https://link.springer.com/article/10.14283/jfa.2020.9

Early detection is critical in our fight to stop or slow Alzheimer’s dementia, and even more so to prevent Alzheimer’s disease (AD). Current diagnosis of Alzheimer’s dementia relies largely on documenting mental decline, at which point, severe cognitive and functional damage has occurred. According to the National Institute on Aging and Alzheimer’s Association Research Framework, Alzheimer’s disease is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct (1). The “Framework” is based on research that confirms Alzheimer’s disease pathologic changes in the brain begin 15-20 years before the development of symptoms (2). The neuropathologic hallmarks of AD include: amyloid plaques, neurofibrillary tangles (NFTs), Glial responses, and synaptic and neuronal loss. This approach enables a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people. It is hypothesized that during the preclinical period, 10-15 years prior to severe symptoms where fibrillar brain amyloid increases with minimal impact on cognition, that disease-modifying therapy can be most effective (3).