Ventral Tegmental Area Disconnection Contributes Two Years Early to Correctly Classify Patients Converted to Alzheimer's Disease: Implications for Treatment.

BACKGROUND: Recent cross-sectional studies highlighted the loss of dopaminergic neurons in the ventral tegmental area (VTA) as an early pathophysiological event in Alzheimer's disease (AD). OBJECTIVE: In this study, we longitudinally investigated by resting-state fMRI (rs-fMRI) a cohort of patients with mild cognitive impairment (MCI) due to AD to evaluate the impact of VTA disconnection in predicting the conversion to AD. METHODS: A cohort of 35 patients with MCI due to AD were recruited and followed-up for 24 months. They underwent cognitive evaluation and rs-fMRI to assess VTA connectivity at baseline and at follow-up. RESULTS: At 24-month follow-up, 16 out of 35 patients converted to AD. Although converters and non-converters to AD did not differ in demographic and behavioral characteristics at baseline, the first group showed a significant reduction of VTA-driven connectivity in the posterior cingulate and precentral cortex. This pattern of additional disconnection in MCI-Converters compared to non-converters remained substantially unchanged at 24-month follow-up. CONCLUSION: This study reinforces the hypothesis of an early contribution of dopaminergic dysfunction to AD evolution by targeting the default-mode network. These results have potential implications for AD staging and prognosis and support new opportunities for therapeutic interventions to slow down disease progression.

Accelerated age-related decline of visual information processing in first-degree relatives of persons with schizophrenia.

A recent cross-sectional study suggested that persons with schizophrenia experience an accelerated age-related decline in performance on the Span of Apprehension task, a visual information processing paradigm. However, this study was not able to determine if such decline was primarily related to genetic loading for schizophrenia, as the decline may have been related to chronic neuroleptic use or other confounds found when studying persons with schizophrenia directly. To help address this question, the current study examined healthy first-degree relatives of persons with schizophrenia over a wide age range to investigate whether such age effects may be related to genetic loading for schizophrenia. Twenty-eight healthy first-degree relatives of persons with schizophrenia (ages 21-72) and 31 healthy controls (ages 19-75) were evaluated using the Span of Apprehension task with cross-sectional methodology. Results replicated and extended the earlier report examining persons with schizophrenia, as the data indicated a statistically significant accelerated age-related decline in performance in the relatives. While the study is limited by cross-sectional methodology, it suggests a genetically driven, age-related decline in visual information processing related to schizophrenia and informs future longitudinal studies that can more definitively address such a possibility.

The effects of mirtazapine on plasma lipid profiles in healthy subjects.

BACKGROUND: The novel antidepressant mirtazapine has been linked to elevated random plasma total cholesterol (TC) levels. The purpose of this study was to evaluate in a more controlled and precise approach the putative effects of mirtazapine on plasma lipids. METHOD: In a double-blind design, 50 healthy subjects (30 women and 20 men) were randomized to receive either mirtazapine (N = 28) or placebo (N = 22) for a 4-week period. The study was conducted from June 1997 to September 1998. The initial dose for the mirtazapine group was 15 mg daily, which was increased to 30 mg daily at the beginning of the second week. Body weight and plasma lipoprotein profiles, including TC, low-density lipoproteins (LDL), high-density lipoproteins (HDL), and triglycerides, were determined at baseline and at weekly intervals throughout the study period. RESULTS: At baseline, there were no group differences in any of the measures. There was a statistically significant increase of 2.5% in mean body weight over the course of the study in the mirtazapine group that appeared to reach a plateau at 3 weeks, while no increase was observed in the placebo group. Mirtazapine subjects also showed significantly increased TC at week 4 (p =.016) and a transient rise in triglycerides that normalized by week 4. No significant changes in any of the other lipid parameters, including HDL, LDL, and TC/HDL ratios, were observed within either group. Changes in TC were significantly and positively correlated with changes in weight (p <.01). CONCLUSION: These results suggest that while mirtazapine may be associated with increased TC, it does not increase LDL levels or affect the ratio of TC to HDL.