILI incidence ranged from 15.6 to 82.8 per 1000 person-years in treatment groups, most were cholestatic and of mild severity. Overall, the risk of DILI was significantly lower in olmesartan users than in valsartan users (hazard ratio: 0.73 [95% confidence interval 0.55-0.96]). In monotherapy patients, the risk was significantly higher in azilsartan users than in valsartan users (hazard ratio: 6.55 [95% confidence interval 5.28-8.12]). CONCLUSIONS: We found a significantly higher risk of suspected DILI in patients receiving azilsartan monotherapy compared with valsartan monotherapy. Our findings emphasize the utility of real-world evidence in advancing our understanding of adverse drug reactions in clinical practice.

Motoric Cognitive Risk and Incident Dementia in Older Adults.

Importance: Motoric cognitive risk (MCR) is a novel predementia syndrome; however, whether it can estimate dementia in a nationwide population or has additive estimation validity over cognitive or motoric components alone remains unknown. Objective: To examine whether modified MCR, which incorporates the timed-up-and-go and one-leg-standing tests, improves estimation validity for incident dementia over using cognitive or motoric components alone. Design, Setting, and Participants: This nationwide cohort study evaluated data from individuals aged 66 years who participated in the National Screening Program for Transitional Ages in Korea from January 1, 2009, to December 31, 2013, and examined the association between MCR and incident dementia using Cox proportional hazards regression analysis. Data were collected from the index date (the date on which the participant had the screening) until dementia onset, death, or the end of the follow-up period, whichever came first. The 2 subtypes were defined as subjective cognitive declines with timed-up-and-go impairment or one-leg-standing impairment. The data set was generated with permission from the Korean National Health Insurance Service, and data analysis was conducted from August 2, 2021, to January 31, 2022. Individuals diagnosed with dementia or psychotic disorders or those who had a documented history of dementia medication use before the index date were excluded. Main Outcomes and Measures: The main outcome was incidence of dementia, defined as an individual receiving their first dementia medication with the relevant International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes after the index date. Results: Among the 1 137 530 participants (53.7% women), 15 380 (1.4%) met the MCR criteria for the timed-up-and-go subtype, and 32 910 (2.9%) met the criteria for the one-leg-standing subtype. The mean (SD) follow-up period was 7.02 (1.38) years. Participants with MCR demonstrated an approximately 2-fold higher risk of incident dementia than those without MCR (timed-up-and-go subtype, adjusted hazard ratio, 2.03; 95% CI, 1.94-2.13; one-leg-standing subtype, adjusted hazard ratio, 2.05; 95% CI, 1.98-2.12). Conclusions and Relevance: In this cohort study of participants aged 66 years of the National Screening Program for Transitional Ages, modified motoric cognitive risk had higher adjusted hazard ratios of incident dementia than individual cognitive or motoric components. Motoric cognitive risk may be a practical screening tool for estimating dementia among individuals in their mid-60s ; however, further investigation of the clinical and neurobiological aspects is necessary.

Exploring shared neural substrates underlying cognition and gait variability in adults without dementia.

BACKGROUND: High gait variability is associated with neurodegeneration and cognitive impairments and is predictive of cognitive impairment and dementia. The objective of this study was to identify cortical or subcortical structures of the brain shared by gait variability measured using a body-worn tri-axial accelerometer (TAA) and cognitive function. METHODS: This study is a part of a larger population-based cohort study on cognitive aging and dementia. The study included 207 participants without dementia, with a mean age of 72.6, and 45.4% of them are females. We conducted standardized diagnostic interview including a detailed medical history, physical and neurological examinations, and laboratory tests for cognitive impairment. We obtained gait variability during walking using a body-worn TAA along and measured cortical thickness and subcortical volume from brain magnetic resonance (MR) images. We cross-sectionally investigated the cortical and subcortical neural structures associated with gait variability and the shared neural substrates of gait variability and cognitive function. RESULTS: Higher gait variability was associated with the lower cognitive function and thinner cortical gray matter but not smaller subcortical structures. Among the clusters exhibiting correlations with gait variability, one that included the inferior temporal, entorhinal, parahippocampal, fusiform, and lingual regions in the left hemisphere was also associated with global cognitive and verbal memory function. Mediation analysis results revealed that the cluster's cortical thickness played a mediating role in the association between gait variability and cognitive function. CONCLUSION: Gait variability and cognitive function may share neural substrates, specifically in regions related to memory and visuospatial navigation.

Impact of COVID-19 Pandemic on Children Visiting Emergency Department for Mental Illness: A Multicenter Database Analysis from Korea.

We aimed to identify changes in the proportion of pediatric emergency department (PED) visits due to mental illness during the coronavirus disease 2019 (COVID-19) pandemic. This was a retrospective observational study of visits to the PED at six university hospitals from January 2017 to December 2020. We included children aged 5−17 years who were diagnosed with a mental illness. We used segmented regression analysis to identify the change in the proportion of patients with mental illness. A total of 845 patients were included in the analysis. After the first case of COVID-19 was reported in Korea, the number of PED visits significantly decreased by 560.8 patients per week (95% confidence interval (CI): −665.3 to −456.3, p < 0.001). However, the proportion of patients with mental illness increased significantly, by 0.37% per week (95% CI: 0.04% to 0.70%, p = 0.03), at this time point. Subgroup analyses revealed that emotional disorders significantly increased by 0.06% per month (95% CI: 0.02% to 0.09%, p < 0.001) during the pandemic. Our study revealed that an increased proportion of patients with mental illness visited the PED during the COVID-19 pandemic. Specifically, we identified that the proportion of emotional disorders continues to rise during this pandemic.

Predicting intraoperative hypotension using deep learning with waveforms of arterial blood pressure, electroencephalogram, and electrocardiogram: Retrospective study.

To develop deep learning models for predicting Interoperative hypotension (IOH) using waveforms from arterial blood pressure (ABP), electrocardiogram (ECG), and electroencephalogram (EEG), and to determine whether combination ABP with EEG or CG improves model performance. Data were retrieved from VitalDB, a public data repository of vital signs taken during surgeries in 10 operating rooms at Seoul National University Hospital from January 6, 2005, to March 1, 2014. Retrospective data from 14,140 adult patients undergoing non-cardiac surgery with general anaesthesia were used. The predictive performances of models trained with different combinations of waveforms were evaluated and compared at time points at 3, 5, 10, 15 minutes before the event. The performance was calculated by area under the receiver operating characteristic (AUROC), area under the precision-recall curve (AUPRC), sensitivity and specificity. The model performance was better in the model using both ABP and EEG waveforms than in all other models at all time points (3, 5, 10, and 15 minutes before an event) Using high-fidelity ABP and EEG waveforms, the model predicted IOH with a AUROC and AUPRC of 0.935 [0.932 to 0.938] and 0.882 [0.876 to 0.887] at 5 minutes before an IOH event. The output of both ABP and EEG was more calibrated than that using other combinations or ABP alone. The results demonstrate that a predictive deep neural network can be trained using ABP, ECG, and EEG waveforms, and the combination of ABP and EEG improves model performance and calibration.

Construction and validation of a cerebral white matter hyperintensity probability map of older Koreans.

BACKGROUND AND PURPOSE: Although two white matter hyperintensity (WMH) probability maps of healthy older adults already exist, they have several limitations in representing the distribution of WMH in healthy older adults, especially Asian older adults. We constructed and validated a WMH probability map (WPM) of healthy older Koreans and examined the age-associated differences of WMH. METHODS: We constructed WPM using development dataset that consisted of high-resolution 3D fluid-attenuated inversion recovery images of 5 age groups (60-64 years, 65-69 years, 70-74 years, 75-79 years, and 80+ years). Each age group included 30 age-matched men and women each. We tested the validity of the WPM by comparing WMH ages estimated by the WPM and the chronological ages of 30 healthy controls, 30 hypertension patients, and 30 S patients. RESULTS: Older age groups showed a higher volume of WMH in both hemispheres (p < 0.001). About 90% of the WMH were periventricular in all age groups. With advancing age, the peak of the distance histogram from the ventricular wall of the periventricular WMH shifted away from the ventricular wall, while that of deep WMH shifted toward the ventricular wall. The estimated WMH ages were comparable to the chronological ages in the healthy controls, while being higher than the chronological ages in hypertension and stroke patients. CONCLUSIONS: This WPM may serve as a standard atlas in research on WMH of older adults, especially Asians.

Association between diurnal temperature range and emergency department visits for multiple sclerosis: A time-stratified case-crossover study.

Although multiple sclerosis (MS) has been the leading cause of neurologically-induced disability in young adults, risk factors for the relapse and acute aggravation of MS remain unclear. A few studies have suggested a possible role of temperature changes on the relapse and acute aggravation of MS. We investigated the association between short-term exposure to wide diurnal temperature ranges (DTRs) and acute exacerbation of MS requiring an emergency department (ED) visit. A total of 1265 patients visited EDs for acute aggravation of MS as the primary disease in Seoul between 2008 and 2014 from the national emergency database. We conducted a conditional logistic regression analysis of the time-stratified case-crossover design to compare DTRs on the ED visit days for MS and those on control days matched according to the day of the week, month, and year. We examined possible associations with other temperature-related variables (ambient temperature, between-day temperature change, and sunlight hours). Short-term exposure to wide DTRs immediately increased the risk of ED visits for MS. Especially, 2-day average (lag0-1) DTR levels on the day of and one day prior to ED visits exhibited the strongest association (an 8.81% [95% CI: 3.46%-14.44%] change in the odds ratio per 1 °C increase in the DTR). Other temperature-related variables were not associated with MS aggravation. Our results suggest that exposure to wider DTR may increase the risk of acute exacerbation of MS. Given the increasing societal burden of MS and the increasing temperature variability due to climate change, further studies are required.

Pre-attentive Visual Processing in Alzheimer's Disease: An Event-related Potential Study.

INTRODUCTION: While identifying Alzheimer's Disease (AD) in its early stages is crucial, traditional neuropsychological tests tend to lack sensitivity and specificity for its diagnosis. Neuropsychological studies have reported visual processing deficits of AD, and event-related potentials (ERPs) are suitable to investigate pre-attentive processing with superior temporal resolution. OBJECTIVE: This study aimed to investigate visual attentional characteristics of adults with AD, from pre-attentive to attentive processing, using a visual oddball task and ERPs. METHODS: Cognitively normal elderly controls (CN) and patients with probable AD (AD) were recruited. Participants performed a three-stimulus visual oddball task and were asked to press a designated button in response to the target stimuli. The amplitudes of 4 ERPs were analyzed. Mismatchnegativity (vMMN) was analyzed around the parieto-occipital and temporo-occipital regions. P3a was analyzed around the fronto-central regions, whereas P3b was analyzed around the centro-parietal regions. RESULTS: Late vMMN amplitudes of the AD group were significantly smaller than those of the CN group, while early vMMN amplitudes were comparable. Compared to the CN group, P3a amplitudes of the AD group were significantly smaller for the infrequent deviant stimuli, but the amplitudes for the standard stimuli were comparable. Lastly, the AD group had significantly smaller P3b amplitudes for the target stimuli compared to the CN group. CONCLUSION: Our findings imply that AD patients exhibit pre-attentive visual processing deficits, known to affect later higher-order brain functions. In a clinical setting, the visual oddball paradigm could be used to provide helpful diagnostic information since pre-attentive ERPs can be induced by passive exposure to infrequent stimuli.

Association between lifetime coffee consumption and late life cerebral white matter hyperintensities in cognitively normal elderly individuals.

Coffee consumption is associated with cerebral hypoperfusion that may contribute to the development of cerebral white matter hyperintensities (WMH). We investigated the effect of lifetime coffee consumption on the volume of WMH (VWMH) in late life, and compared the effect between men and women since caffeine clearance may be different between sexes. We enrolled 492 community-dwelling cognitively normal elderly individuals (73.4 ± 6.7 years old on average) from the Korean Longitudinal Study on Cognitive Aging and Dementia. We evaluated their patterns and amounts of coffee consumption using a study-specific standardized interview and estimated cerebral VWMH by automatic segmentation of brain fluid-attenuated inversion recovery sequence magnetic resonance images. Higher cumulative lifetime coffee consumption was associated with higher logVWMH in both sexes (p = 0.030). The participants who consumed more than 2 cups of coffee per day on average in their lifetime showed higher logVWMH in late life than those who consumed less. When both sexes were analyzed separately, these coffee-logVWMH associations were found only in women, although the volumes of brain and white matter of women were smaller than those of men. Our findings suggest that prolonged high coffee consumption may be associated with the risk of WMH in late life.

Smaller pineal gland is associated with rapid eye movement sleep behavior disorder in Alzheimer's disease.

BACKGROUND: To investigate the association between pineal gland volume and symptoms of rapid eye movement (REM) sleep behavior disorder (RBD) in Alzheimer's disease (AD) patients without any feature of dementia with Lewy bodies. METHODS: We enrolled 296 community-dwelling probable AD patients who did not meet the diagnostic criteria for possible or probable dementia with Lewy bodies. Among them, 93 were amyloid beta (Aß) positive on 18F-florbetaben amyloid brain positron emission tomography. We measured RBD symptoms using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) and defined probable RBD (pRBD) as the RBDSQ of 5 or higher. We manually segmented pineal gland on 3T structural T1-weighted brain magnetic resonance imaging. RESULTS: The participants with pRBD had smaller pineal parenchyma volume (VPP) than those without pRBD (p <  0.001). The smaller the VPP, the more severe the RBD symptoms (p <  0.001). VPP was inversely associated with risk of prevalent pRBD (odds ratio = 0.909, 95% confidence interval [CI] = 0.878-0.942, p <  0.001). Area under the receiver operator characteristic curve for pRBD of VPP was 0.80 (95% CI = 0.750-0.844, p <  0.0001). These results were not changed when we analyzed the 93 participants with Aß-positive AD separately. CONCLUSIONS: In AD patients, reduced pineal gland volume may be associated with RBD.

Association of Low Blood Pressure with White Matter Hyperintensities in Elderly Individuals with Controlled Hypertension.

BACKGROUND AND PURPOSE: Both hypertension and hypotension increase cerebral white matter hyperintensities. However, the effects of hypotension in individuals with treated hypertension are unknown. We analyzed the association of low blood pressure with the location and amount of white matter hyperintensities between elderly individuals with controlled hypertension and those without hypertension. METHODS: We enrolled 505 community-dwelling, cognitively normal elderly individuals from the participants of the Korean Longitudinal Study on Cognitive Aging and Dementia. We measured blood pressure three times in a sitting position using a mercury sphygmomanometer and defined low systolic and diastolic blood pressure as ≤110 and ≤60 mm Hg, respectively. We segmented and quantified the periventricular and deep white matter hyperintensities from 3.0 Tesla fluid-attenuated inversion recovery magnetic resonance images. RESULTS: Low systolic blood pressure was independently associated with larger volume of periventricular white matter hyperintensity (P=0.049). The interaction between low systolic blood pressure and hypertension was observed on the volume of periventricular white matter hyperintensity (P=0.005). Low systolic blood pressure was associated with the volume of periventricular white matter hyperintensity in individuals with controlled hypertension (F1,248=6.750, P=0.010), but not in those without hypertension (P=0.380). Low diastolic blood pressure was not associated with the volumes of white matter hyperintensities regardless of presence of controlled hypertension. CONCLUSIONS: Low systolic blood pressure seems to be associated with larger volume of periventricular white matter hyperintensity in the individuals with a historyof hypertension but not in those without hypertension.