Objective:To cross-sectionally compare the regional white matter fractional anisotropy (FA) of cognitively normal (CN) older individuals and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD), separately focusing on the normal-appearing white matter (NAWM) and white matter hyperintensities (WMH), and to test the independent effects of presumed degenerative and vascular process on FA differences. Methods:Forty-seven patients with AD, 73 patients with MCI, and 95 CN subjects received diffusion tensor imaging and vascular risk evaluation. To properly control normal regional variability of FA, we divided cerebral white matter into 4 strata as measured from a series of young healthy individuals (H1 ϭ highest; H2 ϭ intermediate high; H3 ϭ intermediate low; H4 ϭ lowest anisotropy stratum). Results:For overall cerebral white matter, patients with AD had significantly lower FA than CN individuals or patients with MCI in the regions with higher baseline anisotropy (H1, H2, and H3), corresponding to long corticocortical association fibers, but not in H4, which mostly includes heterogeneously oriented fibers. Vascular risk showed significant independent effects on FA in all strata except H1, which corresponds to the genu and splenium of the corpus callosum. Similar results were found within NAWM. FA in WMH was significantly lower than NAWM across all strata but was not associated with diagnosis or vascular risk. Conclusions:Both vascular and Alzheimer disease degenerative process contribute to microstructural injury of cerebral white matter across the spectrum of cognitive ability and have different region-specific injury patterns. Neurology ® 2009;73:1722-1728 GLOSSARY AD ϭ Alzheimer disease; ANCOVA ϭ analysis of covariance; ANOVA ϭ analysis of variance; CC ϭ corpus callosum; CN ϭ cognitively normal; DTI ϭ diffusion tensor imaging; FA ϭ fractional anisotropy; MCI ϭ mild cognitive impairment; MDT ϭ minimal deformation template; MMSE ϭ Mini-Mental State Examination; NAWM ϭ normal-appearing white matter; ROI ϭ region of interest; SLF ϭ superior longitudinal fasciculus; UCD ϭ University of California, Davis; WMH ϭ white matter hyperintensities.Fractional anisotropy (FA), a quantitative measure derived from diffusion tensor imaging (DTI), sensitively reflects the microstructural integrity of white matter fibers.1 Decrease in FA of cerebral white matter is known to occur with mild cognitive impairment (MCI) and Alzheimer disease (AD), 2 as well as cognitively normal aging 3 and cerebrovascular vascular disease. 4Little is known, however, about the FA changes within white matter hyperintensities (WMH) occurring in patients with AD or MCI, even though WMH are commonly associated with MCI 5,6 and AD. 5,7 Most previous DTI studies 8-14 of patients with AD and MCI typically compared their white matter with that of cognitively normal (CN) older individuals, without proper consideration of WMH, or focused solely on normal-appearing white matter (NAWM).Moreover, the separate and independent contributions o...

We previously established a type of PEGylated islets to attenuate cellular immune reactions by immobilizing polyethylene glycol (PEG) molecules on islet surfaces, thereby synergistically reducing the dose of immunosuppressant cyclosporine A (CsA; 3 mg/kg/day) to protect transplanted islets. However, higher doses of immunosuppressants should be administered after islet transplantation due to nonspecific inflammation. This study documents that PEGylated islets can be cooperatively protected by the systemic overexpression of heme oxygenase-1 (HO-1), which has a potent cytoprotective function in preventing nonspecific inflammation during an early stage following islet transplantation. Under this scheme, the viability of PEGylated islets was improved; that is, PEG molecules could block cellular immunity and HO-1 could exert its cytoprotective property against inflammation. Interestingly, when employed with a low dose of CsA (1 mg/kg/day), a cooperative action of PEG molecules and HO-1 in immune reactions could result in the complete survival of transplanted islets for 100 days without islet function impairment. However, unmodified islets (control) were completely rejected within 2 weeks despite cotreatment with HO-1 expression and CsA. These results demonstrated that the combinatorial protocol of initial induction of HO-1 expression, followed by the daily administration of a low dose CsA after transplantation of PEGylated islets can be employed as a successful cell therapy in clinical islet transplantation.

BACKGROUND AND PURPOSE GM volume, WMH volume, and FA are each associated with cognition; however, few studies have detected whether these 3 different types of MR imaging measurements exert independent or additive effects on cognitive performance. To detect their extent of contribution to cognitive performance, we explored the independent and additive contributions of GM atrophy, white matter injury, and white matter integrity to cognition in elderly patients. MATERIALS AND METHODS Two hundred and 9 elderly patients participated in the study: 97 were CN adults, 65 had MCI, and 47 had dementia. We measured GM on T1-weighted MR imaging, WMH on FLAIR, and FA on DTI, along with psychometrically matched measures of 4 domains of cognitive performance, including semantic memory, episodic memory, executive function, and spatial abilities. RESULTS As expected, patients with dementia performed significantly more poorly in all 4 cognitive domains, whereas patients with MCI performed generally less poorly than dementia patients, though considerable overlap in performance was present across groups. GM, FA, and WMH each differed significantly between diagnostic groups and were associated with cognitive measures. In multivariate models that included all 3 MR imaging measures (GM, WMH, and FA), GM volume was the strongest determinant of cognitive performance. CONCLUSIONS These results strongly suggest that MR imaging measures of GM are more closely associated with cognitive function than WM measures across a broad range of cognitive and functional impairment.

There have been limited studies of subjective tongue function over long-term follow-up in spite of swallowing and articulation disorders are common complications of glossectomy. To assess long-term subjective swallowing and articulation function after partial glossectomy. A total of 63 patients with the mobile tongue cancer who underwent partial glossectomy without reconstruction were interviewed to score their swallowing and articulation function on a 100-point scale. The relation of this subjective scoring to the perioperative data was subjected to multivariate analysis. The mean patient age was 53·4 (19-81) years, and the mean follow-up duration was 78·9 (14-277) months. Mean swallowing and articulation function score was 87·7 ± 6·1 and 88·6 ± 5·4. Age, follow-up duration, T stage and resection volume were significantly correlated with swallowing function (P = 0·026, 0·029, 0·016, 0·002, respectively); follow-up duration was correlated with articulation function (P = 0·039). Patients who undergo partial glossectomy without reconstruction generally demonstrate good function on long-term follow-up. Subjective dysfunction was correlated with larger resection volume, older age and shorter follow-up duration.