Visual associations to retrieve episodic memory across healthy elderly,mild cognitive impairment,and patients with Alzheimer’s disease

Episodic memory tests need to determine the degree to which patients with moderate to severe memory deficits can still benefit from retrieval support. Especially in the case of Alzheimer’s disease (AD), this may support health care to be more closely aligned with patients’ memory capacities. We investigated whether the different measures of episodic memory of the Visual Association Test-Extended (VAT-E) can provide a more detailed and informative assessment on memory disturbances across a broad range of cognitive decline, from normal to severe impairment as seen in AD, by examining differences in floor effects. The VAT-E consists of 24 pairs of black-and-white line drawings. In a within-group design, we compared score distributions of VAT-E subtests in healthy elderly controls, mild cognitive impairment (MCI), and AD (n = 144), as well as in relation to global cognitive impairment. Paired associate recall showed a floor effect in 41% of MCI patients and 62% of AD patients. Free recall showed a floor effect in 73% of MCI patients and 84% of AD patients. Multiple-choice cued recognition did not show a floor effect in either of the patient groups. We conclude that the VAT-E covers a broad range of episodic memory decline in patients. As expected, paired associate recall was of intermediate difficulty, free recall was most difficult, and multiple-choice cued recognition was least difficult for patients. These varying levels of difficulty enable a more accurate determination of the level of retrieval support that can still benefit patients across a broad range of cognitive decline.     

Fear of falling and falls in older adults with mild cognitive impairment and Alzheimer’s disease

ABSTRACT

The purpose of this study was to explore the influence of social importance on prospective remembering in younger and older adults as a possible factor contributing to the age-prospective memory paradox. Using a between-subjects design, 40 younger and 40 older adults worked on a time-based prospective memory task in which social importance was varied. Overall, younger adults outperformed older adults in the prospective memory task. Importantly, in contrast to younger adults, older adults' prospective memory performance was significantly better in the social importance condition than in the standard condition. This interaction was not reflected in participants' time-monitoring behaviour. Findings are discussed in the context of recent prospective memory theories.     

Social cognition and social functioning in patients with amnestic mild cognitive impairment or Alzheimer’s dementia

The aim of the present study was to examine social cognition and social functioning in a group of amnestic mild cognitive impairment (aMCI) and Alzheimer’s dementia (AD) patients. Thirty one people with aMCI, 29 individuals with AD, and 45 healthy older adults participated in the study. Facial expressions of happiness, anger, fear, disgust, and surprise presented in different intensities had to be labelled. Mentalizing was assessed using first-order belief theory of mind (ToM) stories and everyday social functioning by the Inventory of Interpersonal Situations (IIS), completed by an informant. aMCI patients were impaired in recognizing the emotions anger, disgust, and fear, while AD patients were impaired in recognizing the emotions anger, disgust, and surprise. More importantly, no significant differences between aMCI and AD patients were found on overall emotion recognition. Both the aMCI and AD patients were impaired on the ToM task, but no differences between the aMCI and AD patients were found. On everyday social functioning, only the AD patients showed impairments. No associations between the IIS and ToM were found, but the IIS and emotion perception were significantly correlated. Regression analysis taking all potentially confounding variables into account showed that only mood, but not the social-cognitive task performance or any other cognitive variable, predicted social functioning. aMCI and AD patients demonstrated impairments in mentalizing and facial emotion perception, and showed decrements in everyday social functioning. Informing caregivers about these deficits may help them to understand deficits in social cognition that may be present already in the MCI stage of Alzheimer’s disease.     

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.     

The clinical utility of the auditory P300 latency subcomponent event-related potential in preclinical diagnosis of patients with mild cognitive impairment and Alzheimer’s disease

The present meta-analysis investigated the clinical utility of the auditory P300 latency event-related potential in differentiating patients with Alzheimer’s disease (AD), patients with mild cognitive impairment (MCI), and unaffected controls. Effect size estimates were computed from mean P300 latency measurements at midline electrodes between patients and unaffected controls using the random effects restricted maximum likelihood model. The effects of clinical and ERP/EEG methological variables were assessed in a moderator analysis. P300 latency was found to be significantly prolonged in patients with AD (and MCI) compared to unaffected controls. Shortened P300 latencies were observed when comparing patients with MCI to patients with AD. Clinically relevant differences in P300 latency effect sizes were associated with mean age, interstimulus interval, stimulus difference, target frequency, reference electrode, and sampling rate. The meta-analytic findings provide robust statistical evidence for the use of the auditory P300 latency subcomponent as a biological marker of prodromal AD.     

Artificial grammar learning in Alzheimer’s disease

Patients with early Alzheimer’s disease (AD) exhibit impaired declarative memory although some forms of nondeclarative memory are intact. Performance on perceptual nondeclarative memory tasks is often preserved in AD, whereas conceptual nondeclarative memory is often impaired. A conceptual nondeclarative learning task that has been studied in amnesic patients is the artificial grammar learning (AGL) task. Healthy participants and patients with impaired declarative memory both acquire information about an underlying rule structure in this task and exhibit the ability to identify rule-conforming items, despite the subjective experience of guessing at the response. In this study, 12 patients diagnosed with early AD were tested on the AGL task and a matched recognition task. The patients were able to reliably distinguish rule-conforming items from others, indicating successful AGL. Performance of the AD patients was impaired, relative to controls, on a similar recognition task, although they were found to use information about the grammaticality of study items in an attempt to improve their recognition performance. The AD patients showed a dissociation similar to that seen in anterograde amnesia: impaired recognition memory in conjunction with successful AGL. This finding suggests that the brain areas that support AGL are not compromised early in the course of AD. In addition, the nondeclarative memory of the AD patients acquired during AGL appeared to influence their performance on a declarative memory task, suggesting an interaction between this nondeclarative memory task and declarative memory.     

Normal McCollough effect in Alzheimer’s disease and global amnesia

The McCollough effect (ME), a long-lasting, pattern-contingent aftereffect in normal human vision, was examined in persons with known deficits in memory. We induced MEs in 11 subjects, 5 patients with various severities of Alzheimer’s disease (AD), H.M. (a patient who has global amnesia due to bilateral medial temporal lobectomy and who has been studied for 35 years since his operation), and 5 control subjects. H.M. and the AD patients showed MEs of strength and duration comparable to those of the control subjects. These results demonstrate a dissociation between learning mechanisms that mediate recall and recognition versus mechanisms that mediate the ME. Furthermore, knowledge about the sites of neuropathology in H.M. and in AD are consistent with other sources of evidence implicating early visual areas, especially V1, as a critical locus of the ME.     

Memory profiling in mild cognitive impairment: Can we determine risk for Alzheimer's disease?

Mild cognitive impairment (MCI) is considered a transitional stage between normal ageing and Alzheimer's disease (AD), but not all MCI cases progress to AD and there has been limited focus on how to identify who will progress. Given claims for a characteristic kind of memory impairment in AD involving deficits in encoding and consolidation of information, we propose that ‘memory profiling’ of individuals with MCI may help identify which individuals will progress. We initially set out to establish whether the same characteristic memory profile was present prior to the onset of AD (preAD). Very few studies provided data that allowed us to examine this, but results tentatively supported an encoding/consolidation profile in preAD. A single study tested the clinically important contrast of preAD versus non‐preAD MCI cases and found no difference under any condition or in memory profiles, but interpretation of the findings is limited by short duration of follow‐up, ceiling effects, and task limitations in assessing more complex and qualitative aspects of memory. Although existing data lead to equivocal conclusions, we believe that memory profiling is an endeavour worth pursuing, particularly given the increasing number of people with MCI presenting for clinical assessment. We propose that tests designed specifically to measure memory processes should be sensitive to preAD and are required in prospective longitudinal designs to identify these clinically crucial MCI cases.     

Measuring emotion recognition: Added value in diagnosing dementia of the Alzheimer’s disease type

Neuropsychological tests, particularly for episodic memory, are used to classify patients in memory clinics. Still, the differential diagnosis between dementia of the Alzheimer’s disease type (Dementia-AD), mild cognitive impairment (MCI), or major depressive disorder (MDD) is challenging. However, impairments in other domains, such as emotion recognition, an aspect of social cognition, might have additional value in distinguishing Dementia-AD from MCI and MDD and hence signal progression of neurodegeneration. We evaluated this in patients visiting a memory clinic. Sixty healthy controls (HC) and 143 first time attendants of an academic hospital memory clinic who were eventually classified as Dementia-AD (n = 45), MCI (n = 47), MDD (n = 27), or No Impairment (NI, n = 24) were included. We assessed group differences in Emotion Recognition (Ekman 60 Faces Test (EFT)) and episodic memory (Dutch Rey Auditory Verbal Learning Test (RAVLT)). With multinomial and binomial regression analysis, we assessed whether EFT was added to RAVLT in distinguishing patient groups. Dementia-AD patients had significantly worse emotion recognition than HC, MCI, MDD, and NI groups, but no other between-group differences were found. Episodic memory was impaired in Dementia-AD and MCI patients. We found no memory impairments in the MDD and NI groups. Emotion recognition in addition to episodic memory was significantly better in predicting group membership than episodic memory alone. In conclusion, emotion recognition measurement had added value for differentiation between patients first visiting memory clinics, in particular in distinguishing Dementia-AD from MCI. We recommend the standard inclusion of emotion recognition testing in neuropsychological assessment in memory clinics.     

Memories defining the self in Alzheimer’s disease

ABSTRACT

There is a debate over the extent to which personal identity or the self is preserved in patients with Alzheimer’s disease (AD). Autobiographical memory deficits at early stages of AD could contribute to altering patients’ self. However, the nature of the relationship between autobiographical memory deficits and the self in AD has not been much investigated experimentally. In the present study, we aimed to investigate the integrative meaning of self-defining memories (SDMs) in early stages of AD and to analyse its relationship with the self-concept. The results showed that, when compared to the control group, AD patients less frequently extracted meaning from their SDMs and the meaning was less frequently tied to the self. Patients exhibited some altered aspects of the self-concept (i.e., complexity and strength), though some other components still persisted (i.e., valence and certainty). Correlation analyses showed that the impaired integrative meaning in the AD group was correlated with some changes in self-concept. We suggest that integrative meaning may act as a bridge between autobiographical memories and the self-concept, with reduced integration abilities appearing as a potential mechanism for the deterioration of the self-concept in AD.     

Differential cognitive substrates of verbal episodic memory performance in semantic variant primary progressive aphasia and Alzheimer’s disease

Performance on neuropsychological measures of verbal memory requires cognitive abilities beyond memory. We examined the contribution of semantic knowledge in verbal episodic memory for semantic variant primary progressive aphasia (svPPA) or Alzheimer’s disease (AD). 415 AD and 68 svPPA participants completed measures of episodic memory (visual and verbal) and semantic knowledge. A double dissociation existed visual recall predicted verbal recognition in AD, whereas semantic knowledge contributed to verbal recognition in svPPA.     

Recognition of familiar and unfamiliar melodies in normal aging and Alzheimer’s disease

We tested normal young and elderly adults and elderly Alzheimer’s disease (AD) patients on recognition memory for tunes. In Experiment 1, AD patients and age-matched controls received a study list and an old/new recognition test of highly familiar, traditional tunes, followed by a study list and test of novel tunes. The controls performed better than did the AD patients. The controls showed the “mirror effect” of increased hits and reduced false alarms for traditional versus novel tunes, whereas the patients false-alarmed as often to traditional tunes as to novel tunes. Experiment 2 compared young adults and healthy elderly persons using a similar design. Performance was lower in the elderly group, but both younger and older subjects showed the mirror effect. Experiment 3 produced confusion between preexperimental familiarity and intraexperimental familiarity by mixing traditional and novel tunes in the study lists and tests. Here, the subjects in both age groups resembled the patients of Experiment 1 in failing to show the mirror effect. Older subjects again performed more poorly, and they differed qualitatively from younger subjects in setting stricter criteria for more nameable tunes. Distinguishing different sources of global familiarity is a factor in tune recognition, and the data suggest that this type of source monitoring is impaired in AD and involves different strategies in younger and older adults.     

Anosognosia in Alzheimer’s disease – The petrified self

This paper reviews the literature concerning the neural correlates of the self, the relationship between self and memory and the profile of memory impairments in Alzheimer’s disease (AD) and explores the relationship between the preservation of the self and anosognosia in this condition. It concludes that a potential explanation for anosognosia in AD is a lack of updating of personal information due to the memory impairments characteristic of this disease. We put forward the hypothesis that anosognosia is due in part to the “petrified self.”     

Response to Algarabel et al., 2012 “Recognition memory deficits in mild cognitive impairment”. Reconsidering claims of familiarity disruptions in mild cognitive impairment

There is some debate over the relative impairment of recollection and familiarity in mild cognitive impairment (MCI). A recent publication by Algarabel et al. (2012, Recognition memory deficits in mild cognitive impairment, Aging, Neuropsychology, and Cognition, 19, 608–619) claims to undermine previous studies reporting preserved familiarity in patients with MCI. Here, we respond to their main criticisms, concluding that they are not sufficiently supported by the data presented. The role of recollection and familiarity in MCI remains unresolved and further work will be required to disentangle the mixed literature.     

Working memory in healthy aging and in Parkinson’s disease: evidence of interference effects

Focusing on relevant information while suppressing the irrelevant one are critical abilities for different cognitive processes. However, their functioning has been scarcely investigated in the working memory (WM) domain, in both healthy and pathological conditions. The present research aimed to study these abilities in aging and Parkinson’s disease (PD), testing three groups of healthy participants (young, older and elderly) and one of PD patients, employing a new experimental paradigm. Results showed that the transient storing of irrelevant information in WM causes substantial interference effects, which were remarkable in elderly individuals on both response latency and accuracy. Interestingly, PD patients responded faster and were equally accurate compared to a matched control group. Taken together, findings confirm the existence of similar mechanisms for orienting attention inwards to WM contents or outwards to perceptual stimuli, and suggest the suitability of our task to assess WM functioning in both healthy aging and PD.     

Speech rhythm alterations in Spanish-speaking individuals with Alzheimer’s disease

Rhythm is the speech property related to the temporal organization of sounds. Considerable evidence is now available for suggesting that dementia of Alzheimer’s type is associated with impairments in speech rhythm. The aim of this study is to assess the use of an automatic computerized system for measuring speech rhythm characteristics in an oral reading task performed by 45 patients with Alzheimer’s disease (AD) compared with those same characteristics among 82 healthy older adults without a diagnosis of dementia, and matched by age, sex and cultural background. Ranges of rhythmic-metric and clinical measurements were applied. The results show rhythmic differences between the groups, with higher variability of syllabic intervals in AD patients. Signal processing algorithms applied to oral reading recordings prove to be capable of differentiating between AD patients and older adults without dementia with an accuracy of 87% (specificity 81.7%, sensitivity 82.2%), based on the standard deviation of the duration of syllabic intervals. Experimental results show that the syllabic variability measurements extracted from the speech signal can be used to distinguish between older adults without a diagnosis of dementia and those with AD, and may be useful as a tool for the objective study and quantification of speech deficits in AD.     

Frontotemporal neural systems supporting semantic processing in Alzheimer’s disease

We hypothesized that semantic memory for object concepts involves both representations of visual feature knowledge in modality-specific association cortex and heteromodal regions that are important for integrating and organizing this semantic knowledge so that it can be used in a flexible, contextually appropriate manner. We examined this hypothesis in an fMRI study of mild Alzheimer’s disease (AD). Participants were presented with pairs of printed words and asked whether the words matched on a given visual–perceptual feature (e.g., guitar, violin: SHAPE). The stimuli probed natural kinds and manufactured objects, and the judgments involved shape or color. We found activation of bilateral ventral temporal cortex and left dorsolateral prefrontal cortex during semantic judgments, with AD patients showing less activation of these regions than healthy seniors. Moreover, AD patients showed less ventral temporal activation than did healthy seniors for manufactured objects, but not for natural kinds. We also used diffusion-weighted MRI of white matter to examine fractional anisotropy (FA). Patients with AD showed significantly reduced FA in the superior longitudinal fasciculus and inferior frontal-occipital fasciculus, which carry projections linking temporal and frontal regions of this semantic network. Our results are consistent with the hypothesis that semantic memory is supported in part by a large-scale neural network involving modality-specific association cortex, heteromodal association cortex, and projections between these regions. The semantic deficit in AD thus arises from gray matter disease that affects the representation of feature knowledge and processing its content, as well as white matter disease that interrupts the integrated functioning of this large-scale network.