Alzheimer′s disease (AD) is a major public health challenge with no curative treatment at present and has become the fifth leading cause of death for urban and rural residents in China. Although diagnostic technology has made significant progress in recent years, precise identification of AD still faces certain limitations and challenges due to its heterogeneity and complex pathogenesis. It is possible to shift the paradigm and focus on the key "window" of the early stage of AD dementia to achieve breakthroughs. This article is based on MIND-CHINA (randomized controlled Multimodal INterventions to delay Dementia and disability in rural China) to discuss the etiology, prediction, risk-factors assessment, diagnosis, and intervention research of AD, in order to develop AD prediction and prevention strategies that are in line with China′s national conditions, and make a multi-perspective analysis of the current limitations and challenges on AD diagnosis and prevention to promote the future of precision medicine for AD.

Alzheimer′s disease (AD) is a major public health challenge with no curative treatment at present and has become the fifth leading cause of death for urban and rural residents in China. Although diagnostic technology has made significant progress in recent years, precise identification of AD still faces certain limitations and challenges due to its heterogeneity and complex pathogenesis. It is possible to shift the paradigm and focus on the key "window" of the early stage of AD dementia to achieve breakthroughs. This article is based on MIND-CHINA (randomized controlled Multimodal INterventions to delay Dementia and disability in rural China) to discuss the etiology, prediction, risk-factors assessment, diagnosis, and intervention research of AD, in order to develop AD prediction and prevention strategies that are in line with China′s national conditions, and make a multi-perspective analysis of the current limitations and challenges on AD diagnosis and prevention to promote the future of precision medicine for AD.

Alzheimer's disease (AD) as the most common form of dementia has been recognized as a global public health priority owing to its huge negative impact on sustainable social and economic development.Neuropathological and moleclar neuroimaging studies revealed the disparities between the load of Alzheimer pathology in the brain and the severity of cognitive symptoms,in which cognitive reserve hypothesis has been proposed to interpret this phenomenon.Indeed,epidemiological research has shown that certain intellectual factors such as early-life high education,midlife great work complexity,and leisure-time social,mental,and physical activities are frequently associated with a reduced risk of AD or dementia,possibly by increasing the cognitive reserve capacity,thus delaying the clinical onset of AD or dementia syndrome.The cognitive reserve hypothesis has been supported by neuropathological and moleclar neuroimaging studies,although its neuropathological and neurobiological mechanisms remain largely unknown.The cognitive reserve hypothesis has significant implications for interventions to delay the clinical onset of dementia or AD.Thus,we call for action in China to strengthen multidisciplinary research on cognitive reserve in AD as well as its neurobiological mechanisms.This will help develop intervention programs that are sensitive to Chinese society and clture to delay the clinical onset of AD and dementia.

As the number and proportion of aging population increase,dementia has posed tremendous challenges to the sustainable social and economic development of many countries in the world.Thus,dementia has been identified as a global public health priority.Clinically,there is currently no cure for dementia.However,in the past decades epidemiological research has suggested that cardiovascular risk factors and psychosocial factors over the life-course could significantly affect the risk of dementia occurrence later in life.Of these factors,smoking,diabetes,and midlife hypertension,obesity,and high cholesterol might contribute to the clinical onset of late-life dementia by causing cerebral macro-and microvascular damage and neurodegeneration,whereas high educational attainments in early life and social engagement,physical and mentally-stimulating activities during adulthoods might help maintain late-life cognitive function by increasing cognitive reserve.Thus,theoretically clinical onset of dementia is likely to be postponed by implementing interventions targeting these factors over the lifespan.In recent years,evidence from research in Europe and North America has emerged that multimodal interventions that consist of intensive control of cardiovascular risk factors,balanced diets,physical activity,and cognitive training may help maintain cognitive function among individuals at risk for dementia.We call that population intervention research against dementia should be strengthened in China.Identifying the intervention programmes against dementia that are effective specifically among Chinese population is of high relevance for developing the national dementia action plan,and thus effectively dealing with the huge challenges by dementia.