Translating Visual Short-Term Memory Binding Tasks to Clinical Practice: From Theory to Practice

INTRODUCTION ’s disease (AD) is the most common form of neurodegenerative dementia, accounting 2/3 of all dementia cases and currently recognized as a global public health challenge. In 2015, 46.8million people were estimated to have dementia, and this number is expected to almost double 20 years reaching 75 million in 2030 and 131.5 million in 2050 (1). Early detection may offer best chance of therapeutic success amid these raising numbers. is now recognized that a preclinical period may precede the symptomatic phase up to 25 years (2). The development of suitable behavioral markers to detect and track this stage is important, more expensive and invasive biomarkers are used. One important line of AD research in last decade has provided evidence that the ability to bind object features together in short-term (STM) is affected in AD even at asymptomatic stages (3, 4). In cognition, binding is the that supports the integration of multiple elements together (5–7). in clinical psychology is the Memory Binding Test (MBT), which assesses the binding of category cue (e.g., flower) to a word target [e.g., tulip; see (8) for detail on test] (9–11). However, verbal nature causes susceptibility to semantic interference and cognitive reserve [CR; the ability find alternative ways of performing a task, bypassing any deficits (12, 13)]. Instead, visual shortterm (VSTM) binding relies on the integration of visual features and is less susceptible semantic and verbal strategies. The focus of this article will be on binding of visual information short time scales. Yet, before we tackle this in more depth, it is relevant to define a series terms. clinical practice, “prodromal” is usually the period immediately preceding the onset of , when patients might meet criteria for mild cognitive impairment (MCI) (14) and “preclinical” generally refers to the stage preceding this, before the onset of the clinical phenotype. , the term “preclinical AD” will be restricted to asymptomatic familial Alzheimer’s disease (FAD)—a rare autosomal dominantly inherited variant of Alzheimer’s and clinically healthy (at time of testing) who, over time, developed AD dementia. We will provide brief reasoning for assessing VSTMbinding in AD and a summary of the research lines in the . In the context of clinical practice, we will also reflect on its use for the differential diagnosis of and as a tool for preclinical AD.