Spatial discrimination deficits as a function of mnemonic interference in aged adults with and without memory impairment

Abstract

It is well established that aging is associated with declines in episodic memory. In recent years, an emphasis has emerged on the development of behavioral tasks and the identification of biomarkers that are predictive of cognitive decline in healthy as well as pathological aging. Here, we describe a memory task designed to assess the accuracy of discrimination ability for the locations of objects. Object locations were initially encoded incidentally, and appeared in a single space against a 5x7 grid. During retrieval, subjects viewed repeated object-location pairings, displacements of 1, 2, 3, or 4 grid spaces, and maximal corner-to-opposite-corner displacements. Subjects were tasked with judging objects in this second viewing as having retained their original location, or having moved. Performance on a task such as this is thought to rely on the capacity of the individual to perform hippocampus-mediated pattern separation. We report a performance deficit associated with a physically healthy aged group compared to young adults specific to trials with low mnemonic interference. Additionally, for aged adults, performance on the task was correlated with performance on the delayed recall portion of the Rey Auditory Verbal Learning Test (RAVLT), a neuropsychological test sensitive to hippocampal dysfunction. In line with prior work, dividing the aged group into unimpaired and impaired subgroups based on RAVLT Delayed Recall scores yielded clearly distinguishable patterns of performance, with the former subgroup performing comparably to young adults, and the latter subgroup showing generally impaired memory performance even with minimal interference. This study builds on existing tasks used in the field, and contributes a novel paradigm for differentiation of healthy from possible pathological aging, and may thus provide an avenue for early detection of age-related cognitive decline.

Discrimination performance in aging is vulnerable to interference and dissociable from spatial memory

“…First, a majority of aged rats were impaired on spatial discriminations in which the distance between target and foil locations was ,88 cm. These data support an emerging consensus in the field of cognitive aging that age-associated discrimination deficits in humans and animal models are observed when the test stimuli are similar or share common features (Stark et al 2010(Stark et al , 2013Burke et al 2011;Yassa et al 2011a,b;Ryan et al 2012;Holden et al 2013;Reagh et al 2014Reagh et al , 2016. Moreover, the observation that a subset of aged rats were Figure 5.…”

“…In support of this interpretation, discrimination abilities are impaired in healthy aged humans (Toner et al 2009;Stark et al 2010Stark et al , 2013Holden et al 2012Holden et al , 2013Ryan et al 2012;Reagh et al 2014Reagh et al , 2016, monkeys (Burke et al 2011), and rats (Burke et al 2010(Burke et al , 2011). An intriguing aspect of these deficits is that older adults who do not show episodic memory loss can be impaired relative to young adults at difficult discriminations between similar stimuli, but not easy discriminations between unique stimuli (Stark et al 2013;Reagh et al 2014Reagh et al , 2016. This observation suggests that age-related discrimination deficits could precede broader episodic memory decline.…”

“…Both spatial memory and spatial discrimination require intact hippocampal function (Schenk and Morris 1985;Xavier et al 1999;Gilbert et al 1998Gilbert et al , 2001Gilbert and Kesner 2006;Morris et al 2012), and age-related differences in hippocampal-dependent memory function have recently been linked to differences in discrimination abilities in humans (Stark et al 2013;Reagh et al 2014Reagh et al , 2016, as well as in rats (LaSarge et al 2007). We therefore sought to determine whether spatial memory performance on the water maze task was correlated with spatial discrimination performance across our cohort of young and aged rats.…”

Positivity effect specific to older adults with subclinical memory impairment

“…We then performed a median split, in which participants were divided based on their delayed recall performance on the RAVLT into AU (N ¼ 16, 11 female; mean age 75.7 + 3.9 SD, range ¼ 68-83, RAVLT score ≥12) and AI (N ¼ 16, 10 female; mean age 73.8 + 4.8 SD, range ¼ 63 -81, RAVLT score ≤11). This method of splitting groups into AU and AI has been used previously (Stark et al 2013;Reagh et al 2014Reagh et al , 2015 and is in line with studies that show no differences between AU and young norms, while the AI group differs significantly from the young (Gallagher et al 1993;Stark et al 2010). Importantly, the AI group did not present with memory complaints, nor did they present with memory deficits sufficient for a diagnosis of clinical impairment.…”

Object and spatial mnemonic interference differentially engage lateral and medial entorhinal cortex in humans

“…S1A), and judged each object as belonging indoors or outdoors and left or right relative to the center of the screen. This spatial grid paradigm has been used by our laboratory to index resolution of spatial interference in young and aged adult humans (32). In the subsequent retrieval phase, subjects were presented with four trial types: repeated images (same object in the same location), object lures (similar object in the original object's location), spatial lures (same object in a different location), and completely novel foil images (Fig.…”