Exploring the Association between Amyloid-β and Memory Markers for Alzheimer’s Disease in Cognitively Unimpaired Older Adults

Background Memory tests vary in their sensitivity for detection of pre-symptomatic Alzheimer’s disease (AD). The Visual Short-Term Memory Binding Test (VSTMBT) identifies AD-related performance deficits in older adults who are otherwise cognitively unimpaired. Objective We investigated the association of this psychometric measure with brain amyloidosis and atrophy. Design Cross-sectional mixed and correlational. Setting Cognitive Reserve Study from Columbia University. Participants a sample of 39 cognitively unimpaired older adults (Age: M=65.3, SD=3.07) was obtained from the above study. Measurements Extensive neuropsychological and neuroimaging (MRI and amyloid-β PET) assessments were carried out. Results Performance on the VSTMBT allowed us to split the sample into Low Binding Cost (LBC, N=21) and High Binding Cost (HBC, N=18). Groups were matched according to age [p=0.702], years of education [0.071], and sex [p=0.291]. HBC’s performance was comparable to that seen in symptomatic AD. Groups only differed in their amyloid-β deposition on PET in regions of the right ventral stream linked to visual cognition and affected early in AD pathogenesis (lateral-occipital cortex, p = 0.008; fusiform gyrus, p = 0.017; and entorhinal cortex, p = 0.046). Other regions known to be linked to low-level visual integration function also revealed increased amyloid-β deposition in HBC. Conclusions VSTMB deficits are associated with neuropathogenesis (i.e., amyloid-β deposition) in the earliest affected regions in pre-symptomatic AD. The VSTMB test holds potential for the identification of cognitively unimpaired older adults with very early AD pathogenesis and may thus be a useful tool for early intervention trials or other forms of clinical research.