痴呆
医学
生物标志物
淀粉样蛋白(真菌学)
阿尔茨海默病
认知功能衰退
疾病
人口
临床试验
生物信息学
病理
生物
生物化学
环境卫生
作者
Philip Scheltens,Kaj Blennow,Monique M.B. Breteler,Bart De Strooper,Giovanni B. Frisoni,Stephen Salloway,Wiesje M. van der Flier
出处
期刊:The Lancet
[Elsevier]
日期:2016-07-01
卷期号:388 (10043): 505-517
被引量:2244
标识
DOI:10.1016/s0140-6736(15)01124-1
摘要
Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic markers. MRI and fluorodeoxyglucose PET are established imaging techniques for diagnosis of Alzheimer's disease. Amyloid PET is gaining traction in the clinical arena, but validity and cost-effectiveness remain to be established. Tau PET might offer new insights and be of great help in differential diagnosis and selection of patients for trials. In the search for understanding the disease mechanism and keys to treatment, research is moving increasingly into the earliest phase of disease. Preclinical Alzheimer's disease is defined as biomarker evidence of Alzheimer's pathological changes in cognitively healthy individuals. Patients with subjective cognitive decline have been identified as a useful population in whom to look for preclinical Alzheimer's disease. Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients and moderately positive interim results for lowering amyloid in pre-dementia Alzheimer's disease suggest that, ultimately, there will be a future in which specific anti-Alzheimer's therapy will be combined with lifestyle interventions targeting general brain health to jointly combat the disease. In this Seminar, we discuss the main developments in Alzheimer's research.
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