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Background: Neuropsychiatric symptoms and delusions are highly prevalent among people with dementia. However, multiple roots of neurobiological bases and shared neural basis of delusion and cognitive function remain to be characterized. By utilizing a fine-grained multivariable approach, we investigated distinct neuroanatomical correlates of delusion symptoms across a large population of dementing illnesses., Methods: In this study, 750 older adults with mild cognitive impairment and Alzheimer's disease completed brain structural imaging and neuropsychological assessment. We utilized principal component analysis followed by varimax rotation to identify the distinct multivariate correlates of cortical thinning patterns. Five of the cognitive domains were assessed whether the general cognitive abilities mediate the association between cortical thickness and delusion., Results: The result showed that distributed thickness patterns of temporal and ventral insular cortex (component 2), inferior and lateral prefrontal cortex (component 1), and somatosensory-visual cortex (component 5) showed negative correlations with delusions. Subsequent mediation analysis showed that component 1 and 2, which comprises inferior frontal, anterior insula, and superior temporal regional thickness accounted for delusion largely through lower cognitive functions. Specifically, executive control function assessed with the Trail Making Test mediated the relationship between two cortical thickness patterns and delusions., Discussion: Our findings suggest that multiple distinct subsets of brain regions underlie the delusions among older adults with cognitive impairment. Moreover, a neural loss may affect the occurrence of delusion in dementia largely due to impaired general cognitive abilities., (© 2024. The Author(s).)

Background: White matter (WM) microstructural changes in the hippocampal cingulum bundle (CBH) in Alzheimer's disease (AD) have been described in cohorts of largely European ancestry but are lacking in other populations., Methods: We assessed the relationship between CBH WM integrity and cognition or amyloid burden in 505 Korean older adults aged ≥ 55 years, including 276 cognitively normal older adults (CN), 142 with mild cognitive impairment (MCI), and 87 AD patients, recruited as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) at Seoul National University., Results: Compared to CN, AD and MCI subjects showed significantly higher RD, MD, and AxD values (all p-values < 0.001) and significantly lower FA values (left p ≤ 0.002, right p ≤ 0.015) after Bonferroni adjustment for multiple comparisons. Most tests of cognition and mood (p < 0.001) as well as higher medial temporal amyloid burden (p < 0.001) were associated with poorer WM integrity in the CBH after Bonferroni adjustment., Conclusion: These findings are consistent with patterns of WM microstructural damage previously reported in non-Hispanic White (NHW) MCI/AD cohorts, reinforcing existing evidence from predominantly NHW cohort studies., (© 2023. The Author(s).)

Objectives: Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive long-term memory loss and cognitive dysfunction. Neuroimaging tests for abnormal amyloid-β (Aβ) deposition are considered the most reliable methods for the diagnosis of AD; however, the cost for such testing is very high and generally not covered by national insurance systems. Accordingly, it is only recommended for individuals exhibiting clinical symptoms of AD supported by clinical cognitive assessments. Recently, it was suggested that dysregulated microRNA-485-3p (miRNA-485-3p) in the brain and cerebrospinal fluid is closely related to pathogenesis of AD. However, a relationship between circulating miRNA-485-3p in salivary exosome-enriched extracellular vesicles (EE-EV) and Aβ deposition in the brain has not been observed., Design & Methods: Using quantitative real-time polymerase chain reaction, we analyzed miRNA-485-3p concentration in salivary EE-EV. We used receiver operating characteristic (ROC) curve analysis to evaluate its predictive value for Aβ positron emission tomography (Aβ-PET) positivity in patients with AD., Results: Our results showed that the miRNA-485-3p concentration in salivary EE-EV isolated from patients with AD was significantly increased compared with that in the healthy controls (p < 0.0001). In the analysis of all participants, the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive participants compared to Aβ-PET-negative participants (p < 0.0001). Further analysis using only AD patients also showed that the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive AD patients vs. Aβ-PET-negative AD patients (p = 0.0063). The ROC curve analysis for differentiating Aβ-PET-positive and negative participants showed that the area under the curve for miRNA-485-3p was 0.9217., Conclusion: These findings suggested that the miRNA-485-3p concentration in salivary EE-EV was closely related to Aβ deposition in the brain and had high diagnostic accuracy for predicting Aβ-PET positivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: The neurobiological substrates underlying the relationship of circadian rest-activity rhythm (RAR) alteration with accelerated late-life cognitive decline are not clearly understood. In the present study, the longitudinal relationship of objectively measured circadian RAR with in vivo Alzheimer disease (AD) pathologies and cerebrovascular injury was investigated in older adults without dementia., Methods: The present study included 129 participants without dementia who participated in the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease) cohort. All participants underwent actigraphy at baseline and two consecutive [ 11 C] Pittsburgh compound-B positron emission tomography (PET), [ 18 F] fluorodeoxyglucose-PET, magnetic resonance imaging, and Mini-Mental State Examination (MMSE) at baseline and at a 2-year follow-up assessment. The associations of circadian RAR with annualized change in neuroimaging measures including global amyloid-beta retention, AD-signature region cerebral glucose metabolism (AD-CM), and white matter hyperintensity volume were examined., Results: Delayed acrophase at baseline was significantly associated with greater annualized decline of AD-CM over a 2-year period, but not with that of other neuroimaging measures. In contrast, other circadian RAR parameters at baseline had no association with annualized change of any neuroimaging measures. Annualized decline of AD-CM was also significantly positively associated with the annual change in MMSE scores. Furthermore, a mediation analysis showed that greater reduction in AD-CM mediated the effect of delayed acrophase at baseline on faster decline of MMSE score., Conclusion: The findings indicate that delayed acrophase in late life may cause or predict hypometabolism at AD-signature brain regions, which underlies cognitive decline in the near future., (© 2022 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Objectives: Assessment of depressive symptoms in older adults is challenging especially in the presence of risks in cognitive impairment. We aimed to examine whether the convergence between two measures of depressive symptoms (self-report and observer ratings) is affected by varying levels of cognitive function in older adults., Methods: Self-reported scale of depression, informant-based rating of affective symptoms, and global cognitive function were assessed in 2533 older adults with no impairment, mild cognitive impairment, and Alzheimer's disease. The strength of rank-order correlation between the Geriatric Depression Scale (GDS) and behavioral ratings of the Neuropsychiatric Inventory (NPI) was examined as the metric of convergent validity., Results: The results showed that the strength of convergence between the two measurements gradually decreased as a function of lowered cognitive function. Overall tendency showed that diagnoses of cognitive impairment and lower levels of cognitive function were associated with lower correspondence between the two depression measurements. The loss of convergent validity is especially evident in the behavioral symptom of apathy., Conclusions: Utilizing self-report scales of depression in older adults requires a cautious approach even with minimal or mild levels of cognitive impairment., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Aims: The aim of this study was to investigate the associations of enlarged perivascular spaces (EPVS) in the basal ganglia (BG) and centrum semiovale (CSO) with beta-amyloid (Aβ) and tau deposition in older adults with a diverse cognitive spectrum., Methods: A total of 163 (68 cognitively normal and 95 cognitively impaired) older participants underwent [ 11 C] Pittsburgh compound B and [ 18 F] AV-1451 PET, and MRI. EPVS in the BG and CSO and other small vessel disease markers, such as white matter hyperintensities, lacunes, and deep and lobar microbleeds, were assessed., Results: Increased EPVS in the BG showed a significant association with lower cerebral tau deposition, even after controlling for other small vessel disease markers. Further exploratory analyses showed that this association was significant in cognitively impaired, Aβ-positive, or APOE4-positive individuals, but not significant in the cognitively normal, Aβ-negative, or APOE4-negative participants. In contrast to EPVS in the BG, EPVS in the CSO did not have any relationship with cerebral tau deposition. In addition, none of the two types of EPVS were associated with cerebral Aβ deposition., Conclusion: Brain tau deposition appears to be reduced with increased EPVS in the BG, especially in individuals with cognitive impairment, pathological amyloid burden, or genetic Alzheimer's disease risk., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Ankle-brachial index (ABI), an indicator of atherosclerosis or arterial stiffness, has been associated with Alzheimer's disease (AD) dementia and related cognitive impairment. Nevertheless, only limited information is available regarding its contribution to brain alterations leading to cognitive decline in late-life., Objective: We aimed to investigate the relationship of ABI with in vivo AD pathologies and cerebrovascular injury in cognitively impaired older adults., Methods: Total 127 cognitively impaired (70 mild cognitive impairment and 57 AD dementia) individuals, who participated in an ongoing prospective cohort study, were included. All participants underwent comprehensive clinical and neuropsychological assessment, ABI measurement, apolipoprotein E (APOE) ɛ4 genotyping, and multi-modal brain imaging including [11C] Pittsburgh Compound B (PiB)-positron emission tomography (PET) and [18F] fludeoxyglucose (FDG)-PET, and MRI., Results: General linear model analysis showed significant relationship between ABI strata (low ABI: <1.00, normal ABI: 1.00-1.29, and high ABI: ≥1.30) and AD-signature region cerebral glucose metabolism (AD-CM), even after controlling age, sex, clinical dementia rating-sum of box, and APOE ɛ4 positivity (p = 0.029). Post hoc comparison revealed that low ABI had significantly lower AD-CM than middle and high ABI, while no difference of AD-CM was found between middle and high ABI. There was no significant difference of global Aβ deposition, AD-signature region cortical thickness, and white matter hyperintensity volume between the three ABI strata., Conclusion: Our findings suggest that lower ABI, likely related to atherosclerosis, may contribute to the aggravation of AD-related regional neurodegeneration in cognitively impaired older adults.

Aim: Spouse bereavement is one of life's greatest stresses and has been suggested to trigger or accelerate cognitive decline and dementia. However, little information is available about the potential brain pathologies underlying the association between spouse bereavement and cognitive decline. We aimed to investigate that lifetime spouse bereavement is associated with in vivo human brain pathologies underlying cognitive decline., Methods: A total of 319 ever-married older adults between the ages of 61 and 90 years underwent comprehensive clinical assessments and multimodal brain imaging including [ 11 C] Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, [ 18 F] fluorodeoxyglucose-PET, and magnetic resonance imaging. Participants were classified as experiencing no spouse bereavement or spouse bereavement, and comparisons using propensity score matching (59 cases and 59 controls) were performed., Results: Spouse bereavement was significantly associated with higher cerebral white matter hyperintensity (WMH) volume compared with no spouse bereavement. Interaction and subsequent subgroup analyses showed that spouse bereavement was significantly associated with higher WMH in the older (>75 years) subgroup and among those with no- or low-skill occupations. In addition, spouse bereavement at 60 years or older affects WMH volume compared with no spouse bereavement, whereas spouse bereavement at younger than 60 years did not. No group differences were observed in other brain pathologies between spouse bereavement categories., Conclusions: The findings suggest that the spouse bereavement may contribute to dementia or cognitive decline by increasing cerebrovascular injury, particularly in older individuals and those with no- or low-skill occupations., (© 2022 The Authors Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Late-life depression (LDD) results from multiple psychosocial and neurobiological changes occurring in later life. The current study investigated how patterns of clinical symptoms and brain structural features are classified into LDD subtypes., Method: Self-report scale of depression, behavioral rating of affective symptoms, and brain structural imaging of white matter change and cortical thickness were assessed in 541 older adults with no cognitive impairment or mild cognitive impairment. Latent profile analysis was used to identify distinct subtypes of depression., Results: The latent profile analysis identified four classes with mild to severe depressive symptoms and two classes with minimal symptoms. While the classes primarily differed in the overall severity, the combinatory patterns of clinical symptoms and neuropathological signature distinguished the classes with similar severity. The classes were distinguished in terms of whether or not neurodegenerative risk accompanied the corresponding depressive symptoms. The presence of the negative self-scheme and cortical thinning pattern notably characterized the subtypes of LDD., Limitations: The underlying etiologies of the biological subtypes are still speculative, and the current study lacks clinical history that differentiates late- and early-onset depression., Conclusions: Our finding provides insight in identifying heterogeneities of depressive disorder in later life and suggests that self-report and behavioral symptom profile in combination with white matter lesion and cortical thickness effectively characterizes distinct subtypes of LDD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Functional impairment in daily activity is a cornerstone in distinguishing the clinical progression of dementia. Multiple indicators based on neuroimaging and neuropsychological instruments are used to assess the levels of impairment and disease severity; however, it remains unclear how multivariate patterns of predictors uniquely predict the functional ability and how the relative importance of various predictors differs., Method: In this study, 881 older adults with subjective cognitive complaints, mild cognitive impairment (MCI), and dementia with Alzheimer's type completed brain structural magnetic resonance imaging (MRI), neuropsychological assessment, and a survey of instrumental activities of daily living (IADL). We utilized the partial least square (PLS) method to identify latent components that are predictive of IADL., Results: The result showed distinct brain components (gray matter density of cerebellar, medial temporal, subcortical, limbic, and default network regions) and cognitive-behavioral components (general cognitive abilities, processing speed, and executive function, episodic memory, and neuropsychiatric symptoms) were predictive of IADL. Subsequent path analysis showed that the effect of brain structural components on IADL was largely mediated by cognitive and behavioral components. When comparing hierarchical regression models, the brain structural measures minimally added the explanatory power of cognitive and behavioral measures on IADL., Conclusion: Our finding suggests that cerebellar structure and orbitofrontal cortex, alongside with medial temporal lobe, play an important role in the maintenance of functional status in older adults with or without dementia. Moreover, the significance of brain structural volume affects real-life functional activities via disruptions in multiple cognitive and behavioral functions.

Background: Irisin, an exercise-induced myokine, has been shown to have beneficial effects on cognitive and metabolic functions. However, previous studies assessing the levels of circulating irisin in patients with Alzheimer's disease (AD) or diabetes mellitus (DM) have provided inconsistent results. This suggests that the normal physiological action of irisin may be altered by disease-associated pathological conditions in target organs., Objective: To investigate the association of plasma levels of irisin with cognition and brain structures according to the presence or absence of AD and DM., Methods: Plasma levels of irisin, multi-domain cognition, and volumes of relevant brain regions were assessed using enzyme-linked immunoassay, neuropsychological test, and magnetic resonance imaging, respectively. We classified 107 participants by cognitive (cognitively normal [CN, n = 23], mild cognitive impairment [MCI, n = 49], and AD [n = 35]) and metabolic (non-DM [n = 75] and DM [n = 32]) states., Results: Disease state-stratified multiple regression analyses showed that plasma levels of irisin were positively associated with cognition only in participants without AD (CN plus MCI). By contrast, in participants with AD, these associations lost significance, and furthermore, higher levels of irisin indicated smaller hippocampal, superior temporal, and inferior frontal volumes. The association between plasma irisin levels and cognition was not affected by the presence of DM. Consistently, moderation analysis revealed that the relationship between plasma irisin levels and cognition or brain structures was significantly modified by the presence of AD, not that of DM., Conclusion: Our findings suggest that the beneficial actions of circulating irisin on cognition may be attenuated by AD-induced pathological conditions in the brain., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Physical activities (PA) have been suggested to reduce the risk of Alzheimer's disease (AD) dementia. However, information on the neuropathological links underlying the relationship is limited., Objective: We investigated the role of midlife and late-life PA with in vivo AD neuropathologies in old adults without dementia., Methods: This study included participants from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease (KBASE). The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] fluorodeoxyglucose PET, and magnetic resonance imaging. Using the multi-modal brain imaging data, in vivo AD pathologies including global amyloid deposition, AD-signature region cerebral glucose metabolism (AD-CM), and AD-signature region cortical thickness (AD-CT) were quantified. Both midlife and late-life PA of participants were measured using the Lifetime Total Physical Activity Questionnaire., Results: This study was performed on 260 participants without dementia (195 with normal cognitive function and 65 with mild cognitive impairment). PA of neither midlife nor late-life showed direct correspondence with any neuroimaging biomarker. However, late-life PA moderated the relationship of brain amyloid-β (Aβ) deposition with AD-CM and AD-CT. Aβ positivity had a significant negative effect on both AD-CM and AD-CT in individuals with lower late-life PA, but those with higher late-life PA did not show such results. Midlife PA did not have such a moderation effect., Conclusion: The findings suggest that physically active lifestyle in late-life, rather than that in midlife, may delay AD-associated cognitive decline by decreasing Aβ-induced neurodegenerative changes in old adults.

Background: In assessing the levels of clinical impairment in dementia, a summary index of neuropsychological batteries has been widely used in describing the overall functional status., Objective: It remains unexamined how complex patterns of the test performances can be utilized to have specific predictive meaning when the machine learning approach is applied., Methods: In this study, the neuropsychological battery (CERAD-K) and assessment of functioning level (Clinical Dementia Rating scale and Instrumental Activities of Daily Living) were administered to 2,642 older adults with no impairment (n = 285), mild cognitive impairment (n = 1,057), and Alzheimer's disease (n = 1,300). Predictive accuracy on functional impairment level with the linear models of the single total score or multiple subtest scores (Model 1, 2) and support vector regression with low or high complexity (Model 3, 4) were compared across different sample sizes., Results: The linear models (Model 1, 2) showed superior performance with relatively smaller sample size, while nonlinear models with low and high complexity (Model 3, 4) showed an improved accuracy with a larger dataset. Unlike linear models, the nonlinear models showed a gradual increase in the predictive accuracy with a larger sample size (n > 500), especially when the model training is allowed to exploit complex patterns of the dataset., Conclusion: Our finding suggests that nonlinear models can predict levels of functional impairment with a sufficient dataset. The summary index of the neuropsychological battery can be augmented for specific purposes, especially in estimating the functional status of dementia.

Background: Cognitive training can potentially prevent cognitive decline. However, the results of recent studies using semi-immersive virtual reality (VR)-assisted cognitive training are inconsistent., Objective: We aimed to examine the hypothesis that cognitive training using fully immersive VR, which may facilitate visuospatial processes, could improve visuospatial functioning, comprehensive neuropsychological functioning, psychiatric symptoms, and functional connectivity in the visual brain network in predementia., Methods: Participants over 60 years old with subjective cognitive decline or mild cognitive impairment from a memory clinic were randomly allocated to the VR (n=23) or the control (n=18) group. The VR group participants received multidomain and neuropsychologist-assisted cognitive training in a fully immersive VR environment twice a week for 1 month. The control group participants did not undergo any additional intervention except for their usual therapy such as pharmacotherapy. Participants of both groups were evaluated for cognitive function using face-to-face comprehensive neuropsychological tests, including the Rey-Osterrieth Complex Figure Test (RCFT) copy task; for psychiatric symptoms such as depression, apathy, affect, and quality of life; as well as resting-state functional magnetic resonance imaging (rsfMRI) at baseline and after training. Repeated-measures analysis of variance was used to compare the effect of cognitive training between groups. Seed-to-voxel-based analyses were used to identify the cognitive improvement-related functional connectivity in the visual network of the brain., Results: After VR cognitive training, significant improvement was found in the total score (F 1,39 =14.69, P=.001) and basic components score of the RCFT copy task (F 1,39 =9.27, P=.005) compared with those of the control group. The VR group also showed improvements, albeit not significant, in naming ability (F 1,39 =3.55, P=.07), verbal memory delayed recall (F 1,39 =3.03, P=.09), and phonemic fluency (F 1,39 =3.08, P=.09). Improvements in psychiatric symptoms such as apathy (F 1,39 =7.02, P=.01), affect (F 1,39 =14.40, P=.001 for positive affect; F 1,39 =4.23, P=.047 for negative affect), and quality of life (F 1,39 =4.49, P=.04) were found in the VR group compared to the control group. Improvement in the RCFT copy task was associated with a frontal-occipital functional connectivity increase revealed by rsfMRI in the VR group compared to the control group., Conclusions: Fully immersive VR cognitive training had positive effects on the visuospatial function, apathy, affect, quality of life, and increased frontal-occipital functional connectivity in older people in a predementia state. Future trials using VR cognitive training with larger sample sizes and more sophisticated designs over a longer duration may reveal greater improvements in cognition, psychiatric symptoms, and brain functional connectivity., Trial Registration: Clinical Research Information Service KCT0005243; https://tinyurl.com/2a4kfasa., (©Jae Myeong Kang, Nambeom Kim, Sook Young Lee, Soo Kyun Woo, Geumjin Park, Byeong Kil Yeon, Jung Woon Park, Jung-Hae Youn, Seung-Ho Ryu, Jun-Young Lee, Seong-Jin Cho. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.05.2021.)

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-β 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-β 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.

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 (Aβ) 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 Aβ 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 Aβ deposition or WMH were not., Conclusion: The present findings suggest that amyloid-independent regional neurodegeneration might underlie relations of neuroticism and conscientiousness with AD., (© 2020 The Authors. Psychiatry and Clinical Neurosciences © 2020 Japanese Society of Psychiatry and Neurology.)

For the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD), variable neuroimaging and neuropsychological tests have been used. We aimed to evaluate the correlation of neuropsychological domain with new amyloid positron emission tomography (PET) study and to validate the availability of new PET tracer.We enrolled 20 patients who underwent C-PiB-PET/CT, new PET tracer F-FC119S PET/CT from November, 2014 to July, 2015. Among them, 10 patients were diagnosed with AD and 10 patients with MCI. The current version of Seoul Neuropsychological Screening Battery (SNSB) II was performed for cognitive evaluation. Each parameter of SNSB was compared between 2 patient groups. Spearman correlation analysis between value of SNSB domain and standardized uptake value ratio (SUVR) of PET was also performed.The AD group presented significant poor z-score in Korean-Boston Naming Test(K-BNT) (P = .01),copy score of Rey Complex Figure Test (RCFT) (P = .049), immediate (P = .028)and delayed memory of Seoul Verbal Learning Test (SVLT) (P = .028), recognition of RCFT (P = .004), "animal" of Controlled Oral Word Association Test (COWAT) (P = .041), color reading of Korean-Color Word Stroop test (K-CWST) (P = .014), and Digit Symbol Coding (DSC) (P = .007) compared with MCI group. That means, except attention domain, all other cognitive domains were relatively impaired in AD compared with MCI. In correlation analysis, we found that poor performances on copy score of RCFT in MCI groups were associated with great beta amyloid burden in frontal area in both C-PiB-PET/CT and F-FC119S PET/CT. In AD group, F-FC119S PET presented more extensive correlation in each cognitive domain with multiple cortical areas compared with C-PiB-PET.The degree of amyloid burden assessed on F-FC119S PET was significantly correlated with neuropsychological test in AD, and also MCI patients. The combination of neuropsychological evaluation with novel F-FC119S PET/CT can be used for valid biomarker for MCI and AD.

Background: An emerging body of literature has indicated that moderate alcohol intake may be protective against Alzheimer disease (AD) dementia. However, little information is available regarding whether moderate alcohol intake is related to reductions in amyloid-beta (Aβ) deposition, or is protective via amyloid-independent mechanisms in the living human brain. Here we examined the associations of moderate alcohol intake with in vivo AD pathologies, including cerebral Aβ deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMHs) in the living human brain., Methods and Findings: The present study was part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study that started in 2014. As of November 2016, 414 community-dwelling individuals with neither dementia nor alcohol-related disorders (280 cognitively normal [CN] individuals and 134 individuals with mild cognitive impairment [MCI]) between 56 and 90 years of age (mean age 70.9 years ± standard deviation 7.8; male, n [%] = 180 [43.5]) were recruited from 4 sites (i.e., 2 university hospitals and 2 public centers for dementia prevention and management) around Seoul, South Korea. All the participants underwent comprehensive clinical assessments comprising lifetime and current histories of alcohol intake and multimodal brain imaging, including [11C] Pittsburgh compound B positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG) PET, and magnetic resonance imaging (MRI) scans. Lifetime and current alcohol intake were categorized as follows: no drinking, <1 standard drink (SD)/week, 1-13 SDs/week, and 14+ SDs/week. A moderate lifetime alcohol intake (1-13 SDs/week) was significantly associated with a lower Aβ positivity rate compared to the no drinking group, even after controlling for potential confounders (odds ratio 0.341, 95% confidence interval 0.163-0.714, p = 0.004). In contrast, current alcohol intake was not associated with amyloid deposition. Additionally, alcohol intake was not related to neurodegeneration of AD-signature regions or cerebral WMH volume. The present study had some limitations in that it had a cross-sectional design and depended on retrospective recall for alcohol drinking history., Conclusions: In this study, we observed in middle- and old-aged individuals with neither dementia nor alcohol-related disorders that moderate lifetime alcohol intake was associated with lower cerebral Aβ deposition compared to a lifetime history of not drinking. Moderate lifetime alcohol intake may have a beneficial influence on AD by reducing pathological amyloid deposition rather than amyloid-independent neurodegeneration or cerebrovascular injury., Competing Interests: The authors have declared that no competing interests exist.

Background: Although the existence of proteasomes in human blood, termed circulating proteasomes (c-proteasomes), has been reported previously, their origin and pathophysiological functions remain largely unknown., Objective: Given that c-proteasome activity was significantly reduced in Alzheimer's disease model mice and relatively high frequency of mild cognitive impairment (MCI) is accompanied by chronic tinnitus in aged patients, we examined whether c-proteasome activity in human plasma was associated with cognitive function in patients with chronic tinnitus., Methods: c-Proteasome activity in the plasma of tinnitus patients (N = 55) was measured with fluorogenic reporter substrate, suc-LLVY-AMC. To assess MCI, the Montreal Cognitive Assessment was conducted with a cut-off score of 22/23. All patients underwent audiological and psychoacoustic analyses. Levels of c-proteasomes, Aβ42, and Aβ40 were measured using ELISA, and their association with c-proteasome activity was evaluated., Results: The activity of circulating proteasomes was significantly lower in patients with chronic tinnitus and MCI (p = 0.042), whereas activities of other plasma enzymes showed little correlation. In addition, c-proteasome activity was negatively associated with the level of plasma Aβ and was directly dependent on its own concentration in the plasma of patients with chronic tinnitus., Conclusion: Our current work provides a new perspective for understanding the potential relationship between circulating proteasomes in the plasma and cognitive dysfunction, suggesting a novel, non-invasive biomarker in the context of MCI diagnosis.

Objectives: The present study examined self-reports and informant reports of cognitive function and discrepancies between the two reporting methods in healthy controls (HC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and very mild Alzheimer disease (AD) using three questionnaires., Methods: The study included a total of 300 individuals (mean age: 74.4 ± 5.7 y), including 130 HC, 70 SCD, 51 MCI, and 49 very mild AD patients. Self-ratings and informant ratings of cognitive function were assessed using the Korean Dementia Screening Questionnaire-Cognition (KDSQ-C), AD8, and Subjective Memory Complaints Questionnaire (SMCQ). Awareness of cognitive functioning was measured on the basis of the discrepancy scores between self-reports and informant reports., Results: Group comparisons on questionnaire scores adjusting for age, education, and depressive symptoms showed that self-reports were lowest in HC than other groups, with no differences between SCD and MCI groups. Informant reports were lower in SCD than in MCI, while discrepancy scores were higher in SCD than in MCI (P < .001 for KDSQ-C and SMCQ; P = .076 for AD8). There were no differences in self-reports, informant reports, and discrepancy scores between MCI and AD groups., Conclusions: These results support the usefulness of informant-reported cognitive functioning to classify MCI among elderly with subjective cognitive complaints. In addition, discrepancies between self-reports and informant reports demonstrate that overestimation and underestimation of cognitive function may serve as a clinical indicator of SCD and MCI across the cognitive continuum, respectively., (© 2019 John Wiley & Sons, Ltd.)

Neuropsychiatric symptoms are commonly observed as brain pathology progresses with dementia. Behavioral and affective disturbances underly the distinct neuroanatomical basis of typical symptoms of cognitive impairment; however it remains unclear whether enriched intellectual experience, such as educational attainment, can mitigate the effect of brain structural patterns on neuropsychiatric symptom severity. We utilized the Open Access Series of Imaging Studies (OASIS-3) dataset, which includes brain structural MRI and behavioral symptom evaluation. We included 904 older adults who were mostly cognitively normal, clinically diagnosed with very mild to moderate Alzheimer's disease, or other types of dementia. Canonical correlation analysis was used to identify the patterns of multivariate association between the gray matter structure and neuropsychiatric symptom severity. First, we identified two canonical modes capturing the distinct neuroanatomical basis of common and mood-specific factors of neuropsychiatric symptoms. The first common pattern reflected a smaller volume in the amygdala and adjacent temporal regional thickness. The second mood-specific pattern reflected patterns in lateral and orbital prefrontal regional thickness. In the external correlational analysis, the two canonical correlations reflected global brain volume and white matter lesions; however, the second pattern was not associated with functional impairments or cognitive function. Moreover, older adults with higher education showed an attenuated severity of behavioral symptoms, even with the presence of a brain structural pattern. Our findings suggest that educational attainment, as a proxy of cognitive reserve, can mitigate the severity of behavioral and affective symptoms of dementia., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Subjective memory complaint (SMCs) is a common trait amongst older population. The subjective cognition about their memory could depend on objective cognition. The aim of the current study was to examine the interaction between subjective memory cognition (i.e., SMC) and objective cognition on cognitive functions in participants from older generation., Methods: A total of 219 patients, 181 normal control (NC) patients and 38 patients with mild cognitive impairment (MCI), were examined through standardized and comprehensive clinical evaluation and neuropsychological assessment. The Subjective Memory Complaints Questionnaire was used to assess SMCs along with five cognitive tasks were used to evaluate cognitive decline over following areas: verbal memory, visuospatial memory, attention, fluency, and language., Results: The results of 2 × 2 two-way analysis of variance (ANOVA) showed that there were significant interactions between SMCs and cognitive status (NC, MCI) on memory performances. NC with SMCs showed significantly lower performance in verbal memory and visuospatial memory compared to NCs without SMCs. Conversely, no effect was observed in the MCI group., Conclusion: There are interactions between subjective cognition (i.e., SMC) and objective cognition (i.e., cognitive status) on memory performances in older adults. The roles of SMCs on memory performances should be interpreted with older adults' objective cognitive status.

Several epidemiological and preclinical studies supported the protective effect of coffee on Alzheimer's disease (AD). However, it is still unknown whether coffee is specifically related with reduced brain AD pathologies in human. Hence, this study aims to investigate relationships between coffee intake and in vivo AD pathologies, including cerebral beta-amyloid (Aβ) deposition, the neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH). A total of 411 non-demented older adults were included. Participants underwent comprehensive clinical assessment and multimodal neuroimaging including [ 11 C] Pittsburgh compound B-positron emission tomography (PET), [ 18 F] fluorodeoxyglucose PET, and magnetic resonance imaging scans. Lifetime and current coffee intake were categorized as follows: no coffee or <2 cups/day (reference category) and ≥2 cups/day (higher coffee intake). Lifetime coffee intake of ≥2 cups/day was significantly associated with a lower Aβ positivity compared to coffee intake of <2 cups/day, even after controlling for potential confounders. In contrast, neither lifetime nor current coffee intake was not related to hypometabolism, atrophy of AD-signature region, and WMH volume. The findings suggest that higher lifetime coffee intake may contribute to lowering the risk of AD or related cognitive decline by reducing pathological cerebral amyloid deposition.

Aim: We investigated the effects of metformin on cognitive function in a prospective cohort of older adults., Methods: Participants aged ≥60 years were selected, and their Korean version of the Consortium to Establish a Registry for Alzheimer's Diseases Assessment, including the Mini-Mental State Examination, and activities of daily living were evaluated prospectively. Rapid deterioration of cognitive function was defined as annual change of test scores in the lowest quartile., Results: A total of 732 participants (mean age 76.7 ± 6.6 years) were followed up for 2.9 years (interquartile range 1.0-5.7 years). A linear mixed model showed that diabetes was associated with significant deterioration of Verbal Delayed Free Recall and Recognition scores (P = 0.007 and 0.022, respectively). Among diabetes patients, metformin treatment was not associated with changes of any Korean version of the Consortium to Establish a Registry for Alzheimer's Diseases Assessment component or activities of daily living index. However, rapid deterioration of Mini-Mental State Examination and Verbal Immediate Recall scores was more frequently found in the metformin-taking group, even after adjustment for age, sex, education level, baseline cognitive function, baseline glycated hemoglobin levels, renal and liver function, body mass index, hypertension, dyslipidemia, antidiabetic agents other than metformin, and baseline brain imaging abnormality (odds ratio 4.47, 95% confidence interval 1.24-16.05 and odds ratio 7.37, 95% confidence interval 1.19-45.56)., Conclusions: Metformin treatment was not associated with changes of any of Korean version of the Consortium to Establish a Registry for Alzheimer's Diseases Assessment component scores or activities of daily living index. However, rapid deterioration of Mini-Mental State Examination and Verbal Immediate Recall scores was more frequently found in the metformin-treated group. Geriatr Gerontol Int 2019; 19: 755-761., (© 2019 Japan Geriatrics Society.)

Background: Korea has a periodic general health check-up program that uses the Korean Dementia Screening Questionnaire-Cognition (KDSQ-C) as a cognitive dysfunction screening tool. The Alzheimer Disease 8 (AD8) and Subjective Memory Complaints Questionnaire (SMCQ) are also used in clinical practice. We compared the diagnostic ability of these screening questionnaires for cognitive impairment when completed by participants and their caregivers. Hence, we aimed to evaluate whether the SMCQ or AD8 is superior to the KDSQ-C and can be used as its replacement., Methods: A total of 420 participants over 65 years and their informants were recruited from 11 hospitals for this study. The patients were grouped into normal cognition, mild cognitive impairment, and dementia subgroups. The KDSQ-C, AD8, and SMCQ were completed separately by participants and their informants., Results: A receiver operating characteristic analysis of questionnaire scores completed by participants showed that the areas under the curve (AUCs) for the KDSQ-C, AD8, and SMCQ for diagnosing dementia were 0.75, 0.8, and 0.73, respectively. Regarding informant-completed questionnaires, the AD8 (AUC of 0.93), KDSQ-C (AUC of 0.92), and SMCQ (AUC of 0.92) showed good discriminability for dementia, with no differences in discriminability between the questionnaires., Conclusion: When an informant-report is possible, we recommend that the KDSQ-C continues to be used in national medical check-ups as its discriminability for dementia is not different from that of the AD8 or SMCQ. Moreover, consistent data collection using the same questionnaire is important. When an informant is not available, either the KDSQ-C or AD8 may be used. However, in the cases of patient-reports, discriminability is lower than that for informant-completed questionnaires., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

Background: The Montreal Cognitive Assessment (MoCA) is known to have discriminative power for patients with Mild Cognitive Impairment (MCI). Recently Cognitive Reserve (CR) has been introduced as a factor that compensates cognitive decline. We aimed to assess whether the MoCA reflects CR. Furthermore, we assessed whether there were any differences in the efficacy between the MoCA and the Mini-Mental State Examination (MMSE) in reflecting CR., Methods: MoCA, MMSE, and the Cognitive Reserve Index questionnaire (CRIq) were administered to 221 healthy participants. Normative data and associated factors of the MoCA were identified. Correlation and regression analyses of the MoCA, MMSE and CRIq scores were performed, and the MoCA score was compared with the MMSE score to evaluate the degree to which the MoCA reflected CR., Results: The MoCA reflected total CRIq score (CRI; B = 0.076, P < 0.001), CRI-Education (B = 0.066, P <  0.001), and CRI-Working activity (B = 0.025, P = 0.042), while MMSE reflected total CRI (B = 0.044, P <  0.001) and CRI-Education (B = 0.049, P <  0.001) only. The MoCA differed from the MMSE in the reflection of total CRI (Z = 2.30)., Conclusion: In this study, we show that the MoCA score reflects CR more sensitively than the MMSE score. Therefore, we suggest that MoCA can be used to assess CR and early cognitive decline.

The purpose of this study was to assess scores and processing speed distributions of the instrument, A Quick Test of Cognitive Speed (AQT), in Korean older adults through behavioral and brain imaging approaches. Participants were instructed to say the color names, stimuli's form, and both the color and form. Test scores and processing speeds were measured in these three subtests of color, form, and color-form. A total of 67 patients (22 healthy controls (HC), 22 with mild cognitive impairment (MCI), and 23 with Alzheimer's disease (AD)) participated. Only color-form score and processing speed of the three subtests could be used to differentiate AD from MCI and HC. Color-form score showed the largest effects size (partial η 2  = 0.268) for distinguishing AD, MCI from HC and ROC curve analysis confirmed a high level of sensitivity (0.857) and specificity (0.826) for discrimination between AD and HC. None of the subtests could differentiate HC from MCI. Voxel-based morphometry analysis of brain structure in 27 participants (9 in each group) revealed that gray matter volume of the middle occipital gyrus and inferior parietal cortex were associated with color-form score. This study suggests preliminary evidence in the clinical utility of the AQT for screening AD in older Korean adults. The color-form score could be implemented for clinical utilization in a very brief time. Furthermore, strong positive correlations between color-form scores and the brain areas responsible for visuospatial working memory corroborate the validity of AQT., (Copyright © 2018. Published by Elsevier B.V.)

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder with the clinical symptom of the progressive loss of cognitive function and mild cognitive impairment (MCI) is a translational state between cognitive changes of normal aging and AD. Lipid metabolism and pathogenesis of Alzheimer's disease (AD) are closely linked. Despite obviously discrete lipidome constitutions across lipoproteins, lipidomic approaches of AD has been mostly conducted without considering lipoprotein-dependent alterations. This study introduces a combination of asymmetrical flow field-flow fractionation (AF4) and nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry (nUHPLC-ESI-MS/MS) for a comprehensive lipid profiling in different lipoprotein level of patients plasma with AD and amnestic MCI in comparison to age-matched healthy controls. Lipoproteins in plasma samples were size-sorted by a semi-preparative scale AF4, followed by non-targeted lipid identification and high speed targeted quantitation with nUHPLC-ESI-MS/MS. It shows 14 significantly altered high abundance lipids in AD, exhibiting >2-fold increases (p < 0.01) in LDL/VLDL including triacylglycerol, ceramide, phosphatidylethanolamine, and diacylglycerol. Three lipid species (triacylglycerol 50:1, diacylglycerol 18:1&#95;18:1, and phosphatidylethanolamine 36:2) showing a strong correlation with the degree of brain atrophy were found as candidate species which can be utilized to differentiate the early stage of MCI when simple Mini-Mental State Examination results were statistically incorporated. The present study elucidated lipoprotein-dependent alterations of lipids in progression of MCI and further to AD which can be utilized for the future development of lipid biomarkers to enhance the predictability of disease progress., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Fluorodeoxyglucose (FDG) positron emission tomography (PET) is useful to predict Alzheimer's disease (AD) conversion in patients with mild cognitive impairment (MCI). However, few studies have examined the extent to which FDG PET alone can predict AD conversion and compared the efficacy between visual and computer-assisted analysis directly., Objective: The current study aimed to evaluate the value of FDG PET in predicting the conversion to AD in patients with MCI and to compare the predictive values of visual reading and computer-assisted analysis., Methods and Materials: A total of 54 patients with MCI were evaluated with FDG PET and followed-up for 2 years with final diagnostic evaluation. FDG PET images were evaluated by (1) traditional visual rating, (2) composite score of visual rating of the brain cortices, and (3) composite score of computer-assisted analysis. Receiver operating characteristics (ROC) curves were compared to analyze predictive values., Results: Nineteen patients (35.2%) converted to AD from MCI. The area under the curve (AUC) of the ROC curve of the traditional visual rating, composite score of visual rating, and computer-assisted analysis were 0.67, 0.76, and 0.79, respectively. ROC curves of the composite scores of the visual rating and computer-assisted analysis were comparable (Z = 0.463, p = 0.643)., Conclusions: Visual rating and computer-assisted analysis of FDG PET scans were analogously accurate in predicting AD conversion in patients with MCI. Therefore, FDG PET may be a useful tool for screening AD conversion in patients with MCI, when using composite score, regardless of the method of interpretation.

Acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) may occur after traumatic event and also cause significant life time impairment. P300 event-related potential (ERP) is a potential biological marker for PTSD and can reflect cognitive impairment in information processing and attention. Despite the usefulness of ERP, there are few attempts to reveal relationships between ASD and P300. In the present study, we aimed to determine if the P300 of the patients who were the victims of sexual abuse reflected the quantitative trait of ASD or if P300 is applicable as a state marker for predicting the risk of PTSD.Fifteen female victims of sexual abuse diagnosed with ASD and 18 healthy controls (HCs) without trauma exposure participated in this study. We investigated the P300 ERPs in patients with ASD to compare them with those of HCs. ERPs were acquired from female adults during an auditory oddball task. Between-group differences in amplitudes or latencies of P300 were investigated using repeated-measures analysis of variance.The ASD groups showed reduced P300 amplitudes at the midline centroparietal site as well as reduced accuracy rates during an auditory oddball task compared with the HCs.These results indicate that ASD have abnormalities in the P300 compared to those in HCs. Moreover, the reduction in P300 could be considered a candidate neurophysiological marker for ASD.

We evaluated whether metabolic factors were associated with cognitive decline, compared to baseline cognitive function, among geriatric population. The present study evaluated data from an ongoing prospective community-based Korean cohort study. Among 1,387 participants who were >65 years old, 422 participants were evaluated using the Korean mini-mental status examination (K-MMSE) at the baseline and follow-up examinations. The mean age at the baseline was 69.3 ± 2.9 years, and 222 participants (52.6%) were men. The mean duration of education was 7.1 ± 3.6 years. During a mean follow-up of 5.9 ± 0.1 years, the K-MMSE score significantly decreased (-1.1 ± 2.7 scores), although no significant change was observed in the homeostasis model assessment of insulin resistance (HOMA-IR) value. Participants with more decreased percent changes in K-MMSE scores had a shorter duration of education (p = 0.001), older age (p = 0.022), higher baseline K-MMSE score (p < 0.001), and increased insulin resistance (∆HOMA-IR, p = 0.002). The correlation between the percent changes in K-MMSE and ∆HOMA-IR values remained significant after multivariable adjustment (B = -0.201, p = 0.002). During a 6-year follow-up of older Koreans with normal baseline cognitive function, increased insulin resistance was significantly correlated with decreased cognitive function.

This study aimed to examine the sex-specific association between serum sex hormones and gonadotropins and the cerebral beta-amyloid (Aβ) burden and hippocampal neurodegeneration in subjects with normal cognition and impaired cognition. Two hundred sixty-five older subjects received clinical assessments, serum measurements of sex hormones, gonadotropins, 11 C-Pittsburgh compound B-positron emission tomography, and magnetic resonance imaging. In females, higher free testosterone and gonadotropin levels were associated with lower cerebral Aβ positivity. In males, free testosterone was positively related to hippocampal volume with significant interaction with cognitive status. Further subgroup analyses showed that the association was significant only in impaired cognition but not in normal cognition. Free estradiol was not associated with Aβ burden or hippocampal neurodegeneration in either sex. These results suggest that testosterone might inhibit the early pathological accumulation of Aβ in females and delay neurodegeneration in males., (Copyright © 2017 Elsevier Inc. All rights reserved.)

As a new beta amyloid (Aβ) positron emission tomography (PET) tracer, F-FC119S has shown higher cortical uptake in patients with Alzheimer's disease (AD) than that in healthy control subjects without adverse effects in a previous preliminary study. The aim of this study was to compare F-FC119S PET and C-PiB PET in healthy control (HC) subjects, mild cognitive impairment (MCI) patients, and AD patients.A total of 48 subjects, including 28 HC subjects, 10 MCI patients, and 10 AD patients, underwent static F-FC119S PET (30 minutes after intravenous [i.v.] injection) and C-PiB PET (40 minutes after i.v. injection) on the same day. Both PET images were visually and quantitatively assessed. Standardized uptake value ratios (SUVRs) were calculated for each brain region using the cerebellar cortex as a reference region.None (0%) of the 28 HC subjects and 4 (40%) of 10 MCI patients had positive scans on both PET images. Of the 10 AD patients, 7 (70%) had positive scans on C-PiB PET while 6 (60%) had positive scans on F-FC119S PET. Overall, 47 (98%) of 48 participants showed identical results based on visual analysis. Cortical SUVR of F-FC119S was higher in AD patients (1.38 ± 0.16), followed by that in MCI patients (1.24 ± 0.10) and in HC subjects (1.14 ± 0.05). Compared with C-PiB PET, F-FC119S PET yielded a higher effect size (d = 2.02 vs. 1.67) in AD patients and a slightly lower effect size (d = 1.26 vs. 1.38) in MCI patients. In HC subjects, the nonspecific binding of F-FC119S to white matter (with the frontal cortex-to-white matter SUV ratio of 0.76) was slightly lower than that of C-PiB (ratio of 0.73). There was a significant linear correlation (slope = 0.41, r = 0.78, P < 0.001) between C-PiB and F-FC119S cortical SUVR.We could safely obtain images similar to C-PiB PET imaging Aβ in the brain using F-FC119S PET. Therefore, F-FC119S might be suitable for imaging Aβ deposition.

Objective: Lack of knowledge about a disease could impede early diagnosis and may lead to delays in seeking appropriate medical care. The aim of this study was to explore knowledge of dementia (KOD) and to find the determinants of KOD among three groups: older adults with normal cognition, mild cognitive impairment (MCI), and dementia., Methods: A representative nationwide sample of 6141 Korean elders aged 65 years or older participated in face-to-face interviews and answered 14 questions pertaining to general information, etiology, symptoms, and treatment of dementia. Stepwise multiple regressions and path analyses probed the relationships between various sociodemographic variables and KOD., Results: The percentage of correct responses was only 62%. The item 'A person who remembers things that happened in the past does not have dementia' was answered correctly (false) by only 24.8-27% of the respondents in all groups. Older adults with normal cognition had higher KOD scores than those with MCI or dementia. In the normal-cognition group, KOD scores were higher among highly educated, younger, and literate women with no depression and a family history of dementia. In contrast with the determinants in the normal-cognition group, only the ability to read and write predicted KOD scores in the dementia group., Conclusions: Efforts to enhance KOD in elder adults are needed. Public education regarding the differences between dementia and healthy aging may increase KOD among normal elders and those with MCI. Among elders with dementia, educational materials that do not require literacy may be more helpful in increasing KOD with the aim of preventing treatment delay., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The primary goals of the present study were to develop and validate the Rappel Indicé 24 (RI-24), a shorter version of the original Rappel Indicé, which includes 48 items (RI-48), and to identify the specific brain regions that were correlated with scores on the RI-24. Using these clinical scales, the present study evaluated 91 elderly Korean participants who were classified into 3 groups: normal control (NC; n = 34), patients with mild cognitive impairment (MCI; n = 29), and patients with Alzheimer disease (AD; n = 28). Of the 91 participants, 77 also underwent magnetic resonance imaging scans. The RI-24 delayed cued recall (DCR) scores significantly differed among the NC, MCI, and AD groups. A receiver-operating characteristic curve analysis revealed that the RI-24 was very sensitive (89%) and specific (91%) for the detection of AD. Furthermore, although the time needed to administer the RI-24 was half that needed for the RI-48, the 24-item version showed a high correlation (r= .85 for the DCR score) with the 48-item version. In terms of brain morphological characteristics, voxel-based morphometry analyses revealed a significant positive correlation between DCR score and gray matter volume in the parahippocampal gyrus (r= .468), which plays a role in cued recall. Taken together, the present findings indicate that the RI-24 is a sensitive and reliable test for the detection of memory impairments in patients with MCI and AD despite its brief administration time., (© The Author(s) 2016.)

Objective: To assess the effect of subsyndromal symptoms of depression (SSD) on ratings of disability for individuals with mild cognitive impairment (MCI)., Methods: Data from 405 MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed. Participants were evaluated at baseline and at 6-month intervals over 2 years. Severity of depressive symptoms was rated utilizing the Geriatric Depression Scale. Disability was assessed utilizing the Functional Assessment Questionnaire (FAQ). Other clinical variables included white matter lesion (WML) and intracranial brain (ICV) volumes derived from magnetic resonance imaging, ratings of overall cognitive function (Alzheimer's Disease Assessment Scale, ADAS), and apolipoprotein E (ApoE) status. Demographic variables included age, education, and gender., Results: SSD individuals had a lower volume of WML and higher frequency of ApoE ε4 alleles than nondepressed participants but the two groups did not differ with respect to other clinical or demographic variables. At baseline, SSD individuals were 1.77 times more likely to have poorer FAQ scores than individuals with no symptoms of depression after controlling for the effect of cognitive functioning, ICV, WML, and ApoE status. The presence of SSD at baseline was not associated with a poorer course of disability outcomes, cognitive functioning, or conversion to dementia over 24 months., Conclusions: SSD demonstrated a significant impact on disability for MCI individuals, who are also at high risk for functional limitations related to neurodegenerative disease. Therefore, the treatment of SSD may represent a significant avenue to reduce the burden of disability in this vulnerable patient population., (Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: White matter hyperintensities (WMH) increase cognitive impairment in patients with dementia., Objective: We investigated the impact of WMH on the neuropsychological profiles in patients with mild to moderate dementia., Methods: We consecutively recruited newly diagnosed patients with mild to moderate dementia across South Korea for 1 year. The participants completed neuropsychological tests, magnetic resonance imaging, and structured neurological evaluations. The patients were divided into 3 categories, i.e. minimal, moderate, and severe WMH groups, according to the proportional degree of WMH., Results: 289 patients were recruited; 140 (48.3%) for the minimal WMH group, 99 (34.2%) for the moderate group, and 50 (17.5%) for the severe group. Both advanced age and low general cognitive level were significant contributors to WMH in patients with dementia. After adjusting for age, the neuropsychological correlates of the proportional impact of WMH were frontal executive, language, and attention profiles. However, the only significant neuropsychological correlate was the recognition memory profile after adjusting for both age and general cognitive level simultaneously., Conclusion: The results suggest that the most significant neuropsychological profile impacting the burden of WMH in patients with mild to moderate dementia was the recognition memory profile, regardless of age and general cognitive function., (Copyright © 2011 S. Karger AG, Basel.)