Association of Central Auditory Processing Dysfunction With Preclinical Alzheimer's Disease.

OBJECTIVE: To investigate whether central auditory processing dysfunction measured by the dichotic digit test-1 digit (DDT1) is present in preclinical Alzheimer's disease (AD) individuals who are cognitively normal (CN) older adults with the cerebral beta-amyloid (Aß) deposition and to explore the potential of the DDT1 as a screening test for preclinical AD. STUDY DESIGN: Cross-sectional design. SETTING: A prospective observational cohort study. METHODS: CN older adults with a global clinical dementia rating score of 0 were included. The hearing test battery including pure-tone audiometry, speech audiometry, distortion product otoacoustic emission, and DDT1 was administered to participants. RESULTS: Fifty CN older adults were included. Among them, 38 individuals were included in the Aß deposition negative (AN) group and 12 were included in the Aß deposition positive (AP) group. The DDT1 scores of both the better and worse ears were significantly lower in the AP group than in the AN group (p = .008 and p = .015, respectively). No significant differences were observed between the groups in tests of the peripheral auditory pathways. In multivariable logistic regression analysis adjusted for apolipoprotein E4 positivity, the DDT1 better ear score predicted the AP group (p = .036, odds ratio = 0.892, 95% confidence interval: 0.780-0.985) with relatively high diagnostic accuracy. CONCLUSION: Our findings suggest that Aß deposition may affect the central auditory pathway even before cognitive decline appears. DDT1, which can easily be applied to the old-age population, may have the potential as a screening tool for preclinical AD.

Association of low meal frequency with decreased in vivo Alzheimer's pathology.

Little is known about the association between meal frequency and Alzheimer's disease (AD) in humans. We tested the hypothesis that low meal frequency (LMF) is associated with reduced in vivo AD pathology in human brain, and additionally investigated the mediation of serum ghrelin, a hunger-related hormone, for the association. A total of 411 non-demented older adults were systematically interviewed to identify their dietary patterns including meal frequency and underwent multi-modal neuroimaging for cerebral beta-amyloid (Aß) and tau deposition, glucose metabolism, and cerebrovascular injury. LMF (less than three meals a day) was significantly associated with lower Aß deposition compared to high meal frequency (HMF). In addition, both LMF and reduced Aß deposition were significantly related to elevated serum ghrelin. Our findings suggest that LMF may be related to the lower risk of AD through reduced brain amyloid deposition. Additionally, ghrelin appears mediate the association between LMF and lower amyloid deposition.

Prototype-based Domain Generalization Framework for Subject-Independent Brain-Computer Interfaces.

Brain-computer interface (BCI) is challenging to use in practice due to the inter/intra-subject variability of electroencephalography (EEG). The BCI system, in general, necessitates a calibration technique to obtain subject/session-specific data in order to tune the model each time the system is utilized. This issue is acknowledged as a key hindrance to BCI, and a new strategy based on domain generalization has recently evolved to address it. In light of this, we've concentrated on developing an EEG classification framework that can be applied directly to data from unknown domains (i.e. subjects), using only data acquired from separate subjects previously. For this purpose, in this paper, we proposed a framework that employs the open-set recognition technique as an auxiliary task to learn subject-specific style features from the source dataset while helping the shared feature extractor with mapping the features of the unseen target dataset as a new unseen domain. Our aim is to impose cross-instance style in-variance in the same domain and reduce the open space risk on the potential unseen subject in order to improve the generalization ability of the shared feature extractor. Our experiments showed that using the domain information as an auxiliary network increases the generalization performance. Clinical relevance-This study suggests a strategy to improve the performance of the subject-independent BCI systems. Our framework can help to reduce the need for further calibration and can be utilized for a range of mental state monitoring tasks (e.g. neurofeedback, identification of epileptic seizures, and sleep disorders).

Functional Neural Correlates of Semantic Fluency Task Performance in Mild Cognitive Impairment and Alzheimer's Disease: An FDG-PET Study.

BACKGROUND: Total score (TS) of semantic verbal fluency test (SVFT) is generally used to interpret results, but it is ambiguous as to specific neural functions it reflects. Different SVFT strategy scores reflecting qualitative aspects are proposed to identify specific cognitive functions to overcome limitations of using the TS. OBJECTIVE: Functional neural correlates of the TS as well as the other strategy scores in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia using Fluorine-18-Fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Correlations between various SVFT scores (i.e., TS, mean cluster size, switching (SW), hard switching, cluster switching (CSW)) and cerebral glucose metabolism were explored using voxelwise whole-brain approach. Subgroup analyses were also performed based on the diagnosis and investigated the effects of disease severity on the associations. RESULTS: Significant positive correlation between TS and cerebral glucose metabolism was found in prefrontal, parietal, cingulate, temporal cortex, and subcortical regions. Significantly increased glucose metabolism associated with the SW were found in similar but smaller regions, mainly in the fronto-parieto-temporal regions. CSW was only correlated with the caudate. In the subgroup analysis conducted to assess different contribution of clinical severity, differential associations between the strategy scores and regional glucose metabolism were found. CONCLUSION: SW and CSW may reflect specific language and executive functions better than the TS. The SVFT is influenced by brain dysfunction due to the progression of AD, as demonstrated by the SW with larger involvement of temporal lobe for the AD, and CSW with significant association only for the MCI.

Cognitive reserve proxies, Alzheimer pathologies, and cognition.

This study aimed to explore the moderating effects of the frequently used cognitive reserve (CR) proxies [i.e., education, premorbid intelligence quotient (pIQ), occupational complexity (OC), and lifetime cognitive activity (LCA)] on the relationships between various in vivo Alzheimer's disease (AD) pathologies and cognition. In total, 351 [268 cognitively unimpaired (CU), 83 cognitive impaired (CI)] older adults underwent multi-modal brain imaging to measure AD pathologies and cognitive assessments, and information on CR proxies was obtained. For overall participants, only education moderated the relationship between Aß deposition and cognition. Education, pIQ, and LCA, but not OC, showed moderating effect on the relationship between AD-signature cerebral hypometabolism and cognition. In contrast, only OC had a moderating effect on the relationship between cortical atrophy of the AD-signature regions and cognition. Such moderation effects of the CR proxies were similarly observed in CI individuals, but most of them were not in CU individuals. The findings suggest that the proposed CR proxies have different moderating effects on the relationships between specific AD pathologies and cognition.

An anti-cancer effect of Sambou bamboo saltTM in melanoma skin cancer both in vivo and in vitro models.

Bamboo salt has anti-allergic, anti-inflammatory, anti-oxidant, diabetics, anti-aging, and immune-enhancing effects, which are closely related to anti-cancer effect. The aim of this study was to investigate the anti-cancer effects of Sambou bamboo saltTM (SBS) in melanoma skin cancer in vivo and in vitro models. SBS-administered mice effectively reduced tumor growth and increased survival rate compared with B16F10 cell-inoculated mice without tissue damage, hepatotoxicity, and nephrotoxicity. SBS enhanced levels of immune-enhancing mediators, such as interferon-γ, interleukin (IL)-2, IL-6, IL-12, tumor necrosis factor-α, and IgE in serum and melanoma tissues. Furthermore, SBS enhanced activities of caspases and levels of Bax and p53, whereas decreased levels of Bcl-2. This reduction was a consequence of apoptosis signaling pathway. In conclusion, these results suggest that SBS is a potential substance for cancer therapy. SBS has the potential to be developed either as Korean traditional medicine or as a health functional food for cancer therapy. PRACTICAL APPLICATIONS: In these days cancer is one of the world's largest health problems. Bamboo salt is used as a Korean traditional food or medicine and has beneficial effect on inflammation. We have identified Sambou bamboo saltTM (SBS) is a potential substance for cancer therapy. These insights suggest that SBS can potentially be utilized for health functional foods for cancer treatment as well as improve various cancer diseases such as melanoma skin cancer.

Normative Study of the Block Design Test for Adults Aged 55 Years and Older in Korean Aging Population.

OBJECTIVE: The Block Design Test (BDT) is known to be an effective measure in diagnosing age-related cognitive decline of visuospatial function. The goal of this study is to investigate the effects of age, education years, and gender on the performance of the BDT and to provide normative data in Korean community-dwelling participants who are 55 to 90 years old. METHODS: The participants were 432 non-demented adults aging from 55 to 90 years old. The BDT was administered to participants according to its manual. Multiple linear regressions and analyses of variance were conducted, including age, gender, and educations were used as covariates. RESULTS: Age, educational years, and gender were found to be significantly associated with performance on the BDT. As age increased, BDT performance decreased. Educational years were associated with BDT performance. Men showed higher performance (29.9±10.3) compare to women (26.1±8.7). The BDT is influenced by age, educational years, and gender. CONCLUSION: Unlike the previous study, the current study shows that gender has a significant influence in visuospatial ability in the old population. Present normative data will be useful for clinicians in evaluating aging participants with cognitive impairment.

Validation of the Korean Version of the Anosognosia Questionnaire for Dementia.

OBJECTIVE: Anosognosia is a common phenomenon in individuals with dementia. Anosognosia Questionnaire for dementia (AQ-D) is a well-known scale for evaluating anosognosia. This study aimed to establish a Korean version of the AQ-D (AQ-D-K) and to evaluate the reliability and validity of the AQ-D-K in patients with Alzheimer's disease (AD) dementia. METHODS: We translated the original English version of AQ-D into Korean (AQ-D-K). Eighty-four subjects with very mild or mild AD dementia and their caregivers participated. Reliability of AQ-D-K was assessed by internal consistency and one-month test-retest reliability. Construct validity and concurrent validity were also evaluated. RESULTS: Internal consistencies of the AQ-D-K patient form and caregiver form were high (Cronbach alpha 0.95 and 0.93, respectively). The test-retest reliability of AQ-D-K measured by intra-class correlation coefficient was 0.84. Three factors were identified: 1) anosognosia of instrumental activity of daily living; 2) anosognosia basic activity of daily living; and 3) anosognosia of depression and disinhibition. AQ-D-K score was significantly correlated with the clinician-rated anosognosia rating scale (ARS), center for epidemiological studies-depression scale (CES-D) and state-trait anxiety inventory (STAI). CONCLUSION: The findings suggest that the AQ-D-K is a reliable and valid scale for evaluating anosognosia for AD dementia patients using Korean language.

Comparative study on the effect of hyperthermic massage and mechanical squeezing in the patients with mild and severe meibomian gland dysfunction: An interventional case series.

BACKGROUND: Meibomian glands exist beneath the palpebral conjunctiva; thus, it is invisible to the naked eye without infrared imaging. This study used meibography to group patients with meibomian gland dysfunction (MGD) and assessed the effects of hyperthermic massage and mechanical squeezing in both groups. MATERIALS AND METHODS: Patients with MGD were divided into two groups, according to the degree of meibomian gland loss: group 1, in which the sum of eyelid scores ranged from 0 to 4 (mild to moderate gland loss) and group 2, in which the sum of eyelid scores ranged from 5 to 6 (severe gland loss). Hyperthermic massage and mechanical squeezing were given to both groups once a week for 4 weeks, and only non-preservative artificial tears were allowed. Ocular surface disease index (OSDI), Schirmer's test, meibography score, tear break-up time (TBUT), ocular surface staining, expressible meibomian gland, and quality before and after treatment were compared. RESULTS: Of the 49 patients who completed the 4 weeks of treatment and the evaluation at week 5, 29 were assigned to group 1 and 20 were assigned to group 2. Meibography scores, OSDI, TBUT, and expressibility of meibum had significant differences before and after treatments in both groups. However, there was no significant difference between the changes in clinical signs between group 1 and 2 after treatment. Without grouping, all patients showed significant decreases in meibography score, OSDI, cornea staining score, and increases in TBUT and expressibility of meibum after treatment. CONCLUSIONS: Considering the results of the current study, hyperthermic massage and mechanical squeezing may be effective in patients with meibomian gland loss, regardless of the degree of severity.

Solitary Langerhans cell histocytosis of skull and spine in pediatric and adult patients.

PURPOSE: Langerhans cell histiocytosis (LCH) is a rare neoplasm and has heterogeneous clinical presentation and behavior. We analyzed solitary lytic lesions of the skull and spine in pediatric and adult patients. METHODS: Between 2001 and 2011, 42 patients underwent surgery for LCH. Skull and/or spine involvement were evident in 21 (63.6%) of the 33 pediatric patients and 8 (88.9%) of the 9 adults. The 21 pediatric patients showed the unifocal monosystemic lesions in 10, multifocal monosystemic in 4, and multisystemic in 7. The eight adults comprised seven unifocal lesions and one multifocal monosystemic lesion. Of these cases, we analyzed the clinical courses of solitary LCH of skull and spine in 10 pediatric patients and 7 adults. RESULTS: The median age was 10.1 years (range: 1.1-14.1) in pediatric patients and 34.6 years (range: 26.1-52.0) in adults. The median follow-up was 3.1 years (range: 0.6-9.5). Total excision was done in 15 patients and biopsy in 2. Postoperative adjuvant chemotherapy was done in four pediatric patients and one adult, and comprised mass with dural adhesion (N = 2), skull base lesion (N = 1), atlas mass (N = 1), and vertebral lesion with soft tissue extension (N = 1). During follow-up, recurrence occurred in one pediatric patient who had a skull LCH with a dural adhesion. The patient experienced central diabetes insipidus and scapular pain due to pituitary stalk and scapula involvement 1.3 and 2.4 years later, respectively. CONCLUSION: Even if the solitary lesions of skull and spine show a favorable clinical course, some patients could show aggressive behavior.

Mitochondrial DNA copy number and hnRNP A2/B1 protein: biomarkers for direct exposure of benzene.

The present study was performed to identify biomarkers for exposure of benzene in blood cells and hematopoietic tissues. Peripheral mononuclear cells, hematopoietic stem cells, and leukemia cell lines were cultured in RPMI 1640 media with the addition of 0, 1, and 10 mM of benzene. Hydrogen peroxide was measured using an enzyme immunoassay. Mitochondrial mass, membrane potential, and mitochondrial DNA (mtDNA) copy number were measured using MitoTracker Green/Red probes, and real-time polymerase chain reaction. In addition, two-dimensional gel electrophoresis and mass spectrometry matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology were performed to identify protein markers. The mitochondrial contents and membrane potentials were dramatically increased after three weeks of direct benzene exposure. The hydrogen peroxide level increased significantly after two weeks of treatment with benzene (4.4 ± 1.9 µM/mg protein) compared to the non-benzene treatment group (1.2 ± 1.0; p = 0.001). The mtDNA copy number gradually increased after exposure to benzene. Numerous protein markers showed significant aberrant expression after exposure to benzene. Among them, the heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 was markedly decreased after exposure to benzene. Thus, increased mitochondrial mass, mtDNA copy number, and the hnRNP A2/B1 protein were biomarkers for benzene-related toxicity and hematotoxicity.

Tetrasomy 21 as a sole acquired abnormality without GATA1 gene mutation in pediatric acute megakaryoblastic leukemia: a case report and review of the literature.

We report a case of pediatric acute megakaryocytic leukemia (AMKL) showing 48,XX,+21,+21 as a sole acquired cytogenetic abnormality without the mutation of GATA1 gene. A physical examination showed a phenotypically normal female. Bone marrow findings showed diffuse infiltration of leukemic blasts having scanty cytoplasm with budding blebs and prominent nucleoli, which were negative for myeloperoxide (MPO) stain, Sudan black B stain and periodic acid-Schiff stain. Immunophenotyping of leukemic cells revealed positive expression of CD34, CD13, CD33, CD117, CD41, CD61, CD7 and negative expression of TdT, anti-MPO, CD64, CD56, CD2, CD3, CD5, CD10, CD19, CD20 and CD22. A fluorescence in situ hybridization analysis showed four distinct AML1 signals in 284 of 300 interphase nuclei. The entire six exons of the GATA1 gene (7757bp) were directly sequenced. We could not find any mutations, including known polymorphisms, which are known to be involved in transient myeloproliferative disorder and acute megakaryocytic leukemia of Down syndrome. After achieving complete remission, the tetrasomy 21 disappeared.