An increase in the protein level of the AChE-R variant corresponded to a high AChE inhibition in CSF and favored less cognitive deterioration.

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Abstract. Uddén J, Björntorp P, Arner P, Barkeling B, Meurling L, Rössner S (Karolinska Institute at Huddinge University Hospital, Stockholm, Sweden; and Sahlgren's Hospital, Gothenburg, Sweden). Effects of glucocorticoids on leptin levels and eating behaviour in women. J Intern Med 2003; 253: 225-231.Objective. Long-term treatment with glucocorticoids induces weight gain and increased risk to develop obesity-related metabolic complications. The underlying mechanisms are not fully understood. Glucocorticoid therapy has previously been associated with increased levels of circulating leptin. In this study the eating behaviour was therefore studied in relation to leptin levels before and after shortterm prednisolone treatment. Design. Within-subject design. Subjects. Twelve healthy postmenopausal women with a mean body mass index (BMI) of 28.9 kg m )2 (±0.8 SEM) volunteered after recruitment by an advertisement in the local paper. Interventions. The subjects received 25 mg prednisolone daily for 7 days. Main outcome measurements. Fasting serum samples were obtained before, during and after treatment for determination of leptin and insulin, glucose and fractionated lipoproteins in plasma. The microstructure of the eating behaviour was registered with a universal eating monitor, VIKTOR. Appetite was estimated by visual analogue rating scales and food intake by a 48-h recall. Results. Serum leptin increased after 2 and 7 days of glucocorticoid administration (P < 0.01), and the food intake measured by VIKTOR after 7 days of treatment (P < 0.05). No statistically significant changes were however, found in the 48-h foodrecall or in the subjective appetite registrations. Insulin levels were borderline elevated (P ¼ 0.062) after treatment, but no significant changes of fasting glucose were seen. High density lipoprotein cholesterol (HDL) increased (P < 0.05), whilst low density lipoprotein cholesterol (LDL) decreased (P < 0.05). Conclusion. Food intake was elevated after glucocorticoid administration as observed with an objective, quantitative method, in spite of increased levels of circulating leptin.

A proportion of Alzheimer’s disease (AD) patients treated for several months with cholinesterase (ChE) inhibitors have shown some favorable response on cognition, but the characteristics of the responders are still unclear. This study attempts to identify the characteristics of individuals with a positive behavioral response after a double-blind randomized administration of a single oral dose of tacrine (40 mg) and placebo to AD patients. Furthermore, the relationship between single-dose and long-term responders are examined. Twenty-four mildly to very mildly demented AD patients participated in the study. They all fulfilled the diagnosis of probable AD according to NINCDS-ADRDA criteria. Active treatment (tacrine 40 mg) and placebo was administered in random order on 2 consecutive days, and the effects were evaluated within 2 h using neuropsychological tests (assessing visuospatial ability, episodic memory and attention), registration of EEG activity and measurement of red blood cells (RBC) acetylcholinesterase (AChE), ChE activity and concentrations of tacrine and its metabolites in plasma. Results demonstrated significant improvement, tacrine compared to placebo, in measures of attention, but not in episodic memory or visuospatial ability. A single-dose response was therefore defined in terms of improvement in attention. The tacrine plasma concentration (pcTHA) showed a positively skewed distribution (mean ± SD: 10.5 ± 11.8, range: 1.0–51.8 ng/ml). There were no significant differences between single-dose responders compared to nonresponders in pcTHA, metabolites of tacrine, inhibition of AChE in RBC, tau levels in CSF, AChE activity in CSF or plasma and demographic variables. However, single-dose responders showed a higher right frontal alpha/theta ratio on EEG and had lower glucose metabolism in the parietal-temporal association cortex at baseline. In addition, the frequency of apolipoprotein E (APOE) Ε4 alleles was higher in responders. Interestingly, the single-dose response was related to the long-term response, although not significantly, which probably was due to lack of power. To conclude, the present study identified single-dose responders in terms of improved attentional performance associated with a relatively higher alpha/theta activity in the right frontal regions of the brain measured on EEG and predominance of APOE Ε4 allele.