The Usefulness of 18F-FDG PET to Differentiate Subtypes of Dementia: The Systematic Review and Meta-Analysis.

Background and Purpose: Dementia subtypes, including Alzheimer's dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) in differentiating these subtypes for precise treatment and management. Methods: A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the gold-standard clinical diagnosis for dementia subtypes. Results: From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88-0.98) and specificity was 0.84 (95% CI, 0.70-0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70-0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80-0.91) and the specificity was 0.88 (95% CI, 0.80-0.91). The studies mostly used case-control designs with visual and quantitative assessments. Conclusions: 18F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.

Factors Associated with Smokers Attending More Than One Smoking Cessation Clinic Visit.

Smoking remains a primary cause of cancers, cardiovascular and respiratory diseases and death. Globally, efforts have been made to reduce smoking rates, but the addictive nature of nicotine, a key component of tobacco, makes cessation challenging for smokers. Medical interventions including medical advice and pharmacotherapies are effective methods for smoking cessation. The frequency of medical interventions correlates with success in smoking cessation. This study aims to compare the characteristics of the patients who visited the smoking cessation clinic once with those who visited more than once, in order to identify factors that are associated with repeat clinic visits. A total of 81 patients who have visited the smoking cessation clinic in Kangwon National University Hospital were included. Patients answered the questionnaire at their first visit. If the patient visited only once, the outcome was defined as negative and if the patient visited more than once, the outcome was defined as positive. The proportion of patients who answered "within 5 min" to the Fagerstrom Test for Nicotine Dependence's (FTND) 1st question and answered "yes" to the FTND's 6th question was higher in the negative outcome group. In the logistic regression, patients who had withdrawal symptoms previously were associated with positive outcomes (adjusted OR 3.466, 95% CI 1.088-11.034 and p value = 0.0354). Withdrawal symptoms during previous attempts were positively related to visiting the clinic more than once.

A Preliminary Study on the Potential Protective Role of the Antioxidative Stress Markers of Cognitive Impairment: Glutathione and Glutathione Reductase.

Objective: : To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer's dementia and cognitive decline. Methods: : In all, 20 participants with Alzheimer's dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: : The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer's dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion: : The higher the GR, the lower the prevalence of Alzheimer's dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer's dementia and cognitive decline.

Influence of Sensory Impairments on Incidence of Dementia in the Korean Population.

OBJECTIVE: Previous studies have shown the influence of visual and auditory sensory impairment on dementia incidence. In this study, we tested the hypothesis that the incidence of dementia will increase with visual and auditory impairments than with visual or auditory impairment. METHODS: Data from the Korea National Health Insurance Service database were used, including disease and medication codes from 2009 to 2018, and the 2011 national health check-up results. Participants were grouped based on their sensory abilities: normal, visual impairment, auditory impairment, and both visual and auditory impairments (dual sensory impairment). To compare the incidence of dementia, hazard ratios were calculated for each group, with reference to the normal sensory (NS) group. Sensitivity analyses were performed comparing dementia incidence from 2014 to 2018, excluding the onset of the disease in 2012 and 2013. RESULTS: We identified 8,289 cases of dementia during the seven-year follow-up. In the multiple Cox regression analysis, adjusted for sex, social economic status, age, comorbidities, smoking, alcohol consumption, and activity level, the auditory impairment (hazard ratio= 1.1908) and visual impairment (hazard ratio=1.3553) groups showed a significantly higher dementia incidence than the NS group. Dual sensory impairment (hazard ratio=1.5267) showed the highest incidence. The sensitivity analysis yielded similar results. CONCLUSION: Visual and auditory impairments are associated with an increased risk of dementia, particularly in individuals with dual sensory impairment. Hence, visual and auditory impairments might have increased the risk of dementia through independent pathological processes. Therefore, preventing and correcting sensory impairment is necessary to reduce the risk of dementia.

Dementia Incidence Rate Before and After Implementing the National Responsibility Policy for Dementia Care in Patients With Vascular Risk Factors in Korea.

Background and Purpose: The National Responsibility Policy for Dementia Care was implemented in September 2017 in Korea. This study aimed to compare dementia incidence in Seoul and Gangwon-do before and after the implementation of this policy. Methods: We extracted insurance claim data from the Korean Health Insurance Review and Assessment Service for people diagnosed with diabetes, hypertension, or dyslipidemia for the first time in Seoul and Gangwon-do, Korea. We defined two enrollment groups based on the policy implementation date: 1) January 1, 2015 to December 31, 2016 (Index 1, pre-implementation), and 2) January 1, 2017 to December 31, 2018 (Index 2, post-implementation). Each group was followed up for 1 year from the time of enrollment. Then, we calculated hazard ratios to compare the incidence of dementia between the two groups, and between Seoul and Gangwon-do. Results: In Seoul, the incidence of dementia was significantly lower in Index 2 than in Index 1 (hazard ratio [HR], 0.926; 95% confidence interval [CI], 0.875-0.979). However, the incidence rate did not differ between the 2 groups (HR, 1.113; 95% CI, 0.966-1.281) in Gangwon-do. In Index 1, the incidence of dementia did not differ between Seoul and Gangwon-do (HR, 1.043; 95% CI, 0.941-1.156), but in Index 2, was significantly higher in Gangwon-do than in Seoul (HR, 1.240; 95% CI, 1.109-1.386). Conclusions: After implementing the National Responsibility Policy for Dementia Care, the dementia incidence rate decreased significantly in Seoul, consistent with other studies, but not in Gangwon-do.

Deep learning application for the classification of Alzheimer's disease using 18F-flortaucipir (AV-1451) tau positron emission tomography.

The positron emission tomography (PET) with 18F-flortaucipir can distinguish individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from cognitively unimpaired (CU) individuals. This study aimed to evaluate the utility of 18F-flortaucipir-PET images and multimodal data integration in the differentiation of CU from MCI or AD through DL. We used cross-sectional data (18F-flortaucipir-PET images, demographic and neuropsychological score) from the ADNI. All data for subjects (138 CU, 75 MCI, 63 AD) were acquired at baseline. The 2D convolutional neural network (CNN)-long short-term memory (LSTM) and 3D CNN were conducted. Multimodal learning was conducted by adding the clinical data with imaging data. Transfer learning was performed for classification between CU and MCI. The AUC for AD classification from CU was 0.964 and 0.947 in 2D CNN-LSTM and multimodal learning. The AUC of 3D CNN showed 0.947, and 0.976 in multimodal learning. The AUC for MCI classification from CU had 0.840 and 0.923 in 2D CNN-LSTM and multimodal learning. The AUC of 3D CNN showed 0.845, and 0.850 in multimodal learning. The 18F-flortaucipir PET is effective for the classification of AD stage. Furthermore, the effect of combination images with clinical data increased the performance of AD classification.

Moderation of Marital and Occupational Status on the Effect of Personality Trait on 1 Year Suicidality of Middle-Aged Adults.

OBJECTIVE: This study aimed to examine how marital status, occupational status, and individual personality influence suicidal ideation and suicide attempts among Korean middle-aged adults, and explore the effects of their interaction. METHODS: A total of 2,464 middle-aged adults were surveyed about suicidality in the past year (1-year suicidality). Participants' current marital and occupational status, including other demographic and clinical variables were investigated. Personality traits were assessed using the Big Five Inventory. The dependent variable was the presence of 1-year suicidality. Independent variables were current marital and occupational status. Generalized linear model (GLM) analysis was performed to adjust for other covariates. RESULTS: The group with 1-year suicidality had significantly lower income. It had a lower proportion of full-time employment, and higher percentages of part-time employment and unemployment. The GLM analysis results showed that marital and occupational status had no significant association with 1-year suicidality. Neuroticism and openness were positively associated with 1-year suicidality, whereas conscientiousness and extraversion had a negative association. Interactions between marital status and neuroticism, conscientiousness, and occupational status were significant. CONCLUSION: Individualized social and psychological interventions for suicide prevention are required according to individual personality traits.

Machine learning application for classification of Alzheimer's disease stages using 18F-flortaucipir positron emission tomography.

BACKGROUND: The progression of Alzheimer's dementia (AD) can be classified into three stages: cognitive unimpairment (CU), mild cognitive impairment (MCI), and AD. The purpose of this study was to implement a machine learning (ML) framework for AD stage classification using the standard uptake value ratio (SUVR) extracted from 18F-flortaucipir positron emission tomography (PET) images. We demonstrate the utility of tau SUVR for AD stage classification. We used clinical variables (age, sex, education, mini-mental state examination scores) and SUVR extracted from PET images scanned at baseline. Four types of ML frameworks, such as logistic regression, support vector machine (SVM), extreme gradient boosting, and multilayer perceptron (MLP), were used and explained by Shapley Additive Explanations (SHAP) to classify the AD stage. RESULTS: Of a total of 199 participants, 74, 69, and 56 patients were in the CU, MCI, and AD groups, respectively; their mean age was 71.5 years, and 106 (53.3%) were men. In the classification between CU and AD, the effect of clinical and tau SUVR was high in all classification tasks and all models had a mean area under the receiver operating characteristic curve (AUC) > 0.96. In the classification between MCI and AD, the independent effect of tau SUVR in SVM had an AUC of 0.88 (p < 0.05), which was the highest compared to other models. In the classification between MCI and CU, the AUC of each classification model was higher with tau SUVR variables than with clinical variables independently, which yielded an AUC of 0.75(p < 0.05) in MLP, which was the highest. As an explanation by SHAP for the classification between MCI and CU, and AD and CU, the amygdala and entorhinal cortex greatly affected the classification results. In the classification between MCI and AD, the para-hippocampal and temporal cortex affected model performance. Especially entorhinal cortex and amygdala showed a higher effect on model performance than all clinical variables in the classification between MCI and CU. CONCLUSIONS: The independent effect of tau deposition indicates that it is an effective biomarker in classifying CU and MCI into clinical stages using MLP. It is also very effective in classifying AD stages using SVM with clinical information that can be easily obtained at clinical screening.

Sex differences in the progression of glucose metabolism dysfunction in Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by amyloid plaques and impaired brain metabolism. Because women have a higher prevalence of AD than men, sex differences are of great interest. Using cross-sectional and longitudinal data, we showed sex-dependent metabolic dysregulations in the brains of AD patients. Cohort 1 (South Korean, n = 181) underwent Pittsburgh compound B-PET, fluorodeoxyglucose-PET, magnetic resonance imaging, and blood biomarker (plasma tau and beta-amyloid 42 and 40) measurements at baseline and two-year follow-ups. Transcriptome analysis of data from Cohorts 2 and 3 (European, n = 78; Singaporean, n = 18) revealed sex differences in AD-related alterations in brain metabolism. In women (but not in men), all imaging indicators displayed consistent correlation curves with AD progression. At the two-year follow-up, clear brain metabolic impairment was revealed only in women, and the plasma beta-amyloid 42/40 ratio was a possible biomarker for brain metabolism in women. Furthermore, our transcriptome analysis revealed sex differences in transcriptomes and metabolism in the brains of AD patients as well as a molecular network of 25 female-specific glucose metabolic genes (FGGs). We discovered four key-attractor FGG genes (ALDOA, ENO2, PRKACB, and PPP2R5D) that were associated with amyloid/tau-related genes (APP, MAPT, BACE1, and BACE2). Furthermore, these genes successfully distinguished amyloid positivity in women. Understanding sex differences in the pathogenesis of AD and considering these differences will improve development of effective diagnostics and therapeutic treatments for AD.

Evidence of risky driving in Korean older adults: A longitudinal cohort.

OBJECTIVES: The aim of this study was to determine the differences in the risk factors for dangerous driving between older adults with normal cognition and those with cognitive impairment. DESIGN: The driving risk questionnaire (DRQ) that was applied to a community-dwelling older adult cohort and 2 years of accident/violation records from the National Police Agency were analyzed. We conducted regression analyses with the presence or absence of risky driving based on records (accidents + violations) 2 years before and after evaluation as a dependent variable and dichotomized scores of each risky driving factor as independent variables. RESULTS: According to four identified factors-crash history, safety concern, reduced mileage, and aggressive driving-significant associations were found between risky driving over the past 2 years and crash history and for aggressive driving in the normal cognition group. In the cognitive impairment group, only crash history was significantly associated, although safety concerns showed a trend toward significance. CONCLUSIONS: In this study, it was suggested that the factors of DRQ have a significant association with actual risky driving. Our results are expected to contribute to establishing the evidence for evaluating and predicting risky driving and advising whether to continue driving in clinics.

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.

Risk factors and outcomes of internet gaming disorder identified in Korean prospective adolescent cohort study.

Background and aims: Internet gaming disorder (IGD) is known to cause various psychological and physical complications. Through data collected from an adolescent prospective longitudinal cohort, we examined how IGD is related to lifestyle and physical symptoms, as well as the temporal relationship between them. Methods: This study was conducted as part of iCURE (Internet user Cohort for Unbiased Recognition of gaming disorder in Early Adolescence) in Korea between 2015 and 2019. Sleep and physical activity time, dry eye symptoms, musculoskeletal pain, and near-miss accidents were measured at baseline and followed-up after one year. IGD risk was evaluated using the Internet Game Use - Elicited Symptom Screen (IGUESS). The association between IGD risk and measured variables was analyzed, both at baseline and at follow-up after one year. Results: At baseline, the IGD risk group had significantly less physical activity time and sleep time and had more dry eye symptoms, musculoskeletal pain, and near-miss accidents than the IGD non-risk group. Additionally, in the IGD risk group at baseline, dry eye symptoms, musculoskeletal pain, and near-miss accidents occurred significantly more after one year of follow-up. Discussion and conclusion: The results of this study show that IGD is a significant risk factor that increases the probability of physical disease and trauma in adolescents. Therefore, interventions aimed at reducing IGD risk and protecting the physical and mental health of adolescents are imperative.

Predicting progression to dementia with "comprehensive visual rating scale" and machine learning algorithms.

Background and Objective: Identifying biomarkers for predicting progression to dementia in patients with mild cognitive impairment (MCI) is crucial. To this end, the comprehensive visual rating scale (CVRS), which is based on magnetic resonance imaging (MRI), was developed for the assessment of structural changes in the brains of patients with MCI. This study aimed to investigate the use of the CVRS score for predicting dementia in patients with MCI over a 2-year follow-up period using various machine learning (ML) algorithms. Methods: We included 197 patients with MCI who were followed up more than once. The data used for this study were obtained from the Japanese-Alzheimer's Disease Neuroimaging Initiative study. We assessed all the patients using their CVRS scores, cortical thickness data, and clinical data to determine their progression to dementia during a follow-up period of over 2 years. ML algorithms, such as logistic regression, random forest (RF), XGBoost, and LightGBM, were applied to the combination of the dataset. Further, feature importance that contributed to the progression from MCI to dementia was analyzed to confirm the risk predictors among the various variables evaluated. Results: Of the 197 patients, 108 (54.8%) showed progression from MCI to dementia. Tree-based classifiers, such as XGBoost, LightGBM, and RF, achieved relatively high performance. In addition, the prediction models showed better performance when clinical data and CVRS score (accuracy 0.701-0.711) were used than when clinical data and cortical thickness (accuracy 0.650-0.685) were used. The features related to CVRS helped predict progression to dementia using the tree-based models compared to logistic regression. Conclusions: Tree-based ML algorithms can predict progression from MCI to dementia using baseline CVRS scores combined with clinical data.

Application of QPLEXTM biomarkers in cognitively normal individuals across a broad age range and diverse regions with cerebral amyloid deposition.

The deposition of beta-amyloid (Aß) in the brain precedes the onset of symptoms such as cognitive impairment in Alzheimer's disease (AD); therefore, the early detection of Aß accumulation is crucial. We previously reported the applicability of the QPLEXTM Alz plus assay kit for the prescreening of Aß accumulation. Here, we tested the specific application of the kit in a large cohort of cognitively normal (CN) individuals of varying ages for the early detection of Aß accumulation. We included a total of 221 CN participants with or without brain Aß. The QPLEXTM biomarkers were characterized based on age groups (1st-3rd tertile) and across various brain regions with cerebral amyloid deposition. The 3rd tertile group (>65 years) was found to be the most suitable age group for the application of our assay kit. Receiver operating characteristic curve analysis showed that the area under the curve (AUC, discrimination power) was 0.878 with 69.7% sensitivity and 98.4% specificity in the 3rd tertile group. Additionally, specific correlations between biomarkers and cerebral amyloid deposition in four different brain regions revealed an overall correlation with general amyloid deposition, consistent with previous findings. Furthermore, the combinational panel with plasma Aß1-42 levels maximized the discrimination efficiency and achieved an AUC of 0.921 with 95.7% sensitivity and 67.3% specificity. Thus, we suggest that the QPLEXTM Alz plus assay is useful for prescreening brain Aß levels in CN individuals, especially those aged >65 years, to prevent disease progression via the early detection of disease initiation.

Associations between game use and mental health in early adulthood: A nationwide study in Korea.

BACKGROUND: The number of digital game users is increasing, and so is attention to digital gaming's effects on mental health. We aimed to reveal if risky (game addiction) and usual game use (non-risky) are associated with mental health in early adulthood. METHODS: Using data from the nationwide cross-sectional Korean Epidemic Catchment Area study for psychiatric disorders, 415 participants aged 18-30 years were divided into "non-game," "usual game," and "risky game" user groups based on the previous month's game use and cut-off value of game overuse screening questionnaire. Multiple linear and logistic regressions revealed the association between game use groups, perceived mental health, and lifetime prevalence of clinical mental disorders including suicidal ideation. RESULTS: Among the 415 participants, 167 were non-game users, 175, usual game users, and 73, risky game users. Risky game users self-reported decreased satisfaction and happiness, and a significantly higher lifetime prevalence of major depressive disorder, alcohol dependence, and suicidal ideation. Usual game users were significantly associated with higher lifetime prevalence of alcohol dependence and suicidal ideation. Self-reported happiness partially mediated between game use and lifetime suicidal ideation in risky, but not usual game users. LIMITATIONS: This study is a cross-sectional observational study which was not possible to define the temporal relationship. CONCLUSIONS: Both risky and usual game use are associated with mental health problems in early adulthood, indicating the need for careful mental health screening on not only risky game users but also usual game users.

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.

Development of a Short Form Depression Screening Questionnaire for Korean Soldiers.

BACKGROUND: The frequencies of South Korean soldiers' depression and resulting suicide are increasing every year. Thus, this study aimed to develop and confirm the reliability and validity of a simple short form depression screening scale for soldiers. METHODS: This study was conducted as part of a 2013 research project named 'The Epidemiological Study on the Prevalence of Depression in Military Service and a Search for High Risk Group Management.' Clinical depression was diagnosed using the Korean version of the Mini International Neuropsychiatric Interview and suicide risk was assessed through the Korean version of the Composite International Diagnostic Interview. Furthermore, the Center for Epidemiological Studies for Depression Scale (CES-D), the Stress Response Inventory, and the Barret Impulsiveness Scale were employed. Of the 20 CES-D items, three of the most correlated items with clinical diagnosis were derived to form the short form scale. Analyses for internal consistency, concurrent validity, and factor analysis were implemented for its validation. We performed a receiver operating curve (ROC) analysis using a clinical diagnosis of depression as a gold standard to calculate the area under the curve (AUC) value, cut-off score, and corresponding sensitivity and specificity to that cut-off score. RESULTS: According to the results of the correlation analysis, 7, 18, and 4 were selected to be on our scale. The three-item scale was reliable with a Cronbach's alpha value of 0.720, and a factor was derived from the factor analysis. The ROC analysis showed a high discriminant validity, with an AUC value of 0.891. The sensitivity and specificity were 84.8% and 78.2%, and 71.7% and 91.6%, respectively, for each when the selected cut-off scores were 2 and 3, respectively. Depression screened through the scale when the cut-off score was 2 or 3 was significantly associated with suicidality, stress, and social support. CONCLUSION: The depression screening questionnaire for Korean soldiers developed through this study demonstrated high reliability and validity. Since it comprises only three items, it can be utilized easily and frequently. It is expected to be employed in a large-scale suicide prevention project targeting military soldiers in the future; it will be beneficial in selecting high-risk groups for depression.

The clinical use of blood-test factors for Alzheimer's disease: improving the prediction of cerebral amyloid deposition by the QPLEXTM Alz plus assay kit.

Alzheimer's disease (AD) is the leading cause of dementia, and many studies have focused on finding effective blood biomarkers for the accurate diagnosis of this disease. Predicting cerebral amyloid deposition is considered the key for AD diagnosis because a cerebral amyloid deposition is the hallmark of AD pathogenesis. Previously, blood biomarkers were discovered to predict cerebral amyloid deposition, and further efforts have been made to increase their sensitivity and specificity. In this study, we analyzed blood-test factors (BTFs) that can be commonly measured in medical health check-ups from 149 participants with cognitively normal, 87 patients with mild cognitive impairment, and 64 patients with clinically diagnosed AD dementia with brain amyloid imaging data available. We demonstrated that four factors among regular health check-up blood tests, cortisol, triglyceride/high-density lipoprotein cholesterol ratio, alanine aminotransferase, and free triiodothyronine, showed either a significant difference by or correlation with cerebral amyloid deposition. Furthermore, we made a prediction model for Pittsburgh compound B-positron emission tomography positivity, using BTFs and the previously discovered blood biomarkers, the QPLEXTM Alz plus assay kit biomarker panel, and the area under the curve was significantly increased up to 0.845% with 69.4% sensitivity and 90.6% specificity. These results show that BTFs could be used as co-biomarkers and that a highly advanced prediction model for amyloid plaque deposition could be achieved by the combinational use of diverse biomarkers.

Dual Sensory Impairment and Cognitive Impairment in the Korean Longitudinal Elderly Cohort.

OBJECTIVE: To investigate the effects of single sensory impairment (SSI; visual or auditory) or dual sensory impairment (DSI; visual and auditory) on dementia and longitudinal changes of neuropsychological test scores. METHODS: In this nationwide, prospective, community-based elderly cohort study, KLOSCAD (the Korean Longitudinal Study on Cognitive Aging and Dementia), 6,520 elderly individuals (58-101 years) representing the general population were included. We defined visual and auditory sensory impairment via self-report questionnaire: 932 had normal sensory function, 2,957 had an SSI, and 2,631 had a DSI. Demographic and clinical variables including cognitive outcomes were evaluated every 2 years over 6 years. Through logistic regression, Cox regression, and linear mixed model analysis, the relationship between SSI or DSI and dementia prevalence, dementia incidence, and change in neuropsychological scores were evaluated. RESULTS: At baseline, DSI was significantly associated with increased dementia prevalence compared to normal sensory function (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.17-4.02), but SSI was not (OR 1.27, 95% CI 0.66-2.41). During the 6-year follow-up, the incidence of dementia was significantly higher in the DSI group than in the normal sensory function group (hazard ratio 1.9, 95% CI 1.04-3.46) and neuropsychological scores significantly decreased (ß -0.87, 95% CI [-1.17 to -0.58]). CONCLUSIONS: Our results suggest that coexisting visual and hearing impairments facilitate dementia prevalence, dementia incidence, and cognitive decline, but visual or hearing impairment alone do not. Visual and hearing impairment may lead to dementia or cognitive decline independent of Alzheimer pathology.

Synergistic Effect of Serum Homocysteine and Diabetes Mellitus on Brain Alterations.

BACKGROUND: Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM. OBJECTIVE: This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-ß and tau deposition, and small vessel disease (SVD) related to cognitive impairments. METHODS: A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11C] Pittsburgh Compound B (PiB) PET, [18F] AV-1451 PET, and brain MRI. RESULTS: The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer's disease (AD) pathologies, including amyloid-ß and tau deposition, nor white matter hyperintensity volume as a measure of SVD. CONCLUSION: The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM.