BackgroundGlucose intolerance in patients with amyotrophic lateral sclerosis (ALS) has been inconsistently reported. Evidence for the association of ALS and diabetes mellitus is limited. We aimed to assess the overall and age- and sex-specific risks of ALS among patients with diabetes in Taiwan.MethodsThe study cohort included 615 492 diabetic patients and 614 835 age- and sex-matched subjects as a comparison cohort, followed from 2000 to 2008. We estimated the incidence densities of ALS and calculated the relative hazard ratios (HRs) of ALS (ICD-9-CM 335.20) in relation to diabetes using a Cox proportional hazard regression model, with adjustment for potential confounders, including sex, age, geographic area, urbanization status, Charlson Comorbidity Index, frequency of medical visit, and histories of hypertension, hyperlipidemia, and chronic obstructive pulmonary disease.ResultsOver a 9-year period, 255 diabetic and 201 non-diabetic subjects developed ALS, corresponding to incidence densities of 7.42 and 5.06 per 100 000 person-years, respectively. After adjustment for potential confounders, patients with diabetes experienced a significantly elevated HR of 1.35 (95% confidence interval [CI], 1.10–1.67). A higher covariate adjusted HR was noted in men (HR 1.48; 95% CI, 1.13–1.94) than in women (HR 1.17; 95% CI, 0.84–1.64), while men aged ≤65 years showed the most increased HR of 1.67 (95% CI, 1.18–2.36).ConclusionsThis study demonstrated a moderate but significant association of diabetes with ALS onset, and such association is not confounded by socio-demographic characteristics or certain ALS-related co-morbidities. Further studies are warranted to examine whether the findings observed in our study can be replicated.

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Background: Thiazolidinediones (TZDs) - rosiglitazone and pioglitazone - a class of insulin sensitizer for treating type 2 diabetes, have been reported to exhibit neuroprotective effects in preclinical studies and have good effects in the control of blood sugar for diabetic patients with insulin resistance. However, clinical trials and observational studies have raised the possibility of higher stroke risk in patients treated with rosiglitazone. Whether pioglitazone poses similar stroke risk remains uncertain. Most of the studies on cardiovascular effects of TZDs were based on studies in the USA and Europe. The present study aimed to compare the stroke risk among diabetic patients on TZD to those on non-TZD medications in an Asian population. Methods: The study cohort included 15,981 patients with a diagnosis of diabetes without prior stroke, acute myocardial infarction (AMI) or heart failure who were followed from 2001 to 2010. Patients were classified by their prescriptions into rosiglitazone, pioglitazone and non-TZD groups. The study end points included ischemic and hemorrhagic stroke. In view of the reported association of heart failure and AMI with rosiglitazone, these 2 end points were also included in the present study. Cox hazard proportional models were used to estimate the risk of developing the end points. Likelihood ratio test was used to examine the age-drug interactions. Dose-response effects were evaluated by comparing the incidence rates among patients with different cumulative exposures to TZD. Results: During the 10-year follow-up, the rosiglitazone group showed significantly higher risk of ischemic stroke (multivariate adjusted hazard ratio, HR = 1.39; 95% confidence interval, CI = 1.16-1.66) and heart failure (HR = 1.59; 95% CI = 1.18-2.14) than the non-TZD group. The pioglitazone group did not show significant difference from the non-TZD group in ischemic stroke (HR = 0.97; 95% CI = 0.75-1.26) and heart failure (HR = 0.94; 95% CI = 0.59-1.50). The results also showed a significant dose-dependent effect of higher risk of ischemic stroke with increasing dosage of rosiglitazone, while there was no increased risk at any level of pioglitazone dosage. Conclusions: This population-based cohort study shows that rosiglitazone imposes a higher risk of developing stroke or heart failure in this Asian patient population, suggesting the adverse side effects of rosiglitazone across ethnic boundaries. Pioglitazone, on the other hand, does not increase cardiovascular or stroke risk compared to the non-TZD group among diabetic patients without a history of macrovascular disease.

Background: Primary Progressive Aphasia (PPA) is a neurodegenerative syndrome that presents with speech and language impairments and is generally classified into three variants: semantic (svPPA), nonfluent/ agrammatic (nfvPPA), and logopenic variants (lvPPA). Current understanding of PPA has been mostly derived from English language patients. Expanding PPA research into non-English languages encourages language-specific linguistic-adapted assessments and enriches our knowledge in linguistic features distinct from English language. This presentation focuses on three Chinese linguistic features that differ from English language: lexical tones, classifier, and logographic script. Chinese is a tonal and classifier language in which tones are lexically contrastive, and classifiers are obligatory to quantify nouns numerally. It also adopts logographic script that has complex visuospatial configurations and weak graphemephoneme correspondence. Method:The CLAP (Chinese LanguageAssessment for PPA) battery is designed to characterize the neurolinguistics features of Chinese speaking PPA individuals. In CLAP classifier task, participants are asked to spontaneously produce classifiers specific to numerous nouns and presented with multiple choices when failed. To evaluate Chinese writing skills, participants are tasked with dictating 60 Chinese characters of varying lexicality, character frequency, and stroke number. The motor speech function is assessed by multiple repetitions of Chinese characters that differ in articulation places, manners, and tones. Results:The CLAP project enrolled 20 controls and 33 PPA individuals (7 nfvPPA, 10 svPPA, and 16 lvPPA). In classifier task, svPPA and lvPPA scored lower (p<0.01), though lvPPA were more responsive to choices than svPPA (p<0.001). The classifier score significantly correlated with volumetric changes over the left middle, inferior temporal, and fusiform gyri, brain regions typically associated with semantic functions. For orthographic dictation task, all three PPA variants performed worse than controls (p<0.001), and distinctive dysgraphia phenotypes were noted in each variant (svPPA: phonological plausible and perseveration errors; nfvPPA: motoric, radical and morphemic errors; lvPPA: visual and stroke errors, P<0.001). In motor speech task, nfvPPA showed lower