SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values ,261025 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P=7.3361027 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P=1.7761029) and rs3781834 (P=1.0461028). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P=1.7161025) and rs744373 near BIN1 (P = 1.3961024). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations

Behavioural cue reactivity to alcohol-related and non-alcohol-related stimuli among individuals with alcohol use disorder: an fMRI study with a visual task.

Patients with alcohol use disorder (AUD) have difficulty controlling their alcohol cravings and thus exhibit increased use and early relapse. Although patients tend to respond more strongly to alcohol-related images than to non-alcohol-related images, few researchers have examined the factors that modulate cravings. Here, we examined whole-brain blood oxygen level-dependent (BOLD) responses to behavioural cues in individuals with AUD and in healthy controls (HCs). The participants included 24 patients with AUD and 15 HCs. We presented visual cues consisting of four beverage-related images (juice, drinking juice, sake, and drinking sake), and the cue reactivity of AUD participants was contrasted with that of HC participants. Multiple comparisons revealed that the AUD group had lower BOLD responses than the HC group in the left precuneus (p = 0.036) and the left posterior cingulate cortex (PCC) (p = 0.044) to images of drinking juice and higher BOLD responses than the HC group in the left PCC (p = 0.044) to images of drinking sake. Furthermore, compared to the HCs, the AUD patients had decreased BOLD responses associated with cue reactivity to drinking juice in the left precuneus during the periods from 15 to 18 s (p = 0.004, df = 37) and 18 to 21 s (p = 0.002, df = 37). Our findings suggest that HCs and AUD patients differ in their responses not to images of alcoholic beverages but to images related to alcohol-drinking behaviour. Thus, these patients appear to have different patterns of brain activity. This information may aid clinicians in developing treatments for patients with AUD

Correction: Behavioural cue reactivity to alcohol-related and non-alcohol-related stimuli among individuals with alcohol use disorder: An fMRI study with a visual task.

[This corrects the article DOI: 10.1371/journal.pone.0229187.]

Behavioural cue reactivity to alcohol-related and non-alcohol-related stimuli among individuals with alcohol use disorder: An fMRI study with a visual task.

Patients with alcohol use disorder (AUD) have difficulty controlling their alcohol cravings and thus exhibit increased use and early relapse. Although patients tend to respond more strongly to alcohol-related images than to non-alcohol-related images, few researchers have examined the factors that modulate cravings. Here, we examined whole-brain blood oxygen level-dependent (BOLD) responses to behavioural cues in individuals with AUD and in healthy controls (HCs). The participants included 24 patients with AUD and 15 HCs. We presented visual cues consisting of four beverage-related images (juice, drinking juice, sake, and drinking sake), and the cue reactivity of AUD participants was contrasted with that of HC participants. Multiple comparisons revealed that the AUD group had lower BOLD responses than the HC group in the left precuneus (p = 0.036) and the left posterior cingulate cortex (PCC) (p = 0.044) to images of drinking juice and higher BOLD responses than the HC group in the left PCC (p = 0.044) to images of drinking sake. Furthermore, compared to the HCs, the AUD patients had decreased BOLD responses associated with cue reactivity to drinking juice in the left precuneus during the periods from 15 to 18 s (p = 0.004, df = 37) and 18 to 21 s (p = 0.002, df = 37). Our findings suggest that HCs and AUD patients differ in their responses not to images of alcoholic beverages but to images related to alcohol-drinking behaviour. Thus, these patients appear to have different patterns of brain activity. This information may aid clinicians in developing treatments for patients with AUD

Prevalence and Trends in Alcohol Dependence and Alcohol Use Disorders in Japanese Adults; Results from Periodical Nationwide Surveys

Aims: Nationwide surveys to clarify the characteristics and trends of the drinking behavior of Japanese adults were carried out in 2003, 2008, and 2013. Methods: These were periodical cross-sectional surveys. Subjects were chosen through a stratified two-stage random sampling method. The surveys included drinking frequency and amount, ICD-10 alcoholism diagnostic standards, questionnaire for the determination of harmful alcohol use (AUDIT: Alcohol Use Disorders Identification Test). In 2003, the surveys obtained responses from 2547 people (73% response rate); in 2008, 4123 people (55% response rate); and in 2013, 4153 people (59% response rate). Results: The proportion of lifetime experience of alcohol dependence diagnosed by ICD-10 was 1.9% for male and 0.2% for female, and the estimated number of patients was 1.07 million. The declining trends were observed in the percentage of daily drinkers and the amount of alcohol consumed per week for male. The lowering of the age for consuming their first alcoholic drink and their first drunken experience was observed among female. The gender difference of prevalence of problem drinking is getting smaller. The binge drinking and heavy episodic drinking were observed especially younger generation. The only small proportion of patients with alcohol dependence had received specialized medical care, whereas the many of these visited medical institutions and health screening. Conclusions: The survey observed many hidden alcoholic patients, and showed the possibility that the healthcare facilities and health screening became the place of screening and intervention for alcohol dependence

Low-Grade Inflammation Is Associated with Apathy Indirectly via Deep White Matter Lesions in Community-Dwelling Older Adults: The Sefuri Study

Low-grade inflammation is implicated in the pathogenesis of atherosclerosis, metabolic syndrome, and apathy as a form of vascular depression. We analyzed the brain magnetic resonance imaging findings in 259 community-dwelling older adults (122 men and 137 women, with a mean age of 68.4 years). The serum concentrations of high-sensitivity C-reactive protein (hsCRP) were measured by a quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that the log10 hsCRP value and the presence of a metabolic syndrome were independently associated with confluent but not punctate deep white matter lesions (DWMLs). Path analysis based on structural equation modeling (SEM) indicated that the direct path from the log10 hsCRP to the DWMLs was significant (β = 0.119, p = 0.039). The direct paths from the metabolic syndrome to the log10 hsCRP and to the DWMLs were also significant. The direct path from the DWMLs to apathy (β = −0.165, p = 0.007) was significant, but the direct path from the log10 hsCRP to apathy was not significant. Inflammation (i.e., elevated serum hsCRP levels) was associated with DWMLs independent of common vascular risk factors, while DWMLs were associated with apathy. The present analysis with SEM revealed the more realistic scheme that low-grade inflammation was associated with apathy indirectly via DWMLs in community-dwelling older adults