The Effectiveness Of Item-Specific Encoding And Conservative Responding To Reduce False Memories in Patients With Mild Cognitive Impairment And Mild Alzheimer’s Disease Dementia Part 2

Statistical approach

Repeated-measures ANOVAs were conducted for (1) hits, false alarms to related lures, and false alarms to unrelated lures, (2) d' for gist and item-specific recollection, and (3) C for gist and item-specific recollection with group (AD, MCI, and OC) as a between-subject factor and condition (no strategy, conservative responding, deep encoding, and combined) as a within-subject factor. Post hoc comparisons were performed using the Tukey HSD.

The relationship between conservative reaction and memory has always been an important research direction in the field of psychology. Conservative reaction refers to people's resistance to new things, and memory is an important ability that people need in the cognitive process. So what is the relationship between conservative reaction and memory?

First, there is a certain negative relationship between conservative reaction and memory. Conservative people often have little interest in new things, and they prefer to maintain their existing lifestyle and way of thinking. This attitude of resisting new things will reduce their opportunities to contact new things, which may cause memory decline.

Secondly, conservative reactions will also affect people's cognitive ability. When conservative people face new things, the cognitive resources of the brain will be over-limited, which will lead to a decrease in cognitive efficiency. Therefore, conservative reactions will also have a certain negative impact on people's thinking and understanding ability.

However, the conservative reaction is not entirely negative. As the doctrine of the mean says, "Too much is as bad as too little." It is not a wise choice to pursue new things too radically. Conservative people's familiarity and understanding of existing things also help them maintain a stable mood and mentality, and also protect the stability of their memory.

In short, there is a certain relationship between conservative reaction and memory, but it is not a single positive or negative impact. We need to properly maintain the habits of existing things in our daily lives, and at the same time try to accept new things to achieve a balanced and comprehensive development. It can be seen that we need to improve memory, and Cistanche can significantly improve memory because Cistanche has antioxidant, anti-inflammatory, and anti-aging effects, which can help reduce oxidation and inflammatory reactions in the brain, thereby protecting the health of the nervous system. In addition, Cistanche can also promote the growth and repair of nerve cells, thereby enhancing the connectivity and function of the neural network. These effects can help improve memory, learning ability, and thinking speed, and can also prevent the occurrence of cognitive dysfunction and neurodegenerative diseases.

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Hits

All participants endorsed a lower proportion of true items in the conservative condition (main effect of condition: F(3,135)=24.14; p<0.001, η 2=0.350; M=0.55, SE=0.05) compared to the no strategy (M=0.75, SE=0.03; p<0.001), deep encoding (M=0.83, SE=0.02; p<0.001), and combined (M=0.85, SE=0.02; p<0.001) conditions (Figure 1). 

No main effect of group (F(2,45)=2.68; p=0.080, η 2=0.11) and no interaction between group and condition (F(6,135)=0.50; p=0.809, η 2=0.02) was found.

False alarms to related lures

The AD group showed a higher proportion of false alarms to related lures (main effect of group: F(2,45)=13.81; p<0.001, η 2=0.38; M=0.59, SE=0.05) compared to the OC (M=0.25, SE=0.05; p<0.001) and MCI (M=0.36, SE=0.05; p=0.002) groups across all conditions. 

No difference in false alarms to related lures was found between the MCI (M=0.36, SE=0.05) and OC (M=0.25, SE=0.05; p=0.502) groups. Collapsed across groups, there was a higher proportion of false alarms to related lures in the no strategy condition (main effect of condition: F(3,135)=9.82; p<0.001, η 2=0.18; M=0.51, SE=0.04) compared to the conservative (M=0.37, SE=0.04; p<0.001), deep encoding (M=0.38, SE=0.03; p<0.001), and combined (M=0.33, SE=0.03; p<0.001) conditions. 

An interaction between group and condition was also found (F(6,135)=2.68; p<0.001, η 2=0.11) (Figure 2). After conducting a Tukey HSD test, no significant differences in endorsing related lures were found across conditions in each of the OC and AD groups. 

MCI participants showed a higher proportion of false alarms to related lures in the no strategy condition (M=0.54, SE=0.07) compared to the deep encoding (M=0.30, SE=0.05; p<0.001), and combined (M=0.21, SE=0.06; p<0.001) conditions.

False alarms to unrelated lures

AD participants showed a higher proportion of false alarms to unrelated lures (main effect of group: F(2,45)=19.24; p<0.001, η 2=0.46; M=0.30, SE=0.03) compared to OC (M=0.07, SE=0.03; p<0.001) and MCI (M=0.08, SE=0.03; p=0.004) participants; OC and MCI did not differ. Collapsed across the group, there was a higher proportion of false alarms to unrelated lures in the no strategy condition (main effect of condition (F(3,135)=7.34; p<0.001, η 2=0.14; M=0.22, SE=0.03) compared to the combined (M=0.11, SE=0.02; p<0.001) condition. 

When analyzing the interaction between group and condition (F(6,135)=2.26; p=0.041, η 2=0.09) with Tukey HSD, AD participants showed a higher proportion of false alarms to unrelated lures in the no strategy condition (M=0.45, SE=0.05) compared to the conservative (M=0.25, SE=0.04; p=0.032) and combined (M=0.22, SE=0.03; p=0.002) conditions (Figure 3).

d' and C

D and C statistics were computed to estimate the discrimination and response bias within each condition, respectively. 

Discrimination estimates were computed for both gist memory (d' gist equals the proportion of endorsed true items minus the proportion of endorsed unrelated new items) and item-specific recollection (d' item-specific recollection equals the proportion of endorsed true items minus the proportion of endorsed related lures) (Figures 4 and 5). Response bias (C) by condition was computed with positive values of C representing conservative response bias and negative values signifying a liberal responding bias (Figures 6 and 7). 

These measures were computed according to the formula provided by Macmillan and Creelman (2005), and these data were adjusted when the proportion of responses equaled 1 or 0 with the correction factor ± ½N with N representing the total number of possible false alarm responses.

d' Gist

The AD group demonstrated lower levels of discrimination for gist information than the MCI group, who, in turn, demonstrated lower levels of gist information than the OC group (main effect of group: F(2, 45)=22.59, p<0.001, η 2=0.50; OC: M=2.55, SE=0.14; MCI: M=2.12, SE=0.14; AD: M=1.26, SE=0.14 (OC-MCI p=0.005; OC-AD p<0.001, MCI-AD p<0.001)). 

Regarding the effect of condition (main effect of condition: F(3, 135)=24.84, p<0.001, η 2=0.36), post-hoc analysis revealed that participants showed higher discrimination in the deep encoding (M=2.35, SE=0.10) and combined (M=2.50, SE=0.12) conditions compared to the no strategy (M=1.73, SE=0.12; p<0.001; p<0.001 respectively) and conservative ((M=1.32, SE=0.15); p<0.001, p<0.001 respectively) conditions. 

No difference was found between the deep encoding and combined conditions (p=0.772). No interaction between condition and group was found in the analyses of discrimination for gist information (F(6, 135)=1.27, p=0.274, η 2=0.05) (Figure 4).

d' Item-specific Recollection

Differences in discrimination for item-specific information were found across all groups: lowest in the AD group, better in the MCI group, and the best in the OC group (main effect of group F(2, 45)=29.82, p<0.001, η 2=0.57; OC: M=1.89, SE=0.14; MCI: M=1.16, SE=0.14; AD: M=0.35, SE=0.14 (OC-MCI p=0.005; OC-AD p<0.001; MCI-AD p<0.001)) (Figure 5). 

Across all conditions, participants showed higher discrimination in the deep encoding (main effect of condition: F(3, 135)=40.41, p<0.001, η 2=0.47; M=1.50, SE=0.10), and combined (M=1.73, SE=0.14) conditions compared to the no strategy condition (M=0.79, SE=0.11; p<0.001, p<0.001 respectively). Furthermore, participants showed higher discrimination in the deep encoding and combined conditions compared to the conservative condition (M=0.52, SE=0.10; p<0.001, p<0.001 respectively). 

No difference was found between deep encoding and combined conditions (p=0.078). In terms of discrimination for item-specific recollection, a close examination of the interaction between condition and group (F(6, 135)=3.77, p=0.002, η 2=0.14) revealed that OC and MCI participants showed greater discrimination in the deep encoding (OC: M=2.44, SE=0.17; MCF M=1.60, SE=0.17) and combined (OC: M=2.54, SE=0.24; MCE M=1.98, SE=0.24) conditions compared to the no strategy (OC: M=1.61, SE=0.18; p<0.001, p<0.001 respectively; MCE M=0.63, SE=0.18; p<0.001, p<0.001 respectively)) and conservative conditions (OC: M=0.97, SE=0.19; p<0.001, p<0.001 respectively; MCE M=0.44, SE=0.19; p<0.001, p<0.001 respectively). 

Interestingly, OC participants showed higher discrimination in the no strategy condition compared to the conservative condition (p<0.005) while MCI participants did not (p=0.397). No difference was found between deep encoding and combined conditions (OC: p=0.646; MCE p=0.083). 

Participants in the AD group showed trends toward higher item-specific recollection discrimination in the combined condition (M=0.66, SE=0.24) compared to the no strategy (M=0.13, SE=0.18, p=0.054) and conservative conditions (M=0.15, SE=0.19; p=0.074), although these did not reach statistical significance after post hoc adjustment. 

No differences were found when comparing the no strategy to conservative (p=0.948) and combined conditions (p=0.121). No difference was found between the deep encoding (M=0.48, SE=0.17) and combined conditions (p=0.388).

Response Bias Gist

The AD group showed a more liberal response bias for gist information (main effect of group: F(2, 45)=4.11, p<0.001, η 2=0.15; M=−0.01, SE=0.09) than the MCI group (M=0.37, SE=0.09; p<0.001). 

No difference in response bias was found when comparing OC (M=0.24, SE=0.09) to MCI (p=0.590) and AD (p=0.168) groups. Across all groups, participants showed a more conservative response bias for gist information in the conservative condition (main effect of condition: F(3, 135)=15.92, p<0.001, η 2=0.26; M=0.56, SE=0.10) compared to the no strategy (M=0.08, SE=0.08; p<0.001), deep encoding (M=0.07, SE=0.06; p<0.001), and combined (M=0.09, SE=0.05; p<0.001) conditions. No interaction between condition and group for gist memory was found (F(6, 135)=0.68, p=0.666, η 2=0.03).

Response Bias Item-specific Recollection

The AD group also demonstrated a more liberal response bias for item-specific information (main effect of group: F(2, 45)=20.74, p<0.001, η 2=0.48; M=0.17, SE=0.12) compared to the OC (M=1.18, SE=0.12; p<0.001), and MCI (M=0.95, SE=0.12; p<0.001) groups. 

No difference in response biases was found between the OC and MCI groups (p=0.342). Collapsed across groups, participants showed a more liberal response bias for item-specific information in the no strategy condition (main effect of condition: F(3, 135)=11.91, p<0.001, η 2=0.21; M=0.47, SE=0.10) compared to conservative (M=0.82, SE=0.09; p<0.001), deep encoding (M=0.81, SE=0.07; p<0.001), and combined (M=0.96, SE=0.08; p<0.001) conditions. No interaction between condition and group was found (F(6, 135)=1.42, p=0.212, η 2=0.06).

Correlations of Neuropsychological Tasks and Memorial Discrimination

No clear pattern of correlations between performance on neuropsychological tests and effective use of cognitive strategies was found. The Benjamini-Hochberg correction ((i/m)Q) was applied to control for false discoveries resulting from multiple comparisons (Supplementary Table 2).

Discussion

The results of this experiment revealed that the use of cognitive strategies impacted the performance of all three groups. The increased information conferred by either deep encoding alone or the combined strategies improved discrimination for gist information in all three groups (Figure 4). 

Furthermore, in the OC and MCI groups, both the deep encoding and combined strategies also improved discrimination for item-specific recollection; by contrast, the AD group did not show strategic benefit for item-specific recollection (Figure 5). 

Lastly, the AD group demonstrated a liberal responding bias consistent with past research (Budson, Wolk, et al., 2006), and all participants adopted a more conservative bias using the conservative responding strategy alone (Deason et al., 2017; Waring et al., 2008).

In the present study, the results of combined strategies did not differ from those of deep encoding alone. Thus, it is likely that all the beneficial strategic effects observed in this study were driven by deep encoding. It is, therefore, worth pausing to consider how that deep, item-specific encoding can boost not only item-specific recollection but also gist memory-particularly in the AD group. 

As mentioned in the Introduction, gist memory is general knowledge conveyed by a collection of items or experiences (Reyna & Brainerd, 1995; Schacter et al., 1998). 

When subjects study categorized word lists, the encoding of individual items triggers semantically related activations (Reyna & Brainerd, 1995). Thus, studying robin, blue jay, crow, and canary activates not only nodes specific to those items but also other birds such as cardinal, chickadee, and dove-as well as the superordinate category, bird. However, these semantic networks will be more strongly activated when encoding is deep and semantically based compared to when it is shallow and perceptually based. 

The more strongly activated the networks are, the stronger the gist memory will be. Future research should explore the use of deep encoding in memory paradigms using unrelated words, as these unrelated stimuli would not be expected to generate a strong sense of gist information. 

The present study therefore suggests that when patients with AD are not given a particular encoding strategy, they do not deeply encode items as much as they could and, therefore, they do not fully activate their semantic networks related to those items. 

In this study we demonstrate that patients with AD can successfully adopt a deep encoding strategy that likely provides greater semantic activation, thereby strengthening gist memory in AD. The overall performance of participants in the AD group suggests reliance upon gist memory, an expected finding based on prior literature demonstrating relatively intact gist memory in the early symptomatic stages of Alzheimer's disease dementia (Budson et al., 2000). 

The deep encoding strategy was able to boost gist memory, a novel finding of the present study as past research has not supported the effectiveness of cognitive strategies in this population (Abe et al., 2011; Simmons-Stern et al., 2012; Tat et al., 2016; Waring et al., 2008). 

Also worth considering is why, in the OC group, the conservative responding strategy alone reduced item-specific recollection relative to no strategy, but it did not reduce item-specific recollection when combined with deep encoding. Although further studies will be needed to answer this interesting question, we speculate that, without deep encoding, our OC participants did not experience vivid enough recollections to allow them to endorse previously seen items. 

To put it more simply, in the conservative responding condition, they stopped engaging in the guesses they did in the no strategy condition, many of which were correct! However, the use of the deep item-specific strategy at encoding must have helped to provide vivid, item-specific recollections at retrieval, such that conservative responding in the combined condition was preferentially applied to the non-studied items.

Whereas past studies have suggested that frontal executive abilities may be a critical factor in the effective use of cognitive strategies (Plancher, Guyard, Nicolas, & Piolino, 2009), we found no evidence of a relationship between performance on frontal executive neuropsychological measures and the use of such strategies in the present study. 

The MCI and OC groups performed similarly on measures of frontal executive functioning, whereas the AD group performed at much lower levels than both other groups. Though past research suggested that Alzheimer's disease pathology impacts executive functioning abilities (Budson et al., 2002; Kirova, Bays, & Lagalwar, 2015; Marshall et al., 2011), there was no evidence in the present study that a certain level of executive functioning was necessary to apply the strategies effectively. The present study is not without limitations. 

The relatively small groups used in this study may have increased the risk of false negative errors. It is also possible that participants may have used a previously taught strategy in a later study session thus potentially obscuring the effectiveness of the strategies. However, the present study design incorporated precautions such as counterbalancing the conditions and requiring a minimum of a week between sessions to mitigate this risk. 

Lastly, the participants were all solicited from a relatively small geographic area, potentially undermining the generalizability of these results. Despite these limitations, this study demonstrates that individuals with mild AD dementia or amnestic single-domain MCI can apply a deep encoding strategy to improve their discrimination for gist information despite impaired memory and executive functioning. 

However, these results also demonstrate the limits of cognitive strategies in AD as the AD group was found to reduce only the most severe form of memory distortions-unrelated errors-whereas individuals with more preserved cognitive functions (i.e., MCI group) were able to correct more subtle memory distortions-related errors. Additional research into the ecological effectiveness of these strategies to improve daily functioning for individuals with mild cognitive impairment and mild Alzheimer's disease dementia is warranted-especially when these results are viewed in the context of the lack of disease-modifying treatments. 

Lastly, we would argue that the results of this study add to a growing body of literature that suggests that it is important to not only enhance true memories but also to reduce false memories when designing interventions to delay functional impairment and improve the quality of life for individuals with mild cognitive impairment and Alzheimer's disease dementia (Devitt & Schacter, 2016; Silverberg et al., 2011; Turk et al., 2020).

Acknowledgements:

No authors hold any interests or investments (financial or otherwise) that may construe a potential conflict of interest. This work was supported by the National Institutes of Health and National Institute on Aging (A.E.B., P30- AG013846) and by the Department of Veterans Affairs (A.E.B., CX 001698).

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