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 5 × 7 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.

Keywords: hippocampus; interference; neurocognitive aging; pattern separation; spatial discrimination.

Figure 1

Example of the 5x7 grid (not visible to subjects) dividing the total screen space. (A) Example images during Study (incidental encoding with “Indoor” or “Outdoor” judgments) and Test (second phase with “Move” or “No Move” mnemonic judgments). (B) Diagram of a 1-Move, 2-Move, 3-Move, or 4-Move displacement relative to an object’s original location during encoding (respective decreasing of mnemonic interference). These displacements occurred vertically or horizontally. (C) Diagram of a corner displacement, the minimal amount of mnemonic interference in the MD-S task.

Figure 2

Performance on the MD-S task comparing the Young group to the Aged group. (A) Target Recognition scores. Young and Aged groups did not differ significantly, though a trend may have been present. (B) Total Lure Discrimination scores, assessed via area under the curve (AUC). (C) Lure Discrimination scores at each level of mnemonic interference. Young>Aged (*); not significant (n.s.).

Figure 3

Correlations between Lure Discrimination (AUC) and RAVLT Delayed Recall scores for Young and Aged groups. (A) RAVLT Delay was not significantly correlated with Lure Discrimination in the Young group. (B) RAVLT Delay was significantly correlated with Lure Discrimination in the Aged group. Correlations were Holm-Bonferroni corrected for multiple comparisons.

Figure 4

Performance on the MD-S task compared across the Young, Aged Unimpaired, and AI groups. (A) Target Recognition scores. (B) Total Lure Discrimination scores, assessed via area under the curve (AUC). (C) Lure Discrimination scores at each level of mnemonic interference. Statistically significant comparisons: Young>AU (†); AU>AI (‡); Young>AI (*).

Figure 5

Correlations between Lure Discrimination (AUC) and RAVLT Delayed Recall scores for Aged Unimpaired and Aged Impaired groups. (A) RAVLT Delay was significantly correlated with Lure Discrimination in the Aged Unimpaired group,(B) as well as the Aged Impaired group. Correlations were Holm-Bonferroni corrected for multiple comparisons.

Figure 6

Model of spatial discrimination ability as a function of mnemonic interference at different points along the aging continuum, based on the present data. Young adults demonstrate a linear gain in performance as interference is reduced. This gain is slowed in healthy aging (proposed to be represented by the AU subgroup), but such individuals are able to capitalize on minimal interference in a way that is comparable to young adults. Pathological aging (proposed to be represented by the AI subgroup) features a dramatic shift from performance of young adults as well as healthy aged adults, and it is unclear from the present data and that from other similar tasks whether performance never matches that of other groups, even under conditions of minimal mnemonic interference. We propose that healthy aging shows a characteristic deficit in the intermediate interference range, whereas pathological aging differs throughout the spectrum and most markedly so at minimal levels of interference.