BackgroundAlzheimer’s disease (AD) is the most common form of dementia and patients often have visual disorders. Mild cognitive impairment (MCI) is characterized by a memory deficit when compared with those of a similar age and education level which could indicate an earlier onset of AD. The aim of this study is to measure the changes of the retinal nerve fiber layer (RNFL) thickness of AD and MCI patients in comparison with the normal age controls.MethodsThe RNFL thickness was assessed using optical coherence tomography (OCT) in patients with MCI, AD (mild, moderate and severe) and the age matched controls.ResultsThe thickness of RNFL in the superior quadrant and total mean values are gradually and significantly decreased from MCI to severe AD when compared to that in the controls. There is also a significant reduction of the retinal nerve fiber layer in the inferior quadrant in severe AD patients.ConclusionsOur data indicate that the retinal nerve fiber layer degeneration is paralleled with dementia progression. Owing to its non-invasive and cost effective nature, monitoring RNFL thickness may have a value in assessing disease progression and the efficacy of any treatments.

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Treatment of adult Philadelphia chromosome-positive lymphocytic leukemia is rarely successful. We report here the effects of TZD18, a novel dual ligand specific for peroxisome proliferatoractivated receptor ␣ and ␥ (PPAR␣/␥) on Ph ؉ lymphocytic leukemia cell lines BV173, SD1, and SupB-15. Exposure of these cells to TZD18 resulted in growth inhibition in a dose-and time-dependent manner that was associated with G 1 cell cycle arrest. This effect was much stronger than that mediated by the PPAR␥ ligand pioglitazone (PGZ), which also belongs to the thiazolidinediones (TZD) class of ligands. However, it may not be mediated through PPAR␥ or PPAR␣ activation because antagonists of PPAR␥ and PPAR␣ cannot reverse it. Study of the key regulators of cell cycle progression by Western blot analysis showed that the expression of the cyclin-dependent kinase inhibitor (CDKI) p27 kip1 , but not that of p21 cip1 , was enhanced, whereas that of c-Myc, cyclin E, cyclin D2, and cyclindependent kinases 2 and 4 (CDK-2 and CDK-4) was decreased when these cells were treated with TZD18 (10 or 20 M). Therefore, the up-regulation of p27 kip1 and the down-regulation of CDK-2 and CDK-4 may, at least in part, account for the G 1 cell cycle arrest. Furthermore, a remarkable induction of apoptosis was observed in the cells treated with this dual ligand.No obvious alteration of bcl-2 protein level occurred, but bax was up-regulated in these TZD18-treated cells. Activation of caspase 8 and caspase 9 by TZD18 was also observed. Importantly, NF-B DNAbinding activity was markedly decreased by the TZD18 treatment. In addition, TZD18 enhanced the growth inhibitory effect of imatinib, a specific tyrosine kinase inhibitor therapeutically used in the treatment of Ph ؉ leukemia. Overall, our findings strongly suggest that TZD18 may offer a new therapeutic approach to aid in the treatment of Ph ؉ lymphocytic leukemia. IntroductionAlthough significant progress has been made in the treatment of acute lymphocytic leukemia (ALL), the prognosis for patients with Philadelphia chromosome-positive (Ph ϩ )/Bcr-Abl ϩ adult ALL is still very poor. After first remission, allogeneic stem cell transplantation is the treatment of choice. However, most patients are not eligible for this therapy because of advanced age or lack of a suitable stem cell donor (for reviews, see Redaelli et al 1 and Bassan et al 2 ). Imatinib (Gleevec, previously known as STI571 and CGP57148), the selective tyrosine kinase inhibitor, displayed pronounced antileukemic activity in Ph ϩ chronic myeloid leukemia (CML) and ALL. It is used after allogeneic stem cell transplantation and is recommended for relapsed or refractory Ph ϩ ALL as salvage therapy to facilitate subsequent transplantation. 3 However, quick emergence of resistance to this agent is a major problem in the treatment of patients with Ph ϩ leukemia. Another major obstacle to imatinib-based therapies is the persistence of Ph ϩ cells despite the application of imatinib. Based on these arguments, the development of novel therapeutic a...