Cognitive changes of older adults with an equivocal amyloid load.

ABSTRACT

BACKGROUND: Observational and interventional studies addressing the link between amyloid (Aß) burden and cognitive decline are increasing, but a clear definition of amyloid positivity is still lacking. This may represent a great stake for therapeutic studies enrolling Aß + patients only. The main objective of this study was to define a population with "equivocal" amyloid status, and evaluate their cognitive changes. METHODS: Sixty-five participants over 75 years old, from the Control group of the interventional MAPT study, at risk to develop Alzheimer's disease, were included. Participants were classified into three groups in terms of amyloid load Aß +, Aß - and Equivocal participants (according to visual reading, global standardized uptake (SUVR) cut-offs, or a k-mean clustering method). The cognitive changes over time (memory, executive functions, attention and processing speed) of this Equivocal group were then compared to Aß + and Aß - participants. RESULTS: When classified by visual read, Equivocal participants' memory scores were comparable to the Aß- participants, and greater than in Aß + participants over time. Secondary analyses, using SUVR cut-offs classification, showed different trajectories with Equivocal participants being comparable to the Aß + participants, and lower than Aß-, on executive performance over time. CONCLUSIONS: This original work pointed out a population that may be of great interest for interventional studies, raising the question of how amyloid status should be defined and integrated in such studies. These findings should be replicated in future studies on larger datasets, to confirm what methodological approach would be the most suitable to highlight this specific neuroimaging entity.