Amyloid Accumulation and Cognitive Decline in Clinically Normal Older Individuals: Implications for Aging and Early Alzheimer's Disease

The aberrant accumulation of the amyloid protein is a critical and early event in the Alzheimer's disease (AD) cascade. Given the early involvement of this pathological process, it is not surprising that many clinically normal (CN) older individuals demonstrate evidence of abnormal A beta at postmortem examination and in vivo using either CSF or PET imaging. Converging evidence across multiple research groups suggests that the presence of abnormal A beta among CN individuals is associated with elevated risk of future clinical impairment and cognitive decline. Amyloid positivity in conjunction with biomarkers of neuronal injury offers further insight into which CN are most at risk for short-term decline. Although in its infancy, tau PET has demonstrated early increases among A beta+ that will likely be an important indicator of risk among CN. Overall, the detection of early A beta among CN individuals has provided an important opportunity to understand the contributions of this pathology to age-related cognitive decline and to explore early intervention with disease modifying strategies.