Predictors of Continuous Positive Airway Pressure Adherence and Comparison of Clinical Factors and Polysomnography Findings Between Compliant and Non-Compliant Korean Adults With Obstructive Sleep Apnea.

OBJECTIVE: Continuous positive airway pressure (CPAP) is the preferred treatment for obstructive sleep apnea (OSA). However, compliance with CPAP therapy varies among studies, and studies on its predictors are insufficient in Korea. This study aimed to identify factors that predict compliance with CPAP therapy in patients with OSA. METHODS: We retrospectively reviewed medical records, polysomnography (PSG) records, and self-report questionnaires of patients w ith OSA. Criteria for compliance was the use of CPAP devices for ≥4 h per night for ≥70% of the consecutive 30 nights (i.e., 21 days) during the first 3 months of treatment initiation. The patients were classified into two groups: compliant and non-compliant. Logistic regression analyses were performed to identify the clinical factors and PSG parameters associated with CPAP compliance. RESULTS: Of the 188 participants, 80 were classified into the compliant group and 108 into the non-compliant group. The ratios of stage N1 (p=0.011) and health insurance coverage (p=0.007) were significantly associated with compliance with CPAP, with an explanatory power of 18.6% (R2=0.186, p<0.001). CONCLUSION: Stage N1 ratio and health insurance coverage were significant predictors of CPAP compliance. It is necessary to confirm whether the relationship between a high stage N1 ratio and compliance can be reproduced in a larger sample and in individuals from other countries.

Effects of the APOEɛ4 Allele on the Relationship Between Tau and Amyloid-ß in Early- and Late-Onset Alzheimer's Disease.

BACKGROUND: Little is known regarding the differential effects of the apolipoprotein E (APOE) ɛ4 on the regional topography of amyloid and tau in patients with both early-onset (EOAD) and late-onset Alzheimer's disease (LOAD). OBJECTIVE: To compare the distribution and association of tau, amyloid, and cortical thickness among groups classified by the presence of APOEɛ4 allele and onset age. METHODS: A total of 165 participants including 54 EOAD patients (29 ɛ4-; 25 ɛ4+), 45 LOAD patients (21 ɛ4-; 24 ɛ4+), and 66 age-matched controls underwent 3T MRI, 18F-THK5351 (THK) and 18F-flutemetamol (FLUTE) PET scans, APOE genotyping, and neuropsychological tests. Data for voxel-wise and standardized uptake values from PET scans were analyzed in the context of APOE and age at onset. RESULTS: EOAD ɛ4- patients showed greater THK retention in the association cortices, whereas their EOAD ɛ4+ counterparts had more retention in medial temporal areas. THK topography of LOAD ɛ4+ was similar to EOAD ɛ4 + . THK correlated positively with FLUTE and conversely with mean cortical thickness, being lowest in EOAD ɛ4-, highest in LOAD ɛ4-, and modest in ɛ4+ groups. Even in the APOEɛ4+ groups, THK tended to correlate with FLUTE and mean cortical thickness in the inferior parietal region in EOAD and in the medial temporal region in LOAD. LOAD ɛ4- manifested with prevalent small vessel disease markers and the lowest correlation between THK retention and cognition. CONCLUSION: Our observations suggest the differential effects of the APOEɛ4 on the relationship between tau and amyloid in EOAD and LOAD.

Significant association between increased risk of emergency department visits for psychiatric disorders and air pollutants in South Korea.

BACKGROUND: The association between air pollutants and psychiatric disorders has been investigated in many countries. However, results for the association between air pollutants and emergency room (ER) visits for psychiatric disorders are inconsistent. Further, systematic large-scale studies relating to the same are lacking, especially in South Korea. OBJECTIVE: We aimed to investigate the acute and short-term cumulative effect of air pollutants on ER visits for psychiatric disorders in South Korea. METHODS: The data on nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) and ER visits due to nine representative psychiatric disorders were collected from eight major cities in South Korea for three years. We estimated the relative risk (RR) at lag 0 and a cumulative 11-day RR by increasing a 10-unit for PM and 0.01-unit for NO2 using the Distributed Lag Nonlinear Model. RESULTS: During the study period, a total of 79,092 ER visits for psychiatric disorders were identified and tested for association with NO2, PM2.5, and PM10. The RR at lag 0 of depression per 0.01-unit increase in NO2 was the highest (3.127; 95% confidence interval [CI] 2.933 to 3.332) among the psychiatric disorders. The RRs at lag 0 of anxiety disorders per 10-unit increase in PM2.5 (1.709; 95% CI 1.424 to 2.053) and PM10 (2.168; 95% CI 1.957 to 2.403) were the highest among the psychiatric disorders. SIGNIFICANCE: Air pollutants increased ER visits for psychiatric disorders with the highest RR of depression due to NO2 and anxiety disorder due to PM2.5 and PM10. These results contribute evidence to the positive association between ambient exposure to air pollution and aggravation of psychiatric disorders, indicating air pollution may be a modifiable risk factor in mental health management. IMPACT STATEMENT: We investigated the effect of air pollution on emergency room visits caused by major psychiatric disorders in prominent cities in South Korea. Using the Distributed Lag Nonlinear Model, an advanced analysis method, we calculated the acute effect and short-term cumulative effect. Air pollutants increased ER visits for psychiatric disorders with the highest relative risk of depression due to NO2 and anxiety disorder due to PM2.5 and PM10. These results reveal an association between ambient exposure to air pollution and aggravation of psychiatric disorders and suggest that air pollution may be a modifiable risk factor in mental health management.

Mood and Sleep Status and Mental Disorders During Prolonged Winter-Over Residence in Two Korean Antarctic Stations.

Purpose: Antarctica is a region with extreme climate, characterized by extreme cold and photoperiod. No research has been conducted on the mental health of Korean Antarctic dispatchers. The aim of this study was to investigate the status of mental illness and changes in mood and sleep among Korean crew members staying for a long-term period in the Antarctic station. Methods: From 2017 to 2020, crew members who were dispatched from South Korea to two Antarctic stations for a one-year period participated in this study. The crew were evaluated for mood and sleep status and mental illness through psychological tests and interviews by board-certified psychiatrists once before departure and twice during their stay in Antarctica. The incidence of mental illness was confirmed and changes in sleep and depression were analyzed. Results: A total of 88 participants were included in the final analysis, and 7 of them (8.0%) were diagnosed with mental disorders such as insomnia in early winter. The total Beck Depression Inventory (BDI) score increased significantly in the early winter period, and the total Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Inventory (PSQI) scores increased in both early and late winter. The difference in changes in mood and sleep symptoms before, during, and after dispatch between the two stations was not significant. Conclusion: This is the first study to investigate the mental illness and mood and sleep status of Korean crews dispatched to Antarctica. In early winter, there were significant increases in mental illness and depressive symptoms, and a worsening of sleep status.

[18F]THK-5351 PET Patterns in Patients With Alzheimer's Disease and Negative Amyloid PET Findings.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) does not always mean amyloid positivity. [18F]THK-5351 has been shown to be able to detect reactive astrogliosis as well as tau accompanied by neurodegenerative changes. We evaluated the [18F]THK-5351 retention patterns in positron-emission tomography (PET) and the clinical characteristics of patients clinically diagnosed with AD dementia who had negative amyloid PET findings. METHODS: We performed 3.0-T magnetic resonance imaging, [18F]THK-5351 PET, and amyloid PET in 164 patients with AD dementia. Amyloid PET was visually scored as positive or negative. [18F]THK-5351 PET were visually classified as having an intratemporal or extratemporal spread pattern. RESULTS: The 164 patients included 23 (14.0%) who were amyloid-negative (age 74.9±8.3 years, mean±standard deviation; 9 males, 14 females). Amyloid-negative patients were older, had a higher prevalence of diabetes mellitus, and had better visuospatial and memory functions. The frequency of the apolipoprotein E ε4 allele was higher and the hippocampal volume was smaller in amyloid-positive patients. [18F]THK-5351 uptake patterns of the amyloid-negative patients were classified into intratemporal spread (n=10) and extratemporal spread (n=13). Neuropsychological test results did not differ significantly between these two groups. The standardized uptake value ratio of [18F]THK-5351 was higher in the extratemporal spread group (2.01±0.26 vs. 1.61±0.15, p=0.001). After 1 year, Mini Mental State Examination (MMSE) scores decreased significantly in the extratemporal spread group (-3.5±3.2, p=0.006) but not in the intratemporal spread group (-0.5±2.8, p=0.916). The diagnosis remained as AD (n=5, 50%) or changed to other diagnoses (n=5, 50%) in the intratemporal group, whereas it remained as AD (n=8, 61.5%) or changed to frontotemporal dementia (n=4, 30.8%) and other diagnoses (n=1, 7.7%) in the extratemporal spread group. CONCLUSIONS: Approximately 70% of the patients with amyloid-negative AD showed abnormal [18F]THK-5351 retention. MMSE scores deteriorated rapidly in the patients with an extratemporal spread pattern.

Association Between Subjective-Objective Discrepancy of Sleeping Time and Health-Related Quality of Life: A Community-Based Polysomnographic Study.

OBJECTIVE: This study aimed to investigate the existence of a difference in quality of life (QOL) between individuals with and without significant subjective-objective discrepancy (SOD) in total sleep time (TST). METHODS: From the Sleep Heart Health Study 2, 2540 individuals who had completed polysomnography, a morning sleep survey, and the 36-item Short-Form Health Survey (SF-36) were included in the analyses. The participants were classified as normoestimators (estimation of TST <±60 minutes), underestimators (underestimation of TST ≥60 minutes), or overestimators (overestimation of TST ≥60 minutes). The standardized SF-36 QOL scores were compared among the three groups. An adjusted partial correlation analysis was conducted between SOD and QOL. RESULTS: Of the 2540 participants, 1617 (63.7%), 433 (17.0%), and 490 (19.3%) were assigned to the normoestimator, underestimator, and overestimator groups, respectively. The bodily pain and social functioning components of the SF-36 score were significantly lower in the underestimators than in the normoestimators, whereas the physical functioning component was significantly lower in the overestimators than in the normoestimators. The absolute value of SOD in the TST showed a significant negative correlation with the physical and mental components of the SF-36. CONCLUSIONS: QOL was significantly better in the normoestimator than in the other groups and linearly correlated with the absolute value of SOD. This study suggests that a high prevalence of positive and negative sleep misperception in a community population can be a potential factor associated with poor QOL and potential comorbidities.

Difference in spectral power density of sleep electroencephalography between individuals without insomnia and frequent hypnotic users with insomnia complaints.

Previous spectral analysis studies on insomnia have shown inconsistent results due to their heterogeneity and small sample sizes. We compared the difference of electroencephalogram (EEG) spectral power during sleep among participants without insomnia, insomniacs with no hypnotic use, hypnotic users with no insomnia complaints, and hypnotic users with insomnia complaints using the Sleep Heart Health Study data, which is large sample size and has good quality control. The fast Fourier transformation was used to calculate the EEG power spectrum for total sleep duration within contiguous 30-s epochs of sleep. For 1985 participants, EEG spectral power was compared among the groups while adjusting for potential confounding factors that could affect sleep EEG. The power spectra during total sleep differed significantly among the groups in all frequency bands (pcorr < 0.001). We found that quantitative EEG spectral power in the beta and sigma bands of total sleep differed (pcorr < 0.001) between participants without insomnia and hypnotic users with insomnia complaints after controlling for potential confounders. The higher beta and sigma power were found in the hypnotic users with insomnia complaints than in the non-insomnia participants. This study suggests differences in the microstructures of polysomnography-derived sleep EEG between the two groups.

Genome-wide association study of occupational attainment as a proxy for cognitive reserve.

Occupational attainment, which represents middle-age cognitive activities, is a known proxy marker of cognitive reserve for Alzheimer's disease. Previous genome-wide association studies have identified numerous genetic variants and revealed the genetic architecture of educational attainment, another marker of cognitive reserve. However, the genetic architecture and heritability for occupational attainment remain elusive. We performed a large-scale genome-wide association study of occupational attainment with 248 847 European individuals from the UK Biobank using the proportional odds logistic mixed model method. In this analysis, we defined occupational attainment using the classified job levels formulated in the UK Standard Occupational Classification system considering the individual professional skill and academic level. We identified 30 significant loci (P < 5 × 10-8); 12 were novel variants, not associated with other traits. Among them, four lead variants were associated with genes expressed in brain tissues by expression quantitative trait loci mapping from 10 brain regions: rs13002946, rs3741368, rs11654986 and rs1627527. The single nucleotide polymorphism-based heritability was estimated to be 8.5% (standard error of the mean = 0.004) and partitioned heritability was enriched in the CNS and brain tissues. Genetic correlation analysis showed shared genetic backgrounds between occupational attainment and multiple traits, including education, intelligence, leisure activities, life satisfaction and neuropsychiatric disorders. In two-sample Mendelian randomization analysis, we demonstrated that high occupation levels were associated with reduced risk for Alzheimer's disease [odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.65-0.92 in inverse variance weighted method; OR = 0.73, 95% CI = 0.57-0.92 in the weighted median method]. This causal relationship between occupational attainment and Alzheimer's disease was robust in additional sensitivity analysis that excluded potentially pleiotropic single nucleotide polymorphisms (OR = 0.72, 95% CI = 0.57-0.91 in the inverse variance weighted method; OR = 0.72, 95% CI = 0.53-0.97 in the weighted median method). Multivariable Mendelian randomization confirmed that occupational attainment had an independent effect on the risk for Alzheimer's disease even after taking educational attainment into account (OR = 0.72, 95% CI = 0.54-0.95 in the inverse variance weighted method; OR = 0.68, 95% CI = 0.48-0.97 in the weighted median method). Overall, our analyses provide insights into the genetic architecture of occupational attainment and demonstrate that occupational attainment is a potential causal protective factor for Alzheimer's disease as a proxy marker of cognitive reserve.

Effects of Virtual Reality-Based Cognitive Training in the Elderly with and without Mild Cognitive Impairment.

OBJECTIVE: This study aimed to introduce a 4-week long fully immersive virtual reality-based cognitive training (VRCT) program that could be applied for both a cognitively normal elderly population and patients with mild cognitive impairment (MCI). In addition, we attempted to investigate the neuropsychological effects of the VRCT program in each group. METHODS: A total of 56 participants, 31 in the MCI group and 25 in the cognitively normal elderly group, underwent eight sessions of VRCT for 4 weeks. In order to evaluate the effects of the VRCT, the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet was administered before and after the program. The program' s safety was assessed using a simulator sickness questionnaire (SSQ), and availability was assessed using the presence questionnaire. RESULTS: After the eighth session of the VRCT program, cognitive improvement was observed in the ability to learn new information, visuospatial constructional ability, and frontal lobe function in both groups. At the baseline evaluation, based on the SSQ, the MCI group complained of disorientation and nausea significantly more than the cognitively normal elderly group did. However, both groups showed a reduction in discomfort as the VRCT program progressed. CONCLUSION: We conclude that our VRCT program helps improve cognition in both the MCI group and cognitively normal elderly group. Therefore, the VRCT is expected to help improve cognitive function in elderly populations with and without MCI.

Relationship between the Spectral Power Density of Sleep Electroencephalography and Psychiatric Symptoms in Patients with Breathing-related Sleep Disorder.

OBJECTIVE: Patients with breathing-related sleep disorder (BRSD) often complain of psychiatric symptoms such as depression in addition to snoring, excessive sleepiness, and disturbed sleep. However, the relationship between psychiatric symptoms and severity of sleep apnea in BRSD is controversial. We conducted this study to investigate the relationship between psychiatric symptoms and sleep electroencephalography (EEG) findings in BRSD patients using spectral analysis. METHODS: All participants underwent polysomnography and evaluation using Symptom Checklist-90-Revised (SCL-90-R) scale. We analyzed the absolute spectral power density values of standard EEG frequency bands in the participants (n = 169) with BRSD during the non-rapid eye movement (NREM) sleep period. We performed correlation analysis between the domain scores of SCL-90-R scale and the absolute values of the EEG frequency bands. RESULTS: Significant positive correlation was observed between the absolute spectral power density values in the slow oscillation band and the degree of paranoid ideation (r = 0.226, p = 0.028) and depression (r = 0.216, p = 0.044) in SCL-90-R. The multiple linear regression model showed that higher paranoid ideation domain score (B = 0.007, p = 0.020), younger age (B = -0.011, p < 0.001), and female sex (B = 0.213, p = 0.004) were associated with higher slow oscillation power during NREM sleep. CONCLUSION: The results of the present study suggested a relationship between sleep EEG and psychiatric symptoms in patients with BRSD. This relationship needs to be validated with further studies.

Effect of Cognitive Training in Fully Immersive Virtual Reality on Visuospatial Function and Frontal-Occipital Functional Connectivity in Predementia: Randomized Controlled Trial.

BACKGROUND: Cognitive training can potentially prevent cognitive decline. However, the results of recent studies using semi-immersive virtual reality (VR)-assisted cognitive training are inconsistent. OBJECTIVE: We aimed to examine the hypothesis that cognitive training using fully immersive VR, which may facilitate visuospatial processes, could improve visuospatial functioning, comprehensive neuropsychological functioning, psychiatric symptoms, and functional connectivity in the visual brain network in predementia. METHODS: Participants over 60 years old with subjective cognitive decline or mild cognitive impairment from a memory clinic were randomly allocated to the VR (n=23) or the control (n=18) group. The VR group participants received multidomain and neuropsychologist-assisted cognitive training in a fully immersive VR environment twice a week for 1 month. The control group participants did not undergo any additional intervention except for their usual therapy such as pharmacotherapy. Participants of both groups were evaluated for cognitive function using face-to-face comprehensive neuropsychological tests, including the Rey-Osterrieth Complex Figure Test (RCFT) copy task; for psychiatric symptoms such as depression, apathy, affect, and quality of life; as well as resting-state functional magnetic resonance imaging (rsfMRI) at baseline and after training. Repeated-measures analysis of variance was used to compare the effect of cognitive training between groups. Seed-to-voxel-based analyses were used to identify the cognitive improvement-related functional connectivity in the visual network of the brain. RESULTS: After VR cognitive training, significant improvement was found in the total score (F1,39=14.69, P=.001) and basic components score of the RCFT copy task (F1,39=9.27, P=.005) compared with those of the control group. The VR group also showed improvements, albeit not significant, in naming ability (F1,39=3.55, P=.07), verbal memory delayed recall (F1,39=3.03, P=.09), and phonemic fluency (F1,39=3.08, P=.09). Improvements in psychiatric symptoms such as apathy (F1,39=7.02, P=.01), affect (F1,39=14.40, P=.001 for positive affect; F1,39=4.23, P=.047 for negative affect), and quality of life (F1,39=4.49, P=.04) were found in the VR group compared to the control group. Improvement in the RCFT copy task was associated with a frontal-occipital functional connectivity increase revealed by rsfMRI in the VR group compared to the control group. CONCLUSIONS: Fully immersive VR cognitive training had positive effects on the visuospatial function, apathy, affect, quality of life, and increased frontal-occipital functional connectivity in older people in a predementia state. Future trials using VR cognitive training with larger sample sizes and more sophisticated designs over a longer duration may reveal greater improvements in cognition, psychiatric symptoms, and brain functional connectivity. TRIAL REGISTRATION: Clinical Research Information Service KCT0005243; https://tinyurl.com/2a4kfasa.

Cognitive reserve and the effects of virtual reality-based cognitive training on elderly individuals with mild cognitive impairment and normal cognition.

BACKGROUND: Cognitive reserve (CR) is a concept proposed to account for discrepancies between the extent of brain pathology and clinical manifestations of that pathology. This study aimed to explore the associations between CR and the effects of cognitive training using fully immersive virtual reality (VR). METHODS: A total of 44 older adults (22 cognitively normal, 22 with mild cognitive impairment) underwent eight cognitive training sessions using VR for a period of 4 weeks. CR was assessed using the Cognitive Reserve Index questionnaire (CRIq). To evaluate baseline cognitive function and the effects of VR training, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery was administered to all participants before and after the training. RESULTS: Greater improvement in the total CERAD score was seen for cognitively normal participants with higher versus lower scores on the Education subdomain of the CRIq. Among patients with mild cognitive impairment, none of the CRIq subdomain scores (Education, Working Activity, Leisure Time) were related to a change in CERAD total scores. The CRIq total score did not predict the improvement of global cognition in either group. CONCLUSIONS: This study revealed different impacts of CR on cognitive training according to the participants' cognitive status. It also suggests that employing three proxies of CR rather than using a composite score would provide a more accurate understanding of one's CR.

Spectral Power Analysis of Sleep Electroencephalography in Subjects with Different Severities of Obstructive Sleep Apnea and Healthy Controls.

PURPOSE: Previous spectral analysis studies on obstructive sleep apnea (OSA) involved small samples, and the results were inconsistent. We performed a spectral analysis of sleep EEG based on different severities of OSA using the Sleep Heart Health Study data. This study aimed to determine the difference in EEG spectral power during sleep in the non-OSA group and with different severities of OSA in the general population. PATIENTS AND METHODS: The participants (n = 5,804) underwent polysomnography, and they were classified into non-OSA, mild OSA, moderate OSA, and severe OSA groups. The fast Fourier transformation was used to compute the EEG power spectrum for total sleep duration within contiguous 30-second epochs of sleep. The EEG spectral powers of the groups were compared using 4,493 participants after adjusting potential confounding factors that could affect sleep EEG. RESULTS: The power spectra differed significantly among the groups for all frequency bands (p corr < 0.001). We found that the quantitative EEG spectral powers in the beta and sigma bands of total sleep differed (p corr < 0.001) among the participants in the non-OSA group and with different severities of OSA, controlling for covariates. The beta power was higher and the sigma power was lower in the OSA groups than in the non-OSA group. The beta power decreased in the order of severe OSA, moderate OSA, mild OSA, and non-OSA. CONCLUSION: This study suggests that there are differences between the microstructures of PSG-derived sleep EEG of non-OSA participants and those with different severities of OSA.

Prevalence of DSM-5 mixed features: A meta-analysis and systematic review.

BACKGROUND: The definition of mixed features by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) remains controversal; however, there has been no systematic review of the prevalence of DSM-5 mixed features. We conducted a meta-analysis and systematic review to examine the prevalence of DSM-5-defined mixed features in major depressive episodes (MDE) and manic/hypomanic episodes. METHODS: We systematically searched all literature types (i.e., observational, cross-sectional, cohort, retrospective chart review, and post-hoc analysis) in electronic databases including MEDLINE, Embase, CINAHL, PsycINFO, and Web of Science from 2013 to 2020. RESULTS: A total of 17 studies with 20 samples were selected. The pooled prevalences of the mixed features in MDE and manic/hypomanic episodes were 11.6% (95% confidence interval [CI] = 7.9-16.7%) and 26.8 (95% CI = 17.0-39.5%), respectively. The prevalence of mixed features during major depressive disorder in East Asian countries was the lowest, which ranged from 0-2.2%. The subgroup analysis did not identify any influential factors for substantial heterogeneity. Most of the individual studies demonstrated moderate to high risk of bias. CONCLUSIONS: Despite the increasing attention and controversy surrounding DSM-5-defined mixed features, few studies have systematically estimated the prevalence. Future studies with appropriate design and sample sizes should measure the prevalence of mixed features during MDE and manic/hypomanic episodes.

Association of Subcortical Structural Shapes With Tau, Amyloid, and Cortical Atrophy in Early-Onset and Late-Onset Alzheimer's Disease.

The objectives of this study were to compare the topographical subcortical shape and to investigate the effects of tau or amyloid burden on atrophic patterns in early onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). One hundred and sixty-one participants (53 EOAD, 44 LOAD, 33 young controls, and 31 older controls) underwent [18F]THK5351 positron emission tomography (PET), [18F]flutemetamol (FLUTE) PET, and 3T MRI scans. We used surface-based analysis to evaluate subcortical structural shape, permutation-based statistics for group comparisons, and Spearman's correlations to determine associations with THK, FLUTE, cortical thickness, and neuropsychological test results. When compared to their age-matched controls, EOAD patients exhibited shape reduction in the bilateral amygdala, hippocampus, caudate, and putamen, while in LOAD patients, the bilateral amygdala and hippocampus showed decreased shapes. In EOAD, widespread subcortical shrinkage, with less association of the hippocampus, correlated with THK retention and cortical thinning, while in LOAD patients, subcortical structures were limited which had significant correlation with THK or mean cortical thickness. Subcortical structural shape showed less correlation with FLUTE global retention in both EOAD and LOAD. Multiple cognitive domains, except memory function, correlated with the bilateral amygdala, caudate, and putamen in EOAD patients, while more restricted regions in the subcortical structures were correlated with neuropsychological test results in LOAD patients. Subcortical structures were associated with AD hallmarks in EOAD. However, the correlation was limited in LOAD. Moreover, relationship between subcortical structural atrophy and cognitive decline were quite different between EOAD and LOAD. These findings suggest that the effects of Alzheimer's pathologies on subcortical structural changes in EOAD and LOAD and they may have different courses of pathomechanism.

Cognitive Reserve, Leisure Activity, and Neuropsychological Profile in the Early Stage of Cognitive Decline.

In older adults with normal cognition, cognitive reserve (CR) is known to be associated with the neuropsychological profile. We investigated the association between comprehensive CR and detailed neuropsychological profile in the early stage of cognitive decline. Fifty-five participants with mild cognitive impairment or subjective cognitive decline completed the cognitive reserve index questionnaire (CRIq) that yielded total, education, working activity, and leisure time scores (CRI-Total, CRI-Education, CRI-Working activity, and CRI-Leisure time, respectively). Mini-mental state examination (MMSE) and detailed neuropsychological evaluation were performed. Psychiatric symptom scales were applied to measure depression, apathy, positive or negative affect, and quality of life. Correlation and linear regression analyses of the variables were performed. The effect of CR-Education, CRI-Working activity, and CRI-Leisure time on the composite cognitive score was determined using a multivariable regression model. We observed that for CRI-Total (B = 3.00, p = 0.005), CRI-Education (B = 3.39, p = 0.002), and CRI-Leisure time (B = 2.56, p = 0.015), CR correlated with MMSE scores, while only CRI-Leisure time associated with the naming ability (B = 2.20, p = 0.033) in the detailed neuropsychological test results of the participants. Multivariable regression model also indicated that among CRI subscores, CRI-Leisure time directly affects the composite cognitive score (ß = 0.32, p = 0.011). We found that in the early stage of cognitive decline in older adults, comprehensive CR was associated with global cognition, and only leisure activity was identified to be associated with the detailed neuropsychological profile including naming ability. These results may imply the positive effect of leisure activity on cognitive function in the early stages of cognitive decline.

Associations between vascular risk factors and subsequent Alzheimer's disease in older adults.

BACKGROUND: The clinical guidelines related to the primary prevention of Alzheimer's disease (AD) have focused on the management of vascular risk factors. However, the link between vascular risk factors and AD in older adults remains unclear. This study aimed to determine the association between vascular risk factors and subsequent AD in 178,586 older adults (age ≥ 65 years). METHODS: Participants were recruited from 2009 through 2010 and followed up for 6 years. We assessed various vascular risk factors (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], fasting glucose [FG], systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], and body mass index [BMI]) and their association with AD incidence, categorizing each vascular factor using current clinical guidelines. RESULTS: AD was observed in 6.0% of participants at follow-up. All lipid profiles (TC, LDL-C, HDL-C and TG) were positively associated with the risk of AD. SBP and PP were in negative associations with AD, and DBP was positively associated with AD. BMI exhibited a negative association with AD incidence. We found no significant association between FG and AD risk. The sex difference was observed to have effects on vascular risk factors. CONCLUSIONS: In this study, we comprehensively investigated the association between eight vascular risk factors and the risk of incident AD. Our findings suggest that multiple vascular risk factors are related to the development of AD in older adults. These results can help inform future guidelines for reducing AD risk.

Subjective cognitive decline and subsequent dementia: a nationwide cohort study of 579,710 people aged 66 years in South Korea.

BACKGROUND: Subjective cognitive decline (SCD) is a potential risk factor for dementia. We aimed to investigate the association between SCD and subsequent dementia in a nationwide population-based cohort in South Korea. METHODS: This cohort included 579,710 66-year-old adults who were followed for a total of 3,870,293 person-years (average 6.68 ± 1.33 years per person). All subjects completed a questionnaire about subjective memory impairment, the Pre-screening Korean Dementia Screening Questionnaire (KDSQ-P), which included a validated 5-item derivative, and were determined to have SCD based on a single question assessing memory decline. Depressive symptoms were assessed in all subjects using a 3-item modified geriatric depression scale. Hazard ratios were estimated using the Cox proportional hazards model and compared between subjects with and without SCD. RESULTS: Compared to subjects without SCD, those with SCD were more likely to develop dementia (incidence per 1000 person-years: non-SCD, 5.66; SCD, 8.59). After adjusting for potential confounding factors, the risk of subsequent dementia significantly increased in subjects with SCD, with an adjusted hazard ratio (aHR) of 1.38 (95% confidence interval [CI] 1.34 to 1.41). The risk of subsequent dementia was greatly increased in subjects with higher KDSQ-P scores (aHR = 2.77, 95% CI 2.35 to 3.27). A significant association between SCD and dementia was observed in both depressive and non-depressive symptom groups (aHR = 1.50, 95% CI 1.42 to 1.57 in subjects with depressive symptoms; aHR = 1.33, 95% CI 1.29 to 1.37 in subjects without depressive symptoms; P = 0.001). CONCLUSIONS: In this population of 66-year-old individuals, SCD was significantly associated with an increased risk of subsequent dementia. This association was found in both depressive and non-depressive groups, with an increased risk of dementia in the presence of depressive symptoms. Our findings suggest that SCD indicates a risk for dementia. Further studies are needed to delineate potential approaches to preventing the development of dementia in individuals with SCD.

[¹8F]THK5351 PET Imaging in Patients with Mild Cognitive Impairment.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is a condition with diverse clinical outcomes and subgroups. Here we investigated the topographic distribution of tau in vivo using the positron emission tomography (PET) tracer [¹8F]THK5351 in MCI subgroups. METHODS: This study included 96 participants comprising 38 with amnestic MCI (aMCI), 21 with nonamnestic MCI (naMCI), and 37 with normal cognition (NC) who underwent 3.0-T MRI, [¹8F]THK5351 PET, and detailed neuropsychological tests. [¹8F]flutemetamol PET was also performed in 62 participants. The aMCI patients were further divided into three groups: 1) verbal-aMCI, only verbal memory impairment; 2) visual-aMCI, only visual memory impairment; and 3) both-aMCI, both visual and verbal memory impairment. Voxel-wise statistical analysis and region-of-interest -based analyses were performed to evaluate the retention of [¹8F]THK5351 in the MCI subgroups. Subgroup analysis of amyloid-positive and -negative MCI patients was also performed. Correlations between [¹8F]THK5351 retention and different neuropsychological tests were evaluated using statistical parametric mapping analyses. RESULTS: [¹8F]THK5351 retention in the lateral temporal, mesial temporal, parietal, frontal, posterior cingulate cortices and precuneus was significantly greater in aMCI patients than in NC subjects, whereas it did not differ significantly between naMCI and NC participants. [¹8F] THK5351 retention was greater in the both-aMCI group than in the verbal-aMCI and visualaMCI groups, and greater in amyloid-positive than amyloid-negative MCI patients. The cognitive function scores were significantly correlated with cortical [¹8F]THK5351 retention. CONCLUSIONS: [¹8F]THK5351 PET might be useful for identifying distinct topographic patterns of [¹8F]THK5351 retention in subgroups of MCI patients who are at greater risk of the progression to Alzheimer's dementia.

Difference in spectral power density of sleep EEG between patients with simple snoring and those with obstructive sleep apnoea.

Patients with simple snoring (SS) often complain of poor sleep quality despite a normal apnoea-hypopnoea index (AHI). We aimed to identify the difference in power spectral density of electroencephalography (EEG) between patients with SS and those with obstructive sleep apnoea (OSA). We compared the absolute power spectral density values of standard EEG frequency bands between the SS (n = 42) and OSA (n = 129) groups during the non-rapid eye movement (NREM) sleep period, after controlling for age and sex. We also analysed partial correlation between AHI and the absolute values of the EEG frequency bands. The absolute power spectral density values in the beta and delta bands were higher in the OSA group than in the SS group. AHI also positively correlated with beta power in the OSA group as well as in the combined group (OSA + SS). In conclusion, higher delta and beta power during NREM sleep were found in the OSA group than in the SS group, and beta power was correlated with AHI. These findings are microstructural characteristics of sleep-related breathing disorders.