Lancet neurology
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Review Meta Analysis
CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.
Alzheimer's disease biomarkers are important for early diagnosis in routine clinical practice and research. Three core CSF biomarkers for the diagnosis of Alzheimer's disease (Aβ42, T-tau, and P-tau) have been assessed in numerous studies, and several other Alzheimer's disease markers are emerging in the literature. However, there have been no comprehensive meta-analyses of their diagnostic performance. We systematically reviewed the literature for 15 biomarkers in both CSF and blood to assess which of these were most altered in Alzheimer's disease. ⋯ Swedish Research Council, Swedish State Support for Clinical Research, Alzheimer's Association, Knut and Alice Wallenberg Foundation, Torsten Söderberg Foundation, Alzheimer Foundation (Sweden), European Research Council, and Biomedical Research Forum.
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Movement disorders in children are causally and clinically heterogeneous and present in a challenging developmental context. Treatment options are broad ranging, from pharmacotherapy to invasive neuromodulation and experimental gene and stem cell therapies. ⋯ Identification of the most appropriate treatment is uniquely challenging in children because of the incomplete knowledge about the pathophysiology of movement disorders and their influence on normal motor development; thus, effective therapeutic options for these children remain an unmet need. It is vital to transfer the expanding knowledge of the movement disorders into the development of novel symptomatic or, ideally, disease-modifying treatments, and to assess these therapeutic strategies in appropriately designed and well done trials.
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Review
Increasing uncertainty in CNS clinical trials: the role of placebo, nocebo, and Hawthorne effects.
As modern research continues to unravel the details of the placebo phenomenon in CNS disorders, uncertainty about therapeutic outcomes in trials of treatments for several neurological conditions is growing. Advances in understanding the mechanisms of different placebo effects have emphasised the substantial challenges inherent in interpreting the results of CNS clinical trials. In the past few years, new mechanisms and concepts have emerged in the study of placebo, nocebo, and Hawthorne effects in CNS clinical trials. ⋯ Moreover, different genotypes have been shown to respond differently to placebos-eg, in studies of social anxiety, depression, and pain. Increasing recognition of these factors in the general population raises the question of whether attempts should be made to reduce placebo responses in CNS clinical trials. Both clinical trial design and medical practice could benefit from further investigation of these effects across a range of neuropsychiatric disorders.
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Genetic determinants of stroke, the leading neurological cause of death and disability, are poorly understood and have seldom been explored in the general population. Our aim was to identify additional loci for stroke by doing a meta-analysis of genome-wide association studies. ⋯ NIH, NINDS, NHMRC, CIHR, European national research institutions, Fondation Leducq.