Progress in the Treatment of Alzheimer's Disease Is Needed - Position Statement of European Alzheimer's Disease Consortium (EADC) Investigators.

ß-amyloid-targeting antibodies represent the first generation of effective causal treatment of Alzheimer's disease (AD) and can be considered historical research milestones. Their effect sizes, side effects, implementation challenges and costs, however, have stimulated debates about their overall value. In this position statement academic clinicians of the European Alzheimer's Disease Consortium (EADC) discuss the critical relevance of introducing these new treatments in clinical care now. Given the complexity of AD it is unlikely that molecular single-target treatments will achieve substantially larger effects than those seen with current ß-amyloid-targeting antibodies. Larger effects will most likely only be achieved incrementally by continuous optimization of molecular approaches, patient selection and combinations therapies. To be successful in this regard, drug development must be informed by the use of innovative treatments in real world practice, because full understanding of all facets of novel treatments requires experience and data of real-world care beyond those of clinical trials. Regarding the antibodies under discussion we consider their effects meaningful and potential side effects manageable. We assume that the number of eventually treated patient will only be a fraction of all early AD patients due to narrow eligibility criteria and barriers of access. We strongly endorse the use of these new compound in clinical practice in selected patients with treatment documentation in registries. We understand this as a critical step in advancing the field of AD treatment, and in shaping the health care systems for the new area of molecular-targeted treatment of neurodegenerative diseases.

Default mode network and extrastriate visual resting state network in patients with Parkinson's disease dementia.

AIMS: Using fMRI, we evaluated the default mode network (DMN) and the extrastriate visual resting state network (ESV-RSN) in 14 patients with Parkinson's disease dementia (PDD) as compared with 18 patients with Parkinson's disease (PD) without dementia and 18 healthy controls (HC). METHODS: We analyzed the seed-based functional connectivity of both resting state data and deactivations during a visual complex scene-encoding task. RESULTS: Using the posterior cingulate cortex/precuneus as a seed for the DMN analysis, we observed significant decreases of connectivity in the right inferior frontal gyrus in PDD as compared to PD and HC. Using the caudate nucleus as a seed for the ESV-RSN analysis, we found significant decreases of connectivity in the left and right inferior occipital gyrus in PDD as compared to HC. CONCLUSION: Differences in functional connectivity patterns between PDD and PD/HC were observed in areas known to be engaged in stimulus-driven reorienting of attention and in visual processing.

The default mode network integrity in patients with Parkinson's disease is levodopa equivalent dose-dependent.

Disturbances in the default mode network (DMN) have been described in many neurological and psychiatric disorders including Parkinson's disease (PD). The DMN is characterized by basal activity that increases during rest or passive visual fixation and decreases ("deactivates") during cognitive tasks. The network is believed to be involved in cognitive processes. We examined the DMN in PD patients on dopaminergic medication with normal cognitive performance compared to age- and gender-matched healthy controls (HC) using fMRI and three methodological procedures: independent component analysis of resting-state data, analysis of deactivation during a complex visual scene-encoding task, and seed-based functional connectivity analysis. In the PD group, we also studied the effect of dopaminergic medication on the DMN integrity. We did not find any difference between the PD and HC groups in the DMN, but using the daily levodopa equivalent dose as a covariate, we observed an enhanced functional connectivity of the DMN in the posterior cingulate cortex and decreased activation in the left parahippocampal gyrus during the cognitive task. We conclude that dopaminergic therapy has a specific effect on both the DMN integrity and task-related brain activations in cognitively unimpaired PD patients, and these effects seem to be dose-dependent.