Disrupted memory inhibition in dementia of Alzheimer’s type

Cognitive inhibition has been suggested to deteriorate in Alzheimer’s disease. While numerous studies with different experimental paradigms found evidence on impaired inhibition in attention and memory, evidence in favour of intact memory inhibition has been reported with regard to the phenomenon of retrieval-induced forgetting (Moulin et al., 2002). Here, we adapted the previously used paradigm in order to reduce the contribution of non-inhibitory processes and examined whether retrieval-induced forgetting could still be observed in a sample of participants with diagnosed Alzheimer’s disease. In contrast to the previous finding, we found that retrieval-induced forgetting only occurred in an age-matched control group. These results suggest that inhibitory deficits in Alzheimer’s disease also generalize to memory inhibition that resolves interference occurring during retrieval, whereas effects of retrieval-induced forgetting may still occur when non-inhibitory causes, such as, blocking by previously retrieved content, are not precluded.     

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.     

Self-reference and emotional memory effects in older adults at increased genetic risk of Alzheimer’s disease

The present study investigated whether cognitively healthy older adults who are carriers of the ε4 allele of apolipoprotein E, the most prevalent genetic risk factor for late-onset Alzheimer’s disease, benefit from self-referential processing and emotional processing to the same degree as noncarriers of this gene. Participants encoded emotional and nonemotional narratives using a baseline-orienting task, semantic elaboration, or imagination-based self-referential processing and then completed a recognition memory test. Both groups of older adults showed enhanced recognition memory for narrative information following self-referential processing relative to semantic elaboration, and the magnitude of this memory effect was not affected by ε4 status. However, older adult ε4 carriers did not show an emotional enhancement effect, whereas older adult ε4 noncarriers did. These results indicate that whereas the self-reference effect is not attenuated in cognitively healthy older adults ε4 carriers, deficits in emotional memory may be an early cognitive marker of abnormal decline.     

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.     

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.”     

Computerized assessment of syntactic complexity in Alzheimer’s disease: a case study of Iris Murdoch’s writing

Currently, the majority of investigations of linguistic manifestations of neurodegenerative disorders such as Alzheimer’s disease are conducted based on manual linguistic analysis. Grammatical complexity is one of the language use characteristics sensitive to the effects of Alzheimer’s disease and is difficult to operationalize and measure using manual approaches. In the current study, we demonstrate the application of computational linguistic methods to automate the analysis of grammatical complexity. We implemented the Computerized Linguistic Analysis System (CLAS) based on the Stanford syntactic parser (Klein and Manning, Pattern Recognition, 38(9), 1407–1419, 2005) for longitudinal analysis of changes in syntactic complexity in language affected by neurodegenerative disorders. We manually validated CLAS scoring and used it to analyze writings of Iris Murdoch, a renowned Irish author diagnosed with Alzheimer’s disease. We found clear patterns of decline in grammatical complexity consistent with previous analyses of Murdoch’s writing conducted by Garrard, Maloney, Hodges, and Patterson (Brain, 128(250–260, 2005). CLAS is a fully automated system that may be used to derive objective and reproducible measures of syntactic complexity in language production and can be particularly useful in longitudinal studies with large volumes of language samples.     

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.     

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.     

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.     

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.     

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.     

Gaze tracking patterns on different types of traffic risk in early-stage Alzheimer’s disease

Many fatal accidents are caused by the driver’s inability, upon the occurrence of sudden events, to detect hazards in time, an ability that is based on the driver’s eye movement patterns, the detection of involved persons, events, objects, as well as the length of time spent on noticing same. This study intends to compare risk perception and decision-making in high-risk traffic situations between individuals with AD and controls by exploring gaze tracking and hazard detection patterns. The study included 16 individuals with early-stage AD and 26 controls. During the experiment, participants underwent several vision and cognitive tests and watched twelve videos of high-risk traffic situations while their eye movement patterns were being recorded by the eye tracking device, in order to understand how cognitive abilities affect eye movement patterns during high-risk traffic situations. The results revealed poorer cognitive abilities and diminished risk perception in individuals with AD compared with the controls and thus an inability to predict potential accidents. In terms of high-risk traffic situations involving pedestrians, traffic violations by others and view-blocking events, a significant difference in gaze patterns was found between individuals with AD and healthy seniors. The contribution of this study is in elaborating the effect of different traffic event type and specific cognitive abilities on traffic risk-detection in individuals with AD. The results of this study may aid in the formulation of driver licensing policies and the design of traffic scenarios; they also elucidate the driving behaviors of individuals with AD.     

Association rule learning in neuropsychological data analysis for Alzheimer’s disease

Efficient methods of analysis readily available for clinicians continue to be limited within neuropsychological assessment at the raw data level. Here, a novel approach for generating predictive response patterns and analysing neuropsychological raw data is offered. In order to assess the usefulness of association rule learning as an analysis tool for neuropsychological raw data, Frequent Pattern Growth (FP-Growth) was used to mine patterns from the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery (CERAD-NB) database. Complete assessment data for 84 post-mortem confirmed Alzheimer’s disease (AD) cases and 294 age, race, and education matched controls were analysed across baseline and one-year follow-up using FP-Growth, for the purpose of assessing the clinical utility of a finer analysis at the raw data level and the feasibility of predicting response patterns for clinical/control groups. Output from FP-Growth, in terms of the number of frequent itemsets retained across both evaluation timepoints, was discernable between controls, mild, and moderate to severe Alzheimer’s disease cases (p < .001, and η² = .488). Patterns within raw data scores, both in terms of frequent itemsets and predictive association rules, appear to be differentiable across groups within neuropsychological analysis, which indicates that FP-Growth is applicable as a supplementary analysis tool for neuropsychological assessment by means of offering an additional level of data analysis, predictive item response capabilities, and aiding in clinical decision making.     

Neuropsychological indicators of preclinical Alzheimer’s disease among depressed older adults

Older adults with major depressive disorder (MDD) may also have preclinical Alzheimer’s disease (AD). Differential diagnosis is quite challenging due to the overlapping symptoms of MDD and AD. In the current study, we predicted that impaired long-term memory (an area most affected in early AD), but not executive function (an area affected in MDD and AD), would distinguish older depressed patients who developed AD from those who did not. Patients (N = 120) assessed as having MDD but not dementia at baseline were administered tests of cognitive function and followed longitudinally for subsequent diagnosis of AD. Using structural equation modeling we found a latent construct of long-term memory to be associated with AD to a greater extent than executive functioning. Additional analyses to enhance clinical utility of findings indicated that individual tests of episodic memory were most predictive of AD status. Tests of long-term memory can be utilized by the clinician when assessing for preclinical AD among depressed elderly.     

Discrepancy between subjective autobiographical reliving and objective recall: The past as seen by Alzheimer’s disease patients

This paper investigated whether Alzheimer’s disease (AD) patients may demonstrate a discrepancy between subjective autobiographical reliving and objective recall. To this end, 31 AD patients and 35 controls were asked to retrieve three autobiographical memories. For each memory, participants were asked to rate its subjective characteristics (e.g., reliving, travel in time, visual imagery…). Besides this subjective assessment, we analyzed recall objectively with regard to specificity. Results showed poorer subjective autobiographical reliving and objective recall in AD patients than in controls. A discrepancy (i.e., higher level of subjective reliving than of objective recall) was observed in AD but not in control participants. Despite a compromise in their objective recall, AD patients seemed to attribute a high value to their subjective autobiographical experience. This discrepancy can be attributed to a potential genuine consciousness experience in which mild AD patients can, to some extent, experience some subjective features of the past.     

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.     

Robert Hooke’s model of memory

In 1682 the scientist and inventor Robert Hooke read a lecture to the Royal Society of London, in which he described a mechanistic model of human memory. Yet few psychologists today seem to have heard of Hooke’s memory model. The lecture addressed questions of encoding, memory capacity, repetition, retrieval, and forgetting—some of these in a surprisingly modern way. Hooke’s model shares several characteristics with the theory of Richard Semon, which came more than 200 years later, but it is more complete. Among the model’s interesting properties are that (1) it allows for attention and other top-down influences on encoding; (2) it uses resonance to implement parallel, cue-dependent retrieval; (3) it explains memory for recency; (4) it offers a single-system account of repetition priming; and (5) the power law of forgetting can be derived from the model’s assumptions in a straightforward way.