Longitudinal study of single‐word comprehension in semantic dementia: A comparison with primary progressive aphasia and Alzheimer's disease

Background: Although semantic dementia (SD) is characterised by a multimodal loss of semantic knowledge, it has been demonstrated that lexical‐semantic representations are not equally disrupted in SD and that some categories may be recognised better than others. Little is known, however, about the pattern of the category‐specific comprehension deficits in SD and whether it differs from that of other forms of progressive aphasias.

Aims: This exploratory study aimed to investigate the evolution of category‐specific deficits of single‐word comprehension in progressive aphasias.

Methods & Procedures: A total of 19 patients with a clinical diagnosis of SD, 25 patients with primary progressive aphasia with agrammatic and relatively nonfluent speech (PPA), and 25 patients with Alzheimer's disease (AD) with aphasia were studied longitudinally with the Western Aphasia Battery (WAB). The Auditory Word Recognition subtest of the WAB was utilised to assess comprehension of words derived from different semantic categories.

Outcomes & Results: The analysis revealed that, over time, category‐specific deficits of single‐word comprehension were seen in all three groups of patients. Participants with SD as well as those with PPA and AD were impaired on both pointing to fingers and the right–left orientation task. However, patients with SD were the only group that showed defective recognition of their own body parts. Interestingly, individuals with SD had no difficulties identifying colours, letters, and numbers, even during the follow‐up testing. In addition, in all three groups the extent of category‐specific deficits was associated with the severity of aphasia.

Conclusions: These results indicate that category‐specific deficits of single‐word comprehension are frequently seen not only in patients with SD but also in individuals with PPA or AD, and that the extent of these deficits is associated with the severity of aphasia. However, the pattern of these deficits is often different in these three forms of neurodegenerative conditions and more dissociations between semantic categories are observed as each of these diseases progresses.     

A review of lexical retrieval intervention in primary progressive aphasia and Alzheimer’s disease: mechanisms of change,generalisation, and cognition

Background: While significant benefits of lexical retrieval intervention are evident within the primary progressive aphasia (PPA) and Alzheimer’s disease (AD) literature, an understanding of the mechanisms that underlie change is limited. Change mechanisms have been explored in the post-stroke aphasia literature and offer insight into how change occurs through interventions with progressive language disorders. Exploration of change mechanisms may progress our understanding as to how and why generalisation is likely, or not, to occur, as well as gain insight into the non-linguistic cognitive functions that may play a role.

Aims: This review of the literature aimed to (1) map the mechanisms of change that have been proposed or hypothesised within the PPA and AD lexical retrieval intervention literature to a theoretical framework based on a framework of motor recovery following stroke and accounts of change mechanisms within the post-stroke aphasia literature and explore whether particular mechanisms of change were associated with more effective outcomes; (2) determine whether particular mechanisms of change were associated with within- and across-level linguistic generalisation, and (3) investigate the role of non-linguistic cognitive functions in the lexical retrieval intervention studies reviewed here.

Main Contribution: A search of Medline, PsycINFO, and CINAHL identified 37 papers published between 1982 and April 2016 that reported lexical retrieval intervention in people with PPA or AD, categorised here according to whether the proposed change mechanism was stimulation (12 studies), relearning (21 studies), reorganisation (three studies), or cognitive-relay (two studies). Significant treatment gains, predominantly based on linguistic performance measures, were reported for both diagnostic groups in association with the proposed mechanisms of stimulation and relearning. Significant treatment gains were also reported for people with PPA in association with reorganisation and cognitive-relay mechanisms; these mechanisms were only employed in PPA studies. Varying outcomes for linguistic generalisation were reported in 26 PPA and six AD studies. Nineteen studies incorporated non-linguistic cognitive functions in intervention; these were limited to autobiographical memory (17 studies), episodic memory (three studies), or both (one study).

Conclusion: This review highlights that individuals with PPA and AD benefit from lexical retrieval intervention, irrespective of the mechanism of change, and that linguistic generalisation was reported in studies proposing different change mechanisms. Insufficient exploration of the role of non-linguistic cognitive functions was highlighted with respect to assessment, planning intervention, and interpreting intervention outcomes. Recommendations are made, with a view to heightening our ability to interpret intervention outcomes.     

Efficacy and safety of mitoxantrone use in primary and secondary progressive multiple sclerosis – study site experience based on the therapy of 104 patients

Mitoxantrone (MX) is used in patients with primary and secondary progressive as well as relapsing–remitting type of multiple sclerosis (PPMS, SPMS, RRMS). The objective of our project was to evaluate the efficacy and safety of MX use in patients with PPMS and SPMS. Methods: The retrospective study included 104 patients (mean age 54.2 ± 9.0), with PPMS (13.46%) and SPMS (86.54%) treated with MX. During single cycle of the MX therapy a dose of 12 mg/m² of body surface area was administered and next cycles every three months up to a total dose of 140 mg/m² were realized. Results: The course of the therapy was completed by 95 patients (91.34%) including 73 patients who received a scheduled whole dose. The average cumulative dose per patient was 75.2 mg/m². Thirty-two patients reported nausea after MX administration, 20 revealed increase in the incidence of infection and 19 patients hair loss. Twenty-two patients discontinued therapy (seven patients because of the progress of disability). Independent risk factors for deterioration were: age and the form of PPMS (RR 1.56 [95% CI: 1.17–2.07] and RR 2.8 [95% CI: 1.08–7.21], respectively). Five patients revealed a asymptomatic decrease in EF value <50% or 10% in relation to the previous test. Conclusions: MX therapy enables us to stabilize the disease without causing any significant side effects in most patients with progressive disease as compared to patients with primary progressive disease with a comparable safety profile. Larger benefits of MX therapy are associated with the patients with secondary progressive disease.     

“Brain-Paradox” and “Embeddment” – Do We Need a “Philosophy of the Brain”?

Present discussions in philosophy of mind focuson ontological and epistemic characteristics ofmind and on mind-brain relations. In contrast,ontological and epistemic characteristics ofthe brain have rarely been thematized. Rather,philosophy seems to rely upon an implicitdefinition of the brain as "neuronal object'and "object of recognition': henceontologically and epistemically distinct fromthe mind, characterized as "mental subject' and"subject of recognition'. This leads to the"brain-paradox'. This ontological and epistemicdissociation between brain and mind can beconsidered central for the problems of mind andmind-brain relations that have yet to beresolved in philosophy. The brain itself hasnot been thematized epistemically andontologically, leading to a "brain problem'.The epistemic and ontological dissociationbetween brain and mind presupposes an"isolated' picture of the brain, characterizedby context-independence (i.e. "isolation' frombody and environment). We can describe thisview as an extrinsic relationship betweenbrain, body and environment. However, based onrecent empirical findings about body image andphantom sensations, we can no longer considerthe brain as context-independent or "isolated'from its bodily and environmental context.Instead, the brain must be considered"embedded'. Within the context of 'embeddment',brain and bodily/environmental context seemmutually to determine each other, and hence bereciprocally dependent on each other. We candescribe this as an intrinsic relationshipbetween brain, body and environment.Defining the brain as "embedded' undermines theepistemic and ontological dissociation betweenbrain and mind and consequently resolves the"brain-paradox'. This resolution sheds novellight on problems of mind and mind-brainrelations by relativizing both. It is thereforeconcluded that philosophy should thematizeontological and epistemic characteristics ofthe brain, thereby taking into account the"brain problem' and developing a "philosophy ofthe brain'. This approach not only opens a newfield in philosophy but also extends the focusof empirical investigation in the neurosciencesto take into account the intrinsic relationshipbetween brain, body and environment.     

Do you see what I feel? – Electrophysiological correlates of emotional face and body perception in schizophrenia

ObjectiveWe aimed to elucidate whether impaired affective face processing – behaviourally and with regard to P100 and N170 components – is paralleled by similar deficits in body processing in schizophrenia. Furthermore, we aimed to assess modulations by the processing of emotional or personal identity of the stimuli.MethodsFourteen patients with schizophrenia and 15 healthy controls were assessed with a Delayed Matching-to-Sample Task involving variations of the emotional (same vs. different valence) and personal identity (same vs. different person) of bodies and faces.ResultsPatients showed overall poorer behavioural performance. In controls, P100 amplitudes were enhanced in the “same identity/different emotions” vs. “same identity/same emotion” condition and N170 amplitudes were larger for different vs. same emotions. In the patients, P100 amplitudes were enhanced in the right relative to the left hemisphere for faces, but not for bodies.ConclusionsPatients with schizophrenia show deficient modulation of the P100 and N170 components by emotional and personal identity of faces and bodies, which may relate to deficient context processing.SignificanceOur findings suggest for the first time alterations of the electrophysiological correlates of body processing in schizophrenia.     

Assessing cognition and function in Alzheimer's disease clinical trials: Do we have the right tools?

Several lines of evidence from Alzheimer's disease (AD) research continue to support the notion that the biological changes associated with AD are occurring possibly several decades before an individual will experience the cognitive and functional changes associated with the disease. The National Institute on Aging—Alzheimer's Association revised criteria for AD provided a framework for this new thinking. As a result of this growing understanding, several research efforts have launched or will be launching large secondary prevention trials in AD. These and other efforts have clearly demonstrated a need for better measures of cognitive and functional change in people with the earliest changes associated with AD. Recent draft guidance from the US Food and Drug Administration further elevated the importance of cognitive and functional assessments in early stage clinical trials by proposing that even in the pre-symptomatic stages of the disease, approval will be contingent on demonstrating clinical meaningfulness. The Alzheimer's Association's Research Roundtable addressed these issues at its fall meeting October 28–29, 2013, in Washington, D.C. The focus of the discussion included the need for improved cognitive and functional outcome measures for clinical of participants with preclinical AD and those diagnosed with Mild Cognitive Impairment due to AD.     

Do gender and race impact the use of antithrombotic therapy in patients with stroke/TIA?

The authors examined the relationships between sex and race and antithrombotics prescribed at discharge in the Michigan Medicare population using retrospective medical record abstraction (n = 2,715) for the period January 1, 2001, to June 30, 2001. There were no differences in the use of antithrombotics at discharge by race or sex and no differences in the prescribing of aspirin, warfarin, aspirin/extended release dipyridamole, or clopidogrel by race or sex after adjustment for confounders.     

Behavioural and neural changes after a “choice” therapy for naming deficits in aphasia: preliminary findings

Background: Anomia, difficulty producing words, is a pervasive symptom of many individuals with aphasia. We have developed a treatment for naming deficits—the Phonological Components Analysis (PCA) protocol—that has proven efficacious in improving word-finding abilities for individuals with post-stroke aphasia.

Aims: The aim of this investigation is to present preliminary findings exploring the potential influence of choice—that is the active engagement of a participant in therapy—on our PCA treatment.

Methods & Procedures: Five individuals with aphasia were treated in one of two conditions—Choice or No Choice. Potential changes in neural activation as a function of the treatment were also investigated. Two individuals (one from each condition) underwent functional MRI (fMRI) pre- and post-therapy.

Outcomes & Results: All the individuals demonstrated a significant treatment effect immediately post-treatment and at a 4-week follow-up and four of the five participants at an 8-week follow-up. Three also demonstrated generalisation to untrained items. Unfortunately, no clear-cut patterns emerged to allow us to make claims about the influence of choice, per se, on the behavioural manifestations of improved naming. Interestingly, the participant from the Choice condition showed neural activation changes post-treatment in frontal and parietal regions that were not evident for the participant in the No Choice condition. Moreover, these changes were accompanied by a larger treatment effect for that individual and generalisation to a novel naming task.

Conclusion: The efficacy of PCA treatment for naming deficits is further supported. In addition, the neuroimaging data suggest the possibility that active engagement of an individual in his/her therapy (in this case choosing phonological attributes of a target word) may exercise executive functions important for success in treating anomia. Also, continued exploration of task factors that may promote even better treatment effects using this protocol is warranted, as is continued investigation of the neural underpinnings associated with treatment effects.     

“That really shouldn't have happened”: People with aphasia and their spouses narrate adverse events in hospital

Background: Patients with communication disability are at increased risk of experiencing an adverse event in hospital. Despite forming a particularly vulnerable patient group, little is known about the nature or cause of adverse events experienced by people with aphasia and their spouses in hospital.

Aims: This study aimed to: (a) describe the adverse events experienced by people with aphasia and their spouses in hospital, (b) identify the situations, people, events, and outcomes relevant to the adverse events, and (c) identify commonalities in participant stories of adverse events.

Methods & Procedures: In this narrative inquiry, ten people with chronic aphasia and their spouses participated in in-depth interviews about the adverse events they experienced or witnessed in hospital. A narrative analysis was used to discover common stories of adverse events and common content themes across the stories of experience.

Outcomes & Results: Although a wide variety of adverse event types were identified in the participants' stories, “undesirable events” were among the most common, along with “inappropriate discharge home or inadequate discharge plan”. Reliance upon spouses during communicative interactions featured across the stories, with exclusion of spouses from important interactions on the ward representing a barrier to effective communication and a risk for adverse events. Participants suggested strategies for improving the safety of people with aphasia in hospital in the hope of preventing future adverse events in this population.

Conclusions: Adverse events occurring in hospital were distressing to participants and often related to the presence of aphasia. Hospital policies should acknowledge the role that spouses have with patients with aphasia and ensure their inclusion to assist in prevention and management of adverse events in hospitalised patients with aphasia. The need for better discharge planning and information should also be recognised as a means of preventing adverse events.     

Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy?

OBJECTIVES: The authors investigated the effectiveness of idebenone combined with vitamin B2 and vitamin C in the treatment of patients with Leber hereditary optic neuropathy (LHON) in an early stage as compared with untreated patients with LHON. These agents may stimulate the formation of ATP. MATERIALS AND METHODS: For this retrospective study, the authors selected 28 outpatients with LHON from the Keio University Hospital. These patients were followed for 2 to 19 years from disease onset. They were divided into two groups: 14 untreated patients (11778 mutation in 10 patients, 3460 mutation in 2 patients, and 14484 mutation in 2 two patients); and 14 treated patients (11778 mutation in 11 patients, 3460 mutation in 1 patient, and 14484 mutation in 2 patients). The treated patients were administered medical treatment with idebenone, vitamin B2, and vitamin C for at least 1 year. The current study evaluated the following: 1) number of eyes with visual recovery > or = 0.3; 2) interval between the onset of LHON and the beginning of visual recovery; 3) interval between the onset of LHON and visual recovery to 0.3; and 4) interval between the beginning of medical treatment and the beginning of visual recovery in the treated subjects. RESULTS: There was no significant difference in the number of eyes with visual recovery > or = 0.3 in the two groups with the 3460, 11778, or 14484 mutation. Patients with visual recovery showed a fenestrated scotoma or a clearing of central vision. The mean interval between the onset of LHON and the beginning of visual recovery was significantly shorter in the treated group (11.1 months) than in the untreated group (17.4 months) (P = 0.03). The mean interval between the onset of LHON and visual recovery to 0.3 was significantly shorter in the treated group (17.6 months) than in the untreated group (34.4 months) (P = 0.01). The mean interval between the initiation of medical treatment to the beginning of visual recovery was 5.4 months. CONCLUSIONS: Results suggest that the administration of idebenone, vitamin B2, and vitamin C sped the recovery of vision in patients with LHON.     

“Let me tell you the point”: How speakers with aphasia assign prominence to information in narratives

Background: A central purpose of narration is to convey one's point of view about a narrated event. One's expressed evaluation of a narrated event (modalising behaviour) is often differentiated from one's expression of the sequence of events proper (referential behaviour). Modalising and referential language may be dissociated in aphasia, with modalising language relatively preserved. Use of narrative evaluative devices is one way to modalise, transmit significance, or assign prominence to information in narratives.

Aims: This study examines the frequency of use, co-occurrence, and distribution of multiple evaluative devices in the personal narratives of speakers with aphasia, as compared to that of narratives produced by demographically similar speakers without aphasia.

Methods & Procedures: Participants were 33 demographically matched, English-speaking, middle-aged adults. Of these, 17 had aphasia, and 16 had no neurological disorder. Each group included similar proportions of three demographic subgroups: African-American males, African-American females, and Caucasian females. Each participant told a personal narrative of a frightening experience. Narrative evaluative devices in the narratives were analysed for their frequency, co-occurrence, and distribution in the narrative structure.

Outcomes & Results: The frequency of use of narrative evaluative devices, their co-occurrence, and their distribution in the narrative structure were similar for narratives of individuals with and without aphasia, unless narrative structure was compromised, e.g., in narrators with relatively more severe aphasia.

Conclusions: The relatively intact ability of individuals with aphasia to assign prominence to information in narratives once again raises questions on the neurological underpinnings of modalising language. The clinical potential for assessment and treatment that incorporates narrative evaluative devices needs to be further explored.     

Do hyperactivity,impulsivity and inattention have an impact on the ability of facial affect recognition in children with autism and ADHD?

Psychopathological, genetic and neuropsychological findings indicate an association between autism and attention deficit/hyperactivity disorder (ADHD). The goal of this study was to assess possible differences in facial affect recognition in children with autism (with and without comorbid ADHD), with ADHD and healthy controls. Children aged 6–18 years old with DSM-IV-diagnosis ADHD (n = 30) or autism (n = 40) were included consecutively in the study. Facial affect recognition was assessed with a computer-based program used for teaching emotion processing called the Frankfurt Test and Training of Social Affect (FEFA) using faces and eye-pairs as target material. Additionally three attention-tasks (Sustained attention, Inhibition, Set-Shifting) were administered. Approximately 52% of the autistic children met the criteria for the comorbid diagnosis of ADHD. A MANOVA with post-hoc Scheffé tests revealed a significant difference in the recognition of faces and eye pairs between the group ADHD and controls (P = 0.009). Children with autism and ADHD also differed significantly from healthy participants in the recognition of eye-pairs (P = 0.009). Neither correlations with PDD nor with ADHD symptom scores were able to explain these results. Sustained attention and inhibition deficits had a significant influence on emotion recognition in children with ADHD. Our findings imply that the ability of facial affect recognition is reduced in children suffering from ADHD symptoms, both in autistic and pure ADHD children. ADHD symptoms need to be taken into account in future studies assessing emotion recognition in autistic children and adolescents. Supported by the Koeln Fortune Program/Faculty of Medicine, University of Cologne