This study is the first study of Japanese dementia rates carried out with a protocol similar enough to that of a US study to allow meaningful comparisons. The prevalence rates demonstrated are more similar to US rates than were found in many previous reports in Japan.
The majority of cases of anti-glutamic acid decarboxylase (GAD)-antibody-positive cerebellar ataxia are reported to have high levels of anti-GAD antibody, and the diagnostic value of low titers of anti-GAD antibody in a patient with cerebellar ataxia is still unknown. The purpose of this study was to verify the characteristics of low-titer-anti-GAD-antibody-positive cerebellar ataxia patients and the diagnostic value of low titers of anti-GAD antibody in patients with cerebellar ataxia. The subjects were six patients positive for low-titer GAD antibody (<100 U/mL). We examined them with MRI, including voxel-based morphometry, and with single-photon emission computed tomography and monitored the GAD antibody index in the cerebrospinal fluid. The levels of antineuronal, antigliadin, anti-SS-A, antithyroid antibodies, and of vitamins E, B1, and B12 were determined. Thoracic and abdominal CT scans were performed to exclude a paraneoplastic origin. We treated three patients with immunotherapy. All cases showed cortical cerebellar atrophy. The GAD antibody index in three of the five patients reviewed was >1.0. Two of the six patients were thyroid antibody-positive, and one was both antinuclear- and anti-SS-A antibody-positive. After the administration of immunotherapy to three patients, two showed clear effectiveness, and one, transient effectiveness. Effectiveness was greatest in the two patients with familial occurrence of the disease. In cerebellar ataxia, regardless of family history or isolated illness, it is critical to measure the GAD antibody level, and, even with a low titer level, if the result is positive, immunotherapy should be considered.
Progression-free survival (PFS) and time to progression (TTP) have been reported to correlate with overall survival (OS) in several types of cancers. To our knowledge, however, their use in the evaluation of new agents for AGC has not been investigated. We evaluated the potential of PFS and TTP to act as surrogates of OS in clinical trial settings. Randomized trials of systemic chemotherapy for advanced gastric cancer were identified by comprehensive electronic and manual search. Correlations between PFS/TTP and OS were evaluated. Thirty-six trials with a total of 83 treatment arms and 10,484 patients were selected for analysis. The nonparametric Spearman rank correlation coefficient (ρ) between median PFS/TTP and OS was 0.70 (95% CI, 0.59 to 0.82) and the correlation coefficient between hazard ratios in PFS/TTP and OS was 0.80 (95% CI, 0.68 to 0.92). Correlation tended to be higher in trials reporting PFS (ρ = 0.85; 0.72-0.97) than in those reporting TTP (ρ = 0.60; 0.24-0.97), trials in Non-Asian countries (ρ = 0.80; 0.61-0.99) than Asia (ρ = 0.67; 0.39-0.94), trials in patients with measurable lesions only (ρ = 0.91; 0.77-1.00) than in those including non-measurable lesions (ρ = 0.71; 0.50-0.93), albeit that none of these differences was significant. Our results indicate that improvements in PFS/TTP in advanced gastric cancer strongly correlate with improvements in OS. Further research is needed to clarify the surrogacy of PFS/TTP for OS or the role of PFS as the true end point in future randomized clinical trials of chemotherapy for AGC.
Objective: To determine the age-, sex-, and subtype-specific incidence of dementia and to assess the effect of education level on the incidence in a Japanese population. Methods: 2,286 dementia-free subjects, aged ≧60 years, were followed for 5.9 years through biennial two-phase examinations. Results: 206 cases of dementia were newly diagnosed based on DSM IV. The incidence per 1,000 person-years was 12.0 for men and 16.6 for women. Based on NINCDS-ADRDA criteria, 80 cases of probable Alzheimer disease (AD) and 50 cases of possible AD were diagnosed. Based on NINDS-AIREN criteria, 36 cases of probable vascular dementia (VaD) and 40 cases of possible VaD were diagnosed. Age and education showed the most statistically significant effects for all dementia. Probable AD showed the most remarkable increase with age and decreased with increasing education level (p = 0.001). Probable VaD showed significant effects of sex (p = 0.033) and sex-age interaction (p = 0.048), but not education (p = 0.26). Conclusion: AD was the predominant type of dementia in this recent incidence study conducted in Japan, suggesting a reduction in VaD and an increase in AD. Age, sex, and education effects differed by dementia subtype.
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