Hiroshi Nakano

Nippon Medical School, Edo, Tōkyō, Japan

Are you Hiroshi Nakano?

Claim your profile

Publications (50)34.08 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The Japan Geriatrics Society published a revised version of its position statement regarding the end-of-life care for elderly patients, based on the overall consensus by the members of the ethics committee in 2012. This revision is intended to catch up with current changes of views on the end-of-life care for older people over the past decade. There are many suggestive items regarding the matter in this statement, and the authors believe it will be of specific guidance for those who are caring for older people in their final stage of life in the super-aged society. Also, the statement can be useful in many other countries, where aging of the population is not yet an urgent concern, but will be so in the future. We believe that this “position statement” can offer guidance in an ethical respect for those who are or will be engaged in end-of-life care for older people. We also hope that the release of the current statement provides an avenue for broader discussion in a society with an increasing aged population. Geriatr Gerontol Int 2014; 14: 735–739.
    Geriatrics & Gerontology International 10/2014; 14(4).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bile acids (BAs) play important roles in glucose regulation and energy homeostasis via G protein-coupled receptors, such as enteroendocrine L cell TGR5. The aim of the present study was to investigate the relationship between postprandial BA levels and body composition after ingestion of a standard test meal. Eleven healthy subjects of normal weight (body-mass index, 22.0±1.6kg/m(2) [mean±SD]), ingested a 400-kcal test meal, and blood samples were obtained from them before ingestion and every 30minutes for 120minutes after ingestion. The BA fractions were measured with high-performance liquid chromatography. To evaluate body composition, body impedence analysis was performed 1hour before ingestion of the test meal. Concentrations of both total BA and total glycine-conjugated BA (GCBA) at 30, 60, 90, and 120minutes after test-meal ingestion were significantly higher than those at baseline. The body-mass index was correlated with total GCBA at baseline. Moreover, body fat mass was correlated with total GCBA at 30minutes (r=-0.688, P=0.019) and 60minutes (r=-0.642, P=0.033) and with total BA at 30minutes (r=-0.688, P=0.019) and 60minutes (r=-0.642, P=0.033). The postprandial BA response is inversely related with body fat mass in healthy subjects of normal weight.
    Clinical biochemistry 05/2014; · 2.02 Impact Factor
  • Journal of Nippon Medical School 01/2014; 81(3):188-9.
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess the relationship between the serum level of 1,5-anhydroglucitol (1,5-AG), a marker of postprandial hyperglycemia, and the ratio of the urinary activity of N-acetyl-β-D-glucosaminidase to creatinine (NAG index) in subjects without diabetes mellitus (DM). This was a cross-sectional study with 495 subjects without DM who had an estimated glomerular filtration rate≥30ml/min/1.73m(2). Subjects were divided into tertiles based on serum 1,5-AG levels: high (> 21.0μg/ml), middle (14.0-21.0μg/ml), and low (< 14.0μg/ml). Adjusted odds ratios for an elevated urinary NAG index (> 5.8 U/g creatinine) according to the HbA1c (≤ 5.4%, 5.5%-5.9%, and 6.0%-6.4%) and 1,5-AG tertiles were calculated. The NAG index was negatively correlated with the serum 1,5-AG level in all subjects. The slopes of the regression lines for these variables did not differ significantly between elderly (≥ 65 y) and nonelderly subjects. As compared with high 1,5-AG and HbA1c≤5.4%, the odds ratios for an elevated urinary NAG index increased progressively to 7.71 across the categories of low 1,5-AG and HbA1c of 6.0% to 6.4%. Poor control of postprandial glucose is related to an elevated urinary NAG index in persons without DM.
    Clinica chimica acta; international journal of clinical chemistry 12/2013; · 2.54 Impact Factor
  • Motoshi Ouchi, Hiroshi Nakano
    [Show abstract] [Hide abstract]
    ABSTRACT: As the percentage of elderly persons in Japan increases, so do the rates of overweight, insulin resistance, and elderly onset diabetes. Elderly onset diabetes is characterized by postprandial hyperglycemia, lower HbA1c levels, and less frequent retinopathy. The treatment of elderly onset diabetes involves numerous challenges, such as cognitive impairment, depression, vision/hearing impairment, and difficulty performing activities of daily living. One of the medical treatments, glinides and alpha-glucosidase inhibitors, must be taken before every meal. However, dipeptidyl peptidase 4 inhibitors need to be taken only once or twice daily and are well tolerated by older adults. The target HbA1c should be individualized, and a reasonable goal for HbAlc(NGSP) in healthy adults with good functional status is 7% to 9%.
    Nippon rinsho. Japanese journal of clinical medicine 11/2013; 71(11):2025-9.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Background: This study assessed the relationship between the serum level of 1,5-anhydroglucitol (1,5-AG), a marker of postprandial hyperglycemia, and the ratio of the urinary activity of N-acetyl-β-d-glucosaminidase (NAG) to creatinine (NAG index) in patients with type 2 diabetes mellitus. Subjects and Methods: This was a cross-sectional study with 153 patients who had an estimated glomerular filtration rate of ≥60 mL/min/1.73 m(2) and no proteinuria and who had never been treated with oral hypoglycemic agents or insulin. On the basis of 1,5-AG levels, the patients were divided into a High 1,5-AG group (>14.0 μg/mL) and a Low 1,5-AG group (≤14.0 μg/mL). Results: The logarithmically transformed NAG index was significantly higher in the Low 1,5-AG group than in the High 1,5-AG group when all glycated hemoglobin (HbA1c) levels were included. The logarithmically transformed NAG index was lowest in the High 1,5-AG group with an HbA1c level of ≤6.4% and was highest in the Low 1,5-AG group with an HbA1c level of ≥7.5%. Multivariate regression analysis showed that the NAG index had a higher independent association with 1,5-AG than with HbA1c or the fasting plasma glucose level. In all models, multivariate regression analyses showed that the NAG index was correlated with age. Conclusions: These results suggest that postprandial hyperglycemia correlates with early renal tubule injury in type 2 diabetes mellitus.
    Diabetes Technology &amp Therapeutics 10/2013; · 2.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVES: The aim of this study was to examine the relationship between serum levels of uric acid (UA) and 1,5-anhydroglucitol (1,5-AG) in elderly subjects (60 years or older; mean age, 73.0 ± 7.2 years) with and without type 2 diabetes mellitus (DM). METHODS: Subjects with DM (n = 97) and without DM (n = 360) were recruited from among our outpatients (estimated glomerular filtration rate ≥ 45 ml/min/1.73 m(2), and urine protein equivalent to < 1.0 g/l), and a cross-sectional study was performed with simple linear regression and stepwise multiple linear regression analyses. RESULTS: The mean serum UA levels of men were significantly higher than those of women in both groups. The mean serum 1,5-AG levels of men were significantly higher than those of women in the non-DM group. There were positive correlations (indicated by Pearson's correlation coefficients) between serum UA levels and 1,5-anhydroglucitol levels in all patients and in both men and women. Simple linear regression and multiple linear regression analyses showed that the serum 1,5-AG levels were significantly and positively correlated with the serum UA level in both the non-DM group and the DM group. In the non-DM group, HbA1c levels, as well as 1,5-AG levels, were positively correlated with serum UA levels. Furthermore, the correlation between 1,5-AG and UA levels was stronger in subjects with DM than in subjects without DM. CONCLUSIONS: These results suggest that the serum 1,5-AG level is an independent factor associated with serum UA levels in the nondiabetic state, as in DM.
    Clinical biochemistry 06/2013; · 2.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The aim of the present prospective study was to examine whether lipoprotein (a) [Lp(a)] phenotypes and/or low relative lymphocyte concentration (LRLC) are independently associated with coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). METHODS: Serum Lp(a) concentration, Lp(a) phenotypes, and RLC were analyzed in 214 subjects. Lp(a) phenotypes were classified into 7 subtypes according to sodium dodecyl sulfate-agarose gel electrophoresis by Western blotting. Subjects were assigned to the low-molecular-weight (LMW (number of KIV repeats: 11--22) ) and high-molecular-weight (HMW( number of KIV repeats: >22 )) Lp(a) groups according to Lp(a) phenotype and to the LRLC (RLC: <20.3%) and normal RLC (NRLC; RLC: >=20.3%) groups according to RLC. A CHD event was defined as the occurrence of angina pectoris or myocardial infarction during the follow-up period. RESULTS: During the follow-up period, 30 cases of CHD events were verified. Neutrophil count showed no correlation with CHD, while relative neutrophil concentration and RLC showed positive and negative correlations, respectively, with CHD. The Cox proportional hazard model analysis revealed the following hazard ratios adjusted for LMW Lp(a), LRLC, and LMW Lp(a) + LRLC: (4.31; 95% confidence interval [CI], 1.99-9.32; P < 0.01, 3.621; 95% CI, 1.50-8.75; P < 0.05, and 7.15; 95% CI, 2.17-23.56; P < 0.01, respectively). CONCLUSIONS: Our results suggest that both LMW Lp(a) and LRLC are significant and independent risk factors for CHD and that the combination thereof more strongly predicts CHD in patients with T2DM.
    Lipids in Health and Disease 03/2013; 12(1):31. · 2.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims: This study aimed to evaluate the relationship between improvement of glucose metabolism and plasma levels of diacron-reactive oxygen metabolites (d-ROMs) in patients with type 2 diabetes. Methods: As the first daily profile, the plasma levels of glucose and d-ROMs were determined on admission. Then, after treatment to lower plasma glucose levels, the second daily profile of these levels was evaluated. Fasting plasma glucose (FPG), the total area under the curve (AUC) of the daily plasma glucose profile (AUCDP), the AUC of the postprandial plasma glucose levels (AUCPP), the AUC of the daily plasma d-ROMs profile (AUCd-ROMs), the coefficient of variation (CV) of plasma glucose (CVPG), and the mean amplitude of glycemic excursions (MAGE) were calculated. The relationship between the improvement of glucose metabolism and that of oxidative stress in patients with type 2 diabetes was evaluated. Results: The second determinations of FPG, AUCDP, AUCPP, MAGE, and AUCd-ROMs were significantly lower than those of the first determinations, but no significant difference was observed in CVPG. Linear regression analysis demonstrated significant associations between the changes in AUCd-ROMs and the changes in both FPG and AUCDP, whereas no significant association was observed between the change in AUCd-ROMs and the change in AUCPP, CVPG, or MAGE. Conclusions: This study has demonstrated that improvement of the FPG level, but not of the postprandial glucose level, is associated with a reduction of the plasma level of d-ROMs in patients with type 2 diabetes.
    Journal of Nippon Medical School 01/2013; 80(3):200-10.
  • Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 01/2013; 50(2):208-10.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims: This study aimed to evaluate the relationship between aortic arch calcification (AAC) detectable on chest X-ray films and plasma diacron-reactive oxygen metabolites (d-ROMs) in patients with type 2 diabetes but without cardiovascular disease. Methods: Forty-nine patients with type 2 diabetes but without cardiovascular disease were evaluated with chest X-ray examinations and divided into those with AAC (n=26) and those without AAC (n=23). Biochemical variables, including plasma levels of d-ROMS, high-sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and lipoprotein(a) (Lp(a)), were evaluated after an overnight fast. The relationships of AAC with both inflammation and oxidative-stress variables were evaluated. Results: The plasma level of d-ROMs in subjects with AAC was significantly higher than that in subjects without AAC, whereas plasma levels of hsCRP, PAI-1, and Lp(a) in subjects with AAC were higher, but not significantly so, than those in subjects without AAC. Multivariate linear regression analysis with AAC grade as the dependent variable and plasma levels of d-ROMs, hsCRP, PAI-1, or Lp(a) as independent variables demonstrated a significant association of AAC grade with plasma levels of d-ROMs but not with plasma levels of hsCRP, PAI-1, or Lp(a). Conclusions: The plasma level of d-ROMs is associated with AAC in patients with type 2 diabetes but without cardiovascular disease. Hence, the results of the present study suggest that AAC in these patients is strongly associated with oxidative stress. Furthermore, patients with type 2 diabetes and AAC may be at high risk for the development and progression of various diabetic complications induced by oxidative stress.
    Journal of Nippon Medical School 01/2013; 80(6):410-9.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colestimide, an anion exchange resin, reportedly improves glycemic control in patients with type 2 diabetes. However, no studies of the glucose-lowering effect of colestimide have identified responders and nonresponders. In the present study, we compared glycemic control, lipids, and body-mass index (BMI) among patients with type 2 diabetes receiving colestimide (n=59) until 24 weeks after the start of treatment. Subjects were classified as responders to treatment (n=40), who showed a 15% or greater decrease in glycated hemoglobin (HbA1c) or a 20% or greater decrease in plasma glucose level or both after 24 weeks of colestimide treatment as compared with baseline; nonresponders showed HbA1c>11.5% or fasting plasma glucose (FPG)>250 mg/dL during the course of the study and <15% decrease in HbA1c levels or <20% decrease in FPG levels or both after 24 weeks of colestimide treatment as compared with baseline. In responders, FPG decreased significantly from 196 ± 91 mg/dL to 125 ± 47 mg/dL after 24 weeks (P<0.001), and HbA1c decreased from 9.1% ± 2.0% to 7.0% ± 0.9% (P<0.001). In nonresponders, HbA1c decreased significantly from 7.7% ± 2.9% to 7.6% ± 1.2% (P<0.05). Multiple logistic regression analysis revealed that baseline HbA1c and the presence of cholelithiasis were significant determinants of the response to colestimide treatment when corrected for sex, age, triglyceride levels, and BMI at baseline and the presence of fatty liver. In conclusion, baseline HbA1c and the presence of cholelithiasis have strong and independent influences on the glucose-lowering effect of colestimide.
    Journal of Nippon Medical School 01/2013; 80(3):211-7.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Urinary N-acetyl-β-D-glucosaminidase (NAG) excretion is increased in patients with impaired glucose tolerance (IGT). This study investigated when during the oral glucose tolerance test (OGTT) the plasma glucose, urine glucose, and insulin levels correlate most strongly with urinary N-acetyl-β-d-glucosaminidase (NAG) levels in prediabetic subjects. The OGTT was administered to 80 subjects who had not yet received a diagnosis of diabetes mellitus (DM) and in whom HbA1c levels were ≤6.8% and fasting plasma glucose levels were <7.0 mmol/l. Forty-two subjects had normal glucose tolerance (NGT), 31 had impaired glucose tolerance (IGT), and 7 had DM according to World Health Organization criteria. Serum levels of cystatin C, the estimated glomerular filtration rate, the urinary albumin-to-creatinine (Cr) ratio, urinary and serum β2-microglobulin, and urinary NAG were measured as markers of renal function. NAG levels were significantly higher in subjects with DM and in subjects with IGT than in subjects with NGT. No significant associations were observed between glycemic status and other markers of renal function. Multiple linear regression analysis showed that the NAG level was positively correlated with plasma glucose levels at 120 min of the OGTT and was associated with the glycemic status of prediabetic patients. These results suggest that postprandial hyperglycemia is an independent factor that causes renal tubular damage in prediabetes patients.
    Journal of Clinical Laboratory Analysis 11/2012; 26(6):473-80. · 1.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Urinary N-acetyl-β-d-glucosaminidase (NAG) has been suggested as a marker for early diabetic nephropathy. This study aimed to prospectively investigate the relationship between asymptomatic leukocyturia (ASL) and NAG in women. One hundred and five female outpatients aged 31-86 years were selected for a 10-year follow-up study. We regarded ASL to be present if two consecutive samples were found to have 10 or more leukocytes/high-power field at 400× magnifications in a centrifuged midstream urine sample both at baseline and 10 years later. The urinary activities of NAG to creatinine ratios (NAG index) were measured in random spot urine samples. Patients without ASL at the beginning of the study were followed. The patients with ASL had diabetes mellitus more frequently than those without ASL at baseline and after 10 years. Residual urine volume and the NAG index were significantly higher in the former than in the latter (p = 0.014 and p = 0.002, respectively) at baseline. During the observation period, 15 patients had ASL (30.6%). Although a gradual increase in the NAG index was found during the study in both patients who had ASL and those who did not, the mean NAG index was significantly higher in the latter during study period (6.4 ± 3.0 vs. 9.8 ± 5.5, p = 0.004, 9.4 ± 5.2 vs. 11.5 ± 6.4, p = 0.328, respectively). On multiple logistic regression analysis, the NAG index at the beginning of the study was an independent predictor of ASL. These results demonstrate that the NAG index may serve as an indicator of ASL in women.
    Renal Failure 08/2012; 34(9):1079-83. · 0.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have demonstrated that postprandial hyperglycemia attenuates brachial artery flow-mediated dilation (FMD) in prediabetic patients, in diabetic patients, and even in normal subjects. We have previously reported that postprandial hyperinsulinemia also attenuates FMD. In the present study we evaluated the relationship between different degrees of postprandial attenuation of FMD induced by postprandial hyperglycemia and hyperinsulinemia and differences in ingested carbohydrate content in non-diabetic individuals. Thirty-seven healthy subjects with no family history of diabetes were divided into 3 groups: a 75-g oral glucose loading group (OG group) (n = 14), a test meal group (TM group) (n = 12; 400 kcal, carbohydrate content 40.7 g), and a control group (n = 11). The FMD was measured at preload (FMD0) and at 60 minutes (FMD60) and 120 (FMD120) minutes after loading. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were determined at preload (PG0, IRI0) and at 30 (PG30, IRI30), 60 (PG60, IRI60), and 120 (PG120, IRI120) minutes after loading. Percentage decreases from FMD0 to FMD60 were significantly greater in the TM group (-21.19% ± 17.90%; P < 0.001) and the OG group (-17.59% ± 26.64%) than in the control group (6.46% ± 9.17%; P < 0.01), whereas no significant difference was observed between the TM and OG groups. In contrast, the percentage decrease from FMD0 to FMD120 was significantly greater in the OG group (-18.91% ± 16.58%) than in the control group (6.78% ± 11.43%; P < 0.001) or the TM group (5.22% ± 37.22%; P < 0.05), but no significant difference was observed between the control and TM groups. The FMD60 was significantly correlated with HOMA-IR (r = -0.389; P < 0.05). In contrast, FMD120 was significantly correlated with IRI60 (r = -0.462; P < 0.05) and the AUC of IRI (r = -0.468; P < 0.05). Furthermore, the percentage change from FMD0 to FMD120 was significantly correlated with the CV of PG (r = 0.404; P < 0.05), IRI60 (r = 0.401; p < 0.05) and the AUC of IRI (r = 0.427; P < 0.05). No significant correlation was observed between any other FMDs and glucose metabolic variables. Differences in the attenuation of postprandial FMD induced by different postprandial insulin levels may occur a long time postprandially but not shortly after a meal.
    Cardiovascular Diabetology 08/2012; 11:98. · 4.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate long-term, multiple risk factor intervention on physical, psychological and mental prognosis, and development of complications and cardiovascular disease in elderly type 2 diabetes patients. Our randomized, controlled, multicenter, prospective intervention trial included 1173 elderly type 2 diabetes patients who were enrolled from 39 Japanese institutions and randomized to an intensive or conservative treatment group. Glycemic control, dyslipidemia, hypertension, obesity, diabetic complications and atherosclerotic disease were measured annually. Instrumental activity of daily living, cognitive impairment, depressive symptoms and diabetes burden were assessed at baseline and 3 years. There was no significant difference in clinical or cognitive parameters at baseline between the two groups. The prevalence of low activities of daily living, depressive symptoms and cognitive impairment was 13%, 28% and 4%, respectively, and was similar in the two groups. A small, but significant difference in HbA1c between the two groups was observed at 1 year after the start of intervention (7.9% vs 8.1%, P < 0.05), although this significant difference was not observed after the second year. With the exception of coronary revascularization, there was no significant difference in fatal or non-fatal events between the two groups. Composite events were also similar in the two groups. This study showed no significant differences in fatal or non-fatal events between intensive and conventional treatment. The present study might clarify whether treatment of risk factors influences function and quality of life in elderly diabetic patients.
    Geriatrics & Gerontology International 04/2012; 12 Suppl 1:7-17.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the association of low-density lipoprotein, high-density lipoprotein and non-high-density lipoprotein cholesterol with the risk of stroke, diabetes-related vascular events and mortality in elderly diabetes patients. This study was carried out as a post-hoc landmark analysis of a randomized, controlled, multicenter, prospective intervention trial. We included 1173 elderly type 2 diabetes patients (aged ≥ 65 years) from 39 Japanese institutions who were enrolled in the Japanese elderly diabetes intervention trial study and who could be followed up for 1 year. A landmark survival analysis was carried out in which follow up was set to start 1 year after the initial time of entry. During 6 years of follow up, there were 38 cardiovascular events, 50 strokes, 21 diabetes-related deaths and 113 diabetes-related events. High low-density lipoprotein cholesterol was associated with incident cardiovascular events, and high glycated hemoglobin was associated with strokes. After adjustment for possible covariables, non-high-density lipoprotein cholesterol showed a significant association with increased risk of stroke, diabetes-related mortality and total events. The adjusted hazard ratios (95% confidence intervals) of non-high-density lipoprotein cholesterol were 1.010 (1.001-1.018, P = 0.029) for stroke, 1.019 (1.007-1.031, P < 0.001) for diabetes-related death and 1.008 (1.002-1.014; P < 0.001) for total diabetes-related events. Higher non-high-density lipoprotein cholesterol was associated with an increased risk of stroke, diabetes-related mortality and total events in elderly diabetes patients.
    Geriatrics & Gerontology International 04/2012; 12 Suppl 1:18-28.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective was to examine the effects of colestimide on blood glucose, visceral fat, adipocytokines, and bile acid conjugate fractions in Japanese patients. This study was an open-label, randomized, case-control, crossover study of colestimide 3 g/day in 40 Japanese patients with type 2 diabetes mellitus (T2D) and hypercholesterolemia. Patients were assigned to the colestimide group in which pravastatin and colestimide were administered orally and to the statin group in which pravastatin alone was administered orally. The principal outcome measures were serum lipid levels, fasting plasma glucose level in the early morning, hemoglobin A1c (HbA(1c)), visceral fat area (VFA), and serum 1,5-anhydroglucitol (1,5-AG) level. Serum low-density lipoprotein cholesterol levels significantly decreased from 113±38 mg/dl at baseline to 90±20 mg/dl (P=.009) at week 12 of colestimide administration. HbA(1c) significantly decreased from 7.4%±0.9% at baseline to 6.9%±0.9% (P=.001) at week 12 of colestimide administration. Serum 1,5-AG levels increased from 9.4±10.1 μg/ml to 12.4±9.5 μg/ml (P=.05) at week 12 of colestimide administration. The statin group showed no significant changes in lipids and 1,5-AG. However, ΔVFA was inversely correlated with Δcholic acid, and multivariate analysis revealed that ΔVFA was a significant explanatory variable. Colestimide holds promise not only for the treatment of hypercholesterolemia but also for the possible improvement of T2D and visceral fat obesity.
    Journal of diabetes and its complications 01/2012; 26(1):34-9. · 2.11 Impact Factor
  • Kenzo Oba, Hiroshi Nakano
    Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 01/2012; 49(2):175-8.
  • Hiroshi Nakano, Noriaki Matsumura
    [Show abstract] [Hide abstract]
    ABSTRACT: Initially thought to be virtually free of negative effects, benzodiazepines are now known to carry risks of dependence, withdrawal, and negative side effects. Among the most controversial of these side effects are cognitive effects. Long-term treatment with benzodiazepines has been described as causing impairment in several cognitive domains, such as visuospatial ability, speed of processing, and verbal learning. Conversely, long-term benzodiazepine use has also been described as causing no chronic cognitive impairment, with any cognitive dysfunction in patients ascribed to sedation or inat- tention or considered temporary and associated with peak plasma levels. Complicating the issue are whether anxiety disorders themselves are associated with cognitive deficits and the extent to which patients are aware of their own cognitive problems. In an attempt to settle this debate, meta-analyses of peer-reviewed studies were conducted and found that cognitive dysfunction did in fact occur in patients treated long term with benzodiazepines, and although cognitive dysfunction improved after benzodiazepines were withdrawn, patients did not return to levels of functioning that matched benzodiazepine-free controls. Neuroimaging studies have found transient changes in the brain after benzodiazepine administration but no brain abnormalities in patients treated long term with benzo- diazepines. Such findings suggest that patients should be advised of potential cognitive effects when treated long term with benzodiazepines, although they should also be informed that the impact of such effects may be insignificant in the daily functioning of most patients. (J Clin Psychiatry 2005;66(suppl 2):9-13)
    Nippon rinsho. Japanese journal of clinical medicine 12/2011; 69 Suppl 10(Pt 2):157-61.