Accelerated cognitive decline after the COVID-19 pandemic in a community population of older persons with cognitive impairment: A 4-year time series analysis in the Tokyo Metropolis area.

Aim: The coronavirus disease 2019 (COVID-19) pandemic has led to lifestyle restrictions and might be associated with long-term changes in cognitive function. The aim of the present study was to elucidate the overall effect of the COVID-19 pandemic on the cognitive trajectory of a cohort of patients with cognitive impairment.

Methods: We enrolled 160 patients who had been making regular visits to a medical center for dementia.

Telomere shortening in the oral epithelium in relation to alcohol intake, alcohol dehydrogenase (ADH-1B), and acetaldehyde dehydrogenase (ALDH-2) genotypes and clinicopathologic features.

Background: Progressive telomere shortening with age or chronic inflammation may lead to genomic instability that characterizes the early stage of carcinogenesis. Certain risk factors, such as drinking alcoholic beverages or smoking, predispose the oral mucosa to squamous cell carcinoma. The ADH1B and ALDH2 genotypes can influence the risk of cancer due to alcohol drinking.

Evaluation of serum carbohydrate-deficient transferrin by HPLC and MALDI-TOF MS.

Background: The percentage of carbohydrate-deficient transferrin (%CDT) in serum is a marker of habitual alcohol intake that can be determined by antibody detection of abnormal disialo sugar chains at D432 and D630. However, this approach lacks specificity for alcoholic liver disease. To decrease the false-positive rate in patients with non-alcoholic liver diseases, we developed a screening method using the disialo sugar chain at D630 alone.

Lack of genetic association between TREM2 and late-onset Alzheimer's disease in a Japanese population.

Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimer's disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al.

Genome-wide association study identifies a potent locus associated with human opioid sensitivity.

Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. Although opioid sensitivity is well known to vary widely among individual subjects, several candidate genetic polymorphisms reported so far are not sufficient for fully understanding the wide range of interindividual differences in human opioid sensitivity.

Higher serum free glycerol levels in a group of alcoholics than in controls.

Background: The biomarkers of excessive alcohol intake reported thus far have not always been reliable. We discovered the presence of free glycerol (FG) by high-performance liquid chromatography (HPLC) in the serum of alcoholic patients but not in healthy persons, and a higher percentage of the alcoholics were positive for serum FG than for gamma-glutamyl transpeptidase, mean corpuscular volume, or carbohydrate-deficient transferrin (%CDT). Therefore, in this study, we investigated whether the same results as with HPLC could be obtained by measuring FG with an easy-to-use autoanalyzer and whether the serum FG measured by this method would be useful as a biomarker of excessive alcohol intake.

A health-risk appraisal model and endoscopic mass screening for esophageal cancer in Japanese men.

A strong association between inactive aldehyde dehydrogenase-2 (ALDH2) and risk of esophageal cancer has been demonstrated in East Asian drinkers. An alcohol flushing questionnaire asking about past and current tendency for facial flushing to occur after drinking a glass (≈180 mL) of beer predicts the presence of inactive ALDH2 among Japanese aged 40 years or older with a sensitivity and specificity of approximately 90%. We invented a health-risk appraisal (HRA) model that makes it possible to identify Japanese men who are at high risk for esophageal cancer based on their past and current alcohol flushing tendency, drinking, smoking, and intake of vegetables and fruits.

[Prevalence of psychiatric disorders among homeless people in one area of Tokyo].

Objectives: This study is the first ever field survey in Japan of the prevalence of psychiatric disorders among homeless people in one area of Tokyo. The main aim of was to make accurate diagnoses by a psychiatrist to give an accurate picture.

Methods: The survey period was from December 30, 2008 to January 4, 2009.

Gender differences in the effects of ADH1B and ALDH2 polymorphisms on alcoholism.

Background: Gender differences are known to exist in the prevalence, characteristics, and course of alcohol dependence. Elucidating gender differences in the characteristics of alcohol dependence is important in gender-based medicine and may improve treatment outcomes. Many studies have shown that genetic factors are associated with the risk of alcohol dependence in both genders.

Development of squamous neoplasia in esophageal iodine-unstained lesions and the alcohol and aldehyde dehydrogenase genotypes of Japanese alcoholic men.

We investigated the development of esophageal neoplasia in biopsy specimens of the distinct iodine-unstained lesions (DIULs) ≥ 5 mm detected in 280 of 2,115 Japanese alcoholic men who underwent screening by esophageal iodine staining. Low-grade intraepithelial neoplasia (LGIN) was diagnosed in 155 of them, high-grade intraepithelial neoplasia (HGIN) in 57, and invasive SCC in 35. The size of the DIULs increased with the degree of neoplasia.

p53 protein accumulation, iodine-unstained lesions, and alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotypes in Japanese alcoholic men with esophageal dysplasia.

Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2(*)1/(*)2) and less-active alcohol dehydrogenase-1B (ADH1B(*)1/(*)1) increase the risk of esophageal cancer in East Asian drinkers, and esophageal cancer multiplicity is strongly associated with ALDH2(*)1/(*)2. p53 alterations are key molecular events in multifocal carcinogenesis in the esophagus. We studied 260 esophageal-cancer free Japanese alcoholics with esophageal dysplasia diagnosed by biopsy of distinct iodine-unstained lesions (DIULs) ≥5mm.

Mortality 6 years after inpatient treatment of female Japanese patients with eating disorders associated with alcoholism.

Aims: This study was conducted to clarify the mortality of patients with eating disorders associated with alcoholism. We focused on the mortality rate 6 years after inpatient treatment of patients with eating disorders associated with alcoholism compared with eating disorder patients without alcoholism and alcoholic patients without eating disorders.

Methods: The subjects were 164 female Japanese patients 30 years of age or younger with eating disorders or alcoholism who were inpatients at some time during the period from 1990 to 1998 at the Japanese National Hospital Organization, Kurihama Alcoholism Center.

Genetics of alcohol dependence.

Twin, family, and adoption studies have consistently shown that genetic factors play an important role in the pathogenesis of alcohol dependence. Numerous studies have aimed to identify genes that contribute to susceptibility to alcohol dependence. Whole-genome linkage studies have identified several chromosomal regions that are linked with alcohol dependence.

Alcohol and aldehyde dehydrogenase polymorphisms and a new strategy for prevention and screening for cancer in the upper aerodigestive tract in East Asians.

The ethanol in alcoholic beverages and the acetaldehyde associated with alcohol consumption are Group 1 human carcinogens (WHO, International Agency for Research on Cancer). The combination of alcohol consumption, tobacco smoking, the inactive heterozygous aldehyde dehydrogenase-2 genotype (ALDH2*1/*2) and the less-active homozygous alcohol dehydrogenase-1B genotype (ADH1B*1/*1) increases the risk of squamous cell carcinoma (SCC) in the upper aerodigestive tract (UADT) in a multiplicative fashion in East Asians. In addition to being exposed to locally high levels of ethanol, the UADT is exposed to a very high concentration of acetaldehyde from a variety of sources, including that as an ingredient of alcoholic beverages per se and that found in tobacco smoke; acetaldehyde is also produced by salivary microorganisms and mucosal enzymes and is present as blood acetaldehyde.

Role of GABRA2 in moderating subjective responses to alcohol.

Background: Human twin studies have shown that certain responses to alcohol, including subjective perceptions, are genetically influenced. Previous studies have provided evidence that a low level of response to alcohol predicts future alcohol use disorders in humans. Recent genetic studies suggest an association between alcohol dependence and genetic variation in the γ-aminobutyric acid A (GABA(A)) receptor α2 subunit gene (GABRA2).

Polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and the blood and salivary ethanol and acetaldehyde concentrations of Japanese alcoholic men.

Background: The effects of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) on alcohol metabolism are striking in nonalcoholics, and the effects of genetic polymorphism of alcohol dehydrogenase-1B (ADH1B) are modest at most, whereas genetic polymorphisms of both strongly affect the susceptibility to alcoholism and upper aerodigestive tract (UADT) cancer of drinkers.

Methods: We evaluated associations between ADH1B/ADH1C/ALDH2 genotypes and the blood and salivary ethanol and acetaldehyde levels of 168 Japanese alcoholic men who came to our hospital for the first time in the morning and had been drinking until the day before.

Results: The ethanol levels in their blood and saliva were similar, but the acetaldehyde levels in their saliva were much higher than in their blood, probably because of acetaldehyde production by oral bacteria.

[Relationship between drinking, smoking, and dietary habits and the body mass index of Japanese alcoholic men].

Malnutrition and emaciation in alcoholics is associated with various alcoholism-related diseases, including Wernicke's encephalopathy, aero-digestive tract cancer, and serious metabolic disorders. We used a self-administered questionnaire survey for structured dietary habit screening to evaluate the dietary profiles of 467 Japanese alcoholic men aged 40 years or over and their relationship to body mass index (BMI). Their average daily ethanol consumption was 119 +/- 65 g (845 +/- 463 kcal).

Effect of a comprehensive lifestyle modification program on the bone density of male heavy drinkers.

Background: Heavy alcohol drinking is implicated in osteoporosis. Although abstinence is rapidly followed by a restoration of osteoblastic activity, little is known about the contributions of alcohol-related factors or the effectiveness of a lifestyle modification program (LMP) on bone density.

Methods: We conducted a study of 138 male alcoholic patients to investigate whether drinking history and concurrent factors were associated with the bone density of the calcaneus.

Chronic atrophic gastritis and metachronous gastric cancer in Japanese alcoholic men with esophageal squamous cell carcinoma.

Background: The risk of metachronous gastric cancer is high in Japanese with esophageal squamous cell carcinoma (SCC), especially in alcoholic men, suggesting a common background underlying the gastric and esophageal cancers.

Methods: Endoscopic follow-up ranging from 7 to 160 months (median, 47 months) after the initial diagnosis was performed in 99 Japanese gastric-cancer-free alcoholic men (56.8 +/- 6.