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Among the natural bases, guanine is the most oxidizable base. The damage caused by oxidation of guanine, commonly referred to as oxidative guanine damage, results in the formation of several products, including 2,5-diamino-4H-imidazol-4-one (Iz), 2,2,4-triamino-5(2H)-oxazolone (Oz), guanidinoformimine (Gf), guanidinohydantoin/iminoallantoin (Gh/Ia), spiroiminodihydantoin (Sp), 5-carboxamido-5-formamido-2-iminohydantoin (2Ih), urea (Ua), 5-guanidino-4-nitroimidazole (NI), spirodi(iminohydantoin) (5-Si and 8-Si), triazine, the M+7 product, other products by peroxynitrite, alkylated guanines, and 8,5′-cyclo-2′-deoxyguanosine (cG). Herein, we summarize the present knowledge about base pairs containing the products of oxidative guanine damage and guanine. Of these products, Iz is involved in G-C transversions. Oz, Gh/Ia, and Sp form preferably Oz:G, Gh/Ia:G, and Sp:G base pairs in some cases. An involvement of Gf, 2Ih, Ua, 5-Si, 8-Si, triazine, the M+7 product, and 4-hydroxy-2,5-dioxo-imidazolidine-4-carboxylic acid (HICA) in G-C transversions requires further experiments. In addition, we describe base pairs that target the RNA-dependent RNA polymerase (RdRp) of RNA viruses and describe implications for the 2019 novel coronavirus (SARS-CoV-2): When products of oxidative guanine damage are adapted for the ribonucleoside analogs, mimics of oxidative guanine damages, which can form base pairs, may become antiviral agents for SARS-CoV-2.

Background Maintenance of instrumental activities of daily living (IADL) and social role (SR) is crucial to keep independent life because the decline in SR and IADL was a significant predictor of dependence in basic ADL in later. The independent effect of physical and cultural leisure activities and their effect modification on the IADL remains unknown. Methods We prospectively observed 3241 elderly with intact IADL at baseline for 5 years. Higher level functional capacity such as IADL and SR was assessed using the Tokyo Metropolitan Institute of Gerontology Index of competence (TMIG index). Results The mean age of the participants was 72.3 years (standard deviation 5.1), and 46.9% were male, and 90.9% of them received a follow-up assessment. Of the participants, 10.4% developed an IADL decline. Engagement in leisure physical activity was associated with a significantly lower risk of IADL decline (adjusted risk ratio, 0.73; 95% confidence interval [CI], 0.60 to 0.89), and cultural leisure activity was also associated with lower risk of IADL decline (adjusted risk ratio, 0.77; 95% CI, 0.63 to 0.95) independent of potential confounders. We also found significant and positive interaction between physical and cultural leisure activities at risk for IADL decline (P = 0.024) and SR decline (P = 0.004). Conclusions We found an independent association of physical and cultural leisure activities with a lower risk for functional decline in IADL and SR with positive interaction. Combined engagement in physical and cultural activities may effectively prevent from IADL decline and SR decline.

Background: Several studies have suggested that periodontal disease can exacerbate the pro-inflammatory status of the brain. Tooth loss is one of the alternative evaluation indices of periodontal disease. There are few data on the relationship between tooth loss and memory impairment, depending on the apolipoprotein E (APOE) ɛ4 genotype. Objective: To determine if tooth loss is associated with mild memory impairment (MMI) and if this association is modified by the presence of the APOE ɛ4 allele. Methods: A nested case-control study was conducted from 2007 to 2012 in Japan. Five hundred and thirty-seven Japanese subjects aged 65 years and over who were cognitively intact at baseline were analyzed. MMI at follow-up was evaluated. Results: The median number of teeth at baseline was significantly lower in MMI participants (n = 179) than in controls (n = 358) (MMI: median 21.0, interquartile range 10.0–25.0 versus controls: 24.0, 14.0–27.0). After adjustment for demographics, vascular risk factors, and APOE ɛ4 allele, the multivariate adjusted odds ratio (OR) of ≤8 teeth was 1.97 (95% confidence interval [CI], 1.13–3.44) compared to 25–32 teeth. Participants with both the presence of at least 1 APOE ɛ4 allele and ≤8 teeth had a higher risk of MMI compared with those with neither (OR, 2.82; 95% CI, 1.15–6.91). Those with either risk factor alone did not have a higher risk of MMI. Conclusions: A lower number of teeth is related to risk of MMI. This may be primarily true for those individuals with an APOE ɛ4 allele.

Cataract surgery improves visual acuity and drastically increases the capacity for light reception to the retina. Although previous studies suggested that both light exposure and visual acuity were associated with cognitive function, the relationships between cataract surgery, visual acuity, and cognitive function have not been evaluated in large populations. In this cross-sectional study, we measured cognitive function using the Mini-Mental State Examination and best-corrected visual acuity in pseudophakic (previous cataract surgery) and phakic (no previous cataract surgery) elderly individuals. Of 945 participants (mean age 71.7 years), 166 (17.6%) had pseudophakia and 317 (33.5%) had impaired cognitive function (score ≤26). The pseudophakic group showed significantly better visual acuity than the phakic group (p = 0.003) and lower age-adjusted odds ratio (ORs) for cognitive impairment (OR 0.66; p = 0.038). Consistently, in multivariate logistic regression models, after adjusting for confounding factors, including visual acuity and socioeconomic status, ORs for cognitive impairment were significantly lower in the pseudophakic group than in the phakic group (OR 0.64; 95% confidence interval 0.43-0.96; p = 0.031). This association remained significant in sensitivity analysis, excluding participants with low cognitive score ≤23 (n = 36). In conclusion, in a general elderly population, prevalence of cognitive impairment was significantly lower in pseudophakic individuals independently of visual acuity. The association was also independent of several major causes of cognitive impairment such as aging, gender, obesity, socioeconomic status, hypertension, diabetes, sleep disturbances, depressive symptoms, and physical inactivity.

Purpose To determine whether there is a significant association between prior cataract surgery and cognitive function in an elderly Japanese cohort. Setting Nara Medical University, Nara, Japan. Design The Fujiwara-kyo Eye Study was a cross-sectional epidemiological study. Methods The subjects were ≥ 68-years who lived in the Nara Prefecture and responded to recruitment notices. All of the subjects received comprehensive ophthalmological examinations, and answered questionnaires on their socio-demographic and medical history including prior cataract surgery. The association between prior cataract surgery and cognitive function was determined. Results A total of the 2764 subjects whose mean age was 76.3±4.8 years (±standard deviation) was studied. Of these, 668 individuals (24.2%) had undergone cataract surgery. Of these, 150 (5.4%) had dementia as determined by the Mini-Mental State Examination (MMSE) score ≤23, and 877 individuals (31.7%) had mild cognitive impairment (MCI; MMSE score 24–26). The subjects who had prior cataract surgery had significantly lower odds ratio (OR) of having MCI (OR = 0.78, 95% confidence interval; CI 0.64–0.96, P = 0.019) than those who had not had cataract surgery after adjusting for age, sex, body mass index, education, hypertension, diabetes, depression, and history of stroke. The OR was still lower when the visual acuity was also added to the adjusted factors (OR 0.79, 95% CI 0.64–0.97, P = 0.025). However, prior cataract surgery did not contribute significantly to the low OR for dementia. Conclusions Cataract surgery may play a role in reducing the risk of developing MCI independently of visual acuity but not for dementia.

Human telomere DNA (Htelo) and telomeric repeat-containing RNA (TERRA) are integral telomere components containing the short DNA repeats d(TTAGGG) and RNA repeats r(UUAGGG), respectively. Htelo and TERRA form G-quadruplexes, but the biological significance of their G-quadruplex formation in telomeres is unknown. Compounds that selectively bind G-quadruplex DNA and RNA are useful for understanding the functions of each G-quadruplex. Here we report that engineered Arg-Gly-Gly repeat (RGG) domains of translocated in liposarcoma containing only Phe (RGGF) and Tyr (RGGY) specifically bind and stabilize the G-quadruplexes of Htelo and TERRA, respectively. Moreover, RGGF inhibits trimethylation of both histone H4 at lysine 20 and histone H3 at lysine 9 at telomeres, while RGGY inhibits only H3 trimethylation in living cells. These findings indicate that G-quadruplexes of Htelo and TERRA have distinct functions in telomere histone methylation.

Context: In contrast with randomized controlled trials, observational studies have suggested that physiological levels of melatonin are reduced in patients with dementia or depression, but the relationship has not been evaluated in large populations. Objective: The objective was to determine the relationships between physiological levels of melatonin and cognitive function and depressive symptoms. Design and Participants: A cohort of 1105 community-dwelling elderly individuals was enrolled in this cross-sectional study (mean age, 71.8 ± 7.1 y). Measures: Urinary 6-sulfatoxymelatonin excretion (UME) and Mini-Mental State Examination (MMSE; n = 935) and Geriatric Depression Scale (GDS; n = 1097) scores were measured as indices of physiological melatonin levels, cognitive function, and depressive symptoms, respectively. Results: With increases in UME quartiles, the prevalence of cognitive impairment (MMSE score ≤ 26) and depressed mood (GDS score ≥ 6) significantly decreased (P for trend = .003 and .012, respectively). In multivariate logistic regression models, after adjusting for confounders such as age, gender, socioeconomic status, physical activity, and sleep/wake cycles, higher UME levels were significantly associated with lower odds ratios (ORs) for cognitive impairment and depressed mood (ORs: Q1 = 1.00; Q2 = 0.88 and 0.76; Q3 = 0.66 and 0.85; Q4 = 0.67 and 0.53; P for trend = .023 and .033, respectively). In addition, the highest UME group showed a significantly lower OR for depressed mood than the lowest UME group (Q4 vs Q1: OR, 0.53; 95% confidence interval, 0.32–0.89; P = .033). UME levels above the median value were significantly associated with a lower OR for cognitive impairment, even after further adjustment for depressive symptoms (OR = 0.74; 95% confidence interval, 0.55–0.99; P = .043). Conclusions: Significant associations of higher physiological melatonin levels with lower prevalence of cognitive impairment and depressed mood were revealed in a large general elderly population. The association between physiological melatonin levels and cognitive function was independent of depressive symptoms.

Background Tooth loss may be a modifiable risk factor for memory disorders, but the causal relationship has not been evaluated sufficiently. Objective This 5-year prospective cohort study investigated the effect of tooth loss on the development of mild memory impairment (MMI) among the elderly. Methods Data are from the baseline and follow-up examinations of 2,335 community residents who were cognitively intact at baseline. The number of remaining teeth at baseline was classified as zero, 1-8, 9-16, 17-24, and 25-32. The main outcome for the analysis was the development of MMI at follow-up. Results After adjustment for potential confounding factors in multivariable logistic regression analysis, the odds ratio of per 1 tooth loss at baseline was 1.02 (95% confidence interval, 1.00-1.03). The odds ratio of edentulism for MMI was 2.39 (1.48-3.86) compared to 25-32 teeth. The odds ratio of becoming edentulous compared to retaining 1-8 teeth in the 1-8 teeth group at baseline was 4.68 (1.50-14.58). Conclusion Tooth loss predicts the development of MMI among the elderly.

Objective To evaluate the risk factors for new-onset overactive bladder (OAB) in older subjects. Methods The present study enrolled 4427 subjects aged ≥65 years who had participated in the Fujiwara-kyo study. The prevalence of OAB at baseline and 1 year later was evaluated using the OAB symptom score questionnaire. The incidence and remission rate of OAB were calculated. We identified the risk factors for OAB by evaluating the difference in characteristics (including sex, age, body mass index, life style, comorbidities, depressive status, metabolic syndrome, and sum of voiding symptoms) between those with and without new-onset OAB. In addition, the independent risk factors were determined by multivariate analysis. Results Of the 4427 subjects, 3685 completely replied to the self-administrated questionnaires at baseline and 1 year later. The incidence and remission rate of OAB was 11.9% and 29.8%, respectively. The male/female ratio, sum of voiding symptoms, alcohol consumption and smoking, hypertension, and depressive status in subjects with new-onset OAB, were significantly greater than those in subjects without new-onset OAB. A multivariate analysis, including sex (odds ratio 2.0, P < .0001), sum of voiding symptoms (odds ratio 1.1, P < .0001), and depressive status (odds ratio 1.8, P < .0001) were independent factors for new-onset OAB in older subjects. Conclusion The results of the present study have demonstrated that male sex, the sum of voiding symptoms, and depression were independent factors for new-onset OAB. It is necessary to determine whether the treatment of patients with voiding symptoms or depression controls for new-onset OAB.

Objectives: To investigate the relationship between swallowing problems and the number of remaining teeth in healthy elderly people. Design: Cross-sectional. Setting: Nara, Japan. Participants: Three thousand six hundred sixty-three male and female volunteers aged 65 and older who were living independently were analyzed. Measurements: Swallowing problems were defined operationally using a questionnaire and the 30-mL water swallow test. Data were collected on the number of remaining teeth, maximum bite force, occlusal status, presence or absence of oral dryness, and medical history. Results: The prevalence of swallowing problems was 15.1% (n = 554) in this population. A positive correlation was observed between the number of remaining teeth and maximum bite force. The number of remaining teeth was categorized according to tertiles. Multiple logistic regression analysis revealed that the adjusted odds ratios for 0 to 13 or 14 to 24 remaining teeth to 25 to 32 remaining teeth for swallowing problems were 2.04 (95% confidence interval (CI) = 1.60�2.60) and 1.31 (95% CI = 1.02�1.70), respectively. Significant increases in these odds ratios were found in a trend test (P < .001). Conclusion: Tooth loss is associated with swallowing problems. Having fewer teeth inhibits masticatory ability, which disturbs the execution of smooth swallowing. Preventive measures against tooth loss at a younger age may be effective at reducing the risk of laryngeal penetration and aspiration at an older age.

Objectives To clarify the relationship between self-reported hearing loss (HL) and 5-year decline in higher-level functional capacity in high-functioning elderly adults. Design Population-based, prospective cohort study. Setting The Fujiwara-Kyo Study, Nara, Japan. Participants Community-dwelling individuals aged 65 and older with a perfect baseline and valid follow-up instrumental activity of daily living (IADL) (n = 3,267), intellectual activity (IA) (n = 2,925), and social role (SR) (n = 2,698) scores. Measurements Self-reported HL was evaluated using a single question: “Do you feel you have hearing loss?” IADLs, IA, and SR were measured using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) subscales. Geriatric syndromes (depressive symptoms, cognitive impairment, sleep disturbance, falls, urinary incontinence, visual impairment) were self-reported at baseline. Blood tests were performed to measure cardiovascular risk factors. Results During 5-year follow-up, new declines developed for 213 participants in IADLs, 272 in IA, and 327 in SR. After adjustment for all covariates, including geriatric syndromes, using multiple logistic regression analysis, self-reported HL at baseline was associated with a decline in IA (odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.04–1.86) and SR (OR = 1.34, 95% CI = 1.02–1.76) but not IADLs (OR = 1.07, 95% CI = 0.76–1.48). Conclusion Self-reported HL was found to be a significant predictor of decline in IA and SR. Preventive intervention against age-related HL may contribute to maintaining high-level functional capacity in independent elderly adults.

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are different types of dementia. However, their clinical symptoms partially overlap and differential diagnosis is occasionally difficult. There is need for additional diagnostic criteria to reliably differentiate between these two conditions. Meanwhile, several imaging studies have showed inconsistent results between DLB and AD. The aim of this study was to use a tractography-based analysis to elucidate white matter alterations in subjects with DLB compared to those with AD and to controls. An understanding of the white matter connectivity differences between AD, DLB and controls will be helpful for differential diagnosis and an understanding of the pathophysiology. Twenty-six subjects with DLB, 26 with AD and 26 controls underwent magnetic resonance diffusion tensor imaging and neuropsychological assessment. Diffusion tensors were computed and fiber-tract maps were created using "dTV II" software. We measured mean fractional anisotropy (FA) values along the uncinate fasciculus (UNC), the inferior occipitofrontal fasciculus (IOFF) and the inferior longitudinal fasciculus (ILF). Both subjects with DLB and AD had lower FA values for the bilateral UNC than controls. Subjects with DLB exhibited significantly lower FA values on both sides of the IOFF and the left side of the ILF than those of controls. Although there were no significant differences between subjects with DLB and AD for any measurements, those with DLB exhibited lower FA values especially in visual-related white matter. These different changes in white matter tracts among groups could be helpful for differential diagnosis and an understanding of the pathophysiology.

Previous studies using the Baumtest (Tree-Drawing Test) reported that tree drawings by elderly people rarely show trees with crowns, in comparison to trees drawn by younger people. This difference may be an index of developmental changes resulting from aging. However, since these studies instructed participants to draw a single fruit-bearing tree, the kinds of trees that elderly people visualized may have been different from those visualized by younger people. In this study, 111 mentally healthy people over 65 years of age were divided into two groups: Group 1 (N = 61, mean age = 72.7 years) was asked to draw a single tree and Group 2 (N = 50, mean age = 73.4 years) was asked to draw a single fruit-bearing tree. The results show that the frequency of trees with crowns drawn by Group 1 was lower than Group 2 (Chi2(1) = 21.04, p < .01). This suggests that the decrease in trees with crowns drawn by elderly people resulted from differences in instructions, in addition to possible developmental changes.

The apolipoprotein E (apoE) genotype is an important genetic risk factor for Alzheimer's disease (AD). In the central nervous system (CNS), most apoE is produced by astrocytes and is present in unique high-density lipoprotein (HDL)-like particles that have distinct properties from apoE derived from other sources. To develop an efficient system to produce astrocyte-derived apoE in large quantities, we produced and characterized immortalized cell lines from primary astrocyte cultures derived from human APOE knock-in mice. APOE2, APOE3, and APOE4 expressing cell lines were established that secrete apoE in HDL-like particles at similar levels, cholesterol composition, and size as those produced by primary astrocytes. In physiological buffers, astrocyte-secreted apoE3 and E4 associated equally well with amyloid-beta. Under the same conditions, only a small fraction of A beta formed sodium dodecyl sulfate (SDS)-stable complexes with apoE (E3 > E4). These immortalized astrocytes will be useful for studying mechanisms underlying the isoform-specific effects of apoE in the CNS.

Background Tooth loss induces changes to the anatomy of the oral cavity. We hypothesized that tooth loss may disturb smooth swallowing in healthy elderly people. The purpose of this study was to investigate the effect of tooth loss on the development of swallowing problems in an independent elderly population. Methods This was a 5-year prospective cohort study conducted in Nara, Japan. Included in this analysis were 1,988 community residents aged 65 years or older without swallowing problems at baseline. The participants were classified into quartile groups according to the number of remaining teeth at the baseline survey: 0-12, 13-22, 23-26, and 27-32 teeth. A decrease in the number of teeth during the survey was calculated by subtracting follow-up number from baseline number. Main outcome was the development of swallowing problems at follow-up. Results During follow-up, 312 individuals developed swallowing problems. After adjustment for confounding factors by multiple logistic regression analysis, the odds ratios for developing swallowing problems in participants with 13-22 or 0-12 teeth were 2.42 (95% confidence interval [CI], 1.61-3.63) and 2.49 (95% CI, 1.68-3.69), respectively, compared to participants with 27-32 teeth, demonstrating a significant relationship. The odds ratio of per 1 tooth decrease over 5 years was 1.08 (95% CI, 1.02-1.13), showing a significant association. Conclusions Swallowing problems due to aging are more likely to develop in individuals with fewer teeth.

The present study investigated whether physical performance and musculoskeletal pain (MSP) are associated with self-perceived hearing handicap (HH) among high-functioning older adults.We analyzed a total of 3982 community-dwelling high-functioning older adults (age 65 years and older). HH was assessed using the Hearing Handicap Inventory for Elderly-Screening. Self-reported hearing impairment (HI) was evaluated using a single question. We measured handgrip strength, walking speed (WS) and standing balance for assessments of physical performance. The severity of MSP assessed by interviews took into account its duration, limitation of daily activity and frequency.The prevalence of HH and HI in our sample was 22.2% and 28.1%, respectively. After adjusting for other two physical performance measures, MSP, sex, age, education, marital status, risk factors for hearing loss, instrumental activity of daily living, depression, cognitive function and self-reported HI, the odds ratios for HH in the second fastest, the second slowest, and the slowest WS quartile were 1.14 (95% CI = 0.81-1.58), 1.29 (95% CI = 0.92-1.79), and 1.58 (95% CI = 1.11-2.23), respectively, compared with the fastest WS quartile. A significant dose-response relationship was found between slower WS and HH (P for trend = 0.01). No significant association with HH was found in handgrip strength, standing balance and MSP.WS is associated with self-perceived HH in high-functioning older adults. The present study suggests that exercise programs to improve walking ability might be effective in preventing HH of self-sustainable older adults.

To investigate factors associated with activities of daily living in independently living elderly persons in a community.The potential subjects were 4,472 individuals aged 65 years and older who voluntarily participated in a large cohort study, the Fujiwara-kyo study. We used self-administered questionnaires consisting of an activities of daily living (ADL) questionnaire with the Physical Fitness Test established by the Ministry of Education, Culture, Sports, Science and Technology (12 ADL items) to determine the index of higher-level physical independence, demographics, Geriatric Depression Scale, and so on. Mini-mental state examination, measurement of physical fitness, and blood tests were also carried out. A lower ADL level was defined as having a total score of the 12 ADL items (range, 12-36 points) that was below the first quartile of a total score for all the subjects. Factors associated with a low ADL level were examined by multiple logistic regression.A total of 4,198 remained as subjects for analysis. The male, female and 5-year-old groups showed significant differences in the median score of 12 ADL items between any two groups. The highest odds ratio among factors associated with lower ADL level by multiple logistic regression with mutually adjusted independent variables was 4.49 (95%CI: 2.82-7.17) in the groups of "very sharp pain" or "strong pain" during the last month. Low physical ability, self-awareness of limb weakness, a BMI of over 25, low physical activity, cerebrovascular disorder, depression, low cognitive function, unable "to see normally", unable "to hear someone", "muscle, bone and joint pain" were independently associated with lower ADL level.Multiple factors are associated with lower ADL level assessed on the basis of the 12 ADL items.

We evaluated the natural history of nocturia and determined factors influencing the incidence or remission of nocturia.Study subjects were 4,427 volunteers 65 years old or older who participated in the Fujiwara-kyo Study. The nocturia prevalence was assessed at baseline and 1 year later. Nocturia incidence and remission rates were calculated and factors influencing these results were evaluated based on characteristics, including gender, age, body mass index, HbA1c, creatinine clearance, life style, comorbidities, depressive status, metabolic syndrome and voiding symptoms. Independent factors were determined by multivariate analysis.Of the 4,427 subjects 3,685 provided complete replies to self-administered questionnaires at baseline and 1 year later. The prevalence of nocturia at baseline and 1 year later was 47.0% and 50.3%, and nocturia incidence and remission rates were 20.0% and 15.4%, respectively. Male gender, high body mass index, voiding symptom deterioration and new onset overactive bladder were independent factors associated with the nocturia incidence. Male gender, sum of the voiding symptoms, age and new onset overactive bladder were independent negative factors associated with nocturia remission.The prevalence of nocturia worsened with time, although nocturia in older subjects progressed dynamically. Male gender, age, body mass index, sum of voiding symptoms, voiding symptom deterioration and new onset overactive bladder influence the natural history of nocturia.

Metabolic syndrome contains many risks for medical diseases such as cardiovascular disease and diabetes, which might precipitate depressive symptoms in the older people. However, the association between depressive symptoms and metabolic syndrome in Japanese community-dwelling older people is unclear. This study was performed to answer this important question.Cross-sectional analyses were performed on 3796 community-dwelling independent older people (≥ 65 years, 1911 men and 1885 women) from the 2007-2008 baseline examination of the Fujiwara-kyo study, a prospective cohort study on successful aging. Depressive symptoms were assessed using the 15-item short form of the Geriatric Depression Scale and metabolic syndrome was defined according to the 2005 International Diabetes Federation. Covariates were social supports, negative life events, health behavior, education, cognitive function, anthropometric status, and others. Multiple logistic regression analyses were performed to determine the relationships between depressive symptoms and these variables.The prevalence of depressive symptoms (Geriatric Depression Scale-15 ≥ 6) and metabolic syndrome were 14.8% and 16.6%, respectively. Significant protective factors against depressive symptoms were higher education, more opportunity for drinking of alcohol, better social supports, and more walking daily. Metabolic syndrome was statistically associated with depressive symptoms (adjusted odds ratio = \ 1.32, 95% confidence interval = 1.03-1.68). Other risk factors significantly associated with depressive symptoms were sleep disturbance, visual or hearing impairment, and negative life events.The present study showed an association between metabolic syndrome and depressive symptoms in ambulatory Japanese older people, as in western countries.

Alzheimer's disease (AD) classically presents with gray matter atrophy, as well as feature significant white matter abnormalities. Previous evidence indicates the overall burden of these pathological changes continues to advance as the disease progresses. The aim of this study was to investigate whether pathological alterations of white matter tracts correlate with the course of AD disease progression. 35 AD patients and 29 normal controls were recruited to the study and administered baseline magnetic resonance diffusion tensor imaging (DTI) acquisition and a cognitive function assessment at the time of initial evaluation. Subjects were re-evaluated with secondary DTI scan and cognitive function assessment at intervals of about 1.5 years on average. For the DTI acquired scans, we calculated diffusion tensor parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (DR), and axial diffusivity (DA) along with the uncinate fasciculus (UNC), the inferior longitudinal fasciculus (ILF), and the inferior occipitofrontal fasciculus (IOFF). Compared to baseline, a significant mean FA reduction of the bilateral UNC, as well as a significant mean DR increase of the left UNC, was evident in AD patients at follow-up. Compared with normal controls, AD patients exhibited significant diffusion parameter abnormalities in their UNC, ILF, and IOFF. Taken together, these results indicate that progressive pathological white matter alterations can be quantified using the DTI parameters utilized here and may prove to be a useful biological marker for monitoring the pathophysiological course of AD.

Little is known about the usefulness of the Hearing Handicap Inventory for the Elderly-Screening (HHIE-S) and a single question (SQ) in assessing hearing impairment (HI) and the impact of HI on quality of life (QOL). The objective of this study was to examine the reliability, validity, and associations with QOL measures (i.e., subjective well-being, depressive symptoms, subjective loneliness, and physical functioning) of the HHIE-S and the SQ in the elderly community. A self-report questionnaire including HHIE-S, SQ, Philadelphia Geriatric Center Morale Scale, Geriatric Depression Scale, UCLA Loneliness Scale, and the Tokyo Metropolitan Institute of Gerontology Index of Competence was administered to community elderly (781 males and 950 females). Among them, 97 males and 100 females also responded voluntarily to a request for test–retest and auditory tests. The criterion validity was tested by using pure-tone averages. Regarding the reliability of HHIE-S, Cronbach’s alpha coefficient was 0.91, Spearman–Brown coefficient was 0.90, and intra-class correlation coefficient was 0.85. Regarding the test–retest reliability of SQ, kappa coefficient was 0.65. HHIE-S had significantly lower sensitivity in identifying >25-dB HI, but significantly higher specificity for the detection of >40-dB HI than SQ. HHIE-S had stronger associations with QOL measures than did SQ. HHIE-S had high reliability, while SQ had insufficient reliability. HHIE-S was more specific in detecting HI and more sensitive in assessing the impact of HI on QOL than SQ. HHIE-S is a more effective instrument for assessing HI and QOL research than SQ in the elderly community.

There are no data concerning a relationship between alcohol and bone status from a large-scale community-based study of elderly Japanese men. The baseline survey for the Fujiwara-kyo Osteoporosis Risk in Men Study was performed in 2174 male participants during the period from 2007 to 2008 in Nara Prefecture, Japan. Among them 1665 fitted the following inclusion criteria: (a) age ≥65years, (b) no diseases or drug therapy that could affect bone mineral density (BMD). We analyzed 1421 men with complete information about alcohol intake. We found that alcohol intake and BMD were positively correlated after adjustment for age, body mass index, natto intake, milk intake, smoking, physical activity, education, marital status, and hypertension. Adjusted total hip BMD of men with alcohol intake >39g/day was 0.90g/cm(2) and that of abstainers was 0.85g/cm(2). With regard to bone turnover markers, alcohol intake was inversely associated with serum levels of osteocalcin and tartrate-resistant acid phosphatase isoenzyme 5b. A two-piece linear regression model revealed a positive relationship between alcohol intake and crude mean BMD for the total hip in those with alcohol intake of less than 55g/day. In contrast, alcohol intake and BMD in those with an alcohol intake of 55g/day or more was inversely correlated. The present large-scale study of elderly Japanese men revealed that although an alcohol intake of

Neuroimaging studies show increased diffusivity and decreased anisotropy in Alzheimer's disease (AD) patients by diffusion tensor imaging (DTI). Previous reports have analyzed a correlation with cognitive function and DTI parameters, but their results are inconsistent. A reason for this might be a region of interest (ROI) method, used to calculate parameters for DTI, because this method has various usages of how to place a ROI and includes summations of values for various neuronal fiber tracts, resulting in contamination of unintended fibers. To improve the instability with ROI placement, a tractography-based method might be useful. Our coworker reported decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) of uncinate fasciculus (UF) in patients with AD by tractography. To confirm whether DTI parameter values are related to severity of cognitive function in patients with AD, we measured mean diffusion anisotropy and diffusivity of coregistered voxels along the tracking lines (i.e. tract of interest) of UF.The subjects were 30 patients with probable AD (NINCDS-ADRDA criteria). Assessment of cognitive function was carried out according to the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog). A 1.5-T clinical magnetic resonance unit was used to obtain diffusion tensor images. Diffusion tensors were computed and fiber-tract maps were created using 'dTV II' DTI software developed by Masutani et al. We measured mean FA and ADC values along the bilateral UF.FA values were positively correlated with MMSE score (r= 0.67) and were negatively correlated with ADAS-Jcog score (r=-0.62), while ADC values were negatively correlated with MMSE score (r=-0.58) and were positively correlated with ADAS-Jcog score (r= 0.59).FA and ADC values might reflect the severity of cognitive dysfunction. The tract-of-interest method might be a useful tool for objectively evaluating DTI parameters in AD.

It has been reported that tooth loss is associated with Alzheimer's disease (AD) and dementia. The purpose of this study was to investigate the association between tooth loss and mild memory impairment (MMI) among the elderly. We examined 3,061 community residents aged 65 years or older who had a score of 24 or more on the Mini-Mental State Examination. The subjects were divided according to their score for the three-word delayed recall test into control (score: 3 or 2) and MMI (score: 1 or 0) subjects. The subjects underwent a dental examination, an interview to determine their medical history, a self-administered questionnaire (inclusive of higher-level functional capacity, drinking and smoking habits, and frequency of going out), and a 10-m walking test. Fewer remaining teeth, going out once a week or less frequently, and a slow walking speed on a 10-m walking test were found at a significantly higher prevalence in the MMI group (n=101) than in the control group (n=2,960), after adjustment for sex, age, and the level of education. Multiple logistic regression analysis using these items revealed that the odds ratio of 0-10 remaining teeth for MMI was 1.71 (95% CI 1.05-2.78), compared to individuals with 22-32 remaining teeth. A significant increase was also found in a trend test to examine the increasing odds ratios of 22-32, 11-21, and 0-10 remaining teeth. We consider that tooth loss is associated with MMI later in life.

Perospirone is classified as a second-generation antipsychotic agent for the treatment of schizophrenia. Perospirone binds with high affinity to serotonin 5-HT2A receptors and dopamine D2 receptors. There are no reports of clinical comparisons of perospirone and risperidone in multicenter studies. To clarify the clinical traits of perospirone in the treatment of schizophrenia, the clinical efficacies and side-effects of perospirone and risperidone were compared in a randomized clinical multicenter trial.Sixty-six schizophrenia patients were enrolled in the trial. The Positive and Negative Syndrome Scale (PANSS) total, positive, negative and general symptoms scores and Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) scores were investigated at 0, 4, 8 and 12 weeks.Significant reductions in the PANSS total and subscale scores were observed in both the perospirone and risperidone groups, with no significant between-group differences at 4 and 12 weeks. Risperidone improved the total scores and overall psychopathologic symptom total scores more effectively than perospirone at week 8. There were no significant differences in the DIEPSS scores at 0, 4, 8 and 12 weeks between the perospirone and risperidone groups. The numbers of patients who dropped out did not differ between the perospirone and risperidone groups.Perospirone was as effective as risperidone against positive and negative symptoms in patients with schizophrenia. Both antipsychotic agents were equally well-tolerated.

Mild cognitive impairment (MCI) is considered the transitional stage between normal cognition and dementia. The aim of this study was to use tractography based analysis to elucidate alterations in subjects with MCI compared with subjects with early Alzheimer's disease (AD) and controls. Seventeen subjects with early AD, 16 with MCI and 16 controls underwent magnetic resonance diffusion tensor imaging (DTI) and neuropsychological assessment. Diffusion tensor tractographies were computed and fiber-tract maps were generated using "dTV II" DTI software. We measured mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values along the uncinate fasciculus (UNC), posterior cingulate fasciculus (PCF) and corticospinal tract (CST). There were statistically significant differences in the FA and ADC values of the UNC and PCF between subjects with early AD and controls. Subjects with MCI exhibited significantly lower FA values on both sides of the PCF relative to controls. However, there were no significant differences between subjects with early AD and MCI for any measurement. Our results suggest that alterations in the PCF precede the onset of dementia.

Until now reduced estrogen level has been considered to affect some psychiatric symptoms, because there are sex differences in onset of Schizophrenia and Alzheimer's disease. Estrogen is associated with cognitive functions, and it has been reported to protect oxidative damage of DNA related to base excision repair (BER). Some patients with Xeroderma Pigmentosum, who have normal BER and impaired nucleotide excision repair (NER), are known to be suffering from mental retardation. Therefore we hypothesized that impaired NER was partly associated with pathology of mental disorder and investigated the effects of estrogen on NER for ultraviolet-induced DNA damage. The N2a neuroblastoma cell line was used as a representative of neuronal cells and 17p-estradiol was selected as one of the most active estrogen derivatives. There were no significant effects of 17p-estradiol on prevention of DNA damage, promotion of DNA repair, or cell survival at the concentration of 0-0.1 microM 17p-estradiol (below cytotoxicity level). These results described that estrogen might not directly affect NER except through another DNA repair system.

A novel full-length human cDNA homologous to Glia Maturation Factor-beta (GMF-beta) gene was isolated. Sequence analysis of the entire cDNA revealed an open reading frame of 426 nucleotides with a deduced protein sequence of 142 amino acid residues. The deduced amino acid sequences of its putative product is highly homologous to human GMF-beta (82% identity) and named for GMF-gamma. Northern blot analysis indicated that a message of 0.9 kb long, but not 4.1 kb of GMF-beta, is predominantly expressed in human lung, heart, and placenta.

We treated successfully using the Ross procedure a 14-year old with a congenitally stenotic bifoliate aortic valve associated with anomalous origin of the right coronary artery. The anomalous artery arose from the same aortic sinus that gave rise to the main stem of the left coronary artery, and reached the right atrioventricular groove by traversing the tissue plane between the aortic root and the subpulmonary infundibulum. Both coronary arteries were reimplanted using a single arterial button.

Prevalence of anti-HCV antibody in 1193 hospitalized patients (848 males and 345 females) in psychiatric department was investigated. Overall prevalence ratio was 9.1%, indicating significantly higher than that of healthy blood donors. In the classification of ICD-10, the prevalence of the inpatients diagnosed in schizophrenia group and psychoactive substance use group accounted for 6.2% and 13.8%, respectively. However, adequate reasons such as sanitary issues were not found to account for the high prevalence. Only the age of the patients could account for the high prevalence in the schizophrenic group. In the psychoactive substance abuse group, the sanitary issues might be a major cause of the very high prevalence of anti-HCV antibody, while other factors such as dysfunction of the immune system might be considered to account for it.

The effects of foods on the pharmacokinetics and clinical efficacy of quazepam, a benzodiazepine derivative, in healthy persons were examined. Six healthy Japanese male subjects were randomly divided into three groups and each subject was treated with quazepam under the following three conditions by the crossover method. For the fasting state, subjects were administered 15 mg quazepam 11 hours after a meal. For the postprandial state, subjects were administered 15 mg or 30 mg quazepam 2 hours after a meal. Mean peak plasma concentration (Cmax) of quazepam was significantly higher [1.6-2.8 fold] with administration 2 hours after a meal than 11 hours after a meal. However, in regard to 15 mg of quazepam administration, the area under the curve (AUC) did not differ between administration 2 hours after a meal and 11 hours after a meal. In addition, differences were observed neither in other pharmacokinetic parameters or blood metabolite concentration under all of the study conditions, nor in clinical evaluation of subjective symptoms, complete blood count, or biochemical analyses between administrations 2 and 11 hrs after a meal. The present study showed that administration 2 hours after a meal did not affect subjective symptoms or physical functions so much; therefore it suggested favorable tolerance of this drug. However, it was also suggested that, in actual clinical use, it is important to evaluate the physical function including measurements of vital signs and hematological test results, carefully considering the effects of foods and daily life-style.

We examined the effects on astrocytes of ACTH, which is used to treat West syndrome. We stimulated cultured rat astrocytes with ACTH(1-24), corticotropin-releasing factor, and dexamethasone, and examined changes in neurotrophic factor mRNAs by reverse transcription-PCR. Down-regulation of ciliary neurotrophic factor mRNA expression was observed by stimulation with ACTH(1-24), but the expression of nerve growth factor, brain-derived neurotrophic factor, and nerotrophin-3 mRNAs was unaffected. Northern blot analysis revealed that the decrease in ciliary neurotrophic factor mRNA occurred 4 h after stimulation with more than 10 nM of ACTH(1-24). Up-regulation of nerotrophin-3 mRNA expression was found after stimulation with 1 mM dexamethasone. These results suggest that ACTH(1-24) administrated in West syndrome may influence the expression of neurotrophic factors in astrocytes in vivo.

We describe a patient with general paresis who developed progressive dementia and a cerebellar syndrome including wide-based gait, slurred speech, and intention tremor. Quantitative analysis by means of a Patlak plot of single-photon emission computed tomography (SPECT) with 99mTc-ethyl cysteinate dimer showed generally low blood flow in the cerebrum and the cerebellum. After antisyphilitic therapy, blood flow in the brain, especially in the cerebellum, improved noticeably, as did the cognitive disorder and the cerebellar syndrome.

Background . We reviewed the outcomes of double-chambered right ventricle repair. Methods . Between 1969 and 1998, 40 patients underwent surgical repair of a double-chamber right ventricle. The patients ranged in age from 3 months to 52 years (mean, 12.8 ± 11.6 years). Right ventricular outflow tract pressure gradients were from 20 to 170 mm Hg (mean, 65.0 ± 38.5 mm Hg) An associated ventricular septal defect was present in 27 patients (67.5%). Four patients were older than 30 years of age. Results . There were no hospital or late deaths. Mean postsurgical follow-up was 16.5 ± 8.9 years (range, 2.5 to 31 years). No patient required further surgery to relieve obstruction of right ventricular outflow tract. Conclusions . Surgical repair of a double-chambered right ventricle yields excellent hemodynamic and functional results over both the short and long term.

Perineural invasion is a prominent clinical feature of pancreatic cancer which causes difficulty in curative resection. In the present study, the human pancreatic cancer cell lines, PaCa-2, AsPC-1, SW1990 and Capan-2, were all found to express abundant c-ret proto-oncogene mRNA and RET protein, a member of the receptor-tyrosine-kinase superfamily, identified as being a receptor for glial-cell-line-derived neurotrophic factor (GDNF). In an invasion assay, the migration of pancreatic cancer cells was markedly induced by co-cultivation with human glioma cells, T98G or A172, capable of producing and secreting GDNF. Anti-GDNF antibody in conditioned media of glioma cells suppressed much of the migratory activity. Checkerboard analysis of the migration showed both chemotactic and chemokinetic activity of GDNF. There was no detectable expression of another GDNF receptor component, a glycosyl-phosphatidylinositol-linked receptor (GFR alpha-1), in pancreatic-cancer cell lines, suggesting that the neural invasion of pancreatic-cancer cells spreads along a concentration gradient of GDNF produced from peripheral ganglions through direct interaction of GDNF with its receptor, the c-ret proto-oncogene product. Immunochemical localization of GDNF in human celiac ganglionic tissue supported this contention.

Background This cross-sectional study investigated the relationship between the number of remaining teeth to mild memory impairment (MMI), which is a preclinical stage of dementia, and to cognitive impairment. Methods The subjects were aged 65 years or older and were grouped according to their score for the Mini-Mental State Examination (MMSE), the three-word delayed recall test in the MMSE, and the Geriatric Depression Scale into the control group (n = 3,696), the MMI group (n = 121), and the low MMSE score (23 or lower) group (n = 214). We collected data on the number of remaining teeth, the length of the edentulous period, health-related lifestyle, medical history, blood pressure, height, and body weight. Fasting venous blood samples were also obtained. Results Multiple logistic regression analysis, adjusted for depressive symptoms, age, sex, length of education, and other explanatory variables, revealed that the odds ratios of 0-10 remaining teeth to 22-32 remaining teeth were 1.679 (95% CI 1.073-2.627) for MMI and 2.177 (95% CI 1.510-3.140) for a low MMSE score. A significant relationship was also found between the length of the edentulous period and the risk of a low MMSE score (odds ratio 3.102, 95% CI 1.432-6.720) (15 years or more/less than 15 years). Conclusions Our findings suggest that tooth loss is associated with cognitive function.

From January 1978 through February 1989, 110 tricuspid annuloplasties (De Vega's procedure) were performed in association with mitral and combined mitral and aortic valve disease. Preoperatively, 106 (96%) of 110 patients were in New York Heart Association functional class III or IV. There were seven early deaths (6.3%), and 3 patients, 2 with mitral lesions and 1 with a combined lesion, died during a follow-up period of 3 to 52 months (mean follow-up, 22 months). Four patients (3.6%) required reoperation because of biological mitral valve failure at 5 to 8 years after tricuspid annuloplasty (mean period, 6.6 years). Twenty-three (62%) of 37 randomly selected patients evaluated by echocardiography and 14 (70%) of 20 patients evaluated by right ventriculography showed complete disappearance of tricuspid regurgitation after tricuspid annuloplasty in 1 to 18 months (mean period, 3.3 months). Seventy-seven (96%) of the survivors were in functional class I or II after tricuspid annuloplasty. The actuarial survival rate for the TAP series including early deaths was 85.8% +/- 7.4% at 10 years and the actuarial rate of freedom from reoperation on the tricuspid valve was 96.7% +/- 1.4%. Our surgical experience indicates that the De Vega's annuloplasty, as the method of first choice, is a simple, reliable procedure and resulted in improvement in 90% of patients with moderate to severe functional tricuspid regurgitation.