A Longitudinal Study Of Episodic And Semantic Autobiographical Memory in AMCI And Alzheimer’s Disease Patients Part 1

Abstract: 

Background: The main objective of this study was to analyze the evolution of autobiographical memory (both episodic and semantic) in patients with mild cognitive impairment, patients with Alzheimer's disease, and a healthy control group. 

With the trend of an aging population, mild cognitive impairment has become an increasingly common phenomenon. Although it does not seriously affect a person's daily life, it still brings inconvenience and certain annoyance. The most common complaint is memory loss, especially short-term memory.

However, we should not worry too much or be depressed. The relationship between mild cognitive impairment and memory is relatively complex. Although many people may feel upset and anxious, there are some measures we can take to help relieve symptoms, improve memory, and improve the quality of life.

Some simple changes can be of great help. For example, maintain a healthy lifestyle, including a balanced diet, adequate sleep, moderate exercise, and relaxation. Reducing stress and anxiety is particularly important, which can be achieved by practicing meditation, yoga, listening to music, and so on.

In addition, attention and concentration training is also an effective means to improve memory. Methods such as mnemonics, notes, reminders, and regular review can be used appropriately to help oneself better remember and manage information. These exercises can help us improve self-confidence and self-esteem and overcome self-doubt and negative emotions.

In summary, mild cognitive impairment is not a terrible disease. We can change our habits and attitudes to deal with it, improve our memory and quality of life, and restore our confidence and optimism. Becoming a positive person can avoid psychological stress and bring good luck and happiness. 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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We compared these groups at two-time points: first, at baseline, and in a follow-up after 18 months. Method: Twenty-six healthy older adults, 17 patients with mild amnestic cognitive impairment, and 16 patients with Alzheimer's disease, matched on age and educational level, were evaluated at both time points with the Autobiographical Memory Interview. 

Results: The results showed significant longitudinal deterioration in episodic and semantic autobiographical memory in patients with mild cognitive impairment and in patients with Alzheimer's disease, but not in healthy older adults. 

Conclusions: The deterioration of AD's episodic and semantic autobiographical memory is confirmed; however, although the episodic was impaired in aMCI, a pattern that evolved toward deterioration over eighteen months was observed for the semantic autobiographical memory.

Keywords: autobiographical memory; mild cognitive impairment; Alzheimer's disease.

1. Introduction

Autobiographical memory (AM) is a type of declarative memory that refers to the personal past and allows the recovery of personal semantic data as well as incidental or episodic memories, which means bringing first-person past situations experienced into the present. 

It has been well established that the normal aging process is generally associated with changes in various cognitive domains, including memory, and memory impairment is the most common cognitive symptom of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) [1]. However, knowledge about the progression of AM over time is scarce. 

The lack of research on this topic is surprising, given that changes in memory are one of the key factors in both normal aging and cognitive pathologies experienced by older adults. These changes appear from the beginning of the course of neurodegenerative diseases, and they continue to deteriorate with the progression of disease severity [2]. 

Studying the progression of AM over time is an important line of research that will help us understand the evolution of AM and the possible changes that occur in this type of memory. AM is a uniquely human form of memory that moves beyond the recall of experienced events by also integrating with these memories their interpretation and personal evaluations. 

Autobiographical memories are rich in thoughts, emotions, and evaluations of what happened, and they provide explanatory frameworks that contain human intentions and motivations [3]. AM constitutes our personal history and allows us to build an identity and continuity [4]. 

AM brings together general knowledge from one's past (semantic memory) and from specific events (episodic memory) [5]. Semantic memory is objective memory related to the accumulated knowledge of the world that has been organized conceptually, reflects our knowledge of the world, and contains generic information acquired in different contexts [6]. 

Episodic memory refers to the capacity to recall individual events associated with the perceptual and sensory details collected in the context of a specific time and place; the essence of this type of memory is its specificity. 

The main difference lies in the fact that episodic memories allow us to re-experience the event, whereas semantic memories do not involve the re-experiencing of events although they contain information that includes general knowledge. 

Due to the multi-modal nature of AM retrieval, several functional domains are engaged during recollection. 

Two meta-analyses [7,8] report that consistent with previous reviews of AM imaging studies, nearly all the studies on AM retrieval reported an activation of the prefrontal cortex, which plays an important role in episodic memory retrieval. 

In addition, they point out that more than half of the AM imaging studies reported an activation in the medial temporal lobe region (MTL), especially the hippocampus, a region that the authors identify as a core contributor to the episodic AM network. 

Several authors have shown that normal aging affects the nature of episodic AM and reduces access to contextually specific details [4], whereas studies that have examined semantic memory functioning in aging indicate that it can be preserved or even facilitated in older adults [9]. 

Some authors even point out that older adults, on average, produce fewer episodic details but more semantic information during AM retrieval than younger adults [10]. The results with aMCI patients have shown impaired episodic AM, but contradictory results for semantic AM. At the neuroanatomical level, there is a decrease in the volume of the hippocampus and the entorhinal cortex of the medial temporal lobes of aMCI patients [11]. 

When atrophy occurs in these regions, this could be a sensitive predictor of progression from aMCI to AD [12]. 

Memory performance for autobiographical episodes is impaired; however, aMCI patients produce autobiographical narratives characterized by a decrease in episodic details and an increase in semantic memories [12,13], These results are consistent with studies showing that aMCI patients scored worse on the memory of autobiographical incidents than healthy older adults [14,15] but better than AD patients [15]. 

However, personal semantic memory remains relatively preserved [12] because when the semantic autobiographical memory is not linked to a context, it is not dependent on the hippocampus. 

This suggests that although aMCI might be associated with impaired remote semantic memory related to impersonal information such as famous faces, it does not appear to affect autobiographical memory for personal semantic information, especially information connected to a personally relevant event [12]. In some studies, no differences were detected between the AM of healthy older adults and that of an aMCI group, although the aMCI group performed better than the AD group. 

More specifically, AD patients remembered both remote and recent periods worse than HOC, while the aMCI group differed significantly with HOC only for recent memory [15]; in contrast, other research [16] demonstrated that personal semantic memory is compromised in aMCI patients in comparison with healthy elderly controls. 

AM was found to be impaired in AD patients, and semantic retrieval was poorer in AD patients than in healthy controls and aMCI patients [15,17]. 

In addition, these results were also observed for autobiographical incidents (episodic) [15], but Barnabe only observed differences between AD patients and healthy controls [17]. 

This worse AM has shown different temporal profiles [4], with better retrieval being observed for old memories than for recent ones in AD when AM is evaluated as a global score (semantic and episodic AM grouped) [16]. 

However, when considered alone, episodic memories tend to be impaired regardless of the time interval, whereas old semantic memories tend to be better preserved than recent ones [18]. It should be noted that the relative preservation of old semantic autobiographical memories occurs only for mild AD because, with the progression of the disease, these memories also become prone to substantial loss. 

It can be argued that representations of personally relevant knowledge that became part of semantic memories earlier in life are more strongly integrated into the brain, better consolidated, and therefore, less degraded by AD [19]. 

The episodic memory findings suggest that the more frequently retrieved autobiographical memories generally become more independent from the hippocampal complex, and might thus be better protected from early hippocampal damage related to AD [20]. 

Evidence shows a deterioration in autobiographical memory at the onset of the neurodegenerative disease typical of dementia, but not how the deterioration progresses toward more severe symptoms. 

To our knowledge, few longitudinal studies [2,14,21] have contrasted the evolution of AM impairments, even though it is important to know how the deterioration will advance to determine what aspects of episodic and semantic memory will be affected. 

To discover the evolution of autobiographical memory, we studied groups of healthy older controls, aMCI, and AD for 18 months. 

We compared the three groups at baseline and in the follow-up-first for episodic autobiographical memory, and second for semantic memory-to discover the differences in their performance. Moreover, the longitudinal evolution of each group was analyzed for each type of memory to find out the possible changes after eighteen months.

2. Materials and Methods

2.1. Participants

Initially, 91 subjects participated in the study, although only 59 completed it; only older adults over 65 years old (range 65–87, average 75.94) who completed the cognitive and neuropsychological assessment at baseline (T1) and follow-up (T2) were selected for this study on AM. 

Participants were classified into three groups: healthy older controls (HOC; n = 26), amnestic Mild Cognitive Impairment (aMCI; n = 17), and dementia-type Alzheimer (AD; n = 16) (see Table 1 for sociodemographic).

The general inclusion criteria for the study were: age > 65, no significant asymptomatic neurovascular disease, history of previous symptomatic stroke, medical condition significantly affecting the brain, motor-sensory defects, alcohol or drug abuse/dependence, serious psychiatric symptoms, or depressive symptomatology. 

Patients in the aMCI group met the diagnostic criteria specified by Petersen [22], and they were at levels 2 and 3 on the Global Deterioration Scale (GDS) [23]. 

The inclusion criteria for AD were: diagnosis of AD determined by the DSM-V [24] and reaching levels 3 and 4 on the Global Deterioration Scale [23]. 

Via the use of G*Power (G*Power 3.1.9.7, Düsseldorf, Germany) in computation, a priori statistical power analysis indicated a minimum total sample size of 66 for a power of 0.95 (α = 0.05; 1 − β = 0.95; three groups; 2 measurements, and correlation among repeated measures of 0.5) to detect a medium effect size (f = 0.25), in an F test of repeated measures for within–between interaction. 

Finally, with n = 59, a sensitivity statistical power analysis indicated that this design can detect a medium effect size of 0.25 (f = 0.2628; α = 0.05; 1 − β = 0.95).

2.2. Procedure

Clinical diagnosis was the result of an extensive evaluation, which included medical history and physical and neuropsychological examinations, and was determined by consensus between the neurologists and neuropsychologists (see Table 1 for neuropsychological data). 

Instruments for clinical assessment are described below. All participants (or close family members) gave written informed consent for participation in the study. 

The study was conducted according to the guidelines of the Declaration of Helsinki. After the baseline assessment, the participants were informed that they would be called for a follow-up evaluation after about 18 months.  91 participants initiated the study, met the inclusion criteria, and were assessed and assigned to the groups. 

Five HOC refused to participate in the follow-up; in the aMCI group, 13 dropped out of the study-6 refused to participate in the follow-up, and 7 were re-diagnosed with dementia during follow-up; in the AD group, 14 dropped out of the study-4 because of death, 7 due to a worse GDS score, and 3 refused to participate in the follow-up.

2.3. Materials

2.3.1. General Cognitive Screening

In addition to the GDS [23] and the Center for Epidemiologic Studies-Depression Scale (CES-D) [25], all the participants completed a comprehensive battery of neuropsychological tests assessing the main cognitive domains. 

The CES-D was developed as a measure of depressive symptomatology in the general population. This scale has 20 elements included in previously validated depression scales. As a cut-off point, 16 is usually used, which indicates the presence of clinically significant symptoms. 

The Mini-Mental State Examination (MMSE) [26] was used as an index of global cognitive functioning; the maximum score is 30 points. Language ability was assessed using the Categorical and Phonological fluency subtests of the Revised Barcelona Test (TBR) [27]. 

Verbal memory (short-term recall and delayed recall) was assessed using the Spain–Complutense Verbal Learning Test (TAVEC) [28], a list of 16 words from four different categories (kinds of fruit, spices, items of clothing, and tools) are presented orally five times to the participants; after each presentation, subjects are assessed on the number of words remembered correctly. 

Then, after 20 minutes, the subjects' delayed recall is assessed. Attention and working memory were tested using Digit Span forwards and backward [29]. The copy and delayed recall of the Rey Complex Figure [30] were used as measures of visuospatial construction and non-verbal anterograde memory, respectively.

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