| Summary: | Dementia, particularly Alzheimer’s disease (AD), is a growing pandemic that presents profound challenges to healthcare systems, families, and societies throughout the world. By 2050, the number of people living with dementia worldwide could almost triple, from 47 to 132 million, with associated costs rising to $3 trillion. To reduce the future incidence of dementia, there is an immediate need for interventions that target the disease process from its earliest stages. Research programs are increasingly starting to focus on midlife as a critical period for the beginning of AD-related pathology, yet the indicators of the incipient disease process in asymptomatic individuals remain poorly understood. We address this important knowledge gap by examining evidence for cognitive and structural brain changes that may differentiate, from midlife, healthy aging and pathological AD-related processes. This review crystallizes emerging trends for divergence between the two and highlights current limitations and opportunities for future research in this area.
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