Parity As a Protective Biomarker Against Silent Brain Infarction in Community-Dwelling Older Adults: The Sefuri Study.

BACKGROUND: Although several studies have reported an association between parity and increased risk of stroke, this relationship remains controversial. AIMS: The present study aimed to determine whether parity is associated with silent brain infarction (SBI), independent of other confounders. METHODS: We analyzed the brain magnetic resonance imaging findings in 576 of community-dwelling older adults with a mean age of 72.1 years. All female participants were asked to provide information regarding the total number of live births, their age at the last parity, and their age at menopause. RESULTS: The prevalence of SBI and the number of infarcts per participant were higher in men than in women. Although all women who had given birth (0, 1-2, 3-4, or 5+ times) exhibited lower age-adjusted odds ratios (ORs) for SBI than men, a significant difference was observed between women with ≧5 births and men after adjustment for common vascular risk factors (OR: .348, 95% confidence interval [95% CI]: .123-.986). Among women who had given birth, the relationship between fertility and SBI was attenuated, but was enhanced after adjustment for age at the last parity (OR: .300, 95% CI: .102-.886). CONCLUSIONS: Our findings indicate that fertile women may be protected against SBI or cerebral small vessel disease via the biological effects associated with reproductive activity, and that high fertility may be a marker of protection against SBI. However, late childbearing may blunt protective effects of fertility against SBI.

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 (ß = 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 (ß = -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.

Chronic Kidney Disease and Subclinical Brain Infarction Increase the Risk of Vascular Cognitive Impairment: The Sefuri Study.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the complex associations among chronic kidney disease (CKD), subclinical brain infarction (SBI), and cognitive impairment. METHODS: We used structural equation modeling (SEM) to examine the complex relationships among CKD, SBI, and cognitive function with Mini-Mental State Examination (MMSE; global function) and modified Stroop test (executive function) in a population-based cohort of 560 non-demented elderly subjects. RESULTS: Path analysis based on SEM revealed that the direct paths from estimated glomerular filtration rate (eGFR) to SBI and from SBI to executive function were significant (ß = -.10, P = .027, and ß = .16, P < .001, respectively). Furthermore, the direct path from eGFR to executive function was also significant (ß = -.12, P = .006), indicating that the effects of CKD on executive function are independent of SBI. The direct paths from age and education to global cognitive function were highly significant (ß = -.17 and .22, respectively, P < .001), whereas the direct path from eGFR to MMSE was not significant. CONCLUSIONS: Our findings indicate that CKD confers a risk of vascular cognitive impairment or executive dysfunction through mechanisms dependent and independent of SBI. Treating CKD may be a potential strategy to protect against vascular cognitive impairment or executive dysfunction in healthy elderly subjects.

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.

Brief intervention in the workplace for heavy drinkers: a randomized clinical trial in Japan.

AIMS: To investigate the effectiveness of brief intervention (BI) conducted in the workplace for heavy drinkers. METHODS: A randomized controlled trial was conducted at six companies in Japan. Participants were heavy drinkers who met the inclusion criteria and were randomized into three groups: the BI group, BI with diary group and a control group. Outcomes (total drinks, binge drinking episodes and alcohol-free days) were evaluated at 3 and 12 months. RESULTS: The 304 participants recruited were allocated to the three groups and 277 participated in all follow-up evaluations. Dropout rates in the respective groups were 7.0, 14.9 and 5.5%. Some improvements were observed in all the groups. In particular, alcohol-free days in the BI group were significantly increased by 93.0% at 12 months. Total drinks at 12 months were reduced by 41 g per week in the BI group compared with the control group, although the intergroup difference was not significant. CONCLUSION: BI in the workplace is effective for increasing the number of alcohol-free days. However, the effectiveness on decreasing alcohol consumption was unclear, which could be explained by alcohol screening itself causing a reduction in drinking.

Neurodegenerative changes in patients with clinical history of bipolar disorders.

Neurodegeneration in bipolar disorder (BPD) is poorly understood. Therefore, the current study was designed to assess the immunohistochemical changes in neurodegenerative markers in patients with BPD. Eleven consecutive autopsy cases diagnosed with BPD were analyzed. Sections were obtained from archival paraffin blocks of representative areas and stained using conventional methods, as well as immunostained with several antibodies to screen for neurodegenerative diseases. Age- and non-argyrophilic grains (AGs) degeneration matched controls were selected for each case. Clinical information was retrospectively collected from medical charts. All patients were men, and the average age of death was 70 years. Neuropathological diagnoses included dementia with grains (2), argyrophilic grain disease (2), corticobasal degeneration (CBD, 1), Lewy body disease (1), hypoxic encephalopathy (1) and cerebral infarction (1). All cases showed AGs to various degrees. Three patients died in their 50s; one demonstrated dementia with Lewy bodies, while the other two showed abundant AGs in the thalamus and amygdala. Of the three patients who died in their 60s, one showed AGs preferentially in the thalamus and amygdala, while the others demonstrated limbic predominance. The patients who died in/after their 70s demonstrated AGs similar to controls, except for the patient with CBD. Our data provides potentiality that neurodegenerative diseases may be an underlying pathology in certain cases of BPD.

Leisure-Time Physical Inactivity Associated with Vascular Depression or Apathy in Community-Dwelling Elderly Subjects: The Sefuri Study.

BACKGROUND: Although physical inactivity is a major public health problem, the causative factors for physical inactivity per se are poorly understood. To address this issue, we investigated the relationship between deep white matter lesions (DWMLs) on magnetic resonance imaging, apathy, and physical activities using structural equation modeling (SEM). METHODS: We examined 317 community-dwelling elderly subjects (137 men and 180 women with a mean age of 64.5 years) without dementia or clinically apparent depression. Physical activity was assessed with a questionnaire consisting of 3 components (leisure-time, work, and sport activities). RESULTS: The mean score from the apathy scale (a visual analogue version of Starkstein's apathy scale) of the Grades 2-3 DWML group was 420 (95% confidence interval [CI] 379-461), which was lower (more apathetic) than the Grade 0 DWML group score of 478 (95% CI 463-492) after adjustment for education as a covariate. SEM showed that the direct paths from DWMLs or education to apathy were significant, and the direct path from apathy to leisure-time activity was highly significant (ß = .25, P < .001). The degree of apathetic behavior was negatively associated with sport activity in female subjects and positively associated with TV watching in male subjects. CONCLUSIONS: The results of the study show that DWMLs are one of the major factors that cause apathetic behavior and that apathy has significant negative effects on leisure-time physical activity in community-dwelling elderly subjects. Even a minor level of apathy without major depression would have a significant impact on activities of daily living and quality of life.

[The Basic Act on Measures against Alcohol-related Health Harm and Role of General Psychiatrists--With focus on SBRIT and Deadly Triangle].

Japan has just enacted a national law for alcohol, that named "Basic Act on Measures Against Alcohol-related Health Harm". This article includes 5 topics; i) General psychiatrists have the roles and responsibilities in this law, ii) All psychiatrists need to know about alcohol-related health harm and alcohol-related problem, iii) Alcohol dependence is attributed to change of neurotransmitter in the brain, iv) Mood disorder is more likely to be complicated by alcohol dependence and/or hazardous drinking. Some of the patients with the above-mentioned complicated disease have alcohol-induced mood disorder, v) If the patient has alcohol-induced mood disorder, it will place priority on alcoholism treatment and will be important to quickly resolve with abstinence. Finally, the proposals are made as follows; i) Making a guideline, ii) Physicians skilled at SBIRT (Screening, Brief Intervention, and Referral to Treatment) should be qualified as a certifying physician, and having the qualification should allow reimbursing medical institutions for the alcohol related service provided.

Early menopause and the risk of silent brain infarction in community-dwelling elderly subjects: the Sefuri brain MRI study.

Our previous study showed that the male predominance of silent brain infarction (SBI) was largely because of higher prevalence of alcohol habit and smoking in men than in women. In the present study, we further conducted an analysis of brain magnetic resonance imaging findings to examine whether early menopause contributes to SBI in community-dwelling subjects. Women were queried as to the age and cause of menopause, the total number of children, and the age at giving birth to her last child. Among 306 female subjects aged 60 years or older, univariate analysis showed that early menopause (total or natural) was significantly associated with SBI but age at natural menopause, number of children, and age at the last parity were not. In the total of 715 subjects (283 men and 432 women with a mean age of 67.2 years), the forward stepwise method of logistic analysis revealed that natural early menopause (odds ratio [OR] 4.28, 95% confidence interval [CI] 1.07-17.11), in addition to age, hypertension, alcohol intake, and smoking, was a significant factor concerning SBI. Also in the subgroup of female subjects aged 60 years or older, natural early menopause was a significant factor concerning SBI (OR 4.35, 95% CI 1.05-18.08) adjusted for covariates. Although the prevalence of natural early menopause was low (3.3% of 306 female subjects), natural menopause before the age of 40 years may be a risk for SBI or small-vessel disease of the brain.

Dual task walking reveals cognitive dysfunction in community-dwelling elderly subjects: the Sefuri brain MRI study.

The aim of our study was to investigate the effects of subclinical brain lesions and cognitive function on gait performance with or without concurrent cognitive task in community-dwelling elderly subjects. Participants without dementia (92 men and 109 women with a mean age of 67.8 years) underwent brain magnetic resonance imaging, neuropsychologic tests, and gait measurements. Impaired gait velocity of the Timed Up and Go test was associated with deep white matter lesions (odds ratio [OR], 2.338; 95% confidence interval [CI], 1.120-4.880) and diabetes mellitus (OR, 2.725; 95% CI, 1.120-6.630) after adjusted for age, sex, education, and cognitive function tests. Impaired gait velocity of dual task walking was associated with age and the score of Rivermead Behavioral Memory Test (OR, .899/1 point higher; 95% CI, .813-.994), whereas deep white matter lesions were not significantly associated with dual task walking. The present study showed that gait represents not only physical functioning but also subclinical cognitive dysfunction particularly memory impairment in healthy elderly subjects.

Prevalence of hazardous drinking and suspected alcohol dependence in Japanese primary care settings.

OBJECTIVE: We aimed to assess the prevalence of hazardous drinking and potential alcohol dependence among Japanese primary care patients, and their readiness to change and awareness of others' concerns. METHODS: From July to August 2023, we conducted a multi-site cross-sectional study as a screening survey for participants in a cluster randomized controlled trial. The trial included outpatients aged 20-74 from primary care clinics. Using the Alcohol Use Disorders Identification Test (AUDIT) alongside a self-administered questionnaire, we evaluated the prevalence of hazardous drinking and suspected alcohol dependence, patients' readiness to change, and their awareness of others' concerns. RESULTS: Among the 1388 participants from 18 clinics, 22% (95% confidence interval (CI): 20% to 24%) were identified as engaging in hazardous drinking or suspected of being alcohol dependent. As the AUDIT scores increased, so did their readiness to change. However, only 22% (95%CI: 16% to 28%) of those with scores ranging from 8 to 14 reported that others, including physicians, had expressed concerns about their drinking during the past year. For those with scores of 15 or higher, the figure was 74%. CONCLUSIONS: This study underscores the need for universal or high-risk alcohol screening and brief intervention in Japanese primary care settings. Trial registry UMIN-CTR (https://www.umin.ac.jp/ctr/) (UMIN000051388).

[Treatment outcome of alcoholics in a general hospital alcoholic clinic: effects of adopting moderation as a practical treatment goal].

It's almost 50 years since medical treatment for alcoholism began to be practiced in Japan in 1960s. Since then, treatment goal for alcohol use disorders has always been absolute abstinence, and only severe cases have been treated. Recently, many people are concerned about lifestyle-related diseases, suicides, depression, and drunken-driving accidents. Reduction in alcohol consumption of heavy drinkers began to draw attention, and brief motivational intervention study was launched at last in 2007 in Japan. In 2009 we set up alcohol clinic in a general hospital in order that the alcoholics may get easier access to their treatments. The basic roles of our alcohol satellite clinicare as follows: 1. Assessment and diagnosis of patient's alcohol-related problem are our primary role. 2. Referral to a specialized hospital is offered in case special treatments for alcohol dependence are needed. 3. Our standard treatment is a brief intervention, not exceeding 3 sessions, to enhance the patients' self-efficacy. 4. Our treatment goal is not limited to total abstinence. Moderation of drinking can also be a goal. We examined the treatment outcome to verify these roles and meanings. Of all the patients visited this hospital from 2009 to 2011, 77 patients were diagnosed as alcohol dependent. Out of those 77 patients, 21 patients set up a moderation of drinking as their temporal treatment goal and 10 achieved good outcome at the inquiry point of 8 to 41 (average: 22) months after intervention. This result suggests that moderation can be a practical treatment goal in some alcoholics.

[Investigation into drinking problem of patients who visited a general hospital in central and northern Okinawa].

In Japan, many problems related to alcohol are pointed out from before. We believe that there is a unique drinking culture in Okinawa, such as a large amount of alcohol. Therefore, we estimate many people in Okinawa have a drinking problem. We conducted a survey of patients who visited general hospital (medical or surgical or orthopedic) in 2007. The purpose of this study is to collect basic data for introducing alcoholics to specialized treatment as early as possible, detecting the person who drink large amounts of alcohol, performing early intervention for people who drink large amount of alcohol, and advancing cooperation with specialized medical agencies of alcohol. As a result, Among the patients who visited general hospital in Okinawa, many problem drinkers are concentrated in the young age. and they have strong fears of health. The possibility of early intervention with intervention techniques, such as brief intervention, has been suggested.

[Survey of physicians and alcohol-dependent patients in regard to the goals of treatment of alcohol dependence].

We conducted a survey of alcohol-dependent patients at the time of their first visit and physicians in regard to the goals of treatment of alcohol dependence. There were 99 replies from patients, and replies from physicians related to 64 of the patients' replies were also received, and in 25.0% of them it was judged possible to make reducing the amount of alcohol consumed a temporary or final goal. Having a mild drinking problem, the absence of a personality disorder or mental retardation, the presence of a strong motivation in regard to treatment, etc., were cited as reasons for the physicians' judgments. In addition, the number of diagnostic criteria of the ICD-10 for dependence syndrome that applied was shown to be significantly related to the judgments regarding treatment goals. However, as for Alcohol Dependence Scale (ADS), there was no significant relationship with the treatment goal.

A randomized controlled trial of the web-based drinking diary program for problem drinking in multi workplace settings.

OBJECTIVES: To assess the effectiveness of a web-based brief intervention (BI) program to record daily drinking among people with problem drinking in workplace settings. METHODS: A two-armed, parallel-group, randomized controlled trial were conducted at six workplaces in Japan. After obtaining written consent to participate in the study, workers with an Alcohol Use Disorders Identification Test (AUDIT) score of 8 or higher were randomly assigned into two groups. The participants allocated to the intervention group recorded their daily alcohol consumption for 4 weeks using the program, while those allocated to the control group received no intervention. Outcome measures included the amount of alcohol consumption in past 7 days using the Timeline Follow-Back method in the program at baseline, 8th week, and 12th week and written AUDIT score at baseline and 12th week. RESULTS: Hundred participants were assigned to either the intervention group (n = 50) or control group (n = 50). The results of two-way repeated measures ANOVA showed a statistically significant interaction between the group and the week factors in the two primary outcomes (number of alcohol-free days, total drinks) and secondary outcomes (AUDIT score) (p = .04, .02, and .03, respectively). The between-group effect sizes (Hedges' g; 95% CI) of the outcomes at 12th week were 0.53; 0.13-0.93 (total drinks), 0.44; 0.04-0.84 (AUDIT score), 0.43; 0.03-0.83 (number of alcohol-free days). CONCLUSIONS: The web-based BI program for problem drinking was considered to be effective in reducing alcohol consumption and the AUDIT score in workplace settings.

Clinical correlating factors and cognitive function in community-dwelling healthy subjects with cerebral microbleeds.

We performed brain gradient-echo T2(∗)-weighted magnetic resonance imaging (GE-MRI) in community-dwelling healthy people to investigate the clinical correlates (i.e., possible risk factors) and cognitive function in subjects with cerebral microbleeds (MBs). We examined 368 healthy subjects age 39 years or older living in a Japanese rural community, performing baseline and clinical assessments and brain MRI (T2(∗)-weighted, T1-weighted, T2-weighted, and FLAIR). We assessed global cognitive function in subjects age 60 years or older using the Mini-Mental State Examination (MMSE). An MMSE score >1.5 standard deviations (SD) below the mean score for a particular age group was considered subnormal. MBs were present in 14 of 368 subjects overall (3.8%; 11 males and 3 females) and in 14 of 225 subjects age≥60 years (6.2%). In a logistic regression analysis, older age (odds ratio [OR]=2.649/10 years; 95% confidence interval [CI]=1.465-4.788) and male sex (OR=6.876; 95% CI=1.801-26.248) were significantly related to the presence of MBs. The presence of silent brain infarction and white matter lesions was correlated with MBs, suggesting that MBs were the consequence of small-vessel diseases. There was a significant association between the presence of MBs and subnormal cognition defined by MMSE (OR=5.226; 95% CI=1.463-18.662). Our data suggest that in healthy community-dwelling subjects, MBs may be a consequence of small-vessel disease, which is correlated with aging, male sex, and subnormal cognition.

[Effectiveness of drinking plan and drinking diary in intervention program (HAPPY program) for heavy drinkers].

We examined the effectiveness of a drinking plan (goal setting), and a drinking diary (self monitoring), in the intervention program (HAPPY program), for heavy drinkers in the workplace. 115 people participated, and 80 people were evaluated three months later and 31 people were evaluated one year later. We classified the drinking plans in the limitation of the quantity, non-drinking days, and the device of low risk drinking model. 75 people made the drinking diary for 12 weeks after brief intervention and studied three months later and 31 people were analyzed one year later. We evaluated on heavy drinking days of 28 days, and non-drinking days of 28 days and standard drinks of 7 days. The limitation of the quantity model is effective for low risk drinking. The non-drinking day model is easily achieved, but not effective for low risk drinking. The device of low risk drinking model improved drinking habits for a long-term. The drinking diary for 12 weeks after intervention improved drinking habits for a long-term. The drinking plan (goal setting), and drinking diary (self monitoring), in intervention program for heavy drinkers were effective for prevention of lifestyle-related disease and alcoholism.

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.

Alcohol intake and quantitative MRI findings among community dwelling Japanese subjects.

BACKGROUND AND PURPOSE: The relationship between alcohol consumption and subclinical findings on magnetic resonance imaging (MRI) remains uncertain. We examined the relationship between light to moderate alcohol intake and silent brain infarction (SBI), white matter lesions (WMLs), and cerebral atrophy. METHODS: Cranial MRI was performed on subjects>or=40 years residing in a rural community in Japan (n=385; mean age, 67.2). Alcohol intake and type was determined using a detailed questionnaire; subjects were categorized into three groups: non-drinkers, light drinkers (<7 drinks per week), and moderate drinkers (>or=7 drinks per week). Former drinkers were considered non-drinkers. Periventricular WMLs, deep WMLs and cerebral atrophy were measured quantitatively using a computer-assisted processing system (%PVWML, %DWML, and %Brain, respectively). RESULTS: Compared with non-drinkers, the prevalence odds ratios for SBI were significantly higher in light and moderate drinkers, after multivariate adjustment. After adjusting for age, sex, and other related factors, the geometric mean %PVWML volumes in light and moderate drinkers were 1.27% and 1.52%, respectively, significantly larger than those for non-drinkers (0.95%). The geometric mean %DWML volume in light drinkers was 0.10%, which was larger than the value for non-drinkers (0.06%); the value for moderate drinkers (0.13%) was significantly larger than that for non-drinkers. The geometric mean %Brain values for non-, light, and moderate drinkers were 92.1, 91.9 and 90.8%, respectively; a statistically significant difference was found between non-drinkers and moderate drinkers. CONCLUSIONS: The present study indicates that regular drinking, including even low levels of consumption, may be a risk factor for subclinical findings detected on MRI in community-dwelling Japanese people.