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.     

A rule-based categorization deficit in Alzheimer's disease?

This study examined the categorization processes that Alzheimer's disease (AD) patients use during assessments of semantic memory. Rule-based categorization involves the careful, analytic processing of strict criteria to determine category membership, particularly for items from graded categories with ambiguous category membership; similarity-based categorization requires an overall comparison of a test stimulus with a prototype or remembered exemplar of the category and is relatively effective for the rapid categorization of items with unambiguous category membership. To assess these processes in AD, patients were asked to decide the category membership of test stimuli for categories with poorly defined or fuzzy boundaries (e.g., VEGETABLE) and for categories with well-defined boundaries (e.g., FEMALE) and then to judge the representativeness of the test stimulus for its chosen category. A subgroup of AD patients demonstrated a typical pattern of impaired semantic memory compared to healthy control subjects; that is, difficulty deciding the category membership of test items from fuzzy categories. Among these patients, we found no deficit in category membership decisions about items taken from well-defined categories. We also found that AD patients and healthy controls do not differ in their representativeness judgments of items within a correctly judged category. These findings are most consistent with the hypothesis that rule-based categorization difficulty limits semantic memory in AD.     

Does diabetes protect or provoke Alzheimer's disease? Insights into the pathobiology and future treatment of Alzheimer's disease

Diabetes mellitus has long been considered a risk factor for the development of vascular dementia. Epidemiologic evidence has suggested that diabetes mellitus significantly increases risk for the development of Alzheimer's disease, independent of vascular risk factors. As insulin's role as a neuromodulator in the brain has been described, its significance for AD has also emerged. Insulin dysregulation may contribute to AD pathology through several mechanisms including decreased cortical glucose utilization particularly in the hippocampus and entorhinal cortex; increased oxidative stress through the formation of advanced glycation end-products; increased Tau phosphorylation and neurofibrillary tangle formation; increased b-amyloid aggregation through inhibition of insulin-degrading enzyme. Future treatment of AD might involve pharmacologic and dietary manipulations of insulin and glucose regulation.     

Are semantic errors actually semantic?: Evidence from alzheimer's disease

Patients with Alzheimer's disease (AD) produce a high rate of semantic errors when naming to confrontation. This is considered to be one of the many consequences of their semantic memory deficit. However, it has been shown, in aphasic patients with focal lesions, that semantic errors could arise from impairment to any one of the levels in the naming process. To check this hypothesis in AD, we assessed in 15 patients the capacity to name and access semantic knowledge (by multiple-choice probe questions) about 14 objects presented successively in the visual, tactile, auditory, and verbal modalities. In the visual naming task, 33 errors were recorded: 26 (78.8%) were semantic and 7 (21.2%) were unrelated errors. Of the 26 semantic errors, 8 were related to a deficit of the semantic knowledge related to the item and 17 to a deficit in the retrieval of the phonological form of the word. One was associated with a deficit of access to semantic knowledge in the visual modality. The 7 unrelated errors were associated with a loss of semantic knowledge for 4 and deficit of access to the phonological form for 3. In conclusion, this study shows that semantic errors do not systematically reflect a deficit of semantic knowledge in Alzheimer's disease. It also seems that unrelated errors are more frequently related to semantic deficits than semantic errors in this population.     

Macro-event recognition in healthy ageing,Alzheimer’s disease,and mild cognitive impairment

Event perception and cognition is integral to our everyday experience and functional ability. A commonly reported complaint in Alzheimer’s disease (AD) is the inability to follow narratives – be it textual, conversational, video, or pictures. This phenomenon has received little systematic research so far. In the current study, we developed a novel paradigm to examine macro-event recognition in individuals with AD in the early stage and its preceding stage of mild cognitive impairment (MCI) in comparison with cognitively healthy older adults, using pictures depicting events. In Experiment 1, we examined participants’ ability to integrate pictorially depicted sub-events into macro-events. The pictures were presented in a scrambled order, and participants were expected to arrange them in the temporally and causally appropriate sequence, as dictated by the macro-event schema. Additionally, we investigated the effect of cueing the appropriate event schema by providing a word cue (verb). In Experiment 2, macro-event recognition was examined again using a cognitively less taxing paradigm, where pictures depicting sub-events were presented in correct order, but staggered, and recognition speed was measured. We observed significant deficits in the AD and MCI groups’ performance compared with the cognitively healthy older adults, across both experiments, suggesting event perception and cognition is impaired early in the course of AD. There was no effect of cueing on the performance of any of the groups. The theoretical and clinical implications of these findings are discussed.     

Inflated and contradictory category naming deficits in Alzheimer's disease?

Although some studies have documented category-specific deficits in patients with Alzheimer's disease, others have not. One possible reason is that where control groups have been used in previous studies, they have performed at ceiling; and this may spuriously affect the incidence and type of deficit reported (especially with common statistical techniques such as z-scores). We examined this issue in 18 Alzheimer's patients and 26 elderly controls, who named two picture sets: a simple set that typically produces ceiling effects (Set 1) and one that produces a normal distribution in controls (Set 2). Sets 1 and 2 produced inconsistent and even contradictory deficits in the same patients. The results also show that ceiling effects may inflate the number of living thing deficits and hence, distort the reported ratio of living to nonliving cases.     

The cloze technique in Arabic: Words or semantic units?

The wide gap between written and spoken variants of the Arabic language turns reading comprehension into a criterion of formal learning. The cloze technique for assessing reading comprehension is a promising tool, but it involves a decision as to whether the elision of complete words, as in English, is to be preferred to the elision of semantic units that are whole words in English but compounded in Arabic and certain other languages. In effect, the question is whether Arabic is decoded mainly by way of perceptual or semantic units. Omitted words or semantic units within words, at the rate of every fifth, sixth, or seventh unit, were replaced by 584 Arab pupils in the fifth, sixth, or seventh grades of Arab schools in Israel. Age and frequency-of-omission trends tended to favor the whole-word elision method, while presumed difficulty of passage agreed with the semantic-unit method. The two methods were shown to be equally valid by a criterion of teacher grades. In sum, the cloze method appears well adapted to Arabic, and there is no apparent reason to abandon the whole-word method used with English and other languages.The generous help of the Institute of Research for Arab Education and Development at the University of Haifa is gratefully acknowleged. The paper was completed while the first author was on sabbatical leave at the University of South Florida, Tampa, Florida.     

The picture superiority effect in categorization: visual or semantic?

Two experiments are reported whose aim was to replicate and generalize the results presented by Snodgrass and McCullough (1986) on the effect of visual similarity in the categorization process. For pictures, Snodgrass and McCullough's results were replicated because Ss took longer to discriminate elements from 2 categories when they were visually similar than when they were visually dissimilar. However, unlike Snodgrass and McCullough, an analogous increase was also observed for word stimuli. The pattern of results obtained here can be explained most parsimoniously with reference to the effect of semantic similarity, or semantic and visual relatedness, rather than to visual similarity alone.     

Is surface dysgraphia tied to semantic impairment? Evidence from a case of semantic dementia

Recent models of lexical processing suggest that written spelling partly depends upon the semantic system. According to these models, a deterioration in word meanings would necessarily lead to a spelling impairment, especially for low-frequency and orthographically irregular words. We report a case study of a patient (MK) with semantic dementia who presents impairments in knowledge of word meanings and surface dysgraphia. By specifically identifying concepts that are still known or that are partially or completely deteriorated, we show that the patient's spelling deficit is highly correlated with word comprehension. These data confirm that surface dysgraphia is directly linked to the breakdown in semantic memory.     

The cholinergic lesion of Alzheimer's disease: pivotal factor or side show?

A profound loss of cortical cholinergic innervation is a nearly invariant feature of advanced Alzheimer's disease (AD). The temporal course of this lesion and its relationship to other aspects of the disease have not yet been fully clarified. Despite assertions to the contrary, a review of the evidence suggests that a perturbation of cholinergic innervation is likely to be present even in the very early stages of AD. This cholinergic lesion is unlikely to be a major determinant of the clinical symptoms or of the neuropathological lesions. Nonetheless, it almost certainly contributes to the severity of the cognitive and behavioral deficits, especially in the areas of memory and attention. The cholinergic lesion may also influence the progression of the neuropathological process through complex interactions with amyloidogenesis, tau phosphorylation and neuroplasticity.     

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.     

Cognitive changes in pregnancy: mild decline or societal stereotype?

This research compared pregnant and non‐pregnant women's perceptions of cognitive change and their performance on 13 sensitive memory and attention tasks (Study 1) and two complex driving simulation tasks (Study 2). The pregnant, but not the non‐pregnant, women rated their cognitive abilities as worse than before, but only two performance measures from Study 1 differentiated the two groups (speed of language processing and attentional switching). Study 3 examined beliefs about pregnancy‐related cognitive decline. Women and men with and without immediate experience of pregnancy rated pregnant women's cognitive abilities as slightly worse than before pregnancy. Memory ratings were worse from women and from those with immediate experience of pregnancy. It is concluded that there may be some mild effects of pregnancy on performance of some specific cognitive functions but that cultural expectations based on a stereotype of cognitive decline also contribute to pregnant women's perception of cognitive change. Copyright © 2008 John Wiley & Sons, Ltd.     

Specific language impairment: a deficit in grammar or processing?

Specific Language Impairment (SLI) is observed in children who fail to acquire age-appropriate language skills but otherwise appear to be developing normally. There are two main hypotheses about the nature of these impairments. One assumes that they reflect impairments in the child's innate knowledge of grammar. The other is that they derive from information-processing deficits that interfere with several aspects of language learning. There is considerable evidence that SLI is associated with impaired speech processing; however, the link between this deficit and the kinds of grammatical impairments observed in these children has been unclear. We suggest that the link is provided by phonology, a speech-based code that plays important roles in learning linguistic generalizations and in working memory.     

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.     

Heterogeneity in verbal memory: a marker of preclinical Alzheimer's disease?

Demonstrations of memory changes in those at risk for Alzheimer's disease by the presence of the APOE e4 allele have been inconsistent to date. The present study went beyond traditional analyses of central tendency (i.e., group differences on mean test scores) and also conducted distribution analyses to search for subtle cognitive differences in subgroups of normal-functioning elderly persons with the APOE e4 genotype. The results of the study revealed that (a) the e4 and non-e4 groups failed to differ in terms of their mean scores on tests of memory and verbal skills; and (b) relative to the non-e4 group, the e4 subjects had significantly greater heterogeneity of variance on the memory measures but not on fundamental verbal skills. Logistic regression analyses indicated that the discrepancy in scores on the memory measures was a significant predictor of genotype group membership (82% correct classification rate). Implications of these findings for the detection of a preclinical phase of AD are discussed.     

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.     

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.