Approved Research

Exploring the complex interplay between lifestyle factors, brain pathology, and cognitive reserve in cognitive decline and dementia

Lay summary

In 2015, ~47 million people worldwide were affected by dementia disorders, and the cost was estimated at $818 billion. Because of its huge societal costs and serious threats to social care systems in almost all countries in the world, dementia has been recognized by World Health Organization (WHO) as a global public health priority. Given the facts that there is no cure neither a disease-modifying therapy available for Alzheimer's Disease (AD), developing effective strategies for primary and secondary prevention becomes crucial. To achieve this goal, it is essential to identify modifiable risk and protective factors for dementia, and to discern the specific disease processes or mechanisms leading to dementia.

In the past decade, neuroepidemiology and clinical studies have suggested the link of major modifiable lifestyle or cardiometabolic risk factors with cognitive decline and dementia is largely mediated by cerebrovascular disease, especially with regards to cerebral small vessel disease and the gene-environment interaction is known to play a critical role in cognitive impairment and dementia. However, the detailed mechanisms as well as the intricate effects of lifestyle factors, various brain pathologies, and cognitive reserve on cognitive decline and dementia are not yet explored.

The current 3-year project aims to (1) develop quantitative approaches for assessing cognitive reserve capacity over the lifespan, (2) elucidate the interplay between lifestyle factors, brain pathology, and cognitive reserve in determining late-life cognitive phenotypes, and (3) assess the diagnostic role of neuroimaging markers of various brain pathologies in differentiating mild cognitive impairment (MCI) subtypes (e.g., amnestic vs. non-amnestic MCI) and dementia (e.g., Alzheimer's vs. vascular dementia).

Owing to its huge societal and economic burden, dementia was recognized in 2012 by WHO as a global public health priority. Findings from our project will facilitate the development of intervention strategies against dementia, which will help decrease the risk or delay the onset of dementia, and thus will not only reduce its economic and societal costs, but also help achieve a longer and healthier life in aging societies.