Strategic value-directed learning and memory in Alzheimer's disease and behavioural-variant frontotemporal dementia

In healthy adults, the ability to prioritize learning of highly valued information is supported by executive functions and enhances subsequent memory retrieval for this information. In Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), marked deficits are evident in learning and memory, presenting in the context of executive dysfunction. It is unclear whether these patients show a typical memory bias for higher valued stimuli. We administered a value-directed word-list learning task to AD (n = 10) and bvFTD (n = 21) patients and age-matched healthy controls (n = 22). Each word was assigned a low, medium or high point value, and participants were instructed to maximize the number of points earned across three learning trials. Participants’ memory for the words was assessed on a delayed recall trial, followed by a recognition test for the words and corresponding point values. Relative to controls, both patient groups showed poorer overall learning, delayed recall and recognition. Despite these impairments, patients with AD preferentially recalled high-value words on learning trials and showed significant value-directed enhancement of recognition memory for the words and points. Conversely, bvFTD patients did not prioritize recall of high-value words during learning trials, and this reduced selectivity was related to inhibitory dysfunction. Nonetheless, bvFTD patients showed value-directed enhancement of recognition memory for the point values, suggesting a mismatch between memory of high-value information and the ability to apply this in a motivationally salient context. Our findings demonstrate that value-directed enhancement of memory may persist to some degree in patients with dementia, despite pronounced deficits in learning and memory.     

Everyday‐like memory for objects in ageing and Alzheimer's disease assessed in a visually complex environment: The role of executive functioning and episodic memory

To investigate everyday memory, more and more studies rely on virtual‐reality applications to bridge the gap between in situ approaches and laboratory settings. In this vein, the present study was designed to assess everyday‐like memory from the virtual reality‐based Human Object Memory for Everyday Scenes (HOMES) test (Sauzéon et al., 2012 , Exp. Psychol., 59, 99) in ageing and in Alzheimer's disease (AD). Two aims motivated this study: the first was to assess multiple processes of episodic memory (EM) functioning embedded within contexts closely related to real life in ageing and AD using the multi‐trial free‐recall paradigm, and the second aim was to evaluate the mediating effects of executive functioning (EF), EM, and subjective memory complaints (SMCs) on age differences in the HOMES measures and in AD. To this end, the HOMES test and neurocognitive tests of EF and EM were administered to 23 younger adults, 23 older adults, and 16 patients with AD. The results were: firstly, compared to young adults, elderly adults presented only free‐recall decline that almost disappeared in recognition condition whereas AD patients exhibited a poor clustering, learning, and recognition performance, and also a high amount of false recognition; secondly, age differences as well as AD related deficits on the HOMES test were mediated by both memory and EF measure while those observed on false memory indices were only mediated by EM measure; thirdly, the HOMES indices are related to SMCs even when episodic or EF measures are controlled. Overall, the results supported the fact that the VR‐based memory test is an appropriate device to capture age‐related differences as well as the AD effect with respect to both in situ and laboratory settings.     

Animal models of source memory

Source memory is the aspect of episodic memory that encodes the origin (i.e., source) of information acquired in the past. Episodic memory (i.e., our memories for unique personal past events) typically involves source memory because those memories focus on the origin of previous events. Source memory is at work when, for example, someone tells a favorite joke to a person while avoiding retelling the joke to the friend who originally shared the joke. Importantly, source memory permits differentiation of one episodic memory from another because source memory includes features that were present when the different memories were formed. This article reviews recent efforts to develop an animal model of source memory using rats. Experiments are reviewed which suggest that source memory is dissociated from other forms of memory. The review highlights strengths and weaknesses of a number of animal models of episodic memory. Animal models of source memory may be used to probe the biological bases of memory. Moreover, these models can be combined with genetic models of Alzheimer's disease to evaluate pharmacotherapies that ultimately have the potential to improve memory.     

The Visual Spatial Learning Test: Differential impairment during the premanifest and manifest stages of Huntington's disease

Visual spatial memory was assessed using the Visual Spatial Learning Test (VSLT) in individuals with mild to moderate Huntington's disease (HD), pre‐manifest gene carriers for HD, and demographically similar controls. The VSLT has been demonstrated to be a valid, normed measure of non‐verbal memory involving minimal motoric responses. The VSLT assesses immediate and delayed memory for designs, positions of the designs, and design/position associations. The HD group was significantly impaired (p < .05) relative to both the control and Pre‐HD groups on immediate and delayed memory for the designs, positions, and design/position associations. Although there were no differences between the Pre‐HD and control groups on immediate or delayed memory for designs or positions, the Pre‐HD group was significantly impaired (p < .05) relative to the control group on immediate and delayed memory for design/position associations. The results offer novel insight into a relatively unexamined memory deficit that may occur in gene carriers for HD prior to phenoconversion. The data indicate that the VSLT may be a useful measure of visuospatial memory during the premanifest and manifest stages of HD.     

Characteristic patterns of verbal memory function in patients with Huntington's disease

Various aspects of verbal memory in patients with Huntington's disease (HD) were studied using the California Verbal Learning Test (CVLT). We tested if the level and interplay between 5 parameters of different memory mechanisms and processes were sufficiently specific to allow acceptable discrimination between patients with HD, patients with Parkinson's disease (PD), and patients without known CNS disease or injury. The HD-patients were characterized by a deficit in acquisition, elevated rates of recall errors and increased use of a passive learning strategy. Preserved aspects were shown in retention over time, interference effects and recognition relative to recall. Employing multivariate classification and validation techniques, the 5 CVLT-features demonstrated good separability between the HD-patients and the control patients. Qualitative similarities between subgroups were suggested, but more disease-specific data seemed necessary in further studies. A number of findings suggested a defect in the active organization of items to be encoded and recalled in HD. Similar findings in the PD-group might indicate that this trait is common in several types of 'subcortical dementia'.     

Illness perceptions and coping explain well-being in patients with Huntington's disease

This study sought to investigate the contribution of illness perceptions and coping mechanisms to the explanation of well-being of patients with Huntington's disease (HD). We investigated the Leventhal et al. assumption of the Self-regulation Model that coping mediates the relationship between illness perceptions and patients’ well-being. Illness perceptions, coping, and well-being in 77 HD patients were assessed with validated questionnaires; motor performance and cognitive performance were assessed with Huntington's disease-specific measures. The assumption that illness perceptions influence HD patients’ well-being via coping was not supported. The results indicate that both coping and illness perceptions made a major contribution to the explanation of variance in HD patients’ psychosocial well-being. Variance in their physical well-being was explained by illness perceptions mainly. The need to conduct further research on the interrelationships between illness perceptions, coping, and well-being in this patient category is discussed.     

Action‐semantic and syntactic deficits in subjects at risk for Huntington's disease

Frontostriatal networks play critical roles in grounding action semantics and syntactic skills. Indeed, their atrophy distinctively disrupts both domains, as observed in patients with Huntington's disease (HD) and Parkinson's disease, even during early disease stages. However, frontostriatal degeneration in these conditions may begin up to 15 years before the onset of clinical symptoms, opening avenues for pre‐clinical detection via sensitive tasks. Such a mission is particularly critical in HD, given that patients’ children have 50% chances of inheriting the disease. Against this background, we assessed whether deficits in the above‐mentioned domains emerge in subjects at risk to develop HD. We administered tasks tapping action semantics, object semantics, and two forms of syntactic processing to 18 patients with HD, 19 asymptomatic first‐degree relatives, and sociodemographically matched controls for each group. The patients evinced significant deficits in all tasks, but only those in the two target domains were independent of overall cognitive state. More crucially, relative to controls, the asymptomatic relatives were selectively impaired in action semantics and in the more complex syntactic task, with both patterns emerging irrespective of the subjects’ overall cognitive state. Our findings highlight the relevance of these dysfunctions as potential prodromal biomarkers of HD. Moreover, they offer theoretical insights into the differential contributions of frontostriatal hubs to both domains while paving the way for innovations in diagnostic procedures.     

Modeling recall memory for emotional objects in Alzheimer's disease

ABSTRACT

Objective: To examine whether emotional memory (EM) of objects with self-reference in Alzheimer's disease (AD) can be modeled with binomial logistic regression in a free recall and an object recognition test to predict EM enhancement.?Method: Twenty patients with AD and twenty healthy controls were studied. Six objects (three presented as gifts) were shown to each participant. Ten minutes later, a free recall and a recognition test were applied. The recognition test had target–objects mixed with six similar distracter objects. Participants were asked to name any object in the recall test and identify each object in the recognition test as known or unknown.?Results: The total of gift objects recalled in AD patients (41.6%) was larger than neutral objects (13.3%) and a significant EM recall effect for gifts was found (Wilcoxon: p < .003). EM was not found for recognition in AD patients due to a ceiling effect. Healthy older adults scored overall higher in recall and recognition but showed no EM enhancement due to a ceiling effect. A logistic regression showed that likelihood of emotional recall memory can be modeled as a function of MMSE score (p < .014) and object status (p < .0001) as gift or non-gift.?Conclusion: Recall memory was enhanced in AD patients for emotional objects indicating that EM in mild to moderate AD although impaired can be provoked with strong emotional load. The logistic regression model suggests that EM declines with the progression of AD rather than disrupts and may be a useful tool for evaluating magnitude of emotional load.     

The relationship between executive function and verbal memory in Parkinson's disease

A growing body of evidence suggests that the various cognitive symptoms found in Parkinson's disease (PD) are secondary to executive dysfunction. Studies addressing this possibility for memory impairment specifically have not included measures of working memory nor have they ruled-out potential mediating variables such as overall level of cognitive impairment or depression. The purpose of this study was to include measures of these variables in determining the relationship between multiple aspects of executive function and delayed verbal recall in 32 idiopathic PD patients. Results were consistent with the original hypothesis and further suggest that working memory is a key factor in recall memory and may mediate the relationship between other executive measures and recall in PD.     

Directed forgetting of autobiographical memory in mild Alzheimer's disease

Using the autobiographical directed forgetting method (Barnier et al., 2007), the present paper addressed the intentional inhibitory processes of episodic and semantic autobiographical memory in Alzheimer's disease (AD). Mild AD patients and healthy elderly people were instructed to either forget or to continue remembering previously generated autobiographical events. In a later recall test they were asked to reconstruct the early-generated memories regardless of the forget/remember instruction. Autobiographical reconstruction was further distributed into episodic and semantic memories. Results showed no forget instruction effect on episodic or semantic autobiographical recall with AD patients, whereas healthy elderly people were able to inhibit only episodic autobiographical memories. The findings suggest an impairment of the intentional inhibitory processes in autobiographical memory with AD and a relative preservation of these mechanisms with normal ageing. They also demonstrate an earlier decline in the intentional inhibitory processes compared to the autobiographical deterioration in AD.     

Mechanisms underlying corruption of working memory in Parkinson's disease

Working memory (WM) impairments are reported to occur in patients with Parkinson's disease (PD). However, the mechanisms are unclear. Here, we investigate several putative factors that might drive poor performance, by examining the precision of recall, the order in which items are recalled and whether memories are corrupted by random guessing (attentional lapses). We used two separate tasks that examined the quality of WM recall under different loads and retention periods, as well as a traditional digit span test. Firstly, on a simple measure of WM recall, where patients were asked to reproduce the orientation of a centrally presented arrow, overall recall was not significantly impaired. However, there was some evidence for increased guessing (attentional lapses). On a new analogue version of the Corsi-span task, where participants had to reproduce on a touchscreen the exact spatial pattern of presented stimuli in the order and locations in which they appeared, there was a reduction in the precision of spatial WM at higher loads. This deficit was due to misremembering item order. At the highest load, there was reduced recall precision, whereas increased guessing was only observed at intermediate set sizes. Finally, PD patients had impaired backward, but not forward, digit spans. Overall, these results reveal the task- and load-dependent nature of WM deficits in PD. On simple low-load tasks, attentional lapses predominate, whereas at higher loads, in the spatial domain, the corruption of mnemonic information—both order item and precision—emerge as the main driver of impairment.     

Subjective organization in the episodic memory of individuals with Parkinson’s disease associated with mild cognitive impairment

Word clustering (i.e., the ability to reproduce the same word pairs in consecutive recall trials of an unrelated word list) has been extensively investigated as a proxy of subjective organization (SO) of memorandum. In healthy subjects and in groups of brain-damaged patients, the rate of SO generally predicts accuracy of word list recall. This study aimed at evaluating SO in the performance of patients with Parkinson’s disease (PD) on a word list recall task in order to investigate the basic mechanisms of episodic memory impairment that are frequently observed in these patients. For this purpose, 56 PD patients, who were stratified according to the presence and quality of mild cognitive impairment (MCI), and a group of healthy controls (HCs) were administered a word list task and an extensive battery of neuropsychological tests. Results showed that recall accuracy on the word list task progressively decreased passing from HC to PD patients without cognitive impairment, to patients with single-domain dysexecutive MCI and to patients with multiple-domain dysexecutive and amnesic MCI. Conversely, only the latter PD group showed a lower SO score than that achieved by the other groups. In the overall PD group, correlational and regression analyses demonstrated that SO scores and a composite score of executive functions were not reciprocally related, but both provided an independent and significant contribution to the prediction of word list recall accuracy. These data are discussed in terms of the contribution of executive functions and hippocampal storage processes to the onset of memory impairment in PD.     

Adaptive memory: enhanced source memory for animate entities

ABSTRACT

The animacy effect refers to enhanced memory for animate over inanimate items. In two studies, we examined whether this memory advantage generalises to source memory. A multinomial processing tree model was used to disentangle item recognition, source memory, and guessing processes. In Study 1, animate and inanimate words were presented at different spatial locations on the screen. Animacy was associated with enhanced source memory for the spatial locations of the items. In Study 2, pseudowords were associated with animate and inanimate properties. Replicating previous results, the pseudowords were better remembered when they were associated with animate properties than when they were associated with inanimate properties. What is more, participants had enhanced source memory for the association between the pseudowords and the animate properties. The results strengthen the idea that animate items are associated with richer mnemonic representations than inanimate items.     

Episodic memory effects of gamma frequency precuneus transcranial magnetic stimulation in Alzheimer's disease: A randomized multiple baseline study

Episodic memory decline is the prominent neuropsychological feature of typical Alzheimer's Disease (AD), for which current treatments have a limited clinical response. Recently, gamma entrainment therapy has been used as a non-invasive treatment in AD, providing evidence that it may have the potential to alleviate brain pathology and improve cognitive function in AD patients. At the same time, the precuneus (PC) has been recognized as a key area involved in AD related memory deficits and as a key node of the Default Mode Network. This study aimed to investigate the effectiveness of a 40 Hz Transcranial Magnetic Stimulation (TMS) intervention, delivered bilaterally to the precuneus for 10 days, in improving the patients' episodic memory performance. Secondary outcome variables investigated included general cognitive function, semantic and spatial memory, as well as attention and executive function. A concurrent multiple baseline design across five cases was employed. Four patients completed the study. Visual analysis combined with effect size indices were used to evaluate changes across phases. An increase in the average level of immediate recalled words was observed in three out of four patients. Effect size indices indicated significant improvement of attention skills in two patients. No treatment effect was observed for semantic and visual memory, or for executive function. An immediate treatment effect was observed in all patients' general cognitive function as assessed with the Alzheimer's Disease Assessment Scale (mean reduction of 5 points), which was maintained and improved further three months post-treatment. The neuropsychological evaluations indicated improved performance three months post-treatment in immediate and delayed recall, attention, phonological verbal fluency, anxiety, and neuropsychiatric symptoms. This study provides preliminary evidence for the efficacy of a novel non-pharmacological treatment using gamma-band TMS in addressing cognitive dysfunction in AD.     

Awareness of memory task impairment versus everyday memory difficulties in dementia

The study investigated different types of awareness of memory dysfunction in dementia, specifically judgements concerning memory task performance or appraisal of everyday memory functioning and also exploring the neuropsychological correlates of such awareness. This was investigated in 76 people with dementia, comprising 46 patients with Alzheimer's disease (AD) and 30 patients with vascular dementia (VaD). The Memory Awareness Rating Scale (Clare et al., 2002, Neuropsychol Rehabil, 12, 341–362) was used, which includes an Objective‐Judgement Discrepancy (OJD) technique involving comparison of subjective evaluation of performance on specific memory tasks with actual performance, and a Subjective Rating Discrepancy (SRD) technique, which compares self versus informant judgement of everyday memory function. The AD and VaD groups showed lower awareness than a normal control group for both types of measures, the AD group showing less awareness than the VaD group on the OJD measure. Regression analyses supported associations for both groups between memory impairment and the OJD measure and between naming impairment and the SRD measure. The findings are discussed in terms of neurocognitive theories accounting for loss of awareness in dementia.     

主观记忆减退老年人情节记忆的行为表现及其脑机制

情节记忆是个体对特定时间,特定地点所经历的特定事件的记忆.主观报告情节记忆下降是主观记忆减退老年人最典型的表现.与健康对照组老年人相比, 主观记忆减退老年人情节记忆下降的速率更快, 罹患老年性痴呆的风险更高, 但其情节记忆加工的脑机制尚不明确.前人研究提示, 主观记忆减退老年人在外在记忆行为尚未出现损伤的情况下, 其大脑情节记忆相关脑区的神经活动已经出现异常.探究主观记忆减退的记忆神经环路关键节点和路径的异常, 揭示神经环路在老年痴呆发生发展中的变化规律, 对深入理解老年痴呆的发病机制有重要的科学意义.同时, 主观记忆减退老年人作为特殊的记忆损伤群体, 对其神经环路的深入探究, 也必将为揭示人类记忆的神经机制做出独特的贡献.     

Musical and verbal memory in Alzheimer’s disease: A study of long-term and short-term memory

Musical memory was tested in Alzheimer patients and in healthy older adults using long-term and short-term memory tasks. Long-term memory (LTM) was tested with a recognition procedure using unfamiliar melodies. Short-term memory (STM) was evaluated with same/different judgment tasks on short series of notes. Musical memory was compared to verbal memory using a task that used pseudowords (LTM) or syllables (STM). Results indicated impaired musical memory in AD patients relative to healthy controls. The deficit was found for both long-term and short-term memory. Furthermore, it was of the same magnitude for both musical and verbal domains whether tested with short-term or long-term memory tasks. No correlation was found between musical and verbal LTM. However, there was a significant correlation between verbal and musical STM in AD participants and healthy older adults, which suggests that the two domains may share common mechanisms.     

Increasing the salience of fluency cues does not reduce the recognition memory impairment in Alzheimer's disease!

In Alzheimer's disease (AD), it is now well established that recollection is impaired from the beginning of the disease, whereas findings are less clear concerning familiarity. One of the most important mechanisms underlying familiarity is the sense of familiarity driven by processing fluency. In this study, we attempted to attenuate recognition memory deficits in AD by maximizing the salience of fluency cues in two conditions of a recognition memory task. In one condition, targets and foils have been created from the same pool of letters (Overlap condition). In a second condition, targets and foils have been derived from two separate pools of letters (No‐Overlap condition), promoting the use of letter‐driven visual and phonetic fluency. Targets and foils were low‐frequency words. The memory tasks were performed by 15 patients with AD and 16 healthy controls. Both groups improved their memory performance in the No‐Overlap condition compared to the Overlap condition. Patients with AD were able to use fluency cues during recognition memory as older adults did, but this did not allow to compensate for dysfunction of recognition memory processes.     

The effects of emotional content on source monitoring in fibromyalgia patients

Source confusion refers to a person’s failure to distinguish whether an event has been actually seen or simply imagined. Nevertheless, prior research has demonstrated a reduction of source confusion for negative arousing information. According to the emotional-congruence effect, this emotional benefit is likely observed in patients suffering from chronic pain. This hypothesis was tested on 15 patients suffering of fibromyalgia syndrome (FMS) and 15 healthy women. In a source-monitoring task, participants had to decide whether positive, negative, and neutral words were imagined or seen with a picture. The results showed recognition deficits and more source confusion for FMS patients compared to controls. Contrary to the hypothesis of negativity bias in fibromyalgia, patients exhibited enhanced recognition for both positive and negative words. Moreover, they showed better source memory for the imagined items than for those seen with a picture. Overall, these results indicate that FMS affects episodic memory.