Predictive factors of clinical response to cholinesterase inhibitors in mild and moderate Alzheimer's disease and mixed dementia: a one-year naturalistic study.

BACKGROUND: Naturalistic studies evaluate individuals in their usual way of living, presenting more "real-life" data regarding patients and their diseases. OBJECTIVE: To investigate demographic, clinical, and genetic factors that could be predictive of good response to cholinesterase inhibitors (ChEI) treatment in Alzheimer's disease (AD) and AD + cerebrovascular disease (CVD). PATIENTS AND METHODS: A total of 129 patients were diagnosed with AD or AD + CVD and with mild-to-moderate dementia. After a 12-month treatment, 97 patients completed the study. They were evaluated at baseline and after three, six, and 12 months of ChEI (donepezil or rivastigmine or galantamine) use. APOE genotype and CYP2D6 polymorphisms were determined for all of the participants. In each visit, we used cognitive, functional, mood, and behavior scales. We classified patients according to their scores in the Mini-Mental State Examination (MMSE). Good responders were defined as those scoring ≥2 in the MMSE at 12 months. RESULTS: The rate of good clinical response was 27.8%. In a longitudinal analysis, the patients with mild AD and also good responders at three months were considered to be good responders at 12 months. There was no correlation between ChEI dose, APOE and CYP2D6 polymorphisms, and the pattern of clinical response. CONCLUSION: A higher rate of good response was observed in this study compared to that in previous investigations. The pharmacogenetic aspects do not seem to have an influence in the response.

Differences in adipose tissue inflammation and oxidative status in C57BL/6 and ApoE-/- mice fed high fat diet.

Apolipoprotein E deficient (Apo E-/-) mice are more resistant to the development of obesity compared to C57BL/6 wild type mice. They also hold a high basal oxidative status due to the loss of antioxidant action of apolipoprotein E. Since obesity is also an inducer of inflammation, we studied the effect of high-fat diet on obesity and oxidative stress in C57BL/6 and Apo E-/- mice for 9 weeks. The results confirmed that Apo E-/- mice fed high-fat diet are more resistant to the increase of both body weight and adiposity compared to C57BL/6 mice. Despite this, Apo E-/- mice presented a higher basal oxidative stress that was enhanced by high-fat diet. Macrophage infiltration, macrophage forming crown-like structures and proinflammatory adipokines (interleukin 6 and tumor necrosis factor alpha) were all higher in adipose tissue from Apo E-/- compared to C57BL/6 mice, regardless of diet type. In conclusion, although Apo E-/- mice are more resistant to becoming obese, they develop more severe adipose tissue inflammation companied by its consequences.