Midlife Intakes of the Isoflavone Genistein and Soy and the Risk of Late-life Cognitive Impairment: The JPHC Saku Mental Health Study.

BACKGROUND: The number of people with cognitive impairment, including dementia, in the world is steadily increasing. Although the consumption of isoflavones and soy is associated with a reduced risk of cardiovascular disease, it might also be associated with cognitive impairment. The low number of studies investigating the association between soy/isoflavone intake and cognitive function warrant additional research. METHODS: The Japan Public Health Center-based prospective (JPHC) Study is a large population-based cohort. Midlife dietary intake of soy and the isoflavone genistein was assessed on two occasions: in the years 1995 and 2000. In 2014-2015, 1,299 participants from Nagano prefecture completed a mental health screening. Of these, a total of 1,036 participants were included in analyses. Logistic regression was used to determine Odds Ratios (OR) and 95% Confidence Intervals (CI) for the association between midlife energy-adjusted genistein and soy food intake and cognitive impairment. RESULTS: There were 392 cases of cognitive impairment (346 cases of MCI and 46 cases of dementia). Compared to the lowest dietary quartile of energy-adjusted genistein intake, the highest quartile was significantly associated with cognitive impairment (OR = 1.51; 95% CI, 1.02-2.24; P for trend = 0.03) in the final multivariable analysis. CONCLUSION: High midlife intake of the isoflavone genistein is associated with late-life cognitive impairment.

Risk of Nonalcoholic Fatty Liver Disease in Patients With Schizophrenia Treated With Antipsychotic Drugs: A Cross-sectional Study.

BACKGROUND: Although the prevalence of metabolic syndrome in patients with schizophrenia is higher than the prevalence in the general population, little is known regarding nonalcoholic fatty liver disease (NAFLD) in patients with schizophrenia. PROCEDURES: We analyzed the medical records of patients with schizophrenia/schizoaffective disorder (N = 253) who received an abdominal echography. RESULTS: In total, 108 patients (42.7%) showed NAFLD on abdominal echography. Of these, 13 patients (12.0%) showed signs of fibrosis on abdominal echography. In terms of age distribution, NAFLD was more prevalent in younger patients, particularly in female patients. We also found that body mass index, the total dose of antipsychotic drugs that carry a risk of metabolic syndrome, and the total dose of antipsychotic drugs that carry a risk of hyperprolactinemia were significantly associated with NAFLD (P < 0.001, 0.049, and 0.041, respectively). In our exploratory analysis, we found that signs of fibrosis in NAFLD were more highly associated with female patients (P = 0.023). Importantly, the risk in younger female patients may be specific to patients with schizophrenia compared with the general population. CONCLUSIONS: Considering that antipsychotic drugs were associated with the development of NAFLD, early detection and management of NAFLD should be conducted in patients with schizophrenia.

Quantitative Assessment of the Retina Using OCT and Associations with Cognitive Function.

PURPOSE: To determine the association of retinal thickness with cognitive function in Japanese persons. DESIGN: Cross-sectional, population-based survey. PARTICIPANTS: A total of 1293 Japanese persons aged 65 to 86 years who resided in the Saku area in the Japan Public Health Center-Based Prospective Study participated in the eye and mental health screening. METHODS: Participants underwent comprehensive ophthalmic assessment, including fundus photography, measurement of intraocular pressure, and determination of refraction status. We assessed the thickness of the macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GC-IPL), and ganglion cell complex (GCC, which includes the retinal nerve fiber layer and GC-IPL), and the full thickness in the macula and peripapillary retinal nerve fiber layer (ppRNFL) using spectral-domain (SD) OCT. Cognitive tests consisted of the Mini-Mental State Examination, Wechsler Memory Scale Revised logical memory I/II subtest, clock drawing test, and Clinical Dementia Rating Scale. These were used to designate the participants in the following 3 groups: Normal, those with mild cognitive impairment (MCI), and those with dementia. Multivariable logistic regression models were used to analyze associations between retinal thickness and cognitive function after adjusting potential confounding factors. MAIN OUTCOME MEASURES: Association of retinal thickness with cognitive function. RESULTS: Among the 1293 potential subjects, 114 were excluded for a diagnosis of depression, 64 were excluded for retinal disease, and 140 were excluded for scanning errors or suboptimal OCT images. The remaining 975 participants (mean age, 73.2 years) were included in this analysis. Significant differences were found in the 3 groups in all layers and GCC thickness, but not in ppRNFL thickness. After adjusting for age, sex, educational status, and refraction, full macular thickness and GCC thickness were inversely associated with the presence of dementia, but ppRNFL thickness was not. Furthermore, GC-IPL, GCC, and full macular thicknesses were all associated with the presence of dementia in the inferior sectors. CONCLUSIONS: Macular thickness was associated with the presence of dementia, but ppRNFL was not. Our results suggest that OCT measurements of the macula could be superior to those of the ppRNFL in assessing neurodegenerative changes and a potentially useful diagnostic biomarker of cognitive function.

[Survey on the actual condition of psychiatrists and psychiatric services in Japan. (Part 1): Basic data on number and distribution of psychiatrists].

BACKGROUND: To ensure that psychiatric services adequately meet the needs of the Japanese people, planning a prospective design based on a needs analysis is required. Presently, the distribution of medical resources in Japan is skewed and the priorities of psychiatric services are unclear. OBJECTIVE: To determine the current status of psychiatric services. METHOD: The definition of a psychiatrist was determined by qualified specialists of the Japanese Society for Psychiatry and Neurology (JSPN). Of the 11,169 candidates who applied for the specialist psychiatry examination, 246 were excluded due to a lack of personal information and 4 due to refusal. The remaining 10,919 agreed to allow the verification of their personal data. This study was conducted with the approval of the JSPN. The total number of psychiatrists, their demographic backgrounds, the number of psychiatrists by prefecture, and the number of psychiatrists in each secondary medical care block in Japan were calculated. RESULTS: Of the 10,919 psychiatrists included in this analysis, 2,124 were female and 8,790 were male. Approximately 90% were < 65 years old, and 42% were < 45 years old. Their primary work places were as follows: psychiatric hospitals (n = 5,233, 47.9%); university departments of psychiatry (n=1,353, 12.4%); general hospitals (n = 1,064, 9.7%); psychiatric clinics (n = 2,456, 22.5%); nonpsychiatric clinics (n = 687, 6.3%); and nonclinical work places such as basic science departments (n = 124, 1.1%). The number of psychiatrists per 100,000 inhabitants in each prefecture was determined. The highest numbers of psychiatrists were from Kochi (13.20), Tokyo (12.76), and Tokushima (12.24), and the lowest numbers were from Ibaraki (5.34), Aomori (5.36), and Saitama (5.67). The number of psychiatrists per 100,000 inhabitants in Kochi was 1.48 per area (100 km square), and Tokyo showed the highest at 75.99 psychiatrists per area, followed by Osaka and Kanagawa. The five Tohoku prefectures and Hokkaido had the fewest psychiatrists per area. CONCLUSION: For planning the future management of psychiatric services, continuous investigation of the actual number of psychiatrists and the status of psychiatric services in Japan is required with the constant cooperation of the JSPN.

[Survey on the actual condition of psychiatrists and psychiatric services in Japan. (Part 2): Change in geographical working area and setting of each psychiatrist].

BACKGROUND: The shortage of psychiatrists has recently become a public concern; however, the reason for this shortage has not been clearly discussed or explained on the basis of real data. We assumed that it is not only due to the lack of the absolute number of psychiatrists, but also due to an imbalance in their distribution in geographical working areas and settings. OBJECTIVE: To evaluate the change in distribution of Japanese psychiatrists. METHOD: We analyzed the change in the geographical working area and setting of each psychiatrist from September 2006 to March 2009 using data obtained from psychiatrists who applied for the Board Certification Examination of the Japanese Psychiatric Association. Our data included 6,881 psychiatrists. RESULTS: With regard to the geographical working area, the number of psychiatrists in ordinance-designated cities (urban areas) increased by 2.2%, whereas that in other areas decreased by 3.0%. On examination of work settings, we noted a 16.0% decrease in the number of psychiatric departments in general hospitals and a 20.0% increase in the number of psychiatric clinics. Surprisingly, more than 10% of middle-aged psychiatrists (10.3% of 36 45-year-olds and 12.2% of 46-55-year olds) who worked in general hospitals moved to clinics. CONCLUSION: The present study revealed that, although psychiatrists did not tend to move from rural to urban areas, they showed a tendency to move from general hospitals to psychiatric clinics.

The association between midlife living arrangement and psychiatrist-diagnosed depression in later life: who among your family members reduces the risk of depression?

This study investigates the longitudinal association between living arrangements and psychiatrists' diagnosis of depression in the general population. In 1990, 1254 Japanese men and women aged 40-59 years were enroled and completed questionnaires on the living arrangement in the Japan Public Health Center-based Prospective Study (JPHC Study) and participated in a mental health screening (2014-2015). The study diagnosed a major depressive disorder (MDD) assessed by well-trained certified psychiatrists through medical examinations. During the follow-up, a total of 105 participants (36 men and 69 women) aged 64-84 years were diagnosed with MDD by psychiatrists. Living with a child (ren) was associated with a reduced risk of MDD for men but not for women; the respective multivariable ORs (95% CIs) were 0.42 (0.19-0.96) and 0.59 (0.32-1.09). These associations remained unchanged after adjusting for living with spouse and parent(s). In conclusion, living with a child (ren) was associated with a reduced risk of MDD in men, suggesting the role of a child (ren) in the prevention of MDD.

Coping in Mid- to Late Life and Risk of Mild Cognitive Impairment Subtypes and Dementia: A JPHC Saku Mental Health Study.

BACKGROUND: The relationship between coping in mid- to late life and cognitive functions remains unclear. OBJECTIVE: To investigate the relationship between habitual coping behaviors of a large Japanese population in their mid- to late-lives and their risk of cognitive decline 15 years later. METHODS: Overall 1,299 participants were assessed for coping behaviors (in 2000) and cognition (2014-2015). We used the Stress and Coping Inventory to assess the frequency of six coping behaviors (i.e., consulting, planning, positive reappraisal, avoidance, fantasizing, and self-blame). Logistic regression analyses were conducted to examine odds ratios (ORs) for the diagnosis of mild cognitive impairment (MCI), MCI subtypes (single- and multiple-domain MCI), and dementia for coping behaviors. RESULTS: Among the eligible 1,015 participants (72.6 [SD = 5.5] years old in 2014-2015), the numbers for cognitively normal, single-domain MCI, multiple-domain MCI, and dementia were 650 (64.0%), 116 (11.4%), 213 (21.0%), and 36 (3.5%), respectively. Among the six coping behaviors, avoidant coping was significantly associated with noticeable cognitive decline (multiple-domain MCI and dementia). This association remained significant after adjusting for sex, age, education, diagnosis of current major depressive disorder, past history of ischemic heart disease, diabetes, regular alcohol consumption, and smoking (OR = 2.52, 95% CI = 1.23 to 5.15). No significant association with other coping behaviors was found. CONCLUSION: Avoidant coping in mid- and late life is associated with cognitive decline among older people.

Association between vegetable, fruit, and flavonoid-rich fruit consumption in midlife and major depressive disorder in later life: the JPHC Saku Mental Health Study.

We evaluated the association between vegetable and fruit consumption - particularly flavonoid-rich fruits - in mid-life and major depressive disorder (MDD) in later life. We also evaluated the association of nutrients in fruits and vegetables with MDD. Vegetable and fruit consumption and nutrient intake for 1204 individuals were averaged from data obtained in 1995 and 2000. MDD was diagnosed by certified psychiatrists in 2014-2015. Logistic regression was used to examine the odds of MDD according to quintile of vegetable and fruit consumption and quartile of nutrient intake. We fitted two regression models, using hierarchical adjustment for age, sex, employment status, alcohol consumption, current smoking, and physical activity. Bias-corrected and accelerated bootstrap confidence intervals were used to obtain accurate information. In fully adjusted models, the highest quintile of total fruit consumption excluding juice and flavonoid-rich fruit consumption showed decreased odds of MDD compared with the lowest quintile (OR = 0.34, 95% CI = 0.15-0.77; OR = 0.44, 95% CI = 0.20-0.97, respectively). No significant association was found for total vegetables and fruits, total vegetables, or total fruits. No significant association was found for any nutrient. This study provides novel information on the association between MDD and flavonoid-rich fruits.

Impact of the COVID-19 pandemic on patients with mental health problems and the differences among diagnostic categories.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a total upending of our daily lives. While anxiety and depression were frequently reported among the general population, the pandemic's impact on patients with mental health problems remains unknown. METHODS: A cross-sectional questionnaire survey involving 1,166 patients was conducted at one psychiatric hospital and one mental health clinic. RESULTS: Symptom deterioration was reported in 23% to 34% of the patients and 9% to 20% reported increase in drug dosage. No significant differences were reported in these items among diagnostic categories. Patients with F3 (mood disorders) reported more psychological stress during the pandemic's beginning and during the emergency. Patients with F2 (schizophrenia, schizotypal, and delusional disorders) did online shopping and meetings less frequently, and reported poorer adherence of 3C's, while mask management was stricter in patients with F4 (neurotic, stress-related, and somatoform disorders). Symptom deterioration was significantly associated with increase in drug dosage, new physical symptoms, anxiety unrelated to COVID-19, stress at the beginning of pandemic, stress during the 'state of emergency', poor adaptability to environmental change, daily life changes, decrease in sleeping time, and decrease in time spent outside. CONCLUSION: One third of patients reported symptom deterioration during the pandemic, which was associated with stress and daily life changes. Patients with good adaptability to environmental changes might resilient against symptom deterioration. Providing continuous support to help patients manage their daily life in this COVID-19 era may minimize the risk of symptom deterioration.

Association Between Dietary Fish and PUFA Intake in Midlife and Dementia in Later Life: The JPHC Saku Mental Health Study.

BACKGROUND: The relationship between midlife dietary habits and risk of dementia remains unclear. OBJECTIVE: To investigate the association between dietary fish and n-3 polyunsaturated fatty acid (PUFA) consumption in midlife and risk of dementia in later life. METHODS: This population-based cohort study assessed food frequency (average intake in 1995 and 2000) and cognition (2014-2015) in 1,127 participants (aged 45-64 in 1995). We used logistic regression analyses to calculate odds ratios (ORs) for dementia and mild cognitive impairment (MCI) diagnoses for consumption quartiles of fish, PUFA-rich fish, total n-3 PUFAs, total n-6 PUFAs, types of PUFAs, and n-3/n-6 PUFA ratio. Estimated ORs were adjusted for age; sex; education; smoking status; alcohol consumption frequency; physical activity; histories of cancer, myocardial infarction, and diabetes mellitus; and depression. RESULTS: Significantly reduced risks of dementia over non-dementia (MCI plus cognitively normal) were observed in the second (OR = 0.43 (95% CI = 0.20-0.93)), third (OR = 0.22 (95% CI = 0.09-0.54)), and highest quartiles (OR = 0.39 (95% CI = 0.18-0.86)) for fish; the third (OR = 0.39 (95% CI = 0.16-0.92)) and highest quartiles (OR = 0.44 (95% CI = 0.19-0.98)) for eicosapentaenoic acid (EPA); the second (OR = 0.39 (95% CI = 0.18-0.84)), third (OR = 0.30 (95% CI = 0.13-0.70)), and highest quartiles (OR = 0.28 (95% CI = 0.12-0.66)) for docosahexaenoic acid (DHA); and the third (OR = 0.36 (95% CI = 0.16-0.85)) and highest quartiles (OR = 0.42 (95% CI = 0.19-0.95)) for docosapentaenoic acid (DPA). CONCLUSION: High intake of fish in midlife might aid in preventing dementia.

Are Analogue or Digital Clocks Friendlier for People Living with Dementia?

BACKGROUND: In ageing population, it is desirable to reduce the impact of cognitive decline on daily life. While various types of dementia-friendly environments have been proposed, the question still remains regarding whether analogue or digital clocks are friendlier for people with dementia. METHODS: In clinical practice, we normally use our original clock reading test (10 analogue and 10 digital clocks) to assess patients' ability to read a clock. In the present study, a retrospective medical record survey was conducted. Fifty-five participants who had done the test were identified. The result of the test was compared between analogue and digital clocks. Additionally, to assess specific ability to read analogue clocks, an "analogue-digital gap" was defined as the difference between patients' performance for analogue and digital clocks. Univariate and multivariate analyses were conducted to detect significant factors associated with reading ability specific to analogue clocks. RESULTS: The analogue clock proved less readable than the digital clock, even after adjusting for MMSE total score (p = 0.003). Multivariate analysis revealed reading ability of the analogue clock was significantly associated with MMSE calculation and clock drawing test (p = 0.009 and 0.040, respectively). CONCLUSIONS: In the present study, the digital clock was friendlier than the analogue clock for patients with dementia. Compared to the digital clock, reading analogue clocks might require more widespread cognition, such as working memory and visuospatial processing. While our finding was a general tendency, and individual assessment is necessary, it might help the development of personalized environmental adjustments.

Plasma phospholipid n-3 polyunsaturated fatty acids and major depressive disorder in Japanese elderly: the Japan Public Health Center-based Prospective Study.

The beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on depression are not definitively known. In a previous population-based prospective cohort study, we found a reverse J-shaped association of intake of fish and docosapentaenoic acid (DPA), the intermediate metabolite of EPA and DHA, with major depressive disorder (MDD). To examine the association further in a cross-sectional manner, in the present study we analyzed the level of plasma phospholipid n-3 PUFAs and the risk of MDD in 1,213 participants aged 64-86 years (mean 72.9 years) who completed questionnaires and underwent medical check-ups, a mental health examination, and blood collection. In multivariate logistic regression analysis, odds ratios and 95% confidence intervals were calculated for MDD according to plasma phospholipid n-3 PUFA quartiles. MDD was diagnosed in 103 individuals. There were no significant differences in any n-3 PUFAs (i.e., EPA, DHA, or DPA) between individuals with and without MDD. Multivariate logistic regression analysis showed no significant association between any individual n-3 PUFAs and MDD risk. Overall, based on the results of this cross-sectional study, there appears to be no association of plasma phospholipid n-3 PUFAs with MDD risk in the elderly Japanese population.

Regional dopamine synthesis in patients with schizophrenia using L-[beta-11C]DOPA PET.

The dopamine hypothesis has been the most widely known theory concerning schizophrenia. However, the exact mechanism including presynaptic dopaminergic activity and its relationship with symptom severity still remains to be revealed. We measured presynaptic dopamine synthesis using positron emission tomography (PET) with L-[beta-(11)C]DOPA in 18 patients with schizophrenia (14 drug-naive and 4 drug-free patients) and 20 control participants. Dopamine synthesis rates, expressed as k(i) values, were obtained using a graphical method, and the occipital cortex was used as reference region. Regions of interest were placed on the prefrontal cortex, temporal cortex, anterior cingulate, parahippocampus, thalamus, caudate nucleus, and putamen. Psychopathology was assessed with the Positive and Negative Symptom Scale (PANSS). We found significantly higher k(i) values in patients than in controls in the left caudate nucleus, but not in the other regions. The k(i) values in the thalamus exhibited a significant positive correlation with the PANSS total scores. Furthermore, a significant positive correlation was observed between the PANSS positive subscale scores and k(i) values in the right temporal cortex. Patients with schizophrenia showed higher dopamine synthesis in the left caudate nucleus, and dopaminergic transmission in the thalamus and right temporal cortex might be implicated in the expression of symptoms in schizophrenia.

Reproductive history and risk of cognitive impairment in Japanese women.

OBJECTIVE: While exposure to endogenous estrogen may be associated with better cognitive performance, it is still unclear whether it has an association with mild cognitive impairment (MCI) or dementia. The aim of this study was to clarify the effects of reproductive history, as a surrogate marker of exposure to endogenous estrogen, on the risk of cognitive impairment (MCI or dementia) in women. STUDY DESIGN: A total of 747 women aged 40-59 years in the Saku area (Nagano Prefecture) were followed as part of the Japan Public Health Center-based Prospective (JPHC) Study, which started in 1990. Participants had undergone a mental health examination in 2014-2015. MAIN OUTCOME MEASURES: We used multiple logistic regression to analyze the association between reproductive history, obtained at baseline and 10-year follow-up, with current cognitive impairment diagnosed by a trained psychiatrist, adjusting for various lifestyle factors. RESULTS: Among 670 eligible women, current cognitive impairment was diagnosed in 227, 196 of whom had MCI and 31 dementia. A longer reproductive period had a significantly inverse association with cognitive impairment (P-trend = 0.032). In particular, women with a reproductive period ≥38 years compared with ≤33 years had a significantly lower risk of cognitive impairment (multivariable adjusted odds ratio=0.62, 95% confidence interval=0.40-0.96). CONCLUSIONS: A longer reproductive period was associated with a lower risk of cognitive impairment, which suggests that a longer exposure to endogenous estrogen may have a protective effect against cognitive impairment.

The association between midlife serum high-density lipoprotein and mild cognitive impairment and dementia after 19 years of follow-up.

A third of dementia cases could be attributable to modifiable risk-factors. Midlife high-density lipoprotein cholesterol (HDL-C) is a measure which could help identify individuals at reduced risk of developing age-related cognitive decline. The Japan Public Health Centre-based prospective (JPHC) Study is a large population-based cohort which started in 1990. This study included 1299 participants from Saku area in Nagano prefecture. Participants had HDL-C measured in 1995-1996, and underwent a mental health screening in 2014-2015. Of these, 1114 participants were included in MCI analyses, and 781 participants were included in dementia analyses. Logistic regression models were used to determine odds ratios (OR) and 95% confidence intervals (CI) for the association between HDL-C quartiles and MCI and dementia, respectively. For dementia analysis, quartiles 2-4 were collapsed due to low number of cases. Missing data was addressed through multiple imputations. There were 386 cases of MCI and 53 cases of dementia. Compared to the lowest HDL-C quartile, the highest HDL-C quartile was significantly inversely associated with MCI (OR = 0.47, 95% CI, 0.28-0.79) in the multivariable analysis. High HDL-C (quartiles 2-4) was inversely associated with dementia compared to low HDL-C (quartile 1) (OR = 0.37, 95% CI, 0.16-0.88). This study has found that high midlife HDL-C levels are inversely associated with both late-life MCI and dementia in a Japanese population.

Diet quality and depression risk in a Japanese population: the Japan Public Health Center (JPHC)-based Prospective Study.

The association of overall diet quality based on the Japanese Food Guide Spinning Top with risk of depression is not known. This prospective cohort study aimed to determine whether higher adherence to the Japanese food guide reduced the risk of depression. Of 12,219 residents enrolled at baseline, we extracted 1,112 participants who completed a 5-year follow-up (1995) and participated in a mental health screening (2014-2015). Diet quality was scored based on adherence to the Japanese food guide and the ratio of white to red meat according to the Alternative Healthy Index and ranged from 0 (worst) to 80 (best). We calculated odds ratios and 95% confidence intervals for current psychiatrist-diagnosed depression per quartile of total score and of eight component scores with the lowest quartile as reference. Mean age of the participants was 73 years and 59% were women. Total diet quality score was not significantly associated with risk of depression 20 years after the baseline assessment. Among the eight components on the diet quality score, there was a significantly reduced risk for the highest quartile of the white to red meat ratio score. In conclusion, our results do not indicate that higher adherence to the Japanese food guide prevents depression.

Role of ventral striatal dopamine D1 receptor in cigarette craving.

BACKGROUND: Several theories of cigarette craving suggest that dopaminergic function in the ventral striatum plays an important role. The objective of this study was to determine correlations between craving-related brain activation and dopamine D1 receptor (D1R) binding in smokers. METHODS: Twelve smokers and 12 nonsmoking controls underwent [(15)O]H(2)O-positron emission tomography activation study and D1R-binding study using [(11)C]SCH 23390, and the correlations between receptor binding and cue-induced regional cerebral blood flow (rCBF) changes were assessed. Consecutive D1R-binding changes were examined during a period of 6 months of postsmoking abstinence in five smokers. RESULTS: Cue-induced activation was observed in the left ventral striatum including the nucleus accumbens in smokers. D1R binding in the ventral striatum showed a negative relationship with cue-induced craving and rCBF changes. D1R binding was significantly low in smokers, and there was a trend of increase after smoking abstinence. CONCLUSIONS: D1R binding and cue-induced rCBF changes in the ventral striatum suggest the important role of D1R in this region in cigarette craving.

Mapping of central dopamine synthesis in man, using positron emission tomography with L-[beta-11C]DOPA.

OBJECTIVE: To estimate the presynaptic function of the central dopaminergic system, positron emission tomography measurement of the endogenous dopamine synthesis rate was performed with L-[beta-11C]DOPA. In the present study, we developed a simple method for calculating an indicator of the dopamine synthesis rate with L-[beta-11C]DOPA on a voxel-by-voxel basis for parametric mapping. METHODS: After intravenous injection of L-[beta-11C]DOPA, dynamic scanning was performed on ten healthy men for 89 min. The dopamine synthesis ratio was calculated on a voxel-by-voxel basis as the ratio of the area under the time-activity curves of brain regions to the reference brain region, that is, occipital cortex. The overall uptake rate constant as an indicator of dopamine synthesis was also calculated by kinetic and graphical analyses. RESULTS: The dopamine synthesis ratio calculated by the present method was in good agreement with the indicators of dopamine synthesis calculated by kinetic and graphical analyses, although a systemic underestimation was observed, especially when the integration interval was set in the early phase of the scan duration. In particular, underestimations were prominent in brain regions with relatively lower influx rate constant K1. CONCLUSIONS: By this method, regional dopamine synthesis could be estimated on a voxel-by-voxel basis. This method does not need an arterial input function and should prove to be useful for clinical research.

Quantitative analyses of 18F-FEDAA1106 binding to peripheral benzodiazepine receptors in living human brain.

UNLABELLED: N-(5-Fluoro-2-phenoxyphenyl)-N-(2-(18)F-fluoroethyl-5-methoxybenzyl)acetamide ((18)F-FEDAA1106) is a potential PET ligand with highly selective and specific binding to peripheral benzodiazepine receptor (PBR). It has been reported that the regional density of PBR in the brain is increased in several neurodegenerative and psychiatric disorders. Thus, a reliable tracer method for evaluating PBR would be of use clinically and for research. To our knowledge, this is the first study to investigate the (18)F-FEDAA1106 binding to PBR in living human brain by PET. We also aimed to evaluate various analytic methods to quantify the density of PBR. METHODS: PET studies with (18)F-FEDAA1106 were performed on 7 healthy men. Volumes of interest (VOIs) were drawn on PET images. In each VOI, binding potential (BP) was calculated by nonlinear least-squares (NLS) fitting based on the 2-tissue compartment model, and the distribution volume (DV) was also estimated by NLS, Logan plot, and multilinear analysis (MA) methods. To estimate errors in calculation of BP and DV, simulation studies were also performed. RESULTS: The DVs estimated with each of the methods were significantly correlated. There was also significant correlation between BP with NLS and DV with NLS, Logan plot, or MA. But the interindividual differences in the distribution volume of the free and nonspecific binding compartment (K(1)/k(2)) were relatively large. In a simulation study, variation of the DV estimated by Logan plot was relatively small, but it was underestimated as the noise increased. By MA, the bias of DV was smaller, but the variation of DV was larger than by Logan plot. Within a 3% noise level, there was almost no difference between Logan plot and MA in both bias and variation. DVs estimated by both Logan plot and MA were underestimated by 10%-20%. Although the variation of DV was larger by NLS than by Logan plot, it was small enough in the noise level of VOI analysis, and the bias of DV was 0%-2%. CONCLUSION: The simulation studies indicated that NLS is a suitable method for the estimation of (18)F-FEDAA1106 binding to PBRs.