Alzheimer’s disease (AD) remains the only leading cause of death for which no disease-modifying treatment exists, and age is by far the greatest risk factor. It is now estimated that 1/3 of older individuals in the U.S. will die with dementia, largely due to AD. Our findings, convergent with reports from autopsy cohorts, CSF and other PET amyloid imaging studies, indicate that a similar proportion of 1/3 of clinically normal (CN) older individuals harbor evidence of amyloid-β (Aβ) accumulation, one of the hallmark pathologies of AD.

It remains unknown whether the majority of these Aβ+ CN will progress to the symptomatic stages of AD and over what time frame; however, the accumulated longitudinal data suggests that many of these individuals are indeed in the “preclinical stages of AD” and are at increased risk for cognitive decline. The challenge is that Aβ is only one piece of the puzzle, and our findings thus far support the hypothesis that evidence of Aβ is necessary, but not sufficient in isolation, to predict imminent decline along the AD trajectory. 

Through the Harvard Aging Brain Study (HABS), we are continuing our quest to both identify which markers, and likely the combination these markers, that will more accurately predict the emergence of clinical symptoms and the rate of subsequent decline at the individual level. The overall goal of HABS is to elucidate the earliest changes in molecular, functional and structural imaging markers that signal the transition from normal cognition to progressive cognitive decline along the trajectory of preclinical Alzheimer's Disease.



Find out more about the A4 clinical trial.