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Clinical Alzheimer’s disease (AD) trials currently face a critical shortfall of thousands of eligible participants, which inflates the duration and cost of the clinical study as well as threatens the scientific merit of promising clinical interventions. This recruitment crisis is further compounded by the fact that underrepresented and marginalized populations—particularly those identifying as a racial or ethnic minority, those with low socioeconomic status, or living in rural areas—have been historically underrepresented in ongoing AD clinical trials despite overwhelming evidence that such populations are at increased risk for developing dementia. As a result of various recruitment barriers, current AD clinical studies frequently reflect a decreasingly representative segment of the US population, which threatens the overall generalizability of these findings. The current narrative review provides an updated examination and critique of common recruitment barriers and potential solutions, as well as a discussion of theoretical approaches that may address barriers disproportionately experienced by underrepresented communities. AD clinical researchers are encouraged to take purposive action aimed at increasing diversity of enrolled AD clinical trial cohorts by actively identifying and quantifying barriers to research participation—especially recruitment barriers and health disparities that disproportionately prevent underrepresented and marginalized populations from participating in research. Furthermore, researchers are encouraged to closely track which individuals who express interest in AD research ultimately enroll in research studies to examine whether AD research participation is appropriately representative of the intended population for whom these new and novel AD interventions are being designed.

We examined baseline and longitudinal associations between plasma neurofilament light (NfL) and total tau (t-tau), and the clinical presentation of Alzheimer's disease (AD). A total of 579 participants (238, normal cognition [NC]; 185, mild cognitive impairment [MCI]; 156, AD dementia) had baseline blood draws; 82% had follow-up evaluations. Plasma samples were analyzed for NfL and t-tau using Simoa technology. Baseline plasma NfL was higher in AD dementia than MCI (standardized mean difference = 0.55, 95% CI: 0.37–0.73) and NC (standardized mean difference = 0.68, 95% CI: 0.49–0.88), corresponded to Clinical Dementia Rating scores (OR = 1.94, 95% CI: 1.35–2.79]), and correlated with all neuropsychological tests (r's = 0.13–0.42). Longitudinally, NfL did not predict diagnostic conversion but predicted decline on 3/10 neuropsychological tests. Baseline plasma t-tau was higher in AD dementia than NC with a small effect (standardized mean difference = 0.33, 95% CI: 0.10–0.57) but not MCI. t-tau did not statistically significant predict any longitudinal outcomes. Plasma NfL may be useful for the detection of AD dementia and monitoring of disease progression. In contrast, there was minimal evidence in support of plasma t-tau.

OBJECTIVE The imagination inflation effect is a type of memory distortion defined as an increased tendency to falsely remember that an item has been seen, or an action has been performed, when it has only been imagined. For patients with very mild Alzheimer's disease (AD), susceptibility to the imagination inflation effect could have significant functional consequences in daily life. METHOD We assessed whether patients with very mild AD were more or less susceptible to the imagination inflation effect when compared with healthy older adults. In the first session, participants were read an action statement such as "fill the pillbox" and engaged in 1 of 3 activities: listened to the statement being read, performed the action, or imagined performing the action. During the second session, participants imagined action statements from the first session, as well as new action statements. During the recognition test, participants were asked to determine whether action statements were or were not performed during the first session. RESULTS We found that imagining performing actions increased the tendency of patients with very mild AD to falsely recall the action as having been performed to an extent similar to that of healthy older adults. CONCLUSION We concluded that, similar to healthy older adults, patients with very mild AD were susceptible to the imagination inflation effect, which we attributed to difficulties with source monitoring and reliance on familiarity.

Much research has documented the costs to memory from Alzheimer’s disease (AD). Individuals with AD are less likely than age- and education-matched controls to recognize or recall previously encountered events (Budson, Wolk, Chong, & Waring, 2006). AD patients also show difficulty remembering source information – specific information about the exact circumstances under which an event was encountered (e.g., Johnson, Hastroudi & Lindsay, 1993). They are less able than controls to remember: (a) whether an item was previously seen or imagined (e.g., Dalla Barba et al., 1999), (b) whether a sentence was completed by oneself or by another (e.g., Multhaup & Balota, 1997), (c) whether words had been previously presented in a red or green color (Tendolkar et al., 1999), (d) whether a fact was said by a man or a woman (Mitchell, Sullivan, Schacter, & Budson, 2006), (e) whether a word was presented during one task or another (Pierce, Sullivan, Schacter, & Budson, 2005; Pierce, Waring, Schacter, & Budson, 2008), (f) whether an item was presented during the study or test session (Budson, Dodson, Daffner, & Schacter, 2005), and (g) source information outside of the laboratory (Budson et al., 2004; Budson, Simons, Waring, Sullivan, Hussion, & Schacter, 2007; see Souchay & Moulin, 2009, for a review). Although the memory deficit from AD is increasingly clear, what is not clear is the extent to which AD patients are aware of this memory deficit. In other words, how well can AD patients monitor and judge the likely accuracy of memories? To foreshadow our results, this paper shows that AD patients are strikingly unaware of the accuracy of their memories. Even when their recognition performance is comparable to that of an older control group, AD patients are unable to distinguish between correct and incorrect recognition responses. Reliably monitoring one’s memory is critically important for knowing how much to trust a particular memory. One problem in particular that patients with AD experience is a high percentage of false memories, both in the laboratory (Budson, Daffner, Desikan, & Schacter, 2000) and in the real world (Budson et al., 2007). For instance, patients who falsely remember that they have already turned off the stove or have taken their medications when they have not will no longer be able to live independently. However, accurately monitoring memories is a potential mechanism for counteracting the influence of false memories when, for example, individuals are aware that a particular memory is likely to be false. Thus, understanding the extent to which patients with AD can monitor and judge the accuracy of their memories is an important clinical issue in addition to being of great theoretical interest. The small literature that has examined memory-monitoring on the part of Alzheimer’s patients has produced conflicting findings (see Pannu & Kaszniak, 2005, and Souchay, 2007 for reviews). On the one hand, patients with mild AD appear no different from healthy controls in using confidence ratings to judge the likely accuracy of answers to general knowledge questions (e.g., Who wrote Alice in Wonderland?) that assess well-learned or semantic information (Backman & Lipinska, 1993; Lipinska & Backman, 1996; see also Cosentino et al., 2007). Similarly, Moulin et al. (2003) observed no differences between AD participants and healthy older controls in monitoring the accuracy of recognition judgments. On the other hand, Souchay et al (2002) showed that AD patients were impaired in monitoring episodic memories. When completing a cued-recall test of recently-learned material, AD patients were much less accurate than older controls in providing feeling-of-knowing (FOK) judgments about the likelihood of recognizing an unrecallable item (Souchay et al., 2002). To our knowledge, no one has examined AD patients’ ability to monitor the likely accuracy of source judgments. In general, this pattern of AD patients – when compared to healthy older adults – showing a preserved ability to monitor the accuracy of semantic memories but an impaired ability to monitor the accuracy of episodic memories parallels a similar pattern that exists when healthy older adults are compared to younger adults. Older adults are either no different from or better than younger adults in monitoring the accuracy of responses to general knowledge questions – either with confidence ratings or by providing FOK judgments (e.g., Allen-Burge & Storandt, 2000; Butterfield, Nelson, & Peck, 1988; Dodson, Bawa, & Krueger, 2007; Perlmutter, 1978; Pliske & Mutter, 1996). However, older adults are much worse than younger adults in monitoring the accuracy of recently-learned (episodic) material: a) they provide less accurate FOK judgments on cued-recall tests (Souchay et al, 2000); and b) their confidence ratings are less well calibrated on both cued-recall tests and source memory tests because of the occurrence of high-confidence errors (Dodson et al., 2007a, 2007b; see also Dodson & Krueger, 2006). Dodson and colleagues proposed a misrecollection account to explain the pattern of older adults’ monitoring performance (Dodson et al., 2007a, 2007b). They suggested that advancing age is associated with an increased susceptibility of miscombining features of different events that in turn produce confidently-held misrecollections – memory problems that are likely caused by deterioration of the hippocampus and surrounding tissue (e.g., Shimamura & Wickens, 2009; Squire et al., 2004; and see Raz et al., 2005 for evidence of accelerated shrinkage of the hippocampus with healthy aging). This account predicts age-related differences in monitoring performance – because of the occurrence of high confidence errors – on all tests that require memory for specific details about recently-learned past events, such as source memory tests. The goals of the present study are twofold. First, given the similarity between older adults and AD patients in that both show relatively preserved monitoring of semantic memories and impaired monitoring of episodic memories (when compared to their respective control groups), we sought to test the misrecollection account as an explanation of the monitoring performance on the part of AD patients. Specifically, if AD patients show a more severe version of the same misrecollection impairment that is exhibited by older adults then we should observe that on a source memory test AD patients are more prone than older adults to make high confidence errors. The second goal is to examine whether the memory-monitoring deficit in AD patients is a byproduct of their overall weaker memory performance or whether this memory-monitoring deficit is a byproduct of a more specific, malfunctioning memory-monitoring mechanism. The answer to this question is unknown because in all extant studies AD patients show worse memory performance than their healthy older counterparts. Thus, worse memory-monitoring by AD patients may be a byproduct of their worse accuracy (see Hertzog et al., 2010 for a similar argument about differences in memory-monitoring between older and younger adults). No study has sought to compare the memory-monitoring abilities of AD patients and healthy older adults when both groups show comparable memory performance. To address these goals, we used a combination recognition and source identification paradigm that involves collecting confidence ratings for both memory judgments (e.g., Dodson, Bawa, & Krueger, 2007; Simons, Peers, Mazuz, Berryhill & Olson, 2010). At encoding, participants heard sentences that were presented by either a female or a male. At test, participants were presented with sentences and made an initial old-new recognition judgment (i.e., Did you encounter it before or is it new?) and for items receiving a judgment of old, participants made a source judgment about who presented the item earlier (i.e., male or female?). For both the recognition and the source judgments, participants rated the likely accuracy of their responses on a confidence scale from 50 (guessing) to 100 (certain). According to our misrecollection account, we should observe that AD patients make more high confidence errors than healthy older adults on the source judgment. Critically, if the monitoring impairment on the part of AD patients is not merely a byproduct of their worse accuracy then we should observe that even when AD patients and healthy older adults show comparable source identification accuracy, the AD patients still will exhibit a monitoring impairment. In other words, matching the AD patients and the older adults on source memory accuracy avoids a potential confound and so any observed differences in monitoring performance on this judgment cannot be attributed to differences in source accuracy.

Although it is generally accepted that patients with amnestic mild cognitive impairment (aMCI) and patients with Alzheimer's disease (AD) have significantly impaired recollection, recent evidence has been mixed as to whether these patients demonstrate impaired memorial familiarity. Recent work suggests that familiarity may remain intact for pictures, but not for words. Further, a recent event-related potential (ERP) study suggests that enhanced conceptual processing of pictures may underlie this intact familiarity. However, to date there has been no direct comparison of perceptual and conceptual-based familiarity for pictures and words in patients with aMCI and AD. To investigate this issue, patients with aMCI, patients with AD, and healthy older adults underwent four study-test conditions of word-word, picture-picture, word-picture, and picture-word. When stimuli undergo form change, it has been suggested that only conceptual processing can help support recognition in the absence of recollection. Our results showed that patients successfully relied on perceptual and conceptual-based familiarity to improve recognition for the within format conditions over the across format conditions. Further, results suggested that patients with aMCI and AD are able to use enhanced conceptual processing of pictures compared to words to allow them to overcome the deleterious effects of form change in a similar manner as controls. These results help us begin to understand which aspects of memory are impaired and which remain relatively intact in patients with aMCI and AD. This understanding can then in turn help us to assess, conceptualize, and build behavioral interventions to help treat these patients.