Visual short-term memory relates to tau and amyloid burdens in preclinical autosomal dominant Alzheimer’s disease

Abstract

Background: Over the past decade, visual short-term memory (VSTM) binding tests have been shown to be one of the most sensitive behavioral indicators of Alzheimer's disease (AD), especially when they require the binding of multiple features (e.g., color and shape). Recently, it has become possible to directly measure amyloid and tau levels in vivo via positron emission tomography (PET). To this point, these behavioral and neurochemical markers have not been compared in humans with AD or at risk for it. Methods: In a cross-sectional study, we compared VSTM performance to tau and amyloid concentrations, measured by PET, in individuals certain to develop AD by virtue of their inheritance of the presenilin-1 E280A mutation. These included 21 clinically unimpaired subjects and 7 subjects with early mild cognitive impairment (MCI), as well as 30 family members who were not carriers of the mutation. Results: We found that VSTM performance correlated strongly with tau in entorhinal cortex and inferior temporal lobe, and also with amyloid when examining asymptomatic carriers only. The condition requiring binding was not preferentially linked to tau-in fact, the non-binding "shape only" condition showed a stronger relationship. Conclusions: The results confirm VSTM's status as an early marker of AD pathology and raise interesting questions as to the course of binding-specific versus non-binding aspects of VSTM in early AD.

Local Functional MR Change Pattern and Its Association With Cognitive Function in Objectively-Defined Subtle Cognitive Decline

“…Recent studies have shown that the temporal lobe is one of the critical areas of pathological changes in multiple types of dementia (Mak et al, 2020;Sanchez et al, 2021). In preclinical AD, tau protein deposition and Aβ burden in the inferior temporal gyrus is related to cognitive performance, mainly memory function (Schultz et al, 2018;Norton et al, 2020;Scott et al, 2020;Vila-Castelar et al, 2020). Tau accumulation in this area may be associated with hippocampal hyperactivity, which is not associated with Aβ (Huijbers et al, 2019).…”

Visual short-term memory impairments in presymptomatic familial Alzheimer's disease: A longitudinal observational study

“…swap errors) were not replicated. Notably, a recent FAD study by Norton and colleagues ( Norton et al, 2020 ), found that the condition requiring conjunctive binding of colour and shape was not preferentially linked to tau (measured by positron emission tomography – PET) but rather that the non-binding “shape only” condition showed a stronger relationship. This emphasizes that much remains to be understood about VSTM binding and that group studies comparing conjunctive and relational binding over time, will provide critical data on which processes are affected, at what stage and in which order.…”

Memory Markers In The Continuum Of The Alzheimer’s Clinical Syndrome

“…The positive aspect of this is that we have for long needed tests that can detect the very early stages of the disease process, preferably, when people are unaware of or are very little concerned about any cognitive or functional impairment. We have learned that at this stage, the VSTMBT is taxing the early growth of amyloid in at risk individuals even before tau deposits or neurodegeneration become apparent [32,35,38]. Such a test would be an ideal tool for clinical trials aiming at dementia prevention as they could enhance recruitment strategies by selecting who will likely meet inclusion criteria (e.g., Aβ+).…”