Pattern separation and pattern completion in Alzheimer's disease: evidence of rapid forgetting in amnestic mild cognitive impairment

Abstract

Over the past four decades, the characterization of memory loss associated with Alzheimer's disease (AD) has been extensively debated. Recent iterations have focused on disordered encoding versus rapid forgetting. To address this issue, we used a behavioral pattern separation task to assess the ability of the hippocampus to create and maintain distinct and orthogonalized visual memory representations in patients with amnestic mild cognitive impairment (aMCI) and mild AD. We specifically used a lag-based continuous recognition paradigm to determine whether patients with aMCI and mild AD fail to encode visual memory representations or whether these patients properly encode representations that are rapidly forgotten. Consistent with the rapid forgetting hypothesis of AD, we found that patients with aMCI demonstrated decreasing pattern separation rates as the lag of interfering objects increased. In contrast, patients with AD demonstrated consistently poor pattern separation rates across three increasingly longer lags. We propose a continuum that reflects underlying hippocampal neuropathology whereby patients with aMCI are able to properly encode information into memory but rapidly lose these memory representations, and patients with AD, who have extensive hippocampal and parahippocampal damage, cannot properly encode information in distinct, orthogonal representations. Our results also revealed that whereas patients with aMCI demonstrated similar behavioral pattern completion rates to healthy older adults, patients with AD showed lower pattern completion rates when we corrected for response bias. Finally, these behavioral pattern separation and pattern completion results are discussed in terms of the dual process model of recognition memory.

Keywords: encoding; familiarity; hippocampus; recognition memory; recollection.

FIGURE 1

An example schematic of the experimental procedure. The trial sequence moves from left to right, with an example of a lure item at Lag 4 and a repeated item at Lag 12. The gray boxes signify lure pairs, the black boxes signify repeated pairs, and the white boxes signify novel items. The correct answer to each example picture appears below the item. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

FIGURE 2

Bias-corrected pattern separation rates for all three groups at each lag.

FIGURE 3

Pattern completion rates for all three groups at each lag.

FIGURE 4

Receiver operating characteristic (ROC) curves. Area under the curve (AUC) discriminability of pattern separation task at Lag 4 between patients with AD and patients with aMCI. Area under the curve (AUC) discriminability of pattern separation task at Lag 40 between patients with aMCI and healthy older adults. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

FIGURE 5

Pattern separation/pattern completion ratios collapsed across the three lags.