Familiarity-based memory as an early cognitive marker of preclinical and prodromal AD

Abstract

There is great interest in the development of cognitive markers that differentiate “normal” age-associated cognitive change from that of Alzheimer's disease (AD) in its prodromal (i.e., mild cognitive impairment; MCI) or even preclinical stages. Dual process models posit that recognition memory is supported by the dissociable processes of recollection and familiarity. Familiarity-based memory has generally been considered to be spared during normal aging, but it remains controversial whether this type of memory is impaired in early AD. Here, we describe findings of estimates of recollection and familiarity in young adults (YA), cognitively normal older adults (CN), and patients with amnestic-MCI (a-MCI). These measures in the CN and a-MCI patients were then related to a structural imaging biomarker of AD that has previously been demonstrated to be sensitive to preclinical and prodromal AD, the Cortical Signature of AD (ADsig). Consistent with much work in the literature, recollection, but not familiarity, was impaired in CN versus YA. Replicating our prior findings, a-MCI patients displayed impairment in both familiarity and recollection. Finally, the familiarity measure was correlated with the ADsig biomarker across the CN and a-MCI group, as well as within the CN adults alone. No other standard psychometric measure was as highly associated with the ADsig, suggesting that familiarity may be a sensitive biomarker of AD-specific brain changes in preclinical and prodromal AD and that it may offer a qualitatively distinct measure of early AD memory impairment relative to normal age-associated change.

The effects of healthy aging, amnestic mild cognitive impairment, and Alzheimer's disease on recollection, familiarity and false recognition, estimated by an associative process-dissociation recognition procedure

“…In AD patients, both recollection and familiarity were affected (Schoemaker et al, 2014). Based on these results, some authors defend the idea of also using familiarity deficits as early markers of cognitive impairment (see, e.g., Koen and Yonelinas (2014) and Wolk et al (2008Wolk et al ( , 2013). …”

“…Our idea stems from recent studies by Cohn, Emrich and Moscovitch (2008), Wolk et al (2008; exp. 1) and Wolk et al (2013), who used the associative recognition procedure as an method for estimating both recollection and familiarity, following the logic of the PD procedure (Yonelinas and Jacoby (2012), for a recent review), given that the intact and rearranged pairs can be understood as the inclusion and exclusion conditions of the PD procedure, respectively. Based on the rate of "old" responses for intact and rearranged pairs, independent estimates of recollection (R) and familiarity (F) can be calculated based on the following (Wolk et al, 2008(Wolk et al, , 2013 ( ) ( ) = -R probability intact probability rearranged ; ( )( ) = − F probability rearranged / 1 R .…”

“…To account for differences between samples in their base rates of false alarms ("old" responses to new pairs -FAN-), familiarity should be corrected by subtracting each participant's FAN from his or her initial familiarity estimate and expressing the difference in terms of a discrimination measure (d′) derived from signal detection theory (Cohn et al, 2008;Wolk et al, 2008Wolk et al, , 2013.…”

Mémoire épisodique dans la maladie d’Alzheimer

“…En revanche, pour ce qui est de la familiarité, certaines études apportent des données en faveur de sa préservation dans les stades légers et modérés de la maladie d'Alzheimer [7,[9][10][11], alors que d'autres suggèrent une altération très précoce [12,13]. Ce manque de consensus peut s'expliquer, au moins en partie, par des différences méthodologiques entre les études.…”

“…L'acceptation d'une paire intacte, en revanche, peut soit être sous-tendue par le rappel conscient de l'association, soit par un sentiment de familiarité vis-à-vis de chacun des deux items. La plupart des études ayant utilisé ce paradigme ont rapporté une altération de la familiarité et de la remémoration consciente dans le trouble cognitif léger amnésique [25] ou dans la maladie d'Alzheimer [12,27]. À l'inverse, Genon et al [11] ont rapporté une altération de la remé-moration consciente associée à une préservation de la familiarité chez des sujets atteints d'une forme légère de maladie d'Alzheimer.…”