Abstract
Long-term episodic memory deficits in Alzheimer's disease (AD) are well characterised but, until recently, short-term memory (STM) function has attracted far less attention. We employed a recently-developed, delayed reproduction task which requires participants to reproduce precisely the remembered location of items they had seen only seconds previously. This paradigm provides not only a continuous measure of localization error in memory, but also an index of relational binding by determining the frequency with which an object is misplaced to the location of one of the other items held in memory. Such binding errors in STM have previously been found on this task to be sensitive to medial temporal lobe (MTL) damage in focal lesion cases. Twenty individuals with pathological mutations in presenilin 1 or amyloid precursor protein genes for familial Alzheimer's disease (FAD) were tested together with 62 healthy controls. Participants were assessed using the delayed reproduction memory task, a standard neuropsychological battery and structural MRI.Overall, FAD mutation carriers were worse than controls for object identity as well as in gross localization memory performance. Moreover, they showed greater misbinding of object identity and location than healthy controls. Thus they would often mislocalize a correctly-identified item to the location of one of the other items held in memory. Significantly, asymptomatic gene carriers – who performed similarly to healthy controls on standard neuropsychological tests – had a specific impairment in object-location binding, despite intact memory for object identity and location. Consistent with the hypothesis that the hippocampus is critically involved in relational binding regardless of memory duration, decreased hippocampal volume across FAD participants was significantly associated with deficits in object-location binding but not with recall precision for object identity or localization. Object-location binding may therefore provide a sensitive cognitive biomarker for MTL dysfunction in a range of diseases including AD.
Highlights
Memory impairment is a central, defining feature of Alzheimer's disease (e.g., Dubois et al, 2007; McKhann et al, 1984)
Gross localization error was computed as the distance between the centre of the target object after it had been dragged to its remembered location and its true location in the memory array
Further analysis revealed that the familial Alzheimer's disease (FAD) group was significantly worse than controls in the longer delay condition (FAD 1⁄4 18.6% vs controls 1⁄4 10.7%, p 1⁄4 .002, t 1⁄4 3.25) but not over shorter delays (FAD 1⁄4 14.4% vs controls 1⁄4 10.6%, p 1⁄4 .13, t 1⁄4 1.54). These analyses show that overall the FAD group was significantly more likely to misbind identity and location of items, and this was detectable with just one block of trials, with the longer delay more likely to reveal greater misbinding
Summary
Memory impairment is a central, defining feature of Alzheimer's disease (e.g., Dubois et al, 2007; McKhann et al, 1984). Instead of asking participants to report whether they detect a change between sample and test arrays, they are requested to reproduce a feature of an object using a continuous, analogue response space (Bays, Catalao, & Husain, 2009; Gorgoraptis, Catalao, Bays, & Husain, 2011; Wilken & Ma, 2004) Such delayed reproduction tasks measure precision of recall and provide an index of the quality of memory representation. Pertzov et al recently introduced a delayed reproduction paradigm that measures precision of recall for ‘what was where?’ They used it to investigate the nature of WM deficits in individuals with focal medial temporal lobe (MTL) damage due to voltage-gated potassium channel antibody (VGKC-Ab) mediated limbic encephalitis (Pertzov et al, 2013) These patients showed a specific impairment in binding object identity to location but had no difficulty remembering the identities and locations on their own. Because of this practical consideration, one of our aims in this study on FAD is to establish the minimum number of trials required to demonstrate differences between cases and healthy controls
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