A multimodal machine learning model for predicting dementia conversion in Alzheimer's disease.

Alzheimer's disease (AD) accounts for 60-70% of the population with dementia. Mild cognitive impairment (MCI) is a diagnostic entity defined as an intermediate stage between subjective cognitive decline and dementia, and about 10-15% of people annually convert to AD. We aimed to investigate the most robust model and modality combination by combining multi-modality image features based on demographic characteristics in six machine learning models. A total of 196 subjects were enrolled from four hospitals and the Alzheimer's Disease Neuroimaging Initiative dataset. During the four-year follow-up period, 47 (24%) patients progressed from MCI to AD. Volumes of the regions of interest, white matter hyperintensity, and regional Standardized Uptake Value Ratio (SUVR) were analyzed using T1, T2-weighted-Fluid-Attenuated Inversion Recovery (T2-FLAIR) MRIs, and amyloid PET (αPET), along with automatically provided hippocampal occupancy scores (HOC) and Fazekas scales. As a result of testing the robustness of the model, the GBM model was the most stable, and in modality combination, model performance was further improved in the absence of T2-FLAIR image features. Our study predicts the probability of AD conversion in MCI patients, which is expected to be useful information for clinician's early diagnosis and treatment plan design.

Impact of Apolipoprotein E4 on the Locus Coeruleus Functional Connectivity in Preclinical Alzheimer's Disease.

Background: Recent interest has surged in the locus coeruleus (LC) for its early involvement in Alzheimer's disease (AD), notably concerning the apolipoprotein ɛ4 allele (APOE4). Objective: This study aimed to discern LC functional connectivity (FC) variations in preclinical AD subjects, dissecting the roles of APOE4 carrier status and amyloid-ß (Aß) deposition. Methods: A cohort of 112 cognitively intact individuals, all Aß-positive, split into 70 APOE4 noncarriers and 42 carriers, underwent functional MRI scans, neuropsychological assessments, and APOE genotyping. The research utilized seed to voxel analysis for illustrating LC rsFC discrepancies between APOE4 statuses and employed a general linear model to examine the interactive influence of APOE4 carrier status and Aß deposition on LC FC values. Results: The investigation revealed no significant differences in sex, age, or SUVR between APOE4 carriers and noncarriers. It found diminished LC FC with the occipital cortex in APOE4 carriers and identified a significant interaction between APOE4 carrier status and temporal lobe SUVR in LC FC with the occipital cortex. This interaction suggested a proportional increase in LC FC for APOE4 carriers. Additional notable interactions were observed affecting LC FC with various brain regions, indicating a proportional decrease in LC FC for APOE4 carriers. Conclusions: These findings confirm that APOE4 carrier status significantly influences LC FC in preclinical AD, showcasing an intricate relationship with regional Aß deposition. This underscores the critical role of genetic and pathological factors in early AD pathophysiology, offering insights into potential biomarkers for early detection and intervention strategies.

Increased Likelihood of Dementia with Coexisting Atrophy of Multiple Regions of Interest.

BACKGROUND: Brain volume is associated with cognitive decline in later life, and cortical brain atrophy exceeding the normal range is related to inferior cognitive and behavioral outcomes in later life. OBJECTIVE: To investigate the likelihood of cognitive decline, mild cognitive impairment (MCI), or dementia, when regional atrophy is present in participants' magnetic resonance imaging (MRI). METHODS: Multi-center MRI data of 2,545 adults were utilized to measure regional volumes using NEUROPHET AQUA. Four lobes (frontal, parietal, temporal, and occipital), four Alzheimer's disease-related regions (entorhinal, fusiform, inferior temporal, and middle temporal area), and the hippocampus in the left and right hemispheres were measured and analyzed. The presence of regional atrophy from brain MRI was defined as ≤1.5 standard deviation (SD) compared to the age- and sex-matched cognitively normal population. The risk ratio for cognitive decline was investigated for participants with regional atrophy in contrast to those without regional atrophy. RESULTS: The risk ratio for cognitive decline was significantly higher when hippocampal atrophy was present (MCI, 1.84, p < 0.001; dementia, 4.17, p < 0.001). Additionally, participants with joint atrophy in multiple regions showed a higher risk ratio for dementia, e.g., 9.6 risk ratio (95% confidence interval, 8.0-11.5), with atrophy identified in the frontal, temporal, and hippocampal gray matter, than those without atrophy. CONCLUSIONS: Our study showed that individuals with multiple regional atrophy (either lobar or AD-specific regions) have a higher likelihood of developing dementia compared to the age- and sex-matched population without atrophy. Thus, further consideration is needed when assessing MRI findings.

A regional brain volume-based age prediction model for neonates and the derived brain maturation index.

OBJECTIVE: To develop a postmenstrual age (PMA) prediction model based on segmentation volume and to evaluate the brain maturation index using the proposed model. METHODS: Neonatal brain MRIs without clinical illness or structural abnormalities were collected from four datasets from the Developing Human Connectome Project, the Catholic University of Korea, Hammersmith Hospital (HS), and Dankook University Hospital (DU). T1- and T2-weighted images were used to train a brain segmentation model. Another model to predict the PMA of neonates based on segmentation data was developed. Accuracy was assessed using mean absolute error (MAE), root mean square error (RMSE), and mean error (ME). The brain maturation index was calculated as the difference between the PMA predicted by the model and the true PMA, and its correlation with postnatal age was analyzed. RESULTS: A total of 247 neonates (mean gestation age 37 ± 4 weeks; range 24-42 weeks) were included. Thirty-one features were extracted from each neonate and the three most contributing features for PMA prediction were the right lateral ventricle, left caudate, and corpus callosum. The predicted and true PMA were positively correlated (coefficient = 0.88, p < .001). MAE, RMSE, and ME of the external dataset of HS and DU were 1.57 and 1.33, 1.79 and 1.37, and 0.37 and 0.06 weeks, respectively. The brain maturation index negatively correlated with postnatal age (coefficient = - 0.24, p < .001). CONCLUSION: A model that calculates the regional brain volume can predict the PMA of neonates, which can then be utilized to show the brain maturation degree. CLINICAL RELEVANCE STATEMENT: A brain maturity index based on regional volume of neonate's brain can be used to measure brain maturation degree, which can help identify the status of early brain development. KEY POINTS: • Neonatal brain MRI segmentation model could be used to assess neonatal brain maturation status. • A postmenstrual age (PMA) prediction model was developed based on a neonatal brain MRI segmentation model. • The brain maturation index, derived from the PMA prediction model, enabled the estimation of the neonatal brain maturation status.

Sex-Related Disparities in the Resting State Functional Connectivity of the Locus Coeruelus and Salience Network in Preclinical Alzheimer's Disease.

Recent studies have demonstrated the pivotal role of locus coeruleus (LC) and salience network (SN) resting state functional connectivity (rsFC) changes in the early stage of Alzheimer's disease (AD). Moreover, sex has been a crucial point of discussion in understanding AD pathology. We aimed to demonstrate the sex-related disparities in the functional connectivity (FC) of the SN and LC in preclinical AD. A total of 89 cognitively normal patients with evidence of amyloid beta (Aß) accumulation ([18F] flutemetamol +) were recruited in the study. A seed-to-voxel analysis was conducted to measure the LC and SN rsFC differences between sexes. In addition, sex by Aß interactive effects on FC values were analyzed with a general linear model. There were statistically significant sex by regional standardized uptake value ratio (SUVR) interactions in the LC FC with the parietal, frontal, and occipital cortices. Moreover, there was a significant sex by global SUVR interaction in the SN FC with the temporal cortex. The findings suggest that there are differential patterns of LC FC and SN FC in males and females with preclinical AD, which interact with regional Aß deposition.

Modulation of associations between education years and cortical volume in Alzheimer's disease vulnerable brain regions by Aß deposition and APOE ε4 carrier status in cognitively normal older adults.

Background: Education years, as a measure of cognitive reserve, have been shown to affect the progression of Alzheimer's disease (AD), both pathologically and clinically. However, inconsistent results have been reported regarding the association between years of education and intermediate structural changes in AD-vulnerable brain regions, particularly when AD risk factors were not considered during the preclinical phase. Objective: This study aimed to examine how Aß deposition and APOE ε4 carrier status moderate the relationship between years of education and cortical volume in AD-vulnerable regions among cognitively normal older adults. Methods: A total of 121 participants underwent structural MRI, [18F] flutemetamol PET-CT imaging, and neuropsychological battery assessment. Multiple regression analysis was conducted to examine the interaction between years of education and the effects of potential modifiers on cortical volume. The associations between cortical volume and neuropsychological performance were further explored in subgroups categorized based on AD risk factors. Results: The cortical volume of the left lateral occipital cortex and bilateral fusiform gyrus demonstrated a significant differential association with years of education, depending on the presence of Aß deposition and APOE ε4 carrier status. Furthermore, a significant relationship between the cortical volume of the bilateral fusiform gyrus and AD-nonspecific cognitive function was predominantly observed in individuals without AD risk factors. Conclusion: AD risk factors exerted varying influences on the association between years of education and cortical volume during the preclinical phase. Further investigations into the long-term implications of these findings would enhance our understanding of cognitive reserves in the preclinical stages of AD.

Cognitive Normal Older Adults with APOE-2 Allele Show a Distinctive Functional Connectivity Pattern in Response to Cerebral Aß Deposition.

The ε2 allele of apolipoprotein E (ε2) has neuroprotective effects against beta-amyloid (Aß) pathology in Alzheimer's disease (AD). However, its impact on the functional connectivity and hub efficiency in cognitively normal older adults (CN) with ε2 is unclear. We investigated the functional connectivity differences in the default mode network (DMN), salience network, and central executive network (CEN) between A-PET-negative (N = 29) and A-PET-positive (N = 15) CNs with ε2/ε2 or ε2/ε3 genotypes. The A-PET-positive CNs exhibited a lower anterior DMN functional connectivity, higher posterior DMN functional connectivity, and increased CEN functional connectivity compared to the A-PET-negative CNs. Cerebral Aß retention was negatively correlated with anterior DMN functional connectivity and positively correlated with posterior DMN and anterior CEN functional connectivity. A graph theory analysis showed that the A-PET-positive CNs displayed a higher betweenness centrality in the middle frontal gyrus (left) and medial fronto-parietal regions (left). The betweenness centrality in the middle frontal gyrus (left) was positively correlated with Aß retention. Our findings reveal a reversed anterior-posterior dissociation in the DMN functional connectivity and heightened CEN functional connectivity in A-PET-positive CNs with ε2. Hub efficiencies, measured by betweenness centrality, were increased in the DMN and CEN of the A-PET-positive CNs with ε2. These results suggest unique functional connectivity responses to Aß pathology in CN individuals with ε2.

Effect of physical activity on the change in carotid intima-media thickness: An 8-year prospective cohort study.

BACKGROUND AND AIMS: There is a demand for longitudinal studies that use both objective and subjective measures of physical activity to investigate the association of physical activity with the change in carotid intima-media thickness (CIMT). In order to investigate such association, we conducted an 8-year follow-up study that used both objective and subjective measures of physical activity. METHODS: This cohort study used subsamples of the ongoing Korean Genome and Epidemiology Study (KoGES). Included participants were between 49 to 79 years of age at baseline. Exclusion criteria included incomplete assessments of pedometer/accelerometer, international physical activity questionnaire (IPAQ), and baseline CIMT. Participants with a history of cardiovascular diseases were further excluded. Linear regression models were used for the main analysis. Age differences were assessed by stratifying the participants into < 60 years and ≥ 60 years. RESULTS: After removing excluded participants, 835 participants were included in the final analysis (age, 59.84 ± 6.53 years; 326 (39.04%) males). 453 participants were < 60 years and 382 participants were ≥ 60 years. The daily total step count was inversely associated with the percent change in overall CIMT over 8-years (ß = -0.015, standard error = 0.007, P = 0.034). This association was present among participants in the < 60-year-old group (ß = -0.026, standard error = 0.010, P = 0.006), but not among participants in the ≥ 60-year-old group (ß = -0.010, standard error = 0.011, P = 0.38). CONCLUSIONS: The findings suggest that taking preemptive actions of increasing physical activity may prevent the incidence of atherosclerosis.

Earlier chronotype in midlife as a predictor of accelerated brain aging: a population-based longitudinal cohort study.

STUDY OBJECTIVES: Evidence suggests that sleep-wake cycle disruption could be an early manifestation of neurodegeneration and might even be a risk factor for developing diseases in healthy adults. We investigated the impact of circadian phase change on structural and functional brain deterioration in a late-adulthood population. METHODS: We analyzed the data of 1874 participants (mean age 58.6 ± 6.3 years, 50.3% female) from the Korean Genome and Epidemiology Study, who were identified as cognitively unimpaired. The mid-sleep time on free days corrected for sleep debt on workdays (MSFsc) at baseline was adopted as an indicator of the chronotype and used to categorize the participants into three groups. The relationships between the chronotype and longitudinal changes in the gray matter volume (GMV) and cognitive function were investigated (mean interval: 4.2 ± 0.5 years). RESULTS: The mean MSFsc of the participants was 2:45 am. The earlier MSFsc was linearly associated with smaller right entorhinal GMV (ß [SE] = 0.02 [0.01]; p = .001) and lower visual memory function test scores at baseline. Longitudinally, the earlier MSFsc at baseline was only significantly associated with more rapid atrophy in the temporal lobe (ß [SE] = 0.18 [0.07]; p = .018) and not with other brain lobes or subregions. Moreover, the earlier MSFsc was associated with more deteriorated verbal learning and visual memory function test scores. CONCLUSIONS: An earlier chronotype in midlife, measured using a questionnaire, can be a valuable indicator for individuals who should be closely monitored for the development of neurodegenerative disorders.

Fine-grained brain tissue segmentation for brain modeling of stroke patient.

Brain segmentation of stroke patients can facilitate brain modeling for electrical non-invasive brain stimulation, a therapy for stimulating brain function using an electric current. However, it remains challenging owing to its time-consuming, labor-dependent, and complicated pipeline. In addition, conventional tools that define lesions into one region rather than distinguishing between the stroke-affected regions and cerebrospinal fluid can lead to inaccurate treatment results. In this study, we first define a novel stroke-affected region as a detailed sub-region of the conventionally defined lesion. Subsequently, a novel comprehensive framework is proposed to segment head-brain and fine-level stroke-affected regions for normal controls and chronic stroke patients. The proposed framework consists of a time-efficient and precise deep learning-based segmentation model. The experiment results indicate that the proposed method perform better than the conventional deep learning-based segmentation model in terms of the evaluation metrics. The proposed method would be a valuable addition to brain modeling for non-invasive neuromodulation.

Association of long-term hyperglycaemia and insulin resistance with brain atrophy and cognitive decline: A longitudinal cohort study.

AIM: To investigate the longitudinal changes in brain volume and cognitive function associated with diabetes at midlife, and to examine whether long-term hyperglycaemia, insulin resistance or secretory function is associated with brain atrophy and cognitive decline. MATERIALS AND METHODS: We used data from 2377 participants with both baseline and 4-year follow-up brain magnetic resonance images and neuropsychological measures from the Ansan cohort of the Korean Genome Epidemiology Study. Time-weighted mean glycaemic values were calculated using all measurements over an average duration of 10.6 years from cohort initiation to baseline visits. RESULTS: Type 2 diabetes was associated with greater white matter volume reduction (adjusted volume difference = -1.96 ml, 95% CI: -3.73, -0.18) and executive function decline (adjusted Z score difference = -0.14, 95% CI: -0.23, -0.05) during the follow-up period of 4.2 years. Decline of verbal and visual memory or verbal fluency was not associated with diabetes. Greater executive function decline was associated with higher time-weighted mean HbA1c level over the preceding 10.6 years (P < .001), but not with insulin resistance markers in the diabetes group. Participants with diabetes, whose time-weighted average HbA1c level was maintained above 6.5% over the previous decade, showed greater decline in executive function and global cognition than the normal glucose group. CONCLUSIONS: Long-term hyperglycaemia was a major independent factor associated with rapid cognitive decline in middle-aged adults with diabetes. Maintaining ideal glucose levels in diabetes at midlife might prevent later rapid cognitive decline.

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.

Night blood pressure variability, brain atrophy, and cognitive decline.

Background: Although blood pressure variability (BPV) has emerged as a novel risk factor for Alzheimer's disease, few studies have examined the effects of night BPV on brain structure and function. This study investigated the association of night BPV with brain atrophy and cognitive function changes. Methods: The analysis included 1,398 participants with valid ambulatory blood pressure (BP) monitoring at baseline and both baseline and 4-year follow-up brain magnetic resonance images who were recruited from the Korean Genome and Epidemiology Study. Participants underwent a comprehensive neuropsychological test battery. BPV was derived from ambulatory BP monitoring and calculated as a standard deviation (SD) of 24-h and daytime and nighttime BP. Results: During the median follow-up of 4.3 years, increased SD of night systolic or diastolic BP was an indicator of total brain volume reduction, while daytime BPV or night average BP was not associated with total brain volume changes. High SD of night systolic BP was associated with reduced gray matter (GM) volume, independent of average night BP, and use of antihypertensive drugs. It also was associated with a reduction of temporal GM volume, mostly driven by atrophy in the left entorhinal cortex and the right fusiform gyrus. In cognitive performance, high variability of night systolic BP was associated with a decrease in visual delayed recall memory and verbal fluency for the category. Conclusion: Increased night BPV, rather than night mean BP, was associated with reduced brain volume and cognitive decline. High night BPV could be an independent predictor for rapid brain aging in a middle-aged population.

Association of Obstructive Sleep Apnea With White Matter Integrity and Cognitive Performance Over a 4-Year Period in Middle to Late Adulthood.

Importance: Obstructive sleep apnea (OSA) is associated with cognitive impairment and brain structural alterations, but longitudinal outcomes are understudied. Objective: To examine the associations of OSA with cognition and white matter (WM) integrity over a 4-year period. Design, Setting, and Participants: This prospective cohort study was conducted in a community-based adult population among participants who had both baseline (2011-2014) and 4-year follow-up (2015-2018) polysomnography, diffusion tensor imaging, and cognitive assessment data. Participants with neurological disorders, anomalous findings on brain magnetic resonance imaging, or inadequate quality of the evaluations were excluded. Data were analyzed from March to November 2021. Exposures: Participants were categorized depending on the presence vs absence of OSA at baseline and follow-up polysomnographic analysis. Main Outcomes and Measures: The main outcomes were proportional changes over a 4-year period in neuropsychological performance and WM integrity. The neuropsychological assessment battery included verbal and visual memory, verbal fluency, Digit Symbol-coding, Trail Making Test-A, and Stroop Test. WM integrity was assessed by fractional anisotropy, axial, and radial diffusivity. To examine interactions with age and sex, participants were subgrouped by age older than 60 years vs 60 years or younger and men vs women. Results: A total of 1998 individuals were assessed for eligibility, and 888 were excluded based on exclusion criteria, leaving 1110 participants (mean [SD] age, 58.0 [6.0] years; 517 [46.6%] men) for analysis, including 458 participants grouped as OSA-free, 72 participants with resolved OSA, 163 participants with incident OSA, and 417 participants with persistent OSA. Incident OSA was associated with altered WM integrity and with concomitant changes in sustained attention compared with participants without OSA (eg, change in Digit Symbol-coding test score, -3.2% [95% CI, -5.2% to -1.2%]). Participants with resolved OSA showed better visual recall at the follow-up (change in Visual Reproduction-immediate recall test, 17.5% [95% CI, 8.9% to 26.1%]; change in Visual Reproduction-delayed recall test, 33.1% [95% CI, 11.3% to 54.9%]), with concordant changes in diffusion parameters at the relevant anatomic areas. In the older group only (age >60 years), persistent OSA was associated with altered WM integrity and cognition (eg, Visual Reproduction-recognition test: ß = -24.2 [95% CI, -40.7 to -7.7]). Sex also was associated with modifying the association of OSA with WM integrity of the left posterior internal capsule, the left genu of corpus callosum, and the right middle cerebellar peduncle only in men and with cognition only in women (eg, Visual Reproduction-immediate recall test: ß = 33.4 [95% CI, 19.1 to 47.7]). Conclusions and Relevance: These findings suggest that dynamic changes in OSA status were significantly associated with WM integrity and cognition, which varied by age and sex. It is possible that adequate interventions for OSA could better preserve brain health in middle to late adulthood.

Development of Amyloid PET Analysis Pipeline Using Deep Learning-Based Brain MRI Segmentation-A Comparative Validation Study.

Amyloid positron emission tomography (PET) scan is clinically essential for the non-invasive assessment of the presence and spatial distribution of amyloid-beta deposition in subjects with cognitive impairment suspected to have been a result of Alzheimer's disease. Quantitative assessment can enhance the interpretation reliability of PET scan; however, its clinical application has been limited due to the complexity of preprocessing. This study introduces a novel deep-learning-based approach for SUVR quantification that simplifies the preprocessing step and significantly reduces the analysis time. Using two heterogeneous amyloid ligands, our proposed method successfully distinguished standardized uptake value ratio (SUVR) between amyloidosis-positive and negative groups. The proposed method's intra-class correlation coefficients were 0.97 and 0.99 against PETSurfer and PMOD, respectively. The difference of global SUVRs between the proposed method and PETSurfer or PMOD were 0.04 and -0.02, which are clinically acceptable. The AUC-ROC exceeded 0.95 for three tools in the amyloid positive assessment. Moreover, the proposed method had the fastest processing time and had a low registration failure rate (1%). In conclusion, our proposed method calculates SUVR that is consistent with PETSurfer and PMOD, and has advantages of fast processing time and low registration failure rate. Therefore, PET quantification provided by our proposed method can be used in clinical practice.

Severity of Daytime Sleepiness and Parkinsonian-Like Symptoms in Korean Adults Aged 50-64 Years.

BACKGROUND AND PURPOSE: While excessive daytime sleepiness can predate Parkinson's disease in late-life, its association with parkinsonian-like (P-L) symptoms in middle age are unknown. Since neurodegeneration can appear decades before a diagnosis of Parkinson's disease, identifying clinical features associated with this early progression is important. The purpose of this study was to determine the association of daytime sleepiness with P-L symptoms in a population-based sample of middle-aged Korean adults. METHODS: During 2013 and 2014, daytime sleepiness and P-L symptoms were assessed in 2,063 males and females aged 50-64 years who were participating in the Korean Genome and Epidemiology Study. The severity of daytime sleepiness was quantified by the score on the Epworth Sleepiness Scale (ESS). Self-reported P-L symptoms included nine motor disorders commonly associated with Parkinson's disease. Participants with parkinsonism and related conditions are excluded. RESULTS: The prevalence of excessive daytime sleepiness (ESS score >10) was 7.0%. The frequencies of P-L symptoms ranged from 0.5% (for "trouble buttoning buttons") to 18.4% (for "handwriting smaller than it once was"). After adjustment for covariates and multiple testing, the relative odds of P-L symptoms comparing the 80th and 20th percentiles of ESS scores was 1.6 (p=0.001) for "voice is softer than it once was," 2.1 (p<0.001) for "balance when walking is poor," and 1.5 (p=0.002) for "loss of facial expression." The prevalence of excessive daytime sleepiness increased from 6.3% to 19.8% when the number of symptoms increased from zero to three (p=0.004). CONCLUSIONS: In Korean adults aged 50-64 years, daytime sleepiness is significantly associated with P-L symptoms. Whether coexisting daytime sleepiness and P-L symptoms predate extrapyramidal and other impairments in later life warrants further investigation.

Sarcopenia is associated with decreased gray matter volume in the parietal lobe: a longitudinal cohort study.

BACKGROUND: Substantial evidence supports an association between physical activity and cognitive function. However, the role of muscle mass and function in brain structural changes is not well known. This study investigated whether sarcopenia, defined as low muscle mass and strength, accelerates brain volume atrophy. METHODS: A total of 1284 participants with sarcopenic measurements and baseline and 4-year follow-up brain magnetic resonance images were recruited from the Korean Genome and Epidemiology Study. Muscle mass was represented as appendicular skeletal muscle mass divided by the body mass index. Muscle function was measured by handgrip strength. The low mass and strength groups were defined as being in the lowest quintile of each variable for one's sex. Sarcopenia was defined as being in the lowest quintile for both muscle mass and handgrip strength. RESULTS: Of the 1284 participants, 12·6%, 10·8%, and 5·4% were classified as the low mass, low strength, and sarcopenia groups, respectively. The adjusted mean changes of gray matter (GM) volume during 4-year follow-up period were - 9·6 mL in the control group, whereas - 11·6 mL in the other three groups (P < 0·001). The significantly greater atrophy in parietal GM was observed in the sarcopenia group compared with the control group. In a joint regression model, low muscle mass, but not muscle strength, was an independent factor associated with a decrease of GM volume. CONCLUSIONS: Sarcopenia is associated with parietal GM volume atrophy, in a middle-aged population. Maintaining good levels of muscle mass could be important for brain health in later adulthood.

Sex differences in deterioration of sleep properties associated with aging: a 12-year longitudinal cohort study.

STUDY OBJECTIVES: The sleep patterns of humans are greatly influenced by age and sex and have various effects on overall health as they change continuously during the lifespan. We investigated age-dependent changes in sleep properties and their relation to sex in middle-aged individuals. METHODS: We analyzed data from 2,640 participants (mean age of 49.8 ± 6.8 years at baseline, 50.6% women) in the Korean Genome and Epidemiology Study, which assessed sleep habits using the Pittsburgh Sleep Quality Index and other clinical characteristics. We analyzed the sleep habit changes that occurred between baseline and a follow-up point (mean interval: 12.00 ± 0.16 years). Associations of age and sex with 9 sleep characteristics were evaluated. RESULTS: Age was associated with most of the sleep characteristics cross-sectionally and longitudinally (P < .05), except for the time in bed at baseline (P = .455) and change in sleep duration (P = .561). Compared with men, women had higher Pittsburgh Sleep Quality Index scores, shorter time in bed, shorter sleep duration, and longer latency at baseline (P ≤ .001). Longitudinal deterioration in Pittsburgh Sleep Quality Index score, habitual sleep efficiency, duration, and latency was more prominent in women (P < .001). The sex differences in these longitudinal sleep changes were mainly noticeable before age 60 years (P < .05). Worsening of Pittsburgh Sleep Quality Index scores, habitual sleep efficiency, and latency was most evident in perimenopausal women. Men presented with greater advancement of chronotype (P = .006), with the peak sex-related difference occurring when they were in their late 40s (P = .048). CONCLUSIONS: Aging is associated with substantial deterioration in sleep quantity and quality as well as chronotype advancement, with the degree and timing of these changes differing by sex.