Network Analysis Revealed the Role of Helplessness as a Central Feature Among Late-Life Depressive Symptoms in Patients With Mild Cognitive Impairment and Early Stage Dementia.

OBJECTIVE: It has been reported that depressive symptoms in older adults are different from those in younger adults, especially when accompanied by cognitive decline. However, few studies have investigated the network structure of depressive symptoms in this population. METHODS: The participants consisted of 627 older adults (>60 yr) who were diagnosed with mild cognitive impairment (MCI) or early stage dementia. Among them, 36.7% were male and the mean age was 76.20±7.71 years. The Korean form of Geriatric Depression Scale (KGDS) was used to evaluate their depressive symptoms and network analyses were performed using bootnet R-package to identify the central features among depressive symptoms. RESULTS: Of all the KGDS items, we found that KGDS 2 (often feel helpless) had the highest node strength followed by KGDS 21 (in good spirits), KGDS 14 (not confident at all), and KGDS 15 (cheerful and happy). In terms of node betweenness, KGDS 2 also showed the highest value. The edge weights of edges connected to node KGDS 2 were strongest in KGDS 3 (restless and fidgety) and KGDS 28 (easily get tired). CONCLUSION: In this study, we presented which symptoms are central among the elderly with MCI and early stage dementia. This result not only increases the understanding of depressive symptoms in this group but would also help determine target symptoms in the treatment program.

Gender Differences in Items of the Instrumental Activities of Daily Living in Mild Cognitive Impairment and Alzheimer's Disease Dementia.

Background and Purpose: Each item in the instrumental activities of daily living (IADL) questionnaire has differential importance to an individual's life functioning based on gender. However, IADL has mostly been utilized for its total score alone, without gender specificity. We identify the impact of each item on the transition from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease dementia (ADD), and determine if the impact of each item differs by gender. Methods: Subjects were aMCI or ADD with a global clinical dementia rating of 0.5 or 1. The sample size was 146 men and 154 women. We used logistic regression analysis to determine the effect of each item of IADL on the transition from aMCI to ADD. Results: The odds ratio (OR) for "remembering recent events" had similar values: 27.2 for men, and 27.7 for women. Gender difference was identified in the item with the highest OR value. For women, the "using transportation" item was 63.3, and for men, "conducting financial affairs" was overwhelmingly high at 89.1. Conclusions: Functional decline on items with relatively higher ORs may indicate higher probability of a transition from aMCI to ADD. The OR of "conducting financial affairs" was relatively higher for both genders. In terms of gender differences, "conducting home repair" for men, and "using transportation" for women, have relatively higher impact. This study demonstrates that during the transition from aMCI to ADD, each item of IADL shows a staggered decline in functioning, and that this decline is gender-specific.

Unpaired deep learning for pharmacokinetic parameter estimation from dynamic contrast-enhanced MRI without AIF measurements.

DCE-MRI provides information about vascular permeability and tissue perfusion through the acquisition of pharmacokinetic parameters. However, traditional methods for estimating these pharmacokinetic parameters involve fitting tracer kinetic models, which often suffer from computational complexity and low accuracy due to noisy arterial input function (AIF) measurements. Although some deep learning approaches have been proposed to tackle these challenges, most existing methods rely on supervised learning that requires paired input DCE-MRI and labeled pharmacokinetic parameter maps. This dependency on labeled data introduces significant time and resource constraints and potential noise in the labels, making supervised learning methods often impractical. To address these limitations, we present a novel unpaired deep learning method for estimating pharmacokinetic parameters and the AIF using a physics-driven CycleGAN approach. Our proposed CycleGAN framework is designed based on the underlying physics model, resulting in a simpler architecture with a single generator and discriminator pair. Crucially, our experimental results indicate that our method does not necessitate separate AIF measurements and produces more reliable pharmacokinetic parameters than other techniques.

Cortical Iron Accumulation as an Imaging Marker for Neurodegeneration in Clinical Cognitive Impairment Spectrum: A Quantitative Susceptibility Mapping Study.

OBJECTIVE: Cortical iron deposition has recently been shown to occur in Alzheimer's disease (AD). In this study, we aimed to evaluate how cortical gray matter iron, measured using quantitative susceptibility mapping (QSM), differs in the clinical cognitive impairment spectrum. MATERIALS AND METHODS: This retrospective study evaluated 73 participants (mean age ± standard deviation, 66.7 ± 7.6 years; 52 females and 21 males) with normal cognition (NC), 158 patients with mild cognitive impairment (MCI), and 48 patients with AD dementia. The participants underwent brain magnetic resonance imaging using a three-dimensional multi-dynamic multi-echo sequence on a 3-T scanner. We employed a deep neural network (QSMnet+) and used automatic segmentation software based on FreeSurfer v6.0 to extract anatomical labels and volumes of interest in the cortex. We used analysis of covariance to investigate the differences in susceptibility among the clinical diagnostic groups in each brain region. Multivariable linear regression analysis was performed to study the association between susceptibility values and cognitive scores including the Mini-Mental State Examination (MMSE). RESULTS: Among the three groups, the frontal (P < 0.001), temporal (P = 0.004), parietal (P = 0.001), occipital (P < 0.001), and cingulate cortices (P < 0.001) showed a higher mean susceptibility in patients with MCI and AD than in NC subjects. In the combined MCI and AD group, the mean susceptibility in the cingulate cortex (ß = -216.21, P = 0.019) and insular cortex (ß = -276.65, P = 0.001) were significant independent predictors of MMSE scores after correcting for age, sex, education, regional volume, and APOE4 carrier status. CONCLUSION: Iron deposition in the cortex, as measured by QSMnet+, was higher in patients with AD and MCI than in NC participants. Iron deposition in the cingulate and insular cortices may be an early imaging marker of cognitive impairment related neurodegeneration.

Central features in health-related quality of life in older adults: network analysis using nationwide survey data.

BACKGROUND: Population ageing is a global phenomenon that necessitates consideration of health-related quality of life (HRQoL) in older adults. Previous studies have investigated related factors including mobility, social support and living situations. AIMS: This study aimed to provide a network perspective on factors related to HRQoL. METHOD: Cross-sectional nationwide data were obtained from the Korean National Health and Nutrition Examination Survey conducted from 2018 to 2020 for network analyses. Data for participants aged 65 years or above were analysed, resulting in a total of 4317 eligible cases. The variables included were EQ-5D (a measure of HRQoL), household income, education, living situation, subjective perceived health, Charlson Comorbidity Index (a measure of medical comorbidities), stress, exercise per week, alcohol consumption and smoking. Three networks were produced: (a) EQ-5D dimensions network, (2) EQ-5D dimensions, lifestyle and psychosocial factors network, and (3) overall EQ-5D index, lifestyle and psychosocial factors network. Node centralities, bridge centralities and edges of the networks were examined. RESULTS: The most central EQ-5D dimension was the ability to carry out usual activities. In the second network, subjective health, stress and anxiety/depression were revealed as nodes with high bridge centralities. Subjective health, exercise, and Charlson Comorbidity Index were nodes closely linked to the overall EQ-5D index. CONCLUSIONS: The results emphasise the importance of enhancing functional independence and subjective health cognition, increasing routine exercise and reducing stress as targets for interventions to improve HRQoL in older adults.

Blood-brain barrier breakdown is linked to tau pathology and neuronal injury in a differential manner according to amyloid deposition.

The blood-brain barrier (BBB) breakdown has been suggested as an early marker for Alzheimer's disease (AD); yet the relationship between BBB breakdown and AD-specific biomarkers based on the amyloid/tau/neurodegeneration framework is not clear. This study investigated the relationship between BBB permeability, AD-specific biomarkers, and cognition in patients with cognitive impairment. In this prospective study, we enrolled 62 participants with mild cognitive impairment or dementia between January 2019 and October 2020. All participants were assessed through cognitive tests, amyloid positron emission tomography (PET), dynamic contrast-enhanced magnetic resonance imaging (MRI) for BBB permeability (Ktrans), cerebrospinal fluid studies for Aß42/40 ratio, phosphorylated-tau Thr181 protein (p-tau), total tau protein (t-tau), and structural MRI for neurodegeneration. In amyloid PET (+) group, higher cortical Ktrans was associated with lower Aß40 (r = -0.529 p = 0.003), higher Aß42/40 ratio (r = 0.533, p = 0.003), lower p-tau (r = -0.452, p = 0.014) and lower hippocampal volume (r = -0.438, p = 0.017). In contrast, cortical Ktrans was positively related to t-tau level. (r = 0.489, p = 0.004) in amyloid PET (-) group. Our results suggest that BBB permeability is related to AD-specific biomarkers, but the relationship can vary by the presence of Aß plaque accumulation.

Diagnostic Tools for Alzheimer's Disease: A Narrative Review Based on Our Own Research Experience.

Alzheimer's disease (AD), one of the most representative neurodegenerative diseases, has diverse neurobiological and pathophysiological mechanisms. Treatment strategies targeting a single mechanism have repeated faced failures because the mechanism of neuronal cell death is very complex that is not fully understood yet. Since complex mechanisms exist to explain AD, a variety of diagnostic biomarkers for diagnosing AD are required. Moreover, standardized evaluations for comprehensive diagnosis using neuropsychological, imaging, and laboratory tools are needed. In this review, we summarize the latest clinical, neuropsychological, imaging, and laboratory evaluations to diagnose patients with AD based on our own experience in conducting a prospective study.

Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease.

Apolipoprotein (APOE) is implicated and verified as the main risk factor for early-onset Alzheimer's disease (AD). APOE is a protein that binds to lipids and is involved in cholesterol stability. Our paper reports a case of a sporadic early-onset AD (sEOAD) patient of a 54-year-old Korean man, where a novel APOE Leu159Pro heterozygous mutation was revealed upon Whole Exome Sequence analysis. The proband's CSF showed downregulated levels of Aß42, with unchanged Tau levels. The mutation is in the Low-Density Lipoprotein Receptor (LDLR) region of the APOE gene, which mediates the clearance of APOE lipoproteins. LDLR works as a high-affinity point for APOE. Studies suggest that APOE-LDLR interplay could have varying effects. The LDLR receptor pathway has been previously suggested as a therapeutic target to treat tauopathy. However, the APOE-LDLR interaction has also shown a significant correlation with memory retention. Leu159Pro could be an interesting mutation that could be responsible for a less damaging pattern of AD by suppressing tau-association neurodegeneration while affecting the patient's memory retention and cognitive performance.

Choroid Plexus Volume and Permeability at Brain MRI within the Alzheimer Disease Clinical Spectrum.

Background Mounting evidence suggests that the choroid plexus (CP) plays an important role in the pathophysiology of Alzheimer disease (AD), but its imaging profile in cognitive impairment remains unclear. Purpose To evaluate CP volume, permeability, and susceptibility by using MRI in patients at various stages of cognitive impairment. Materials and Methods This retrospective study evaluated patients with cognitive symptoms who underwent 3.0-T MRI of the brain, including dynamic contrast-enhanced (DCE) imaging and quantitative susceptibility mapping (QSM), between January 2013 and May 2020. CP volume was automatically segmented using three-dimensional T1-weighted sequences; the volume transfer constant (ie, Ktrans) and fractional plasma volume (ie, Vp) were determined using DCE MRI, and susceptibility was assessed using QSM. The effects of CP volume, expressed as the ratio to intracranial volume, on cognition were evaluated using multivariable linear regression adjusted for age, sex, education, apolipoprotein E ε4 allele status, and volumetric measures. Results A total of 532 patients with cognitive symptoms (mean age, 72 years ± 9 [SD]; 388 women) were included: 78 with subjective cognitive impairment (SCI), 158 with early mild cognitive impairment (MCI), 149 with late MCI, and 147 with AD. Among these, 132 patients underwent DCE MRI and QSM. CP volume was greater in patients at more severe stages (ratio of intracranial volume × 103: 0.9 ± 0.3 for SCI, 1.0 ± 0.3 for early MCI, 1.1 ± 0.3 for late MCI, and 1.3 ± 0.4 for AD; P < .001). Lower Ktrans (r = -0.19; P = .03) and Vp (r = -0.20; P = .02) were negatively associated with CP volume; susceptibility was not (r = 0.15; P = .10). CP volume was negatively associated with memory (B = -0.67; standard error of the mean [SEM], 0.21; P = .01), executive function (B = -0.90; SEM, 0.31; P = .01), and global cognition (B = -0.82; SEM, 0.32; P = .01). Conclusion Among patients with cognitive symptoms, larger choroid plexus volume was associated with severity of cognitive impairment in the Alzheimer disease spectrum. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Chiang in this issue.

Magnetic susceptibility in the deep gray matter may be modulated by apolipoprotein E4 and age with regional predilections: a quantitative susceptibility mapping study.

PURPOSE: To examine the relationship between apolipoprotein E gene (APOE) mutation status and iron accumulation in the deep gray matter of subjects with cognitive symptoms using quantitative susceptibility mapping (QSM). METHODS: A total of 105 patients with cognitive symptoms were enrolled. QSM data were generated from 3D gradient-echo data using an STI Suite algorithm. A region of interest-based analysis with QSM was performed in the deep gray matter. Differences between APOE4 carriers and non-carriers were assessed by analysis of covariance. Multiple regression analysis was performed to identify the factors associated with magnetic susceptibility. RESULTS: Clinical characters such as age, education, MMSE, vascular risk burden, and systolic blood pressure differ between APOE4 carrier and non-carrier groups. The APOE4 carrier group had higher magnetic susceptibility values than the non-carrier group, with significant differences in the caudate (p = 0.004), putamen (p < 0.0001), and globus pallidus (p < 0.0001) which imply higher iron accumulation. In a multiple regression analysis, APOE4 status was found to be a predictor of magnetic susceptibility value in the globus pallidus (p = 0.03); age for magnetic susceptibility value in the caudate nucleus (p = 0.0064); and age and hippocampal atrophy for magnetic susceptibility value in the putamen (p < 0.05). CONCLUSION: Our study demonstrates that magnetic susceptibility in globus pallidus is related to APOE4 status while those of caudate and putamen are related to other factors including age. It suggests that brain iron accumulation in the deep gray matter is modulated by APOE4 and age with differential regional predilection.

Sarcopenia in patients with dementia: correlation of temporalis muscle thickness with appendicular muscle mass.

Cognitive decline is one of the most relevant signs of sarcopenia; however, it is challenging to perform tests for sarcopenia in patients with dementia. In a recent study, temporalis muscle thickness (TMT), an alternative to appendicular muscle mass (ASM), was found to be a valid index for screening sarcopenia. This study aimed to determine whether TMT correlates with ASM and evaluate the relationship between TMT and cognitive function in dementia patients. We recruited patients with a complaint of memory loss who visited the Memory Clinic of Konkuk University Medical Center between November 2014 and December 2020. Patients with probable Alzheimer's disease (AD) without weakness were included. TMT was measured on axial T1-weighted magnetic resonance (MR) images, perpendicular to the long axis of the temporal muscle, at the orbital roof level. ASM was measured using body dual-energy X-ray absorptiometry (DXA). It was calculated as the sum of lean soft tissue mass in the arms and legs, and the value by ASM divided by height squared was used. Inter-rater reliability and intra-rater reliability were good and excellent, respectively. We found a correlation between TMT and skeletal ASM, which was obtained from cranial MR images and DXA, respectively (r = 0.379, p = 0.001). TMT was negatively correlated with age (r = - 0.296, p = 0.014) and positively correlated with body mass index (BMI) (r = 0.303, p = 0.012). Additionally, TMT was correlated with MMSE (r = 0.350, p = 0.003). After adjusting for educational years, there was still a correlation between TMT and MMSE (r = 0.256, p = 0.038). This study demonstrated that TMT correlates with ASM and cognitive function in patients with dementia. Measuring TMT using cranial MR images could help diagnose sarcopenia accessibly and assess cognitive function in patients with dementia.

Brain myelin water fraction is associated with APOE4 allele status in patients with cognitive impairment.

BACKGROUND AND PURPOSE: Apolipoprotein E4 (APOE4) is a major genetic risk factor for Alzheimer's disease. However, the effect of APOE4 status on myelin remains unclear. This study investigated the effect of APOE4 on myelin content in cognitively impaired individuals using T2* gradient echo (GRE)-based myelin water fraction (MWF) imaging. METHODS: Between August 2017 and January 2019, we evaluated 39 cognitively impaired patients (median age, 75 years; male:female = 8:31; Alzheimer's disease: mild cognitive impairment = 11:28). We obtained brain MWF values from white matter hyperintensities (WMHs) and normal-appearing white matter (NAWM). Linear regression analysis was performed to investigate the relationship between the APOE4 status and MWF and cognitive function and MWF. RESULTS: Among the 39 cognitively impaired patients, nine (23.1%) were APOE4 carriers and 30 (76.9%) were noncarriers. APOE4 carriers had a lower hippocampal volume than noncarriers (p = .045), but other brain volume parameters were not differed. After age adjustment, the APOE4 status was significantly associated with reduced MWF in NAWM (ß = -0.310 per allele; p = .049) but not in WMH (ß = -0.258 per allele; p = .113). After age adjustment, MWF in NAWM was significantly associated with Mini-Mental State Examination score (ß = 0.313, p = .031). CONCLUSIONS: T2* GRE-based MWF imaging can reveal myelin loss, particularly in NAWM, in cognitively impaired patients among APOE4 carriers. In vivo MWF in NAWM might be a novel imaging marker of Alzheimer's disease, for clarifying the interactions between the white matter and cognitive dysfunction with respect to the APOE4 status.

Validation of the Korean Quick Dementia Rating System (K-QDRS).

BACKGROUND: The Quick Dementia Rating System (QDRS) is a brief and rapid dementia staging tool that does not require a trained rater. OBJECTIVE: The purpose of this study is to demonstrate the validity, reliability, and diagnostic usefulness of the Korean version of the QDRS (K-QDRS). METHODS: We collected a total of 411 subject-informant dyads including cognitively unimpaired (CU, n = 22), mild cognitive impairment (MCI, n = 198), and dementia (n = 191). The Clinical Dementia Rating (CDR) scale, Korean version of the Mini-Mental State Examination (K-MMSE), Korean version of instrumental activity of daily living (K-IADL), Short Form of the Geriatric Depression Scale, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI), and detailed neuropsychological tests were administered as gold standards of dementia staging, cognition, function, mood, and behavior. RESULTS: Internal consistency of the K-QDRS was excellent with Cronbach's alpha of 0.933. Concurrent validity was also satisfactory, with the K-QDRS correlating highly with the CDR Sum of Boxes (Pearson's r = 0.791), K-MMSE (Pearson's r = -0.518), K-IADL (Pearson's r = 0.727), and CGA-NPI (Pearson's r = 0.700). The K-QDRS was highly correlated with the global CDR, K-IADL, and CGA-NPI. We suggested two types of comparisons (for initial diagnosis and for follow-up evaluation). The cutoff scores for follow-up were 1.0 for MCI, 3.5 for very mild dementia, 6.5 for mild dementia, and 11.0 for moderate dementia. CONCLUSION: The K-QDRS is a valid and reliable dementia rating questionnaire and can be used, briefly and rapidly, in various settings like clinical practices, longitudinal cohort studies, and community primary care.

Evaluation of Reproducibility of Brain Volumetry between Commercial Software, Inbrain and Established Research Purpose Method, FreeSurfer.

BACKGROUND AND PURPOSE: We aimed to determine the intermethod reproducibility between the commercial software Inbrain (MIDAS IT) and the established research-purpose method FreeSurfer, as well as the effect of MRI resolution and the pathological condition of subjects on their intermethod reproducibility. METHODS: This study included 45 healthy volunteers and 85 patients with mild cognitive impairment (MCI). In 43 of the 85 patients with MCI, three-dimensional, T1-weighted MRI data were obtained at an in-plane resolution of 1.2 mm. The data of the remaining 42 patients with MCI and the healthy volunteers were obtained at an in-plane resolution of 1.0 mm. The within-subject coefficient of variation (CoV), intraclass correlation coefficient (ICC), and effect size were calculated, and means were compared using paired t-tests. The parameters obtained at 1.0-mm and 1.2-mm resolutions in patients with MCI were compared to evaluate the effect of the in-plane resolution on the intermethod reproducibility. The parameters obtained at a 1.0-mm in-plane resolution in patients with MCI and healthy volunteers were used to analyze the effect of subject condition on intermethod reproducibility. RESULTS: Overall the two methods showed excellent reproducibility across all regions of the brain (CoV=0.5-3.9, ICC=0.93 to >0.99). In the subgroup of healthy volunteers, the intermethod reliability was only good in some regions (frontal, temporal, cingulate, and insular). The intermethod reproducibility was better in the 1.0-mm group than the 1.2-mm group in all regions other than the nucleus accumbens. CONCLUSIONS: Inbrain and FreeSurfer showed good-to-excellent intermethod reproducibility for volumetric measurements. Nevertheless, some noticeable differences were found based on subject condition, image resolution, and brain region.

Sex-Related Differences in Regional Blood-Brain Barrier Integrity in Non-Demented Elderly Subjects.

The role of the blood-brain barrier (BBB) breakdown has been recognized as being important in Alzheimer's disease pathogenesis. We aimed to evaluate whether regional BBB integrity differed according to sex and whether differences in BBB integrity changed as a consequence of aging or cognitive decline, using dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI). In total, 75 participants with normal cognition (NC) or mild cognitive impairment (MCI) underwent cognitive assessments and MRI examination including DCE-MRI. Regional Ktrans was calculated in cortical regions and the Patlak permeability model was used to calculate BBB permeability (Ktrans, min-1). Females had a lower median Ktrans in the cingulate and occipital cortices. In the "older old" group, sex differences in Ktrans were only observed in the occipital cortex. In the MCI group, sex differences in Ktrans were only observed in the occipital cortex. Age was the only predictor of cognitive assessment scores in the male MCI group; however, educational years and Ktrans in the occipital cortex could predict cognitive scores in the female MCI group. Our study revealed that females may have better BBB integrity in cingulate and occipital cortices. We also found that sex-related differences in BBB integrity are attenuated with aging or cognitive decline.

Regional Differences in Blood-Brain Barrier Permeability in Cognitively Normal Elderly Subjects: A Dynamic Contrast-Enhanced MRI-Based Study.

OBJECTIVE: This study aimed to determine whether there are regional differences in the blood-brain barrier (BBB) permeability of cognitively normal elderly participants and to identify factors influencing BBB permeability with a clinically feasible, 10-minute dynamic contrast-enhanced (DCE) MRI protocol. MATERIALS AND METHODS: This IRB-approved prospective study recruited 35 cognitively normal adults (26 women; mean age, 64.5 ± 5.6 years) who underwent DCE T1-weighted imaging. Permeability maps (Ktrans) were coregistered with masks to calculate the mean regional values. The paired t test and Friedman test were used to compare Ktrans between different regions. The relationships between Ktrans and the factors of age, sex, education, cognition score, vascular risk burden, vascular factors on imaging, and medial temporal lobar atrophy were assessed using Pearson correlation and the Spearman rank test. RESULTS: The mean permeability rates of the right and left hippocampi, as assessed with automatic segmentation, were 0.529 ± 0.472 and 0.585 ± 0.515 (Ktrans, × 10-3 min-1), respectively. Concerning the deep gray matter, the Ktrans of the thalamus was significantly greater than those of the putamen and hippocampus (p = 0.007, p = 0.041). Regarding the white matter, the Ktrans value of the occipital white matter was significantly greater than those of the frontal, cingulate, and temporal white matter (p < 0.0001, p = 0.0007, p = 0.0002). The variations in Ktrans across brain regions were not related to age, cognitive score, vascular risk burden, vascular risk factors on imaging, or medial temporal lobar atrophy in the study group. CONCLUSION: Our study demonstrated regional differences in BBB permeability (Ktrans) in cognitively normal elderly adults using a clinically acceptable 10-minutes DCE imaging protocol. The regional differences suggest that the integrity of the BBB varies across the brains of cognitively normal elderly adults. We recommend considering regional differences in Ktrans values when evaluating BBB permeability in patients with neurodegenerative diseases.

Comparison of Automated Brain Volume Measures by NeuroQuant vs. Freesurfer in Patients with Mild Cognitive Impairment: Effect of Slice Thickness.

PURPOSE: This study aimed to examine the inter-method reliability and volumetric differences between NeuroQuant (NQ) and Freesurfer (FS) using T1 volume imaging sequence with different slice thicknesses in patients with mild cognitive impairment (MCI). MATERIALS AND METHODS: This retrospective study enrolled 80 patients diagnosed with MCI at our memory clinic. NQ and FS were used for volumetric analysis of three-dimensional T1-weighted images with slice thickness of 1 and 1.2 mm. Inter-method reliability was measured with Pearson correlation coefficient (r), intraclass correlation coefficient (ICC), and effect size (ES). RESULTS: Overall, NQ volumes were larger than FS volumes in several locations: whole brain (0.78%), cortical gray matter (5.34%), and white matter (2.68%). Volume measures by NQ and FS showed good-to-excellent ICCs with both 1 and 1.2 mm slice thickness (ICC=0.75-0.97, ES=-1.0-0.73 vs. ICC=0.78-0.96, ES=-0.9-0.77, respectively), except for putamen, pallidum, thalamus, and total intracranial volumes. The ICCs in all locations, except the putamen and cerebellum, were slightly higher with a slice thickness of 1 mm compared to those of 1.2 mm. CONCLUSION: Inter-method reliability between NQ and FS was good-to-excellent in most regions with improvement with a 1-mm slice thickness. This finding indicates that the potential effects of slice thickness should be considered when performing volumetric measurements for cognitive impairment.

Hippocampal blood-brain barrier permeability is related to the APOE4 mutation status of elderly individuals without dementia.

Blood-brain barrier (BBB) disruption, modulated by APOE4 mutation, is implicated in the pathogenesis of cognitive decline. We determined whether BBB permeability differed according to cognitive functioning and APOE4 status in elderly subjects without dementia. In this prospective study, 33 subjects with mild cognitive impairment (MCI) and 33 age-matched controls (normal cognition [NC]) underwent 3 T brain magnetic resonance imaging. The Patlak model was used to calculate tissue permeability (Ktrans). A region-of interest analysis of Ktrans was performed to compare relevant brain regions. Effects of Ktrans on cognitive functioning were evaluated with linear regression analysis adjusted for confounding factors. NC and MCI groups did not differ in terms of vascular risk factors or hippocampal Ktrans, except for hippocampal volume. Hippocampal Ktrans was significantly higher in APOE4 carriers than in non-carriers (p = 0.007). Factors which predicted cognitive functioning included hippocampal volume (beta=-0.445, standard error [SE]=0.137, p = 0.003) and hippocampal BBB permeability (beta = 0.142, SE = 0.050, p = 0.008) after correcting for age, education, and APOE4 status. This suggests that hippocampal BBB permeability is associated with APOE4 mutation, and may predict cognitive functioning. BBB permeability imaging represents a distinct imaging biomarker for APOE4 mutations in NC and MCI subjects and for determining the degree of APOE4-related pathology.

Associations of truncal body composition with cognitive status in patients with dementia.

BACKGOUND: Central obesity in midlife is a risk factor of cognitive decline and dementia, and also one of the factors that make cognitive functions deteriorate rapidly. OBJECTIVE: The objective of this study is to investigate the relationship between truncal body composition (fat and muscle) and cognitive impairment in patients with dementia. METHODS: A total of 81 female over 60 years of age with probable Alzheimer's disease were recruited between November 2014 and September 2015. The Mini-Mental State Examination, Global Deterioration Scale, and Clinical Dementia Rating Scale were used to assess the cognitive functions. Both truncal fat and muscle mass were measured using body dual-energy X-ray absorptiometry and used as a percentage of body weight (TMM% and TFM%). Correlations between truncal composition and cognitive status were assessed by simple correlation analysis, which was followed by partial correlation analysis with age and educational years. RESULTS: TFM% was not related to cognitive impairment. In contrast, TMM% had a significantly negative correlation with all three cognitive assessment scores. After further adjusting for age, educational years, and vascular factors, there was still a relationship between TMM% and cognitive functions. CONCLUSIONS: Unlike truncal fat mass that showed no relevance with cognitive functions, the truncal muscle mass was negatively correlated with cognitive status. The truncal muscle mass is thought to affect cognitive status in dementia patients somehow.

Hospital adverse outcomes of the elderly in a tertiary referral hospital: A prospective cohort study of 9,586 admissions.

OBJECTIVE: This study aimed to evaluate the hospital adverse outcomes (HAO) of admitted older adult patients in a large prospective cohort and investigate the demographic, economic, and health-related characteristics at risk of HAO in all older adult patients admitted in the general ward of a tertiary referral hospital. MATERIALS AND METHODS: We recruited admission episodes of older adult patients aged over 65 years who were admitted at the general ward of Konkuk University Medical Center, which is a tertiary referral hospital, from September 2016 to October 2017. Out of 9,586 admission episodes, 8,263 were included. Modified from the Geriatric Screening for Care-10, six common geriatric health issues, namely, dysphagia, polypharmacy, fecal incontinence, functional mobility, depression, and dementia, were evaluated. Fall, hospital-acquired pressure ulcer (HPU), and mortality were checked daily by experienced nurses during the patients' hospital stay. A logistic regression model was used, and P < 0.05 was the threshold of significance. RESULTS: The incidence rates of fall and HPU were 1.3 % and 4.0 %, respectively. The hospital mortality was 6.1 %. Older adult patients with dysphagia or dementia upon admission were significantly associated with an increased likelihood of falls. Furthermore, age, ER admission, low income, fecal incontinence, or functional immobility increased the HPU incidence. Meanwhile, age, male, ER admission, fecal incontinence, or functional immobility significantly increased the hospital mortality. CONCLUSION: All demographic, economic, and health-related characteristics, except for polypharmacy and depression, affect the incidence of HAO. Intervention to vulnerable older adult patients with HAO risk could improve the treatment outcome.