Salient Cognitive Paradigms to Assess Preclinical Alzheimer's Disease

Despite the growing emphasis to identify early biological markers that can detect the progressive accumulation of brain pathology in the complex pathophysiologic cascade that occurs in Alzheimer's disease (AD), we continue to employ the same neuropsychological paradigms that were developed to detect dementia or frank cognitive impairment. It has become increasingly clear that we cannot expect to measure clinically meaningful change in relationship to these emerging preclinical biomarkers using these traditional cognitive assessment paradigms, nor will we advance the efforts to identify the earliest cognitive changes that emerge in AD. Over the last decade, a few novel promising cognitive assessment paradigms have emerged that have shown promise in identifying subtle cognitive deficits in AD which aids in early detection and monitoring of meaningful cognitive change over time. Some of these cognitive assessment paradigms are reviewed here, including semantic interference, semantic intrusion errors, memory binding, and binding of face and name associations. These paradigms may be useful for AD clinical trials focused on secondary prevention if there is sufficient rigor to suggest that they correlate with AD biomarkers, having robust sensitivity, specificity, and predictive utility among culturally and linguistically diverse populations at-risk for AD.