![]() ![]() The initial silent and asymptomatic stage, referred to as preclinical AD, is characterized by a sequence of pathophysiological hallmarks that start to appear about 20 years before the onset of symptoms. As the disease progresses, the subject’s cognition changes from an initial phase where it is fully preserved to a final stage characterized by dementia. ![]() Initial diagnostic efforts focused on patients at the dementia stage of the disease and, only recently, the importance of a long pre-dementia stage, preceding the clinical onset of the disease symptoms, has been recognized. ![]() The criteria for AD diagnosis have been revised extensively, and experts agree that the hallmark pathological criteria include increased levels of amyloid-beta (Aβ) peptide, which is deposited extracellularly in diffuse and neuritic plaques, and hyperphosphorylated tau (p-tau), a microtubule assembly protein that accumulates intracellularly as neurofibrillary tangles. AD is a progressive neurodegenerative disease, irreversible and disabling, causing a large socioeconomic burden. Alzheimer’s disease (AD) is the most common form of dementia and accounts for 60–80% of cases. The prevalence of dementia worldwide is estimated to be over 45 million people and is predicted to triple by 2050 as a consequence of increased life expectancy, establishing dementia as one of the biggest global public health challenges. The growing body of research on the risk factors for AD and its preclinical stage is favouring the development of AD prevention programmes that, by delaying the onset of Alzheimer’s dementia for only a few years, would have a huge impact on public health. Finally, we summarize currently ongoing clinical trials recruiting participants with preclinical AD or a higher risk for the onset of AD-related cognitive impairment. Secondly, we review the development of public–private partnerships for disease prevention that aim to characterize the AD continuum as well as serving as platforms for secondary prevention trials. Firstly, we summarize the evidence on several AD risk factors, which are the rationale for the establishment of primary prevention programmes as well as revising current primary prevention strategies. In this manuscript, we review current strategies for AD prevention, from primary prevention strategies based on identifying risk factors and risk reduction, to secondary prevention initiatives based on the early detection of the pathophysiological hallmarks and intervention at the preclinical stage of the disease. In addition, the characterization of the long asymptomatic stage of AD is allowing the development of intervention studies and secondary prevention programmes on asymptomatic at-risk individuals, before substantial irreversible neuronal dysfunction and loss have occurred, an approach that emerges as highly relevant. Disappointing results from clinical trials performed in mild–moderate AD dementia combined with clear epidemiological evidence on AD risk factors are contributing to the development of primary prevention initiatives. Due to the progressive aging of the population, Alzheimer’s disease (AD) is becoming a healthcare burden of epidemic proportions for which there is currently no cure. ![]()
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