Whole-genome sequencing study in Koreans identifies novel loci for Alzheimer's disease.

INTRODUCTION: The genetic basis of Alzheimer's disease (AD) in Koreans is poorly understood. METHODS: We performed an AD genome-wide association study using whole-genome sequence data from 3540 Koreans (1583 AD cases, 1957 controls) and single-nucleotide polymorphism array data from 2978 Japanese (1336 AD cases, 1642 controls). Significant findings were evaluated by pathway enrichment and differential gene expression analysis in brain tissue from controls and AD cases with and without dementia prior to death. RESULTS: We identified genome-wide significant associations with APOE in the total sample and ROCK2 (rs76484417, p = 2.71×10-8) among APOE ε4 non-carriers. A study-wide significant association was found with aggregated rare variants in MICALL1 (MICAL like 1) (p = 9.04×10-7). Several novel AD-associated genes, including ROCK2 and MICALL1, were differentially expressed in AD cases compared to controls (p < 3.33×10-3). ROCK2 was also differentially expressed between AD cases with and without dementia (p = 1.34×10-4). DISCUSSION: Our results provide insight into genetic mechanisms leading to AD and cognitive resilience in East Asians. HIGHLIGHTS: Novel genome-wide significant associations for AD identified with ROCK2 and MICALL1. ROCK2 and MICALL1 are differentially expressed between AD cases and controls in the brain. This is the largest whole-genome-sequence study of AD in an East Asian population.

Amisulpride withdrawal akathisia responding to aripiprazole with propranolol in first-onset psychosis: a case report.

BACKGROUND: Akathisia tends to develop as an early complication of antipsychotic treatment in a dose-dependent manner. Although withdrawal akathisia has been reported after the discontinuation or dose reduction of typical antipsychotic drugs, akathisia following atypical antipsychotic drug withdrawal remains a rare phenomenon. CASE PRESENTATION: A 24-year-old woman with an acute psychotic episode was admitted and initially treated with aripiprazole. The aripiprazole dose was titrated up to 30 mg/day over 9 days and maintained for the next 3 days; however, her psychotic symptoms persisted without change. She was switched to amisulpride, with the dose increased over 2 weeks to 1000 mg/day. Subsequently, although the patient's psychotic episode subsided, her serum prolactin levels increased markedly. After discharge, the amisulpride dose was increased to 1200 mg/day owing to auditory hallucinations and was maintained with quetiapine (100-200 mg/day) and benztropine (1 mg/day) for 13 weeks. Given the potential for hyperprolactinemia as a side effect, the amisulpride dose was reduced to 800 mg/day concurrently with the discontinuation of benztropine; however, these changes resulted in severe restlessness without other extrapyramidal symptoms. The withdrawal akathisia disappeared over 2 weeks after switching to aripiprazole (10 mg/day) with propranolol (40 mg/day) and the patient's prolactin levels had normalized after 6 months of aripiprazole monotherapy. CONCLUSIONS: The present case highlights the potential for the development of withdrawal akathisia when the dose of amisulpride is tapered abruptly. Thus, a slow tapering and careful monitoring are recommended when switching from amisulpride to other antipsychotic drugs. Furthermore, this case suggests that changing the regimen to aripiprazole with propranolol may be a potential option for amisulpride withdrawal akathisia superimposed on pre-existing hyperprolactinemia.

Ego-resiliency moderates the risk of depression and social anxiety symptoms on suicidal ideation in medical students.

BACKGROUND: Little is known about the role of protective factors in suicidal ideation among medical students. This study aimed to examine the association between suicidal ideation and protective (self-esteem/ego-resiliency/social support) and risk (depression/social anxiety) factors. METHODS: Data on sociodemographic factors, depression, social anxiety, self-esteem, ego-resiliency, social support, and current suicidal ideation were collected from 408 medical students. A logistic regression model was constructed to identify the independent impact of potential influencing factors on suicidal ideation. Potential moderating effects were also explored. RESULTS: Thirty-eight participants (9.3%) reported experiencing suicidal ideation. Younger age, higher levels of depression, social anxiety, and lower levels of self-esteem, ego-resiliency, and social support were found to be significantly correlated with suicidal ideation. In the final model, higher levels of depression and social anxiety were associated with an increased risk of suicidal ideation, while higher levels of self-esteem and social support were associated with a decreased risk of suicidal ideation. Although the independent effect was not significant, the interactions of ego-resiliency with both depression and social anxiety on suicidal ideation were significant. Higher levels of ego-resiliency acted as a buffer against suicidal ideation among those with higher levels of depression or social anxiety. CONCLUSIONS: In addition to risk factors, this study revealed the underlying protective and moderating factors of suicidal ideation among medical students. Mental health programs focusing on enhancing ego-resiliency, self-esteem, and social support may contribute to suicide prevention in medical students.

Tuberculum sellae meningioma with possible tacrolimus neurotoxicity manifesting as manic-like psychosis after kidney transplantation.

BACKGROUND: Although kidney transplantation is the best treatment option for chronic kidney disease, the accompanying immunosuppressive treatment can induce severe neurotoxicity presenting, on rare occasions, as psychosis. However, a brain tumor synchronous with immunosuppressant neurotoxicity has never been reported in a kidney transplant recipient. Herein, we report the first case of possible tacrolimus neurotoxicity with a meningioma manifesting as manic-like psychosis after kidney transplantation. CASE PRESENTATION: A 63-year-old male presenting with acute psychotic mania was admitted to a psychiatric ward approximately 2 years after kidney transplantation. On brain magnetic resonance imaging, a tuberculum sellae meningioma was found, and hyperintense white matter lesions with possible tacrolimus-induced neurotoxicity were seen on fluid-attenuated inversion recovery images. Interestingly, the patient showed no visual field defects, and his blood tacrolimus concentration was within therapeutic ranges. After 3 weeks of adjunctive treatment with blonanserin, most of the symptoms had abated. CONCLUSIONS: The present case highlights the fact that neuroimaging studies are necessary to investigate underlying causes, as well as immunosuppressant neurotoxicity, which should all be considered when atypical psychiatric symptoms develop after organ transplantation. Further, this case suggests that the additional use of atypical antipsychotics while maintaining immunosuppressants may be effective for manic-like psychotic symptoms secondary to possible immunosuppressant neurotoxicity synchronous with a meningioma.

Life satisfaction and happiness associated with depressive symptoms among university students: a cross-sectional study in Korea.

BACKGROUND: This cross-sectional study investigated the impact of life satisfaction and happiness, as well as the prevalence and correlates of depressive symptoms in a large sample of university students. METHODS: We included 2338 students at 6 universities in 1 metropolitan city and 2 provinces of Korea. Depressive symptoms were assessed by the Beck Depression Inventory, and scores of 16 or higher were categorized as the presence of depression. Various sociodemographic, life satisfaction, happiness, and clinical factors (alcohol consumption and sleep quality) were measured. According to the presence of depression, sociodemographic, life satisfaction, happiness, and clinical characteristics were compared using statistical analyses. Further, a logistic regression model was constructed to examine the impact of life satisfaction, happiness, and clinical factors on depression. RESULTS: Among participants, 13.4% were identified as having depression. Life satisfaction and happiness were associated with a lower risk of depression, while hazardous alcohol drinking and poor sleep quality were related to a higher risk of depression. In addition, female gender, subjective body shape as obese, and insufficient pocket money were found to be significant correlates of depressive symptoms. CONCLUSIONS: This study demonstrated possible risk and protective factors of underlying depressive symptoms. Especially, our findings suggest that improvement in life satisfaction and happiness would be important in the prevention and management of depression. Our findings may contribute to developing specialized mental health programs for prevention, screening, and treatment of depression among university students.

Psychotic mania as the solitary manifestation of neurosyphilis.

BACKGROUND: Neurosyphilis remains a diagnostic challenge in current psychiatric practice because of its pleomorphic psychiatric manifestations. Although neurosyphilis can present with a wide range of psychiatric symptoms, psychotic mania as its solitary manifestation is an unusual phenomenon. CASE PRESENTATION: A 46-year-old man, with no history of any psychiatric disorder, exhibited abruptly developed symptoms of psychotic mania. He was admitted to a psychiatric ward for further evaluation and treatment. Upon admission, his cognitive function was unimpaired, and the hyperactivity was not severe. Also, no abnormalities were found upon neurological examination and brain magnetic resonance imaging. He was initially diagnosed as bipolar disorder with psychotic features. On the 3rd day after admission, he was confirmed as having neurosyphilis by analysis of cerebrospinal fluid and treated with intravenous penicillin-in combination with blonanserin-an atypical antipsychotic drug. After 2 weeks of treatment, most of the symptoms had abated. CONCLUSIONS: The present case emphasizes that patients presenting with atypical psychiatric manifestation should be screened for possible syphilis, particularly in the absence of previous psychiatric history, and suggests that combination of blonanserin with antibiotic therapy may be effective in the treatment of the manic and psychotic symptoms secondary to neurosyphilis.

Amyloid-independent functional neural correlates of episodic memory in amnestic mild cognitive impairment.

PURPOSE: Although amnestic mild cognitive impairment (aMCI) could have various biological characteristics, little attention has been given to the nature of episodic memory decline in aMCI with pathophysiologies other than Alzheimer's disease (AD), i.e., aMCI with low beta-amyloid (Aß) burden. This study aimed to identify the functional neural basis of episodic memory impairment in aMCI with Aß burden negative (aMCI-Aß-) and to compare these results with aMCI with Aß burden positive (aMCI-Aß+). METHODS: Individuals with aMCI (n = 498) were selected from the Alzheimer's Disease Neuroimaging Initiative database. Based on the mean florbetapir standard uptake value ratio, participants were classified as aMCI-Aß- or aMCI-Aß+. Correlations between memory scores and regional cerebral glucose metabolism (rCMglc) were analyzed separately for the two subgroups using a multiple regression model. RESULTS: For aMCI-Aß-, significant positive correlations between memory and rCMglc were found in the bilateral claustrum, right thalamus, left anterior cingulate cortex, left insula, and right posterior cingulate. For aMCI-Aß+, significant positive correlations between memory and rCMglc were found in the temporoparietal areas. These correlation patterns remained unchanged when clinical severity was added as a covariate CONCLUSION: Our findings indicate that memory impairment in aMCI-Aß- is related to multimodal integrative processing and the attentional control system, whereas memory impairment in aMCI-Aß+ is related to the typical brain memory systems and AD signature. These results suggest that although the two subgroups are clinically in the same category as aMCI, the memory impairment process depends on completely different functional brain regions according to their Aß burden level.

Amyloid-Independent Amnestic Mild Cognitive Impairment and Serum Apolipoprotein A1 Levels.

OBJECTIVES: The present study investigated the characteristics of amnestic mild cognitive impairment (aMCI) in subjects with low brain amyloid-beta (Aß) burden. Furthermore, the relationships between amyloid-independent cognitive decline and serum lipid profiles, particularly apolipoprotein A1 (APOA1), were evaluated. DESIGN: Cross-sectional and longitudinal follow-up study. SETTING: University hospital dementia clinic. PARTICIPANTS: 28 aMCI and 35 cognitive normal (CN) elderly. MEASUREMENTS: The study measures included baseline assessments of the subjects' clinical characteristics, lipid profiles, and magnetic resonance imaging and (11)C-labelled Pittsburgh Compound B (PiB) positron emission tomography scans. Based on PiB retention at baseline, the aMCI subjects were divided into low Aß (aMCI-) and high Aß (aMCI+) subgroups. All aMCI subjects were followed up over a 1-year period. RESULTS: The aMCI- group had a longer duration of illness than did the aMCI+ group. None of the aMCI- subjects were diagnosed with Alzheimer disease (AD) dementia during the 1-year follow-up period, whereas 26.7% of aMCI+ subjects developed AD dementia. The aMCI- group also exhibited lower serum APOA1 levels compared with both the aMCI+ and CN groups. Additionally, lower serum APOA1 levels were associated with cognitive decline and brain atrophy independent of Aß deposition and vascular burden. CONCLUSIONS: Patients with aMCI- likely exhibit different clinical and pathophysiological characteristics than patients with aMCI+. Additionally, APOA1 may be an important contributor underlying amyloid-independent neurodegeneration.

Multicenter, randomized, placebo-controlled, double-blind clinical trial of escitalopram on the progression-delaying effects in Alzheimer's disease.

OBJECTIVES: A series of preclinical studies have suggested that selective serotonin reuptake inhibitor antidepressants not only stimulate neurogenesis but also have neuroprotective effects. The present study primarily aimed to investigate whether escitalopram would decelerate the brain atrophy of patients with mild-to-moderate Alzheimer's disease (AD). We also assessed the effects of escitalopram on the cognitive function and neuropsychiatric symptoms of these participants. METHODS: Seventy-four probable AD patients without major depression were recruited from four dementia clinics of university hospitals and randomly assigned in a 1:1 ratio. Each group received 20 mg/day of escitalopram or placebo for 52 weeks. The primary outcome measures were the change rates of hippocampal and whole brain volume on magnetic resonance imaging for 52 weeks. The Alzheimer's Disease Assessment Scale-cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory, and Cornell Scale for Depression in Dementia (CSDD) were also applied. RESULTS: We did not find any significant differences in the changes of hippocampal or whole brain volume between the groups. Escitalopram showed significant beneficial effects on the CSDD score at 28 weeks compared with placebo (t = -2.17, df = 50.42, p = 0.035), but this finding did not persist throughout the study. CONCLUSION: The findings of the present study do not support the role of escitalopram as a progression-delaying treatment for AD. However, the negative results of the present trial should be interpreted cautiously because of the relatively small sample size. Further large-scale escitalopram trials targeting the earlier stages of AD, even prodromal AD, are still needed. Copyright © 2015 John Wiley & Sons, Ltd.

Independent and Interactive Influences of the APOE Genotype and Beta-Amyloid Burden on Cognitive Function in Mild Cognitive Impairment.

This study aimed to investigate the independent and interactive influences of apolipoprotein E (APOE) ε4 and beta-amyloid (Aß) on multiple cognitive domains in a large group of cognitively normal (CN) individuals and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Participants were included if clinical and cognitive assessments, amyloid imaging, and APOE genotype were all available from the Alzheimer's Disease Neuroimaging Initiative database (CN = 324, MCI = 502, AD = 182). Individuals with one or two copies of ε4 were designated as APOE ε4 carriers (ε4+); individuals with no ε4 were designated as APOE ε4 non-carriers (ε4-). Based on mean florbetapir standard uptake value ratios, participants were classified as Aß burden-positive (Aß+) or Aß burden-negative (Aß-). In MCI, APOE ε4 effects were predominantly observed on frontal executive function, with ε4+ participants exhibiting poorer performances; Aß positivity had no influence on this effect. Aß effects were observed on global cognition, memory, and visuospatial ability, with Aß+ participants exhibiting poorer performances. Measures of frontal executive function were not influenced by Aß. Interactive effects of APOE ε4+ and Aß were observed on global cognition and verbal recognition memory. Aß, not APOE ε4+, influenced clinical severity and functional status. The influences of APOE ε4+ and Aß on cognitive function were minimal in CN and AD. In conclusion, we provide further evidence of both independent and interactive influences of APOE ε4+ and Aß on cognitive function in MCI, with APOE ε4+ and Aß showing dissociable effects on executive and non-executive functions, respectively.

Comparison of regional gray matter atrophy, white matter alteration, and glucose metabolism as a predictor of the conversion to Alzheimer's disease in mild cognitive impairment.

We compared the predictive ability of the various neuroimaging tools and determined the most cost-effective, non-invasive Alzheimer's disease (AD) prediction model in mild cognitive impairment (MCI) individuals. Thirty-two MCI subjects were evaluated at baseline with [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET), MRI, diffusion tensor imaging (DTI), and neuropsychological tests, and then followed up for 2 yr. After a follow up period, 12 MCI subjects converted to AD (MCIc) and 20 did not (MCInc). Of the voxel-based statistical comparisons of baseline neuroimaging data, the MCIc showed reduced cerebral glucose metabolism (CMgl) in the temporo-parietal, posterior cingulate, precuneus, and frontal regions, and gray matter (GM) density in multiple cortical areas including the frontal, temporal and parietal regions compared to the MCInc, whereas regional fractional anisotropy derived from DTI were not significantly different between the two groups. The MCIc also had lower Mini-Mental State Examination (MMSE) score than the MCInc. Through a series of model selection steps, the MMSE combined with CMgl model was selected as a final model (classification accuracy 93.8%). In conclusion, the combination of MMSE with regional CMgl measurement based on FDG-PET is probably the most efficient, non-invasive method to predict AD in MCI individuals after a two-year follow-up period.

A normative study of total scores of the CERAD neuropsychological assessment battery in an educationally diverse elderly population.

BACKGROUND: This study aimed to investigate the influences of age, education, and gender on the two total scores (TS-I and TS-II) of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological assessment battery (CERAD-NP) and to provide normative information based on an analysis for a large number of elderly persons with a wide range of educational levels. METHODS: In the study, 1,987 community-dwelling healthy volunteers (620 males and 1,367 females; 50-90 years of age; and zero to 25 years of education) were included. People with serious neurological, medical, and psychiatric disorders (including dementia) were excluded. All participants underwent the CERAD-NP assessment. TS-I was generated by summing raw scores from the CERAD-NP subtests, excluding Mini-Mental State Examination and Constructional Praxis (CP) recall subtests. TS-II was calculated by adding CP recall score to TS-I. RESULTS: Both TS-I and TS-II were significantly influenced by demographic variables. Education accounted for the greatest proportion of score variance. Interaction effect between age and gender was found. Based on the results obtained, normative data of the CERAD-NP total scores were stratified by age (six overlapping tables), education (four strata), and gender. CONCLUSIONS: The normative information will be very useful for better interpretation of the CERAD-NP total scores in various clinical and research settings and for comparing individuals' performance of the battery across countries.

Anxiety Symptoms and Associated Psychological and Job-Related Factors Among Hospital Nurses.

OBJECTIVE: Recently, burnout and mental health issues regarding nurses are reported increasingly. This study aimed to investigate the prevalence of anxiety symptoms among hospital nurses and determine their association with psychological and job-related factors. METHODS: Data on demographics, job-related characteristics, burnout, Type A behavior patterns, self-esteem, and happiness were collected from 515 nurses working at a university hospital in Korea. Anxiety symptoms were assessed using the anxiety subscale of the Hospital Anxiety and Depression Scale, with scores of 8 or higher indicating the presence of anxiety symptoms. Demographic, job-related, and psychological factors were compared according to the presence of anxiety. Logistic regression was conducted to identify factors associated with anxiety symptoms. RESULTS: Two hundred and four (39.6%) participants had anxiety symptoms. Self-esteem and happiness were associated with a lower risk of anxiety symptoms, whereas burnout was associated with a higher risk of anxiety symptoms. Furthermore, being female, having a career of less than five years, and requiring counseling due to stress were associated with a higher risk of anxiety symptoms. Being younger, female, or a basic nurse; having a career of less than five years; partaking in shift work; experiencing job dissatisfaction; requiring counseling due to stress; being exposed to higher levels of burnout; and having lower levels of self-esteem and happiness were all found to be significantly correlated with anxiety symptoms. CONCLUSION: These findings suggest that promoting self-esteem and happiness while reducing burnout may be beneficial in preventing and managing anxiety symptoms among hospital nurses.

Improvement of dementia screening accuracy of mini-mental state examination by education-adjustment and supplementation of frontal assessment battery performance.

This study aimed to investigate whether the demographic variable-adjustment and supplementation of Frontal Assessment Battery (FAB) score can improve the screening ability of Mini-Mental State Examination (MMSE) for dementia and its subtypes. Five hundred forty-one non-demented comparison (NC) and 474 dementia (320 Alzheimer's disease [AD]; 139 non-Alzheimer's disease dementia [NAD]; and 15 mixed AD-NAD dementia) individuals living in the community were included. Education-adjusted MMSE (MMSE-edu) score showed significantly better screening accuracy for overall dementia, AD, and NAD than MMSE raw score. FAB-supplemented MMSE (MMSE-FAB) score had significantly better screening ability for NAD, but not for overall dementia and AD, than MMSE raw score alone. Additional supplementation of FAB to MMSE-edu further increased the ability for overall dementia or NAD screening, but not for AD screening. Further education adjustment of MMSE-FAB also improved its ability for overall dementia, AD, and NAD screening. These results strongly support the usefulness of education-adjustment and supplementation of frontal function assessment to improve screening performance of MMSE for dementia and its subtypes, NAD in particular.

Successful Early Lamotrigine and Aripiprazole Augmentation of Clomipramine in Severe Obsessive-compulsive Disorder.

Lamotrigine and aripiprazole have shown efficacy as augmentation agents of serotonin reuptake inhibitors for treatment-resistant obsessive-compulsive disorder (OCD). To date, the efficacy of lamotrigine/aripiprazole augmentation has not been reported in OCD treatment. Herein, we report the case of a 37-year-old male with severe OCD and comorbid depression whose symptoms markedly improved after low-dose lamotrigine/aripiprazole augmentation to clomipramine. Our report suggests that early glutamatergic/antipsychotic augmentation contributes to rapid remission of OCD symptoms.

Automating Rey Complex Figure Test scoring using a deep learning-based approach: a potential large-scale screening tool for cognitive decline.

BACKGROUND: The Rey Complex Figure Test (RCFT) has been widely used to evaluate the neurocognitive functions in various clinical groups with a broad range of ages. However, despite its usefulness, the scoring method is as complex as the figure. Such a complicated scoring system can lead to the risk of reducing the extent of agreement among raters. Although several attempts have been made to use RCFT in clinical settings in a digitalized format, little attention has been given to develop direct automatic scoring that is comparable to experienced psychologists. Therefore, we aimed to develop an artificial intelligence (AI) scoring system for RCFT using a deep learning (DL) algorithm and confirmed its validity. METHODS: A total of 6680 subjects were enrolled in the Gwangju Alzheimer's and Related Dementia cohort registry, Korea, from January 2015 to June 2021. We obtained 20,040 scanned images using three images per subject (copy, immediate recall, and delayed recall) and scores rated by 32 experienced psychologists. We trained the automated scoring system using the DenseNet architecture. To increase the model performance, we improved the quality of training data by re-examining some images with poor results (mean absolute error (MAE) [Formula: see text] 5 [points]) and re-trained our model. Finally, we conducted an external validation with 150 images scored by five experienced psychologists. RESULTS: For fivefold cross-validation, our first model obtained MAE = 1.24 [points] and R-squared ([Formula: see text]) = 0.977. However, after evaluating and updating the model, the performance of the final model was improved (MAE = 0.95 [points], [Formula: see text] = 0.986). Predicted scores among cognitively normal, mild cognitive impairment, and dementia were significantly different. For the 150 independent test sets, the MAE and [Formula: see text] between AI and average scores by five human experts were 0.64 [points] and 0.994, respectively. CONCLUSION: We concluded that there was no fundamental difference between the rating scores of experienced psychologists and those of our AI scoring system. We expect that our AI psychologist will be able to contribute to screen the early stages of Alzheimer's disease pathology in medical checkup centers or large-scale community-based research institutes in a faster and cost-effective way.

Psychosocial Factors Influencing Quality of Life Among Medical Students.

OBJECTIVE: This study investigated the influence of psychosocial factors on medical students' quality of life (QOL). METHODS: A total of 408 medical students participated in this study. We collected data on participants' sociodemographic details, symptoms of depression and Internet addiction, self-esteem, social support, and QOL. QOL was assessed using the World Health Organization Quality of Life-Abbreviated form, which has four domains (physical health, psychological health, social relationships, and environment). A stepwise multiple linear regression model was constructed to identify factors' independent impact on QOL. RESULTS: Higher levels of depression and Internet addiction were associated with lower scores in all domains of QOL, whereas higher levels of self-esteem and social support were associated with higher scores. Being in third-year versus first-year was associated with higher scores in the physical health and environment domains. Living alone or in dormitories, low or middle socioeconomic status, and insufficient or moderate pocket money were associated with lower scores in the environment domain. Additionally, female students displayed significantly lower scores for physical health, psychological health, and environment than male students, but not for social relationships. There were significant differences in certain domains of QOL due to sociodemographic factors. CONCLUSION: This study demonstrates the psychosocial factors influencing medical students' QOL. Educational strategies focusing on strengthening self-esteem and social support as well as preventing depression and Internet addiction may contribute to improving medical students' QOL.

Microstructural alteration of the anterior cingulum is associated with apathy in Alzheimer disease.

OBJECTIVES: To identify regional alterations of white matter integrity associated with apathy in Alzheimer disease (AD). DESIGN: Cross-sectional study. SETTING: University Dementia Clinic. PARTICIPANTS: Fifty-one very mild or mild probable AD subjects. INTERVENTION: Volumetric magnetic resonance imaging with diffusion tensor imaging. MEASUREMENTS: Volume of interest analyses were performed to compare regional fractional anisotropy (FA) between apathy and apathy-free group, and to test linear relationship between regional FA and apathy severity. Apathy was assessed by the Neuropsychiatric Inventory. RESULTS: Apathy group showed significantly lower FA values than apathy-free group in the left anterior cingulum (A-C), regardless of concomitant depression and psychotropic medications. Left A-C FA values also had significant linear relationship with apathy-composite scores as a measure of apathy severity, even after controlling gray matter density of the ipsilateral anterior cingulate cortex. CONCLUSIONS: Our findings support that communication failure between the anterior cingulate cortex and other brain structures via the A-C contributes to the development and aggravation of apathy in AD, additionally supporting the general notion of disconnection syndrome for clinical manifestation of AD.

Relationship of amyloid-ß burden with age-at-onset in Alzheimer disease.

OBJECTIVE: To investigate the relationship between in vivo brain amyloid-beta (Aß) burden, measured by C-labeled Pittsburgh Compound B (C-PiB) retention, and age-at-onset in patients with Alzheimer disease (AD). DESIGN: Cross-sectional study. SETTING: University Dementia Clinic. PARTICIPANTS: Twenty-two AD patients including 11 early-onset AD (EOAD: onset <65 years) and 11 late-onset AD (LOAD: onset ≥65years) cases with matched dementia severity, duration of illness, and apolipoprotein E ε4 allele number. INTERVENTION: C-PiB positron emission tomography scans. MEASUREMENTS: Both region of interest and voxel-based analyses were performed to compare C-PiB retention between EOAD and LOAD groups, and to test linear relationship between age-at-onset and C-PiB retention. RESULTS: Both region of interest (ROI) and voxel-based analyses revealed that EOAD patients had significantly higher C-PIB retentions than LOAD patients in diffuse brain regions including frontal, lateral parietal, lateral temporal, and occipital cortex, and basal ganglia. Subgroup analyses showed that negative correlation between age-at-onset and C-PiB retention was significant in LOAD but not in EOAD. CONCLUSIONS: Our finding of a heavier Aß burden in the brain of living EOAD patients than LOAD patients is in agreement with those from postmortem studies. The inverse relationship between age-at-onset and Aß burden is possibly associated with aging-related decrease of brain or cognitive reserve and with aging-related increase of brain vulnerability.

Internet Addiction and Its Associations with Clinical and Psychosocial Factors in Medical Students.

OBJECTIVE: Excessive internet use has been associated with various psychiatric symptoms and psychosocial factors. This study aimed to investigate the prevalence of internet addiction (IA) and its associations with clinical (depression/social anxiety) and psychosocial (self-esteem/perceived social support) factors in medical students. METHODS: In total, 408 medical students at one university in Korea were included in this study. IA symptoms were assessed with Young's Internet Addiction Test, and scores of 50 or higher were considered to indicate IA. Participants were asked to complete the Beck Depression Inventory, Social Phobia Inventory, Rosenberg Self-Esteem Scale, and Duke-University of North Carolina Functional Social Support Questionnaire. A logistic regression model was constructed to examine the impact of clinical and psychosocial factors on IA. RESULTS: Forty-seven participants (11.5%) were identified as having IA. Self-esteem was associated with a lower risk of IA, whereas depression and social anxiety were associated with a higher risk of IA. Depression, social anxiety, low self-esteem, and low perceived social support were found to be significant correlates of IA. Young's Internet Addiction Test score positively correlated with Beck Depression Inventory and Social Phobia Inventory scores, but negatively correlated with Rosenberg Self-Esteem Scale and Duke-University of North Carolina Functional Social Support Questionnaire scores. Furthermore, the prevalence of IA was highest in first-year medical students. CONCLUSION: This study revealed the possible risk and protective factors of IA. Our findings indicate that strengthening self-esteem and reducing depression and social anxiety may contribute to the prevention and management of IA in medical students.