Machine learning-based quantification for disease uncertainty increases the statistical power of genetic association studies.

MOTIVATION: Allowance for increasingly large samples is a key to identify the association of genetic variants with Alzheimer's disease (AD) in genome-wide association studies (GWAS). Accordingly, we aimed to develop a method that incorporates patients with mild cognitive impairment and unknown cognitive status in GWAS using a machine learning-based AD prediction model. RESULTS: Simulation analyses showed that weighting imputed phenotypes method increased the statistical power compared to ordinary logistic regression using only AD cases and controls. Applied to real-world data, the penalized logistic method had the highest AUC (0.96) for AD prediction and weighting imputed phenotypes method performed well in terms of power. We identified an association (P<5.0×10-8) of AD with several variants in the APOE region and rs143625563 in LMX1A. Our method, which allows the inclusion of individuals with mild cognitive impairment, improves the statistical power of GWAS for AD. We discovered a novel association with LMX1A. AVAILABILITY AND IMPLEMENTATION: Simulation codes can be accessed at https://github.com/Junkkkk/wGEE_GWAS.

Heritability of cognitive abilities and regional brain structures in middle-aged to elderly East Asians.

This study examined the single-nucleotide polymorphism heritability and genetic correlations of cognitive abilities and brain structural measures (regional subcortical volume and cortical thickness) in middle-aged and elderly East Asians (Korean) from the Gwangju Alzheimer's and Related Dementias cohort study. Significant heritability was found in memory function, caudate volume, thickness of the entorhinal cortices, pars opercularis, superior frontal gyri, and transverse temporal gyri. There were 3 significant genetic correlations between (i) the caudate volume and the thickness of the entorhinal cortices, (ii) the thickness of the superior frontal gyri and pars opercularis, and (iii) the thickness of the superior frontal and transverse temporal gyri. This is the first study to describe the heritability and genetic correlations of cognitive and neuroanatomical traits in middle-aged to elderly East Asians. Our results support the previous findings showing that genetic factors play a substantial role in the cognitive and neuroanatomical traits in middle to advanced age. Moreover, by demonstrating shared genetic effects on different brain regions, it gives us a genetic insight into understanding cognitive and brain changes with age, such as aging-related cognitive decline, cortical atrophy, and neural compensation.

Neuroticism, conscientiousness, and in vivo Alzheimer pathologies measured by amyloid PET and MRI.

AIM: It has been suggested that personality traits, particularly neuroticism and conscientiousness, are risk factors for Alzheimer's disease (AD) and related cognitive decline. However, the underlying pathological links between personality traits and AD-related cognitive impairments remain unclear. Thus, the present study investigated associations of neuroticism and conscientiousness with in vivo cerebral amyloid-beta (Aß) burden, AD-signature regional neurodegeneration, and white matter hyperintensities (WMH) in non-demented middle- and old-aged adults. METHODS: A total of 397 non-demented participants underwent comprehensive clinical and neuropsychological assessments, 11 C-labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. Additionally, the NEO Five-Factor Inventory was administered to both the participants and their informants to measure neuroticism and conscientiousness. RESULTS: Neither neuroticism nor conscientiousness was associated with cerebral Aß deposition or WMH. In contrast, higher neuroticism and lower conscientiousness, reported by informants in particular, were significantly associated with reduced AD-signature region cortical thickness. In regards to the direct and indirect effect of each personality on AD-signature region cortical thickness, only the direct effects were found, whereas indirect effects via Aß deposition or WMH were not. CONCLUSION: The present findings suggest that amyloid-independent regional neurodegeneration might underlie relations of neuroticism and conscientiousness with AD.

Frequency of Depressive Syndromes in Elderly Individuals with No Cognitive Impairment, Mild Cognitive Impairment, and Alzheimer's Disease Dementia in a Memory Clinic Setting.

AIMS: The aims of this study were to investigate the frequency of various depressive syndromes in elderly individuals with no cognitive impairment (NC), mild cognitive impairment (MCI), and Alzheimer's disease dementia (AD) in a memory clinic setting, and then to test whether severe and milder forms of depressive syndromes are differentially associated with the cognitive groups. METHODS: For 216 NC, 478 MCI, and 316 AD subjects, we investigated the frequency of depressive syndromes, defined by three different categories: major and minor depressive disorder (MaDD and MiDD) according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, as well as depression according to the National Institute of Mental Health provisional diagnostic criteria for depression in Alzheimer's disease (NIMH-dAD). RESULTS: The frequency of MaDD did not show any significant difference among NC, MCI, and AD. In contrast, the frequencies of MiDD and NIMH-dAD were higher than those of MaDD and showed significant group differences with a gradual increase from NC to AD. CONCLUSION: The findings suggest that the degenerative process of Alzheimer's disease contributes to the occurrence of mild depressive conditions, but not to severe depression.

Nodakenin Enhances Cognitive Function and Adult Hippocampal Neurogenesis in Mice.

In our previous study, we demonstrated that nodakenin, a coumarin compound isolated from Angelica decursiva, ameliorates learning and memory impairments induced by scopolamine. In the present study, we investigated the effects of nodakenin on the cognitive function in the normal naïve mice in a passive avoidance task, and the results showed that nodakenin significantly increased the latency time in normal naïve mice. In addition, sub-chronic administration of nodakenin increased the number of 5-bromo-2-deoxyuridine (BrdU)-positive cells in the hippocampal dentate gyrus (DG) region. The percentage of BrdU and NeuN (neuronal cell marker)-immunopositive cells was also significantly increased by the nodakenin administration. Western blotting results showed that the expression levels of phosphorylated protein kinase B (Akt) and phosphorylated glycogen synthase kinase-3ß (GSK-3ß) were significantly increased in hippocampal tissue by sub-chronic nodakenin administration. These findings suggest that the sub-chronic administration of nodakenin enhances adult hippocampal neurogenesis in the DG region via Akt-GSK-3ß signaling and this increase may be associated with nodakenin's positive effect on cognitive processing.

Impact of home-based exercise training with wireless monitoring on patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Recent studies have suggested a favorable effect of cardiac rehabilitation (CR) on patients with cardiovascular disease. This study aimed to evaluate the impact of home-based exercise training with wireless monitoring on acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). A total of 55 ACS patients undergoing PCI were randomly divided into home based exercise training with wireless monitoring cardiac rehabilitation (CR, n = 26) and usual care (UC, n = 29). Exercise capacity and quality of life (QOL) were evaluated at baseline and after 12 weeks. Change of metabolic equivalent of the tasks, maximal exercise time and QOL were significantly increased (+2.47 vs +1.43, P = 0.021; +169.68 vs +88.31 sec, P = 0.012; and +4.81 vs +0.89, P = 0.022, respectively), and the change of submaximal rate pressure product, and of submaximal rate of perceived exertion were significantly decreased (-28.24 vs -16.21, P = 0.013; and -1.92 vs -1.62, P = 0.018, respectively) in the CR group compared to the UC group after 12 weeks. CR using home-based exercise training with wireless monitoring led to improvement of exercise capacity and QOL relative to conventional care in ACS patients undergoing PCI. Our findings suggest that early scheduled CR may be considered in ACS patients undergoing PCI.

Effects of Home-based Exercise Training with Wireless Monitoring on the Left Ventricular Function of Acute Coronary Syndrome Patients.

[Purpose] While recent studies have reported that cardiac rehabilitation is an effective treatment, there have been few studies of its effects in rehabilitation for acute coronary syndrome (ACS). Therefore, the purpose of this study was to identify the effects of a home-based exercise training using a wireless electrocardiogram (ECG) monitoring device on ACS patients. [Subjects] Fifty ACS patients were randomly divided into a experimental group of 25 patients and a control group of 25 patients. [Methods] The experimental group received education on the training before discharge from hospital and started home-based exercise training two weeks after discharge from hospital. The control group received conventional treatments. The left ventricular function was measured in both groups before the intervention at and 12 weeks, at the end of the intervention. [Results] Both the experimental group and the control group showed significant improvements in the left ventricular ejection fraction and number of regional wall motion abnormalities. In the comparison of the two groups, the experimental group showed a significantly greater decline in regional wall motion abnormalities than the control group. [Conclusion] Home-based exercise training implemented with a wireless monitoring device was effective at improving the left ventricular function of ACS patients.

A study of effect of the compound physical activity therapy on muscular strength in obese women.

[Purpose] The aim of this study was to determine how compound physical activity affects muscular strength of middle-aged obese women. [Subjects] The research subjects were 40-50 year-old middle-aged women with excess body fat (30%). [Methods] The subjects were randomly assigned to two group, the experimental group and the control group. The experimental group performed two types of exercise programs for 16 weeks. Aerobic physical activity was performed 5 times per week, and anaerobic physical activity was performed every two days, and the exercise program each day was composed of a warm-up, the main exercise, and cooldown. The type of exercise focused on walking at a quick pace, and the intensity of the exercise focused on long periods of exercise at low intensity with the level of HRmax being 40-60%. The weight training, which was useful for beginners, as a type of kinetic load exercise, was applied with a composition recommended by the ACSM for muscle fitness (intensity of 40-60% of 1 RM and 10-15 repetitions). SPSS version 16.0 was used to analyze the data by ANCOVA and the t-test. [Results] The chest, leg, and abdominal strengths were significantly increased in the experimental group, and this indicates that compound physical activity is effective for improvement of muscular strength. [Conclusion] In conclusion, there were significant differences between groups in terms of muscular strength.

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.

Functional Neural Correlates of the WAIS-IV Block Design Test in Older Adult with Mild Cognitive Impairment and Alzheimer's Disease.

The Wechsler Adult intelligence scale-Revised (WAIS-R) Block design test (BDT) is a neuropsychological test widely used to assess cognitive declines in aging population. Previous studies suggest parietal lobe is the key region to influence the performance on the BDT; yet, it has not been clearly identified. The aim of the current study, therefore, is to identify the functional neural correlates of the BDT in older adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia patients. The current study includes 213 cognitively impaired mid to old-aged community dwelling Korean. All participants underwent comprehensive clinical and neuropsychological assessments and 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scans. Performance on the BDT was assessed using the WAIS-IV Korean version. Voxel-wise analyses were used to investigate the correlation between regional cerebral glucose metabolism and BDT performance. The same analyses were conducted on the subgroups categorized by clinical severity based on the Clinical Dementia Rating (CDR). Significant positive correlations between performance on the BDT and regional cerebral glucose metabolism were found bilaterally in the inferior parietal lobules, right thalamus and right middle frontal gyrus. Our results suggest that performance on the BDT in MCI and AD patients functionally relies on the brain regions known to be associated with motor and executive functions in addition to visuospatial function.

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.

Association of carotid and intracranial stenosis with Alzheimer's disease biomarkers.

BACKGROUND: To clarify whether atherosclerosis of the carotid and intracranial arteries is related to Alzheimer's disease (AD) pathology in vivo, we investigated the associations of carotid and intracranial artery stenosis with cerebral beta-amyloid (Aß) deposition and neurodegeneration in middle- and old-aged individuals. Given different variations of the pathologies between cognitive groups, we focused separately on cognitively normal (CN) and cognitively impaired (CI) groups. METHODS: A total of 281 CN and 199 CI (mild cognitive impairment and AD dementia) subjects underwent comprehensive clinical assessment, [11C] Pittsburgh compound B-positron emission tomography, and magnetic resonance (MR) imaging including MR angiography. We evaluated extracranial carotid and intracranial arteries for the overall presence, severity (i.e., number and degree of narrowing), and location of stenosis. RESULTS: We found no associations between carotid and intracranial artery stenosis and cerebral Aß burden in either the CN or the CI group. In terms of neurodegeneration, exploratory univariable analyses showed associations between the presence and severity of stenosis and regional neurodegeneration biomarkers (i.e., reduced hippocampal volume [HV] and cortical thickness in the AD-signature regions) in both the CN and CI groups. In confirmatory multivariable analyses controlling for demographic covariates and diagnosis, the association between number of stenotic intracranial arteries ≥ 2 and reduced HV in the CI group remained significant. CONCLUSIONS: Neither carotid nor intracranial artery stenosis appears to be associated with brain Aß burden, while intracranial artery stenosis is related to amyloid-independent neurodegeneration, particularly hippocampal atrophy.

Long-Term Exposure to PM10 and in vivo Alzheimer's Disease Pathologies.

BACKGROUND: Previous studies indicated an association between Alzheimer's disease (AD) dementia and air particulate matter (PM) with aerodynamic diameter <10µm (PM10), as well as smaller PM. Limited information, however, is available for the neuropathological links underlying such association. OBJECTIVE: This study aimed to investigate the relationship between long-term PM10 exposure and in vivo pathologies of AD using multimodal neuroimaging. METHODS: The study population consisted of 309 older adults without dementia (191 cognitively normal and 118 mild cognitive impairment individuals), who lived in Republic of Korea. Participants underwent comprehensive clinical assessments, 11C-Pittsburg compound B (PiB) positron emission tomography (PET), and magnetic resonance imaging scans. A subset of 78 participants also underwent 18F-AV-1451 tau PET evaluation. The mean concentration of PM with aerodynamic diameter <10µm over the past 5 years (PM10mean) collected from air pollution surveillance stations were matched to each participant's residence. RESULTS: In this non-demented study population, of which 62% were cognitively normal and 38% were in mild cognitive impairment state, exposure to the highest tertile of PM10mean was associated with increased risk of amyloid-ß (Aß) positivity (odds ratio 2.19, 95% confidence interval 1.13 to 4.26) even after controlling all potential confounders. In contrast, there was no significant associations between PM10mean exposure and tau accumulation. AD signature cortical thickness and white matter hyperintensity volume were also not associated with PM10mean exposure. CONCLUSION: The findings suggest that long-term exposure to PM10 may contribute to pathological Aß deposition.

Resting State Glucose Utilization and Adult Reading Test Performance.

Adult reading tests (ART) have been widely used in both research and clinical settings as a measure of premorbid cognitive abilities or cognitive reserve. However, the neural substrates underlying ART performance are largely unknown. Furthermore, it has not yet been examined whether the neural substrates of ART performance reflect the cortical regions associated with premorbid intelligence or cognitive reserve. The aim of the study is to identify the functional neural correlates of ART performance using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in the cognitively normal (CN) middle- and old-aged adults. Voxel-wise analyses revealed positive correlations between glucose metabolism and ART performance in the frontal and primary somatosensory regions, more specifically the lateral frontal cortex, anterior cingulate cortex and postcentral gyrus (PCG). When conducted again only for amyloid-ß (Aß)-negative individuals, the voxel-wise analysis showed significant correlations in broader areas of the frontal and primary somatosensory regions. This is the first neuroimaging study to directly demonstrate the cerebral resting-state glucose utilization associated with ART performance. Our findings provide important evidence at the neural level that ART predicts premorbid general intelligence and cognitive reserve, as brain areas that showed significant correlations with ART performance correspond to regions that have been associated with general intelligence and cognitive reserve.

Prediction of Amyloid Positivity in Mild Cognitive Impairment Using Fully Automated Brain Segmentation Software.

OBJECTIVE: To assess the predictive ability of regional volume information provided by fully automated brain segmentation software for cerebral amyloid positivity in mild cognitive impairment (MCI). METHODS: This study included 130 subjects with amnestic MCI who participated in the Korean brain aging study of early diagnosis and prediction of Alzheimer's disease, an ongoing prospective cohort. All participants underwent comprehensive clinical assessment as well as 11C-labeled Pittsburgh compound PET/MRI scans. The predictive ability of volumetric results provided by automated brain segmentation software was evaluated using binary logistic regression and receiver operating characteristic curve analysis. RESULTS: Subjects were divided into two groups: one with Aß deposition (58 subjects) and one without Aß deposition (72 subjects). Among the varied volumetric information provided, the hippocampal volume percentage of intracranial volume (%HC/ICV), normative percentiles of hippocampal volume (HCnorm), and gray matter volume were associated with amyloid-ß (Aß) positivity (all P < 0.01). Multivariate analyses revealed that both %HC/ICV and HCnorm were independent significant predictors of Aß positivity (all P < 0.001). In addition, prediction scores derived from %HC/ICV with age and HCnorm showed moderate accuracy in predicting Aß positivity in MCI subjects (the areas under the curve: 0.739 and 0.723, respectively). CONCLUSION: Relative hippocampal volume measures provided by automated brain segmentation software can be useful for screening cerebral Aß positivity in clinical practice for patients with amnestic MCI. The information may also help clinicians interpret structural MRI to predict outcomes and determine early intervention for delaying the progression to Alzheimer's disease dementia.

The Ankle-Brachial Index Is Associated with Cerebral ß-Amyloid Deposition in Cognitively Normal Older Adults.

BACKGROUND: Although ankle-brachial index (ABI), an indicator of atherosclerosis or arterial stiffness, has been associated with dementia and Alzheimer's disease (AD), no information is yet available for its contribution to AD pathologies. We investigated the relationship between the ABI and in vivo ß-amyloid (Aß) deposition and AD-specific neurodegeneration in cognitively normal (CN) elderly individuals. METHODS: A total of 256 CN elderly subjects who participated in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study, were included. All subjects underwent comprehensive clinical and neuropsychological assessments, ABI measurement, apolipoprotein E (APOE) genotyping, [11C]Pittsburgh Compound B (PiB)-positron emission tomography (PET), [18F]-fludeoxyglucose PET, and magnetic resonance imaging. RESULTS: A significant positive association was found between the ABI and global cerebral Aß retention measured by PiB-PET, even after controlling for age, sex, and APOE ε4. When three stratified ABI subgroups (ABI < 1.00, 1.00-1.29, and ≥ 1.30) were compared, the highest ABI subgroup (ie, ABI ≥ 1.30) showed significantly higher Aß deposition than that of the other subgroups. This relationship between Aß deposition and the ABI was significant only in APOE ε4 carriers, but not in noncarriers. No significant association was observed between the ABI and neurodegeneration in the AD-signature regions. CONCLUSION: Our findings suggest that a high ABI, possibly related to arterial stiffness, is associated with elevated brain Aß burden in cognitively healthy elderly individuals, particularly in APOE ε4 carriers.

Region-specific association between basal blood insulin and cerebral glucose metabolism in older adults.

BACKGROUND: Although previous studies have suggested that insulin plays a role in brain function, it still remains unclear whether or not insulin has a region-specific association with neuronal and synaptic activity in the living human brain. We investigated the regional pattern of association between basal blood insulin and resting-state cerebral glucose metabolism (CMglu), a proxy for neuronal and synaptic activity, in older adults. METHOD: A total of 234 nondiabetic, cognitively normal (CN) older adults underwent comprehensive clinical assessment, resting-state 18F-fluodeoxyglucose (FDG)-positron emission tomography (PET) and blood sampling to determine overnight fasting blood insulin and glucose levels, as well as apolipoprotein E (APOE) genotyping. RESULTS: An exploratory voxel-wise analysis of FDG-PET without a priori hypothesis demonstrated a positive association between basal blood insulin levels and resting-state CMglu in specific cerebral cortices and hippocampus, rather than in non-specific overall cerebral regions, even after controlling for the effects of APOE e4 carrier status, vascular risk factor score, body mass index, fasting blood glucose, and demographic variables. Particularly, a positive association of basal blood insulin with CMglu in the right posterior hippocampus and adjacent parahippocampal region as well as in the right inferior parietal region remained significant after multiple comparison correction. Conversely, no region showed negative association between basal blood insulin and CMglu. CONCLUSIONS: Our finding suggests that basal fasting blood insulin may have association with neuronal and synaptic activity in specific cerebral regions, particularly in the hippocampal/parahippocampal and inferior parietal regions.

Prediction of Cerebral Amyloid With Common Information Obtained From Memory Clinic Practice.

Background: Given the barriers prohibiting the broader utilization of amyloid imaging and high screening failure rate in clinical trials, an easily available and valid screening method for identifying cognitively impaired patients with cerebral amyloid deposition is needed. Therefore, we developed a prediction model for cerebral amyloid positivity in cognitively impaired patients using variables that are routinely obtained in memory clinics. Methods: Six hundred and fifty two cognitively impaired subjects from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer disease (KBASE) and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohorts were included in this study (107 amnestic mild cognitive impairment (MCI) and 69 Alzheimer's disease (AD) dementia patients for KBASE cohort, and 332 MCI and 144 AD dementia patients for ADNI-2 cohort). Using the cross-sectional dataset from the KBASE cohort, a multivariate stepwise logistic regression analysis was conducted to develop a cerebral amyloid prediction model using variables commonly obtained in memory clinics. For each participant, the logit value derived from the final model was calculated, and the probability for being amyloid positive, which was calculated from the logit value, was named the amyloid prediction index. The final model was validated using an independent dataset from the ADNI-2 cohort. Results: The final model included age, sex, years of education, history of hypertension, apolipoprotein ε4 positivity, and score from a word list recall test. The model predicted that younger age, female sex, higher educational level, absence of hypertension history, presence of apolipoprotein ε4 allele, and lower score of word list recall test are associated with higher probability for being amyloid positive. The amyloid prediction index derived from the model was proven to be valid across the two cohorts. The area under the curve was 0.873 (95% confidence interval 0.815 to 0.918) for the KBASE cohort, and 0.808 (95% confidence interval = 0.769 to 0.842) for ADNI-2 cohort. Conclusion: The amyloid prediction index, which was based on commonly available clinical information, can be useful for screening cognitively impaired individuals with a high probability of amyloid deposition in therapeutic trials for early Alzheimer's disease as well as in clinical practice.