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 1

Abstract

Objective: Patients with mild Alzheimer's disease dementia are more susceptible to false memories than healthy older adults. Evidence that these patients can use cognitive strategies to reduce false memory is inconsistent.

The relationship between false memory and memory is very close. Our brain carries countless information and memories, some of which are wrong. These false memories may be due to our misunderstanding and interpretation of events or things or errors in our brain circuits. But these false memories do not mean that there is a problem with our memory.

Our brain is very complex and has a strong ability to process information and memory. Our brain can constantly reorganize and rebuild our memory to make it more accurate and complete. Therefore, even if there is some false information in our memory, it will not affect our memory, but we need to constantly correct and adjust it. In addition, false memories can also help us improve our memory. When we correct false memories and form correct memories, our brains need to undergo a series of processing and adjustments, which stimulate our brain activity and improve our memory.

Therefore, we should not worry too much about the impact of false memories on our memory. On the contrary, we should actively face and correct these false memories and constantly improve our memory. You can improve your memory by reading books, participating in thinking training, and playing more memory games.

In short, false memories do not affect our memory. On the contrary, they can help us improve our memory. As long as we actively face and correct these false memories and constantly improve our memory ability, we will be able to better grasp knowledge and information and lay a solid foundation for our lives and work. It can be seen that we need to improve our memory. Cistanche can significantly improve memory because it is a traditional Chinese medicine with many unique effects, one of which is to improve memory. The effect of Cistanche comes from the various active ingredients it contains, including tannic acid, polysaccharides, flavonoid glycosides, etc. These ingredients can promote brain health in many ways.

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Method: In the present study, we examined the effectiveness of conservative responding and item-specific deep encoding strategies, alone and in combination, to reduce false memory in a categorized word list paradigm among participants with mild Alzheimer's disease dementia (AD), amnestic single-domain mild cognitive impairment (MCI), and healthy age-matched older controls (OC). A battery of clinical neuropsychological measures was also administered.

Results: Although the use of conservative responding alone tended to reduce performance in the MCI and OC groups, both deep encoding alone and deep encoding combined with conservative strategies led to improved discrimination for both gist memory and item-specific recollection for these two groups. 

In the AD group, only gist memory benefited from the use of strategies, boosted equally by deep encoding alone and deep encoding combined with conservative strategies; item-specific recollection was not improved. No correlation between the use of these strategies and performance on neuropsychological measures was found.

Conclusions: These results suggest that further evaluation of these strategies is warranted as they have the potential to reduce related and unrelated memory errors and increase both gist memory and item-specific recollection in healthy older adults and individuals with amnestic MCI. 

Patients with AD were less able to benefit from such strategies, yet could still use them to reduce unrelated memory errors and increase gist memory.

Keywords

Alzheimer's disease; false memory; executive function; cognitive strategy; mild cognitive impairment; memory.

Introduction

False memories, the belief that items or events have been experienced before when they have not, occur across the lifespan, increase in normal aging, and are further exacerbated by neurocognitive disorders such as Alzheimer's disease (LaVoie, Willoughby, & Faulkner, 2005; Parkin, Bindschaedler, Harsent, & Metzler, 1996; Schacter, Curran, Galluccio, Milberg, & Bates, 1996). 

Whereas some false memories are innocuous, such as believing the groceries that you just bought are on the kitchen table when they are still in the car, others can be dangerous, such as thinking that you had turned off the stove when you had not. 

Correctly recognizing information as having been previously experienced is thought to be based on two forms of information: item-specific recollection and gist memory (Reyna & Brainerd, 1995; Schacter, Norman, & Koutstaal, 1998). 

Item-specific recollection involves the retrieval of specific, contextualized details of a prior experience with a particular item, whereas gist memory is general knowledge conveyed by a collection of items or experiences (Reyna & Brainerd, 1995; Schacter et al., 1998). Item-specific recollection is primarily reliant on the hippocampus, whereas gist memory has been shown to depend upon the entorhinal cortex (Souchay & Moulin, 2009). 

The prototypical cognitive profile of Alzheimer's disease dementia is characterized by impairments in episodic memory that result in reduced encoding, rapid forgetting of new information, and increased false memories (Hildebrandt, Haldenwanger, & Eling, 2009; Weintraub, Wicklund, & Salmon, 2012). 

Early hippocampal involvement by Alzheimer's disease pathology leads to impairment in item-specific recollection, leaving gist memory relatively spared in these earlier disease stages (Braak, Alafuzoff, Arzberger, Kretzschmar, & Del Tredici, 2006; Budson, Daffner, Desikan, & Schacter, 2000). 

Increased false memories in Alzheimer's disease are thought to result from both an over-reliance on gist memory as well as an impaired ability to monitor and inhibit memory decisions (Abe et al., 2011; Budson, Todman, & Schacter, 2006).

False memories have been studied experimentally using the categorized word list (CWL) paradigms (Tat et al., 2016). In this paradigm, a participant is presented with a series of words belonging to taxonomic categories; however, one or more prototypical members of the category are absent during the study. For example, a participant may be presented with a series of related words (e.g. 'pine', 'dogwood', 'willow', 'redwood'). 

In a later recognition memory test, the participant may be presented with words studied previously (e.g. 'pine', 'willow'), prototypical items not seen before (e.g. 'oak', 'birch'), and unrelated new items (e.g. 'boat', 'classical').

Participants with Alzheimer's disease show elevated rates of false recognition in CWL paradigms, likely due to their reliance on gist memory (Budson et al., 2000; Budson, Todman, & Schacter, 2006; Tat et al., 2016). 

In addition, individuals with Alzheimer's disease have been found to respond 'old' to unrelated words much more frequently than do healthy older adults, suggesting a liberal response bias (Budson, Wolk, Chong, & Waring, 2006). 

Cognitive strategies to compensate for increased false memories and other memory impairments resulting from Alzheimer's disease have taken on increased importance given the lack of available disease-modifying medications (Yiannopoulou & Papageorgiou, 2013). 

These cognitive strategies have typically aimed to either enhance item-specific recollection or gist memory (Budson, Sitarski, Daffner, & Schacter, 2002; Malone et al., 2019; McCabe, Presmanes, Robertson, & Smith, 2004). Item-specific encoding is an elaborative, deep encoding process whereby a participant generates one or more distinctive qualities of the study item to improve semantic, contextual, and salient information (i.e., quality of item-specific recollection) for the item (Tat et al., 2016). 

Item-specific encoding will be referred to as deep encoding throughout the remainder of this manuscript. Deep encoding is effective in improving the quality of item-specific recollection in healthy older controls and participants with mild cognitive impairment but not among participants with Alzheimer's disease, potentially due to their impairments in item-specific recollection (Tat et al., 2016). 

Conservative responding is a memory heuristic in which a participant endorses an item as previously encountered only if they are certain of their decision (Waring, Chong, Wolk, & Budson, 2008). 

Conservative responding has been found to reduce the degree of false recognition in word-list paradigms by shifting the metamemorial information that participants employ when making memory decisions (Deason et al., 2017; Waring et al., 2008). 

The use of conservative responding has also been found to shift the response criterion of participants with Alzheimer's disease, although it has not previously been found to meaningfully improve their discrimination of true and false information (Deason et al., 2017; Waring et al., 2008). 

Although healthy older controls and participants with mild cognitive impairment due to Alzheimer's disease have been found to apply cognitive strategies to reduce false memory in categorized list paradigms (Brueckner & Moritz, 2009; Deason et al., 2017; Tat et al., 2016), individuals with Alzheimer's disease dementia have been found to either be ineffective or inconsistent in their application of cognitive strategies (Abe et al., 2011; Budson, Dodson, Daffner, & Schacter, 2005; Budson et al., 2002; Pierce, Waring, Schacter, & Budson, 2008). Further, the effectiveness of combining strategies to reduce false memories in participants with Alzheimer's disease at either the mild cognitive impairment or mild dementia stage remains unexplored.

Cognitive abilities in addition to memory are critical in the use of cognitive strategies among aging and individuals with Alzheimer's disease dementia (Buckner, 2004). 

Executive function is conceptualized as higher-order cognitive functions responsible for monitoring, shifting, manipulating information, and directing attention (Logue & Gould, 2014). Executive function has been associated with the use of cognitive strategies in healthy older adults (Bouazzaoui et al., 2010; Troyer, Graves, & Cullum, 1994). 

Experimental paradigms show evidence of impaired inhibitory and monitoring abilities (two aspects of executive function) in individuals with Alzheimer's disease (Budson, Sullivan, et al., 2002; Flanagan et al., 2016). 

Nonetheless, clear associations between performance on measures of executive function and the use of memory strategies have not yet been observed among individuals with Alzheimer's disease (Budson, Wolk, Chong, et al., 2006; Deason et al., 2012). 

Because executive function is such a broad category (Logue & Gould, 2014), we speculated that this prior lack of association was likely related to which measures of executive function were included in the testing battery. 

We believe that looking for such associations is important, as a more comprehensive understanding of the relationship between executive functioning and the use of cognitive strategies may inform recommendations and interventions for individuals with Alzheimer's and related diseases.

In this study, we examined the effectiveness of two strategies, conservative responding and deep encoding, alone and in combination, to reduce false memory in a CWL paradigm among participants with mild Alzheimer's disease dementia (AD), participants with amnestic single-domain mild cognitive impairment (MCI), and healthy age-matched controls (OC). 

A comprehensive battery of neuropsychological measures was also administered to elucidate which cognitive functions are associated with the use of strategies to reduce false memories. 

We hypothesized that the performance of participants on measures of executive function would be positively related to the effective use of cognitive strategies. We further hypothesized that each participant group would be able to use strategies, alone and in combination, to reduce false memories. 

Lastly, we hypothesized that the MCI group would be less able than the OC group to use these strategies to reduce false memories, and the AD group would be less able than the MCI group to use these strategies to reduce false memories.

Method

Participants

Sixteen participants with a diagnosis of mild Alzheimer's disease dementia (AD), sixteen participants with a diagnosis of amnestic single-domain mild cognitive impairment (MCI), and sixteen healthy age, education, and sex-matched healthy older controls (OC) were recruited (Table 1). 

Participants with AD and MCI were recruited from the VA Boston Healthcare System, the Boston University Alzheimer's Disease Center, and the surrounding community clinics, and diagnosed by a neurologist (AEB) based on 2011 NIA-AA diagnostic criteria for Alzheimer's disease dementia and mild cognitive impairment (Albert et al., 2011; McKhann et al., 2011). 

All participants with MCI were identified as amnestic, single domain, and subtype. Exclusion criteria included: clinically significant depression, alcohol or drug use, cerebrovascular disease, or traumatic brain injury. 

Participants were also excluded if English was not their primary language or their Mini-Mental State Examination (MMSE) score was below 21. In addition, older adults were excluded if they had a history of dementia or any neurodegenerative disorder in themselves or their immediate family. All participants had normal or corrected-to-normal vision and hearing. Written informed consent was obtained from all participants. 

This study was approved by the Institutional Review Board of the VA Boston Healthcare System. This study was completed by the Helsinki Declaration. Participants were compensated $10.00 per hour for their participation.

Materials and Testing

All participants were tested individually either at their home or the VA Boston Healthcare System. Each participant completed four sessions, one session for each of the conditions. 

Sessions lasted for approximately one hour and involved three phases in the following order: a study phase of the word lists presented on a laptop computer, a recognition memory test of the study words with additional related and unrelated unstudied words interspersed as described below, and administration of between 1 and 6 neuropsychological tests of estimated IQ, memory, processing speed, language, and executive function. Neuropsychological measures of executive function were selected due to their emphasis on monitoring, set-shifting, and manipulating information as well as the ability to easily record and identify participant scores to facilitate correlational analysis (Delis, Kaplan, Kramer, & Corporation, 2001; Logue & Gould, 2014). 

The schedule for the neuropsychological tests was as follows: Session 1: Consortium to Establish a Registry for Alzheimer's Disease Word List (CERAD, Becker, Becker, Giacobini, Barton, & Brown, 1997), Trail Making Test Parts A and B (Strauss, Sherman, Spreen, & Spreen, 2006), Mini-Mental State Examination (MMSE; Pangman, Sloan, & Guse, 2000), Boston Naming Test-Short Form (BNT; Mack et al., 1992), Verbal Fluency (FAS/CAT; Mitrushina, 2005), Wechsler Adult Intelligence Scale-Third Edition: Digit Span (WAIS-III Digit Span; Wechsler, 1997) Session 2: D-KEFS Color Word Interference Test (D-KEFS; Delis, Kaplan, Kramer, & Corporation, 2001), Repeatable Battery for the Assessment of Neuropsychological Status Digit Symbol Coding (Randolph, Tierney, Mohr, & Chase, 1998).

Session 3: D-KEFS Sorting Test (Card Set 1 only), D-KEFS Verbal Fluency Category Switching.

Session 4: D-KEFS Twenty Questions.

The computerized word-list memory task was programmed using E-Prime 2.0 and was presented on a laptop computer (Dell Precision M 6700 Core i7 processor, Windows 7, 17.3-inch screen 1920 x 1080 resolution). 

Stimuli words were drawn from a previously published set of normed categorized word list stimuli (Battig & Montague, 1969; Van Overschelde, Rawson, & Dunlosky, 2004). 

Words were presented in Arial Unicode MS font size 48 in black font for 3.5 seconds with an inter-stimulus interval of 0.5 seconds between items of the same list. 

An inter-stimulus interval of 5 seconds was used between study lists. In each condition, participants studied 7 lists of 15 taxonomically related English nouns and were tested on 42 total words with two correct items and two related lures drawn from each of the 7 study lists as well as 14 new words that had no significant lexical relationship to any of the study lists.

Instructions for the computer task were read aloud by study personnel and a small display card was placed below the keyboard with printed instructions in the conservative responding, deep encoding, and combined conditions. 

The instructions in the no strategy condition at study were: "Read each word out loud", and at test were: "How confident are you that this word is 'old' or 'new'? Is this word 'old' or 'new'?". 

In the deep encoding and combined conditions, the study instructions were changed to: "Read each word out loud. What is one unique characteristic of this item or personal experience that differentiates it from other words in this list?". 

In the conservative responding and combined conditions, the test instructions were changed to: "How confident are you that this word is 'old' or 'new'? Is this word 'old' or 'new'? Only say OLD if your confidence was "(6) Certain it is OLD" otherwise say NEW.". Participants completed a simple maze between the study and test phases as a brief distractor task. 

Study staff recorded the responses of the participants during the testing phase by pressing corresponding keyboard buttons. The experimental condition and study stimuli lists were counterbalanced across all participants and groups.

Results

Neuropsychological Testing

Measures used to assess overall cognitive function were administered to all participants during session 1. 

The results of this battery as well as demographic characteristics by group are presented in Tables 1 and 2. One OC participant did not complete the MMSE at the time of testing but received a score of 30 on the Montreal Cognitive Assessment (MoCA) within 6 months of the first session. 

Three participants with AD were unable to complete Trails B and the administration of this task was discontinued. These results broadly revealed that OCs performed in the normal range, participants with MCI performed similarly to the OCs except CERAD delayed recall, and the AD group showed impairment in comparison to both the MCI and OC groups (Table 2 and Supplementary Table 1). 

ANOVAs comparing group performances on neuropsychological measures of executive functions revealed that the MCI group either performed similarly to the OC group or was slightly impaired, whereas the AD group showed impairments compared to both the OC and MCI groups (Table 3 and Supplementary Table 1).

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