Learning and vulnerability to phonological and semantic interference in normal aging: an experimental study.

ABSTRACTThis study compares semantic and phonological interference vulnerability across the full range of learning processes. Method: 43 controls aged 61-88 underwent a neuropsychological examination, French adaptation of the LASSI-L, and an experimental phonological test, the TIP-A. Paired sample t-tests, factorial ANOVA and hierarchical regressions were conducted, psychometric properties were calculated. Results: TIP-A efficiently generated phonological interference between concurrent word lists and was associated with short-term memory, unlike LASSI-L. On LASSI-L, proactive interference was higher than retroactive interference; the opposite pattern was found on TIP-A. Memory performance was better explained by age in the semantic than in the phonological task. Age was not associated with interference vulnerability. Intrusions and false recognition were associated with cognitive functioning regardless of age, particularly in the semantic context. Conclusion: To our knowledge, this is the first study to assess phonological and semantic interference using homologous concurrent word list tasks, and not a working memory build-up or DRM paradigm. The pattern obtained illustrates the weak initial memory trace in a phonological context and results are discussed according to depth-of-processing and dual-process theories. Similar paradigms could be studied among various pathologies for a better understanding of generalised interference vulnerability vs. specific semantic or phonological impairment.

An Examination of Semantic Impairment in Amnestic MCI and AD: What Can We Learn From Verbal Fluency?

INTRODUCTION: The Verbal Fluency Test (VF) is commonly used in neuropsychology. Some studies have demonstrated a marked impairment of semantic VF compared to phonemic VF in Alzheimer's disease (AD). Since amnestic Mild Cognitive Impairment (aMCI) is associated with increased risk of conversion to incident AD, it is relevant to examine whether a similar impairment is observed in this population. The objective of the present empirical study is to compare VF performance of aMCI patients to those of AD and elderly controls matched one-to-one for age and education. METHOD: Ninety-six participants divided into three equal groups (N = 32: AD, aMCI and Controls) were included in this study. Participants in each group were, on average, 76 years of age and had 13 years of education. A repeated measures ANOVA with the Group (AD, aMCI, NC) as between-subject factor and the Fluency condition ("P" and "animals") as within-subject factor was performed. T-tests and simple ANOVAs were also conducted to examine the interaction. RESULTS: There was a significant interaction between the groups and the verbal fluency condition. In AD, significantly fewer words were produced in both conditions. In contrast, participants with aMCI demonstrated a pattern similar to controls in the phonemic condition, but generated significantly fewer words in the semantic condition. CONCLUSION: These results indicate a semantic memory impairment in aMCI revealed by a simple, commonly-used neuropsychological test. Future studies are needed to investigate if semantic fluency deficits can help predict future conversion to AD.

Naming unique entities in the semantic variant of primary progressive aphasia and Alzheimer's disease: Towards a better understanding of the semantic impairment.

While the semantic variant of primary progressive aphasia (svPPA) is characterized by a predominant semantic memory impairment, episodic memory impairments are the clinical hallmark of Alzheimer's disease (AD). However, AD patients also present with semantic deficits, which are more severe for semantically unique entities (e.g. a famous person) than for common concepts (e.g. a beaver). Previous studies in these patient populations have largely focused on famous-person naming. Therefore, we aimed to evaluate if these impairments also extend to other semantically unique entities such as famous places and famous logos. In this study, 13 AD patients, 9 svPPA patients, and 12 cognitively unimpaired elderly subjects (CTRL) were tested with a picture-naming test of non-unique entities (Boston Naming Test) and three experimental tests of semantically unique entities assessing naming of famous persons, places, and logos. Both clinical groups were overall more impaired at naming semantically unique entities than non-unique entities. Naming impairments in AD and svPPA extended to the other types of semantically unique entities, since a CTRL>AD>svPPA pattern was found on the performance of all naming tests. Naming famous places and famous persons appeared to be most impaired in svPPA, and both specific and general semantic knowledge for these entities were affected in these patients. Although AD patients were most significantly impaired on famous-person naming, only their specific semantic knowledge was impaired, while general knowledge was preserved. Post-hoc neuroimaging analyses also showed that famous-person naming impairments in AD correlated with atrophy in the temporo-parietal junction, a region functionally associated with lexical access. In line with previous studies, svPPA patients' impairment in both naming and semantic knowledge suggest a more profound semantic impairment, while naming impairments in AD may arise to a greater extent from impaired lexical access, even though semantic impairment for specific knowledge is also present. These results highlight the critical importance of developing and using a variety of semantically-unique-entity naming tests in neuropsychological assessments of patients with neurodegenerative diseases, which may unveil different patterns of lexical-semantic deficits.

Successful methodology for large-scale surveillance of severe events following influenza vaccination in Canada, 2011 and 2012.

In 2011 and 2012, a nationwide Canadian vaccine safety surveillance network rapidly collected safety data from healthcare workers (HCW) during the first weeks of the annual influenza vaccination campaign. This network provided the first available post-marketing safety data on seasonal influenza vaccines with information on background rates as a comparator. In 2012, these data were used to investigate a possible safety concern regarding a particular vaccine. An online questionnaire was provided to participating HCW two weeks before the annual influenza vaccination campaign for controls, and eight days after influenza vaccination for vaccinees. Control and vaccinees were requested to report health events occurring in the seven days prior to receiving the questionnaire. Control data were used to calculate background rates. HCW reporting a severe event were followed-up by telephone within 48 hours of the online report to validate the report and check on their health status. More than 22,000 vaccinated HCW were enrolled and surveyed over two seasons and > 90% reported no severe event following vaccination. Validated severe event rates were similar in vaccinated HCW and unvaccinated HCW (2.2% vs 2.3%; p < 0.70). The questionnaire was accurately completed for most reported symptoms, matched the validated report and was able to detect events of interest. Prior to the safety concern, the implicated vaccine was in use at one centre. Reassuring safety data were provided to public health authorities 48 hours after the vaccine was temporarily suspended. Data from this and similar networks can be used for rapid evaluation of vaccine safety and for safety assessment as required by the European Medicines Agency in 2015.

Insular ischemic stroke: clinical presentation and outcome.

BACKGROUND: The insula is a small but complex structure located in the depth of the sylvian fissure, covered by the frontal, parietal and temporal operculum. Ischemic strokes limited to the insula are rare and have not been well studied. Our objective is to better define the clinical presentation and outcome of insular ischemic strokes (IIS). METHODS: We reviewed the institutional prospective, consecutive stroke database from two centers to identify patients with IIS seen between 2008 and 2010. We also searched the Medline database using the keywords insula(r), infarction and stroke to identify previously published IIS cases confirmed by MRI. Minimal extension to an adjacent operculum or subinsular area was accepted. Clinicoradiological correlation was performed by distinguishing IIS involving the anterior (AIC) or posterior insular cortex (PIC). We collected clinical, demographic and radiological data. The outcome was determined using the modified Rankin Scale (mRS). RESULTS: We identified 7 patients from our institutions and 16 previously published cases of IIS. Infarcts were limited to the AIC (n = 4) or the PIC (n = 12) or affected both (n = 7). The five most frequent symptoms were somatosensory deficits (n = 10), aphasia (n = 10), dysarthria (n = 10), a vestibular-like syndrome (n = 8) and motor deficits (n = 6). A significant correlation was found between involvement of the PIC and somatosensory manifestations (p = 0.04). No other statistically significant associations were found. IIS presentation resembled a partial anterior circulation infarct (n = 9), a lacunar infarct (n = 2) or a posterior circulation infarct (n = 2). However, most cases presented findings that did not fit with these classical patterns (n = 10). At the 6 month follow up, mRS was 0 in 8/23 (35%) patients, 1-2 in 7/23 (30%) and unknown in 8/23 (35%). CONCLUSIONS: IIS presentation is variable. Due to the confluence of functions in a restricted region, it results in multimodal deficits. It should be suspected when vestibular-like or motor but especially somatosensory, speech or language disturbances are combined in the same patient. The outcome of IIS is often favorable. Larger prospective studies are needed to better define the clinical presentation and outcome of IIS.

Impact of the cognitive status on the memory complaints in MS patients.

OBJECTIVE: Despite the evidence of cognitive deficits in Multiple Sclerosis (MS) patients, evaluation of their cognitive integrity is often limited to the use of clinical interviews and questionnaires. However, the consensus in the literature is that these patients under- or overestimate their deficits and repercussions. The objective of this study was to clarify why some patients overestimate while others underestimate their memory deficits. METHOD: Fifty-four participants (30 MS, 24 controls) completed the Prospective and Retrospective Memory Questionnaire (PRMQ) and were tested on a battery of neuropsychological tests. Based on the test results, MS patients were categorized as having either mild or moderate/severe cognitive deficits. RESULTS: The moderate/severe MS group differed from the two other groups on the Rey Auditory Verbal Learning Test (RAVLT) but did not differ from the control group on the PRMQ. Conversely, the mild MS group did not differ from the control group on the RAVLT but did report significantly more problems than this group on the PRMQ. There was no difference between the two clinical groups on the Depression Index (Beck) but there was a significant correlation (r=.409) between the depression scores and the overestimation of prospective memory problems (PRMQ). CONCLUSION: The results explain the contradiction in the literature. It is the mild group who overestimates, maybe because they are overly concerned by their deficits, whereas the cognitive impairments of the moderate/severe group lead them to underestimate and may make their self-assessment unreliable. Formal testing or information from a significant other would be advisable.

Unruptured Intracranial Aneurysms. A Critical Review of the International Study of Unruptured Intracranial Aneurysms (ISUIA) and of Appropriate Methods to Address the Clinical Problem.

SUMMARY: The preventive treatment of unruptured aneurysms has been performed for decades despite the lack of evidence of a clinical benefit. Reports of observational studies such as the International Study of Unruptured Intracranial Aneurysms (ISUIA) suggest that preventive treatments are rarely justified. Are these reports compelling enough to guide clinical practice? The ISUIA methods and data are reviewed and analysed in a more conventional manner. The design of the appropriate clinical research program is approached by steps, reviewing potential problems, from the formulation of the precise research question to the interpretation of subgroup analyses, including sample size, representativity, duration of observation period, blinding, definition of outcome events, analysis of cross-overs, losses to follow-up, and data reporting. Unruptured intracranial aneurysms observed in ISUIA ruptured at a minimal annual rate of 0.8% (0.5-1%), despite multiple methodological difficulties biased in favour of a benign natural history. Available registries do not have the power or the design capable of providing normative guidelines for clinical decisions. The appropriate method to solve the clinical dilemma is a multicentric trial comparing the incidence of a hard clinical outcome events in approximately 2000 patients randomly allocated to a treatment group and a deferred treatment group, all followed for ten years or more. Observational studies have failed to provide reliable evidence in favour or against the preventive treatment of unruptured aneurysms. A randomized trial is in order to clarify what is the role of prevention in this common clinical problem.

Trial on endovascular treatment of unruptured aneurysms (TEAM): study monitoring and rationale for trial interruption or continuation.

Preventive treatment of unruptured intracranial aneurysms is often performed but has never been proved beneficial as compared to conservative management. In a context of uncertainty, the 'best treatment' that can be offered to each individual is a chance to be treated and thus to be protected from rupture of the aneurysm, and an equal chance not to be treated, and hence to be exempted from possible immediate complications, using randomization. Such action is optimal unless or until an independent committee with privileged access to data judges that, given the comparative outcome of the 2 groups, preventive treatment or conservative management, is generally warranted. Potential reasons to interrupt such a study are reviewed, including insufficient recruitment, poor compliance, excessive cross-overs, unacceptable iatrogenia, and treatments being convincingly different or equivalent. We conclude that insufficient recruitment is the sole realistic event that could lead to premature interruption. This review may provide a deeper understanding of the principles justifying the necessity of the study.

Pattern of intrusions in verbal recall: comparison of Alzheimer's disease, Parkinson's disease, and frontal lobe dementia.

Although some researchers have suggested that intrusions in word list learning are more frequent in Alzheimer's disease, recent studies have shown that this might not be true. In fact, intrusions are common in many neurological degenerative diseases. The goal of the present study was to examine the types of intrusions made by three groups of patients, namely patients with Parkinson's disease (PD), Alzheimer's disease (AD), and dementia with prominent frontal lobe semiology (FD). Although PD patients learned more words (trials 1 to 5 on the RAVLT) than the two other groups, there was no significant difference in the total number of intrusions. However, significant differences between groups were observed for nonrelated intrusions, the proportion of PD patients (15.4%) being lower than the proportion of AD (45.5%) and FD (45.8%) patients with this type of intrusions. No other type of intrusions (same category, recurring, phonemic) significantly differentiated between the three groups. The proactive interference effect (PI), measured as the difference between first recall of list A and list B recall, was stronger in PD than in the two other groups, reflecting the strong positive correlation between total number of words recalled on the RAVLT and severity of the PI effect. Prior list intrusions (intrusions from list A while recalling list B items) were significantly more pronounced in FD than in the two other groups. Finally, free associations (series of intrusions related to one another but not to the target items) were observed almost exclusively in FD patients. These findings illustrate some qualitative differences between various neurological degenerative diseases. They also stress the marked similarities between AD and FD with regards to verbal learning.

Prevalence, and intellectual outcome of unilateral focal cortical brain damage as a function of age, sex and aetiology.

Neurologists and neuropsychologists are aware that aging men are more at risk than women for brain damage, principally because of the well known male-predominant risk for cardiovascular disease and related cerebrovascular accidents. However, a disproportion in prevalence of brain damage between the sexes in childhood may be less suspected. Furthermore, sex-specific risk for other aetiologies of brain damage may be little known, whether in the pediatric or adult populations. Proposals of a sex difference in cognitive recovery from brain damage have also been controversial. Six hundred and thirty five "consecutive" cases with cortical focal lesions including cases of all ages and both sexes were reviewed. Aetiology of the lesion was determined for each case as was postlesion IQ. Risk was highly male prevalent in all age groups, with a predominance of cardiovascular aetiology explaining much of the adult male prevalence. However, several other aetiological categories were significantly male prevalent in juveniles (mitotic, traumatic, dysplasic) and adults (mitotic, traumatic). There was no sex difference in outcome (i.e., postlesion IQ) of these cortical brain lesions for the cohort as a whole, after statistical removal of the influence of lesion extent, aetiology and presence of epilepsy. Mechanisms potentially responsible for sex differences in prevalence, aetiology of brain damage, and recovery, are reviewed and discussed.

Cognitive deficits associated with sleep apnea syndrome: a proposed neuropsychological test battery.

Numerous studies have assessed a wide range of cognitive deficits associated with obstructive sleep apnea syndrome (OSAS). The comparison of these various results, however, is hampered by the fact that different studies employ different neuropsychological tests, even when assessing the same function. The aim of this paper is to present a standardized neuropsychological test battery for the evaluation of OSAS patients. Following a description of the general characteristics of OSAS, we review the main cognitive functions reported as being impaired in OSAS patients. These include general intellectual functioning, attentional functioning, memory and learning abilities, executive functions, and motor performance. Based on this review, we propose a test battery designed to cover these cognitive processes while taking into account the time constraints present in most research and clinical centers. In addition to providing a comprehensive neuropsychological evaluation of OSAS patients, the proposed test battery should facilitate the comparison of results from different laboratories.

Postictal aphasia and paresis: a clinical and intracerebral EEG study.

BACKGROUND: We examined the lateralizing value of postictal language and motor deficits and studied their underlying mechanisms. PATIENTS AND METHODS: The total sample consisted of 35 patients (26 temporals, 8 frontals, 1 parietal) with a good postsurgical outcome (Engel's class I and II). Postictal examination was blindly reviewed on videotapes. In 15 cases (29 seizures), postictal language manifestations were analyzed in relation with the diffusion of the epileptic discharge recorded by intracerebral EEG. Language dominance was determined by the intracarotid amobarbital test. RESULTS: Postictal aphasia was observed only when (1) seizure originated in the dominant hemisphere and (2) ictal activity spread to language areas (Wernicke and/or Broca areas). When the epileptic focus was in the nondominant hemisphere, no postictal aphasia was observed even if there was secondary generalization of ictal activity affecting the language areas of the dominant hemisphere. Postictal motor deficits also had a strong lateralizing value even when seizures were secondarily generalized. CONCLUSION: Postictal aphasia in temporal epilepsies and postical motor deficits in temporal and extra temporal epilepsies provided excellent lateralizing information. Postictal deficits appear to be the result of inhibitory mechanisms induced by previous ictal activity of the structures related to these functions.

Frontal lesions impair the attentional control of movements during motor learning.

This study examined the effects of frontal lobe lesions on the control of movements during motor learning. We compared the performance of patients with unilateral frontal or temporal excisions and controls in two-dimensional aiming movements during adaptation to a transformed visuomotor mapping. Subjects tried to reach a fixed target on a graphics tablet using indirect visual control from a monitor in either: (1) the standard visuomotor mapping, (2) a full inversion of motor space preserving the axis of movement, or (3) a mirror-like inversion of one axis of motor space. In the standard mapping, all groups showed precise and rapid aiming movements. In the full inversion condition, frontal lobe patients showed a stronger tendency than others to initiate movements in the natural direction (capture errors) during adaptation. In the mirror-like inversion, frontal patients showed deficits in both movement initiation and movement corrections. These control deficits disappeared with practice. These data provide evidence for a critical role of frontal cortex in the attentional control of unpracticed movements in man.

Absence of correlation between amobarbital distribution as assessed with SPECT brain perfusion imaging and behavioral manifestations during the intracarotid amobarbital procedure (Wada test).

1. The IAP is used presurgically in patients with temporal lobe epilepsy to predict the effects on LTM and language of the planned temporal lobectomy. This prognosis presumes that a similar pattern of perfusion will result in anesthesia of the same cerebral regions in most patients. 2. Coinjection of Tc-99m HMPAO with the barbiturate during the IAP has been used to ascertain whether this actually is true, with variable results. Moreover, most studies document only unilateral IAPs and do not report on behavioral performance. 3. The authors coinjected Tc-99m HMPAO and amobarbital in 33 IAPs from 18 patients (15 injected bilaterally, 3 unilaterally) to clarify this and to evaluate the relationship of the perfusion pattern to behavioral performance; SPECT results were also compared to angiographic evaluation obtained at the time of catheter placement. 4. SPECT perfusion data was rated for presence/absence and intensity of perfusion to the ACA, MCA, PCA territories and to H, i or c to the injection site. V, STM and LTM were graded according to a standardized protocol. 5. MCAi was perfused in 100% of cases, ACAi in 91%, PCAi in 21% and Hi in only 6%. Cross-over flow was shown in 9 studies; 50% of the patients in whom both sides were injected (on different days) had crossover, involving the ACAc territory in 80% of cases. As expected, injection on the non-ES was associated with a significantly worse LTM performance than on the ES (p = 0.006). There was no relationship between the perfusion pattern and the V level of the patients (a potential confounding variable in memory/language evaluation) during IAP, nor between perfusion pattern and LTM. STM was significantly adversely affected by the presence of crossover perfusion. Angiography in general overestimated the extent of cerebral perfusion demonstrated by SPECT, most probably because of the markedly different injection conditions. 6. Despite the best efforts to standardize injections, the perfusion pattern has been mostly unpredictable in the patients. Moreover, it has little bearing on their behavioral performance, except for the prediction of poor STM performance (the clinical implications of this remaining dubious). Marked LTM alterations after non-ES injections confirm remote hippocampal effects in the presence of only rare direct perfusion of that region. Tc-99m HMPAO/Amobarbital coinjection was unhelpful from a clinical perspective, most probably because a large part of the effects of amobarbital arise from deafferentation of regions not directly perfused by the anesthetic agent.

Effect of focus lateralization on memory assessment during the intracarotid amobarbital procedure.

Despite the use of stimuli that can be processed by both hemispheres, a number of studies have reported lower memory scores after the left intracarotid amobarbital procedure (IAP) than after the right IAP. Because of that, failure after ipsilateral IAP is observed more often in patients with a left temporal seizure focus (LT) than in right temporal patients (RT), possibly needlessly excluding some LT patients from surgery. In order to overcome the deleterious effects of anesthetizing the dominant hemisphere, we designed an IAP protocol that did not promote verbal encoding of the stimuli. For this purpose, a large number of visual and tactile stimuli (colored pictures and real objects) were presented to be recognized later. The effect of seizure focus lateralization was examined in 82 temporal lobe epileptic patients who underwent IAP as part of their presurgical evaluation. As expected, for both RT and LT patients, long-term recognition of pictures presented under the effect of amobarbital was highly sensitive to the presence of a contralateral epileptic focus. However, contrary to what is generally reported, LT patients performed better than RT patients when their left (ipsilateral) hemisphere was anesthetized. In RT patients, although memory scores were lower after the left contralateral injection, the disparity in memory scores between the right and left injection was not as marked as in LT patients. These results are discussed in terms of the influence of type of processing required during the initial encoding on later recognition during IAP.

The 48-Pictures Test: a two-alternative forced-choice recognition test for the detection of malingering.

We tested the validity of the 48-Pictures Test, a 2-alternative forced-choice recognition test, in detecting exaggerated memory impairments. This test maximizes subjective difficulty, through a large number of stimuli and shows minimal objective difficulty. We compared 17 suspected malingerers to 39 patients with memory impairments (6 amnesic, 15 frontal lobe dysfunctions, 18 other etiologies), and 17 normal adults instructed to simulate malingering on three memory tests: the 48-Pictures Test, the Rey Auditory Verbal Learning Test (RAVLT), and the Rey Complex Figure Test (RCFT). On the 48-Pictures Test, the clinical groups showed good recognition performance (amnesics: 85%; frontal dysfunction: 94%; other memory impairments: 97%), whereas the two simulator groups showed a poor performance (suspected malingerers: 62% correct; volunteer simulators 68% correct). The two other tests did not show a high degree of discrimination between the clinical groups and the simulator groups, except in 2 measures: the 2 simulator groups tended to show a performance decrement from the last recall trial to immediate recognition of the RAVLT and also performed better than the clinical groups on the immediate recall of the RCFT. A discriminant analysis with the latter 2 measures and the 48-Pictures Test correctly classified 96% of the participants. These results suggest that the 48-Pictures Test is a useful tool for the detection of possible simulated memory impairment and that when combined to the RAVLT recall-recognition difference score and to the immediate recall score on the RCFT can provide strong evidence of exaggerated memory impairment.

Longitudinal analysis of clock drawing in Alzheimer's disease patients.

Longitudinal changes in the role of conceptual, spatial, and graphic processes in the drawing deficits of patients with Alzheimer's disease (AD) were assessed over a 2-year period. Both the drawing-to-command and copy conditions of the Clock Drawing Test were administered to 33 AD patients as part of three consecutive annual examinations. The drawings from each administration were evaluated for overall accuracy and the types of errors manifested. Although the patients showed a gradual decline in overall accuracy on both command and copy conditions over the three test sessions, they performed more poorly and evidenced a steeper decline on the command condition. Conceptual errors in the command condition were noted in the early stages of AD and increased over the three administrations. Stimulus-bound errors were usually associated with conceptual errors in the same or in a contiguous year. When the patients' performances on the first test session were correlated with their yearly scores on Mattis' Dementia Rating Scale, the presence of conceptual errors was associated with a steep decline on this measure of mental status. These results suggest that drawing deficiencies in AD often reflect impairments in conceptualization and semantic knowledge and that such losses may prove useful in predicting the disease's rate of progression.