Dr Sharon Savage

Background and Objectives: Due to the concern over global rising rates of dementia, increased emphasis has been placed on understanding and moulding the public¿s knowledge and awareness of the condition. There has been limited previous research into predictors of dementia knowledge; overall knowledge amongst the public is low, and it has been widely agreed that more needs to be done to raise awareness of this condition. This study seeks to solidify understanding of public dementia knowledge and introduces dementia worry, motivation to seek information and risk perception as novel concomitants of this knowledge. Research Design and Methods: A convenience sample of 311 UK adults completed a survey on dementia knowledge including Alzheimer¿s disease-specific questions, worry about developing dementia, motivation to seek information and perceived personal risk of getting the disease. Surveys were completed face-to-face and included both closed and open-ended questions. Results: Overall dementia knowledge scores were low, achieving an average of 33% of the total possible score, with 88% of the sample scoring below 50%. Bivariate correlations were performed between dementia knowledge and key variables, revealing significant positive relationships with risk perception (r = 0.179, p =.002), worry (r = 0.140, p =.016) and motivation to seek information (r = 0.139, p =.016). When knowledge was dichotomised into high and low, worry about (p =.28) and perceived risk (p =.19) of dementia was significantly lower for people with low knowledge scores than for people with higher dementia knowledge scores. Motivation to seek information was not significantly different between the high and low knowledge groups (p =.071). Discussion and Implications: Despite the relatively low knowledge scores, findings show a positive relationship between modifiable factors and dementia knowledge, suggesting areas to consider for both further research and publication campaigns. Further implications and limitations of this study are discussed.

Background: Brain iron deposition occurs in dementia. In European ancestry populations, the HFE p.C282Y variant can cause iron overload and hemochromatosis, mostly in homozygous males. Objective: To estimate p.C282Y associations with brain MRI features plus incident dementia diagnoses during follow-up in a large community cohort. Methods: UK Biobank participants with follow-up hospitalization records (mean 10.5 years). MRI in 206 p.C282Y homozygotes versus 23,349 without variants, including T2* measures (lower values indicating more iron). Results: European ancestry participants included 2,890 p.C282Y homozygotes. Male p.C282Y homozygotes had lower T2* measures in areas including the putamen, thalamus, and hippocampus, compared to no HFE mutations. Incident dementia was more common in p.C282Y homozygous men (Hazard Ratio HR = 1.83; 95% CI 1.23 to 2.72, p = 0.003), as was delirium. There were no associations in homozygote women or in heterozygotes. Conclusion: Studies are needed of whether early iron reduction prevents or slows related brain pathologies in male HFE p.C282Y homozygotes.

Background: Progressive difficulties with spoken language occur across the spectrum of degenerative dementia. When not a primary presenting and dominant symptom, language difficulties may be overlooked in favor of more prominent cognitive, behavior, or motor deficits. The aim of this scoping review is to examine the extent and nature of the research evidence describing (1) the spoken language impairments found in non-language led dementias, (2) their impact on everyday living, and (3) the reported language interventions. Methods: We searched PubMed, MEDLINE, OVID-EMBASE, PsycINFO, and SpeechBITE using terms related to spoken language for the following dementia types: Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), cortico-basal syndrome (CBS), behavior variant frontotemporal dementia (bvFTD), early-onset Alzheimer's disease (EOAD), posterior cortical atrophy (PCA), and motor neuron disease associated with FTD (MND+FTD). Risk of bias was assessed with the QualSyst tool. Results: Seventy-three eligible studies were included. A wide range of spoken language impairments were reported, involving both linguistic (e.g., syntactic processing) and other cognitive (e.g., sustained attention) underlying mechanisms. Although the severity of these deficits was scarcely reported, in some cases they manifested as non-fluent, dynamic, and global aphasias. No papers in the review described either the impact of these language impairments on everyday living or language therapies to treat them. Discussion: There is a need to understand better the level of disability produced by language impairment in people living with non¿language-led dementias. Our findings suggest three calls for action: (1) research studies should assess the clinical relevance of any spoken language deficits examined, (2) both linguistic and cognitive underlying mechanisms should be fully described (to inform the design of effective language and behavioral interventions), and (3) trials of language therapy should be conducted in those groups of individuals where significant language impairment is proved.

The term transient epileptic amnesia was coined in 1990 to describe a form of epilepsy causing predominantly amnestic seizures which could be confused with episodes of Transient Global Amnesia. Subsequent descriptions have highlighted its association with 'atypical' forms of memory disturbance including accelerated long-term forgetting, disproportionate autobiographical amnesia and topographical amnesia. However, this highly treatment-responsive condition remains under-recognized and undertreated. We describe the clinical and neuropsychological features in 65 consecutive cases of transient epileptic amnesia referred to our study, comparing these to our previous cohort of 50 patients and to those reported in 102 literature cases described since our 2008 review. Findings in our two cohorts are substantially consistent: The onset of transient epileptic amnesia occurs at an average age of 62 years, giving rise to amnestic episodes at a frequency of around 1/month, typically lasting 15-30 min and often occurring on waking. Amnesia is the only manifestation of epilepsy in 24% of patients; olfactory hallucinations occur in 43%, motor automatisms in 41%, brief unresponsiveness in 39%. The majority of patients describe at least one of the atypical forms of memory disturbance mentioned above; easily provoked tearfulness is a common accompanying feature. There is a male predominance (85:30). Epileptiform changes were present in 35% of cases, while suspected causative magnetic resonance imaging abnormalities were detected in only 5%. Seizures ceased with anticonvulsant treatment in 93% of cases. Some clinical features were detected more commonly in the second series than the first, probably as a result of heightened awareness. Neuropsychological testing and comparison to two age and IQ-matched control groups (n = 24 and 22) revealed consistent findings across the two cohorts, namely elevated mean IQ, preserved executive function, mild impairment at the group level on standard measures of memory, with additional evidence for accelerated long-term forgetting and autobiographical amnesia, particularly affecting episodic recollection. Review of the literature cases revealed broadly consistent features except that topographical amnesia, olfactory hallucinations and emotionality have been reported rarely to date by other researchers. We conclude that transient epileptic amnesia is a distinctive syndrome of late-onset limbic epilepsy of unknown cause, typically occurring in late middle age. It is an important, treatable cause of memory loss in older people, often mistaken for dementia, cerebrovascular disease and functional amnesia. Its aetiology, the monthly occurrence of seizures in some patients and the mechanisms and interrelationships of the interictal features - amnestic and affective - all warrant further study.

Background: Awareness of the diagnosis or related changes in functioning varies in people with dementia (PwD), with implications for the well-being of PwD and their carers. Measuring awareness in a clinical setting could facilitate tailored support and optimize involvement in personal health and care decisions. This scoping review aimed to identify validated methods of assessing awareness in dementia and appraise their clinical utility. Method: A systematic search was conducted of English-language publications that measured awareness in PwD, in 6 electronic databases. Search terms included dement*, Alzheimer*, Pick disease, and awareness, unawareness, anosognosia, insight, denial, metacognit*, or discrepanc*. Results: We screened 30,634 articles, finding 345 articles that met our inclusion criteria. We identified 76 measures, most commonly using a discrepancy questionnaire comparing evaluations of function by PwD and an informant. There were 30 awareness measures developed and validated for use in dementia populations but few designed for general clinical use. Conclusions: Although we found a range of clinical indications for measuring awareness, there were few studies investigating clinical applications and few tools designed for clinical purposes. Further investigation and development of a person-centered tool could facilitate health and care choices in mild-to-moderate dementia.

Introduction: While short-term cognitive impairment following electroconvulsive therapy (ECT) is well described and acknowledged, the relationship between ECT and persistent memory impairment, particularly of autobiographical memory, has been controversial. Methods: We describe the case of a 70-year-old consultant neurophysiologist, AW, who developed prominent, selective autobiographical memory loss following two courses of ECT for treatment-resistant depression. Results: His performance on standard measures of IQ, semantic and episodic memory, executive function and mood was normal, while he performed significantly below controls on measures of episodic autobiographical memory. Conclusions: Explanations in terms of mood-related memory loss and somatoform disorder appear unlikely. We relate AW's autobiographical memory impairment, following his ECT, to reports of similar autobiographical memory impairment occurring in the context of epilepsy, and emphasise the importance of using sensitive approaches to AbM assessment.

Objective: The progressive loss of stored knowledge about word meanings in semantic variant primary progressive aphasia (svPPA) has been attributed to an amodal "storage" deficit of the semantic system. Performance consistency has been proposed to be a key characteristic of storage deficits but has not been examined in close detail and larger participant cohorts. Method: We assessed whether 10 people with svPPA showed consistency in picture naming across 3 closely consecutive sessions. We examined item-by-item consistency of naming accuracy and specific error types, while controlling for the effects of word-related variables such as word frequency, familiarity, and age of acquisition. Results: Participants were very consistent in their accurate and inaccurate responses over and above any effects of the word-related variables. Analyses of error types that compared consistency of semantic errors, correct responses, and other error types (e.g., phonologically related errors, unrelated errors) revealed lower consistency. Conclusions: Our findings support the assumption that semantic features constituting semantic representations of objects are progressively lost in people with svPPA and are therefore consistently unavailable during naming. Variability in the production of error types occurs when distinctive features of an object are lost, resulting in the selection of semantically or visually similar items or in the failure to select an item and a response omission. The assessment of performance consistency sheds light on the underlying impairment of people with semantic deficits (semantic storage vs. access deficit). This can support the choice of an appropriate treatment technique to maintain or reteach semantic information. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective: Accelerated long-term forgetting (ALF) occurs when newly learned information decays faster than normal over extended delays. It has been recognised most frequently in temporal lobe epilepsy, including Transient Epileptic Amnesia (TEA), but can also be drug-induced. Little is known about the evolution of ALF over time and its impacts upon other memory functions, such as autobiographical memory (ABM). Here we investigate the long-term outcome of ALF and ABM in a group of patients with TEA and a single case of baclofen-induced ALF. Methods: Study 1 involved a longitudinal follow-up of 14 patients with TEA over a 10-year period. Patients repeated a neuropsychological battery, three ALF measures (with free recall probed at 30-min and 1-week), and a modified Autobiographical Memory Interview (MAMI). Performance was compared with a group of healthy age-matched controls. In Study 2, patient CS, who previously experienced baclofen-induced ALF, was followed over 4 years, and re-tested now, 18 months after ceasing baclofen. CS repeated a neuropsychological battery, three ALF experimental tasks (each probed after 30 min and 1 week), and a modified autobiographical interview (AI). Her performance was compared with healthy age-matched controls. Results: On ALF measures, the TEA group performed significantly below controls, but when analysed individually, 4 of the 7 patients who originally showed ALF no longer did so. In two, this was accompanied by improvements in ABM for recent but not remote memory. Patient CS no longer demonstrated ALF on standard lab-based tests and now appeared to retain new episodic autobiographical events with a similar degree of episodic richness as controls. Conclusion: Long-term follow up suggests that ALF can resolve, with improvements translating to recent ABM in some cases.

Patients with semantic dementia (SD) can rapidly and successfully re-learn word labels during cognitive intervention. This new learning, however, usually remains rigid and context-dependent. Conceptual enrichment (COEN) training is a therapy approach aimed to produce more flexible and generalisable learning in SD. In this study we compare generalisation and maintenance of learning after COEN with performance achieved using a classical naming therapy (NT). The study recruited a 62-year-old woman with SD. An AB1ACAB2 experimental design was implemented, with naming performance assessed at baseline, post- intervention, 3 and 6 weeks after the end of each treatment phase. Three generalisation tasks were also assessed pre- and post-intervention. Naming post-intervention improved significantly following both therapies, however, words trained using COEN therapy showed a significantly greater degree of generalisation than those trained under NT. In addition, only words trained with COEN continued to show significant improvements compared with baseline performance when assessed 6 weeks after practice ceased. It was concluded that therapies based on conceptual enrichment of the semantic network facilitate relearning of words and enhance generalisation in patients with SD.

Background: Primary progressive aphasia (PPA) affects a range of language and cognitive domains that impact on conversation. Little is known about conversation breakdown in the semantic variant of PPA (svPPA, also known as semantic dementia). This study investigates conversation of people with svPPA. Methods: Dyadic conversations about everyday activities between seven individuals with svPPA and their partners, and seven control pairs were video recorded and transcribed. Number of words, turns, and length of turns were measured. Trouble-indicating behaviors (TIBs) and repair behaviors were categorized and identified as successful or not for each participant in each dyad. Results: In general, individuals with svPPA were active participants in conversation, taking an equal proportion of turns, but indicating a great deal of more trouble in conversation, shown by the significantly higher number of TIBs than evidenced by partners or control participants. TIBs were interactive (asking for confirmation with a shorter repetition of the original utterance or a repetition which included a request for specific information) and non-interactive (such as failing to take up or continue the topic or a minimal response) and unlike those previously reported for people with other PPA variants and dementia of the Alzheimer type. Communication behaviors of the partner were critical to conversational success. Conclusions: Examination of trouble and repair in 10-min conversations of individuals with svPPA and their important communication partners has potential to inform speech pathology interventions to enhance successful conversation, in svPPA and should be an integral part of the comprehensive care plan.

Objective While olfactory hallucinations are relatively rare in epilepsy, a high prevalence (up to 42%) has been reported in one form ¿ Transient Epileptic Amnesia (TEA). TEA is characterized by recurring amnestic seizures and is commonly associated with persistent interictal memory deficits. Despite reports of changes in smell, olfactory ability has not been objectively assessed in this group. The aim of this study was to measure olfactory ability in patients with TEA and explore whether olfactory symptoms relate to other clinical variables. Methods Fifty-five participants with TEA were recruited from The Impairment of Memory in Epilepsy project database. The presence of olfactory symptoms was obtained via case notes and clinical interview. Participants completed questionnaires to evaluate their olfaction and memory function subjectively. Olfactory ability was measured using the University of Pennsylvania Smell Identification Test (UPSIT). TEA participants' performance was compared to 50 matched healthy control participants. A subset of TEA participants (n = 26) also completed a battery of memory tests including standard neuropsychological measures, and assessment of accelerated long-term forgetting and autobiographical memory. Results Olfactory hallucinations were reported in 55% of patients with TEA. A significant reduction in smell identification (UPSIT) was found between patients with TEA and healthy controls (p < 0.001). Epilepsy variables, including history of olfactory hallucinations, were not predictive of olfactory ability. Patients reported ongoing memory difficulties and performed below normative values on objective tests. While no correlation was found between objective measures of memory and olfactory performance, subjective complaints of route finding difficulty was associated with UPSIT score. Conclusions Impairments in odor identification are common in patients with TEA and exceed changes that occur in normal aging. Olfactory hallucinations occurs in approximately half of patients with TEA, but do not always coincide with reduced sense of smell. Olfactory impairment and interictal memory problems both occur frequently in TEA but are not closely associated.

Purpose Transient Epileptic Amnesia (TEA) is a form of adult onset temporal lobe epilepsy characterised by ictal amnesia. The amnesic seizures are often accompanied by interical memory disturbance, involving autobiographical amnesia and accelerated long-term forgetting. Short-term follow-up studies suggest a relatively stable cognitive profile once treated, but recent case reports raise concerns regarding the risk of developing Alzheimer's disease (AD). The current study reports clinical and cognitive outcome in TEA patients over a 20-year period. Methods A cohort of ten TEA patients first reported in 1998 were followed up at two time intervals, each 10 years apart. Information regarding clinical outcomes and subjective reports of memory functioning was gained via GP records and clinical interview. Objective memory function was determined at each time point via a comprehensive neuropsychological assessment, where possible. Results Information was obtained for nine of the original 10 participants. Over the 20-year period, 4 participants died, with no indication of dementia prior to death. One participant was diagnosed with Vascular Dementia. Seizures were generally well controlled. Subjective reports of memory varied, including no concerns, stable memory difficulties, and worsening memory. Neuropsychological assessment at 10 years showed stable performances across most measures. At the 20-year follow up, there was no evidence of a general cognitive decline. Participants showed stability on some measures, with reductions on others. Performance was not consistent with AD. Conclusions No elevated risk of dementia was evident from this TEA series. Although memory difficulties persist over time, the prognosis of TEA appears generally benign.

Patients with semantic dementia (SD) can improve their naming ability through cognitive intervention, with good retention 1 month later. Beyond this time, improvements often fade, yet no studies have investigated how to maintain performance. Nine SD patients completed a 2-month word training program and were then monitored over 6 months: firstly for 2 months without training, followed by a further 4 months, where additional training was provided to revise words, if required. All patients improved their naming immediately postintervention (P<0.001). After 2 months without practice, significant declines occurred in 4 patients. To sustain at least 80% of their postintervention performance 6 months later, 4 patients required minimal revision (<10 sessions over the period), 2 required regular weekly or biweekly revision sessions, with the remaining 3 patients requiring no revision sessions. During this period, group results indicated some decline in words that were initially known, but were not trained. Improvements in naming can be sustained in SD patients, with the support of less intense, but ongoing revision. Training words that are still known appears to help prolong memory of these words.

Patients with semantic dementia (SD) may undergo successful relearning of object names, but these gains are usually restricted to the trained exemplars, demonstrating poor generalization. We hypothesized that generalization could be improved by restoring an item¿s semantic network through specific strategies that recruit the remaining personal semantic memories (conceptual enrichment therapies). We describe the case of a patient with SD who showed greater generalization of learning following a conceptual enrichment therapy than when learning items in a word-retrieval therapy. Our results suggest that enhancing an item¿s semantic network connections may result in improved generalization of learning in SD. A learning mechanism in the presence of compromised hippocampi is also discussed.

Background: Reduced insight commonly occurs in dementia and can be specific to one area of functioning. Despite recent models identifying a role for semantic memory, little investigation of insight has been conducted in semantic dementia (SD), with patients often described as being aware of their language problems. Objective: This study aims to investigate language insight in SD. Method: Twenty-two SD (n = 11 severe, n = 11 mild-moderate) and 9 nonfluent primary progressive aphasic patients completed three experimental language tasks to assess knowledge and awareness of certain words. Skills in evaluating language were tested by comparing performance ratings on the Cookie Theft task with objective scoring. Awareness regarding the existence and previous use of certain words was tested using two additional tasks. Results: While SD patients were as accurate as nonfluent patients in rating their own performance on the Cookie Theft immediately following the task, they were significantly poorer at evaluating the same content re-recorded, or other examples of poor language. Compared to nonfluent patients, severe SD patients also made more errors identifying previously known lowfrequency words. Lastly, when tested on labels for specific aspects of an object, only SD patients made errors regarding the existence, or their past knowledge, of certain words. Conclusion: SD patients show a general awareness of their language impairments, but have difficulty evaluating language content. These difficulties adversely affect the ability to reflect upon current and past language skills producing an underawareness of language deficits. This mild, secondary form of anosognosia appears to increase with greater levels of semantic impairment.

Our objective was to investigate, and establish neuroanatomical correlates of, semantic deficits in amyotrophic lateral sclerosis (ALS) and amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD), compared to semantic dementia (SD) and controls. Semantic deficits were evaluated using a naming and semantic knowledge composite score, comprising verbal and non-verbal neuropsychological measures of single-word processing (confrontational naming, comprehension, and semantic association) from the Sydney Language Battery (SYDBAT) and Addenbrooke's Cognitive Examination-Revised (ACE-R). Voxel based morphometry (VBM) analysis was conducted using the region of interest approach. In total, 84 participants were recruited from a multidisciplinary research clinic in Sydney. Participants included 17 patients with ALS, 19 with ALS-FTD, 22 with SD and 26 age- and education-matched healthy controls. Significant semantic deficits were observed in ALS and ALS-FTD compared to controls. The severity of semantic deficits varied across the clinical phenotypes: ALS patients were less impaired than ALS-FTD patients, who in turn were not as impaired as SD patients. Anterior temporal lobe atrophy significantly correlated with semantic deficits. In conclusion, semantic impairment is a feature of ALS and ALS-FTD, and reflects the severity of temporal lobe pathology.

Background: Primary progressive aphasia (PPA) affects a range of language domains that impact on communication. Little is known about the nature of conversation breakdown in PPA. The identification of trouble in conversation, its repair and the success of repairs has been used effectively to examine conversation breakdown in neurogenic language disorders such as dementia of the Alzheimer type (DAT) and acute onset aphasia. This study investigated trouble and repair in the conversations of people with PPA.Aims: The first aim of this study is to describe the contributions of individuals with PPA and their conversation partner to conversation. The second aim is to describe the trouble that occurs in dyadic conversations between three individuals with PPA and their communication partner. The third aim is to describe the repair behaviours used by the individuals with PPA and their communication partners.Methods & Procedures: Dyadic conversations about everyday activities between three individuals with PPA and their partners and three control dyads were video recorded and transcribed. Number of words, number of turns and length of turns were measured and trouble-indicating behaviours (TIBs) and repair behaviours were categorised.Outcomes & Results: Individuals with PPA had reduced mean length of turn but maintained their share of turn-taking. They demonstrated a variety of TIBs that differed from the noninteractive repairs, which do not require a response from the partner in the conversation and which have been observed in studies of conversation in DAT. Their partners bore the greater burden of highlighting trouble and need for repair using collaborative, interactive, TIBs. Three different conversational profiles were observed in the three PPA dyads, reflecting different patterns of language and cognitive impairment.Conclusions: Individuals with PPA were active participants in conversation effectively indicating and responding to trouble. Understanding trouble and repair in the conversations of individuals with PPA has the potential to enhance assessment and inform clinical practice. © 2014 © 2014 Taylor & Francis.

Background: Anomia is a common and debilitating symptom for many dementia sufferers, but is particularly marked in patients with the semantic variant of primary progressive aphasia, semantic dementia (SD). Recent studies have demonstrated that through cognitive training these patients can re-learn the names of objects, but it remains unclear whether this translates to improved use of these relearned words in contexts other than picture naming. Methods: Five SD patients completed a 2-month, online word training program and were assessed pre- and post-intervention on picture naming and spoken word-picture-matching plus two novel ecological tasks: video description and responses to verbal requests. Results: All participants showed clear gains in naming the trained pictures (p < 0.001). Importantly, improvements were also observed for four out of the five patients on the video description task. Milder patients also demonstrated improved comprehension of verbal instructions. Severe SD patients showed improvements on matching trained words to pictures. As expected, improvements were not found for untrained items. Conclusion: There was clear evidence of generalization especially in patients with milder semantic impairments. Future studies should investigate the utility of this training in other forms of dementia.

We aimed to explore the nature of verbal repetition deficits and infer the cognitive systems involved in primary progressive aphasia (PPA) and Alzheimer's disease (AD). A total of 63 patients (13 semantic variant (sv-PPA), 17 nonflu-ent/agrammatic variant (nfv-PPA), 10 logopenic variant (lv-PPA), 23 AD) and 13 matched healthy controls completed a battery of tests that included naming, word comprehension, digit span, repetition of multisyllabic single words, monosyllabic word span presented under similar and dissimilar phonological conditions, and sentence repetition. All patient groups displayed some level of impairment, however, specific patterns emerged in each variant Participants with sv-PPA were the least impaired, showing marginal difficulties exclusively for sentence repetition, whereas those with lv-PPA had the worst overall performance. Cases with nfv-PPA showed compromised repetition of multisyllabic and phonologically similar words. The deficit in cases with AD was confined to span tasks. These distinctive patterns of language impairments can assist in the differential diagnosis of PPA variants and point toward the vulnerability of specific cognitive systems in each syndrome.

Amyotrophic lateral sclerosis (ALS) is a multisystem disease that overlaps with frontotemporal dementia (FTD). Although FTD patients exhibit prominent deficits in emotion perception and social cognition, these domains have received relatively little attention in ALS. Moreover, direct comparisons between ALS and FTD on emotion processing tasks remain lacking. Twenty-nine patients with ALS (16 with coexisting FTD (FTD-ALS) and 13 without dementia), 25 behavioural variant FTD patients and 30 healthy controls completed neuropsychological and emotion tasks (Ekman Caricatures and the TASIT). Both ALS and FTD patient groups showed significant deficits on the emotion tasks compared to controls. After dividing ALS patients into those with and without FTD, only the patients with coexisting FTD (FTD-ALS) were impaired. FTD-ALS and FTD patient groups displayed similar levels of impairment, even after controlling for measures of general cognition, and demonstrated similar profiles across different types of emotions. We conclude that patients with FTD-ALS and FTD show similar, significant impairments in emotional processing. By contrast, ALS patients without dementia exhibit preserved emotion processing. Performance on emotion processing tasks may provide a useful clinical tool in identifying those with early FTD-ALS. © 2014 Informa Healthcare.

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA. ©2014 Ballard et al.

Patients with semantic dementia (SD) have significant impairments in naming and comprehension, but demonstrate relatively intact attention, everyday memory, and visuospatial skills. Given these preserved skills, attempts have been made to help re-build vocabulary in SD patients, with promising results. Such reports, however, are generally based upon only one or two cases and have employed variable retraining methods. It is thus unclear which elements of practice are crucial to success. Over two studies, we assessed four patients undergoing a word training program, who ranged in severity from mild to severe impairments to semantic knowledge. All four participants showed significant improvements in their ability to name trained items, with no changes in untrained items over the same time period. Improvements were evident within 3weeks of practice, and could be established from a simple, repetitive practice of word-picture pairing, carried out at the participant's home. Strong effect sizes of the treatment were found in patients with severe deficits. Maintenance of learning was observed on some follow-up assessments, although continued practice is likely to be needed to sustain naming performance. Incorporating generation tasks into the practice may be assistive, but was not essential to success. These data support the utility of implementing simple home-practice programs even for patients with significant language deficits. © 2012 Elsevier Ltd.

Objective: To characterize the patterns of brain atrophy in patients with amyotrophic lateral sclerosis (ALS) with and without cognitive and neuropsychiatric symptoms, in comparison to controls and patients with ALS-frontotemporal dementia (FTD). Methods: A total of 57 participants (ALS = 22; ALS-FTD = 17; controls = 18) were included, following current ALS and FTD criteria. Patients with ALS were further subclassified into ALS with cognitive and behavioral symptoms (ALS-plus; n = 8) and those without (ALS; n = 14). By definition, ALS-plus did not reach the diagnostic threshold for ALS-FTD. All patients underwent neuropsychological and neuropsychiatric assessments, and underwent a brain MRI. Voxel-based morphometry analysis was conducted to establish patterns of brain atrophy. Results: Cortical atrophy in ALS was linked to neuropsychiatric and cognitive changes (ALS-plus vs ALS). Patients with ALS-plus had significant atrophy across motor and somatosensory as well as adjacent frontal and parietal areas, even after strict multiple comparison correction. By contrast, patients with ALS showed no significant cortical atrophy, and only brainstem atrophy. Importantly, atrophy in ALS-plus was not as widespread as in ALS-FTD, with ALS-plus atrophy mostly confined to motor and somatosensory areas, while atrophy in ALS-FTD also included substantial frontal and temporal atrophy. Conclusions: The present findings establish that cortical atrophy in ALS is highly dependent upon neuropsychiatric and cognitive changes. Previous inconsistent findings of cortical atrophy in ALS likely relate to the inclusion of cognitively affected patients and patients with pure motor ALS. © 2013 American Academy of Neurology.

Caregiver burden is greater in frontotemporal dementia (FTD) than in Alzheimer disease (AD). However, little is known of the impact of the 3 main clinical variants of FTD - behavioral-variant frontotemporal dementia (bvFTD), semantic dementia (SemDem), and progressive nonfluent aphasia (PNFA) - or the role of disease severity in caregiver burden. The Zarit Burden Inventory was used to measure caregiver burden of bvFTD (n=17), SemDem (n=20), PNFA (n=20), and AD (n=19) patients. Symptom duration, caregiver age, and relationship type were matched across groups. Moreover, a number of caregiver (mood, social network) and patient variables (functional disability, behavioral changes, relationship with caregiver, and dementia stage) were addressed to investigate their impact on caregiver burden. Caregivers of bvFTD patients reported the highest burden, whereas SemDem and PNFA caregivers reported burden similar to AD. A regression analysis revealed that caregiver burden in FTD, regardless of subtype, was explained by a model combining disease staging, relationship changes, and caregiver depression. Burden increased with disease severity in FTD. This study is the first to show that caregivers of SemDem, PNFA, and AD patients show similar burden, while confirming that bvFTD caregivers show higher burden than AD caregivers. More importantly, this study demonstrates that burden worsens with disease progression in FTD. © 2013 by Lippincott Williams & Wilkins.

We report a case study of a semantic dementia patient, whose episodic memory consolidation was tested over a 2-month period. The results reveal that despite early retention of information, the patient lost all explicit information of the newly learnt material after 2 weeks. By contrast, he retained implicit word information even after a 4-week delay. These findings highlight the critical time window of 2-4 weeks in which newly learnt information should be re-encoded in rehabilitations studies. The results also indicate that learnt information can be still accessed with implicit retrieval strategies when explicit retrieval fails. © 2013 Copyright Taylor and Francis Group, LLC.

Background/Aims: Primary progressive aphasia (PPA) comprises three main subtypes, varying in clinical features, patterns of brain atrophy, and underlying pathology. Differentiation of these variants is important for treatment and planning; however, simple, effective cognitive tests to aid diagnosis are lacking. This study introduces a new language battery - the SYDBAT (Sydney Language Battery) - to assist clinicians. Methods: Fifty-seven PPA patients and 54 age- and education-matched healthy controls were compared on naming, repetition, word comprehension, and semantic association subtests. Results: Significant group differences were found for all tasks, reflecting different language profiles for each group. Using discriminative function analysis, 80% of PPA cases were correctly classified from three SYDBAT scores, from which a simple diagnostic algorithm was defined. Conclusion: The SYDBAT is a fast and simple tool which provides a valuable adjunct to clinicians diagnosing PPA.

Background/Aims: Carer burden has been associated with other carer-reported factors (e.g. depression), but less is known about the influence of more independent variables. We aimed to determine the impact of cognitive deficits, demographic variables and dementia subtype on carer burden. Methods: Patients with Alzheimer's dementia (n = 35) or frontotemporal lobar degeneration (n = 61) underwent assessment of anterograde memory, word generation, impulse control and emotion recognition. Age, sex, relationship type, disease duration and diagnosis were also considered. Carers completed the Zarit Burden Interview. Results: In bivariate regression analyses, carer burden was related to age, diagnosis, memory, impulse control and emotion recognition. Stepwise multivariate regression revealed independent contributions by patient age, memory and emotion recognition, explaining 23% of the variance. Conclusion: The findings could help refine interventions and carer support. Copyright © 2013 S. Karger AG, Basel.

Objective: Word comprehension deficits in neurodegenerative conditions are most striking in the syndrome of semantic dementia. Tests of word comprehension typically examine concrete and abstract nonemotion words. Whether or not understanding of words describing emotion concepts (e.g., insulted, fascinated) is also impaired in the dementias has not been systematically investigated. Method: Patients with semantic dementia (SD; n = 8), behavioral-variant frontotemporal dementia (bvFTD; n = 8), Alzheimer's disease (AD; n = 12), as well as healthy controls (n = 15) completed newly designed emotion word comprehension tasks. Participants also undertook the Graded Synonyms Test, an abstract and concrete nonemotion word comprehension measure. Results: Degradation of knowledge about negative and positive emotion words was most impaired in SD. Correlation analyses in the SD group also showed that knowledge of emotion words correlated with the understanding of abstract nonemotion words. The bvFTD group was impaired only when making associations for emotion words. The AD cohort did not differ from controls on any measures of word comprehension. Conclusions: Impairment in word knowledge is greatest in the syndrome of SD, compared with bvFTD and AD, and includes concrete words, abstract words as well as emotion words. Importantly, word comprehension deficits affect positive and negative emotions. © 2012 American Psychological Association.

Logopenic progressive aphasia (LPA) is defined clinically by impairments of naming and sentence repetition. The relationship between these impairments and their neural basis has, however, not yet been determined. We aimed to localize cortical thinning associated with naming and repetition deficits using cortical thickness measurements. Consecutive LPA cases (n = 15) were matched with healthy controls (n = 16). All LPA cases underwent general cognitive testing and language assessment using the Progressive Aphasia Language Scale. Word retrieval and verbal short-term memory, the core cognitive processes involved in LPA, were assessed using visual confrontation naming and forward digit-span tasks. Cortical thickness was estimated vertex-by-vertex using Freesurfer. The pattern of cortical thinning for the LPA group as well as the location of cortical thinning linked to the impairment of each core cognitive process was estimated using general linear models. LPA cases showed extensive left-sided cortical thinning in which the temporo-parietal junction had the greatest involvement. Impaired naming was associated with cortical thinning of the supramarginal gyrus (BA 40), while reduced digit-span score, regarded as a surrogate marker for sentence repetition, was correlated with thinning of the left superior temporal gyrus (BA 22 and 42). These results suggest that the core manifestations of LPA emerge from the damage to segregated and non-overlapping cortical regions typically affected in this focal presentation of Alzheimer's disease. © 2012-IOS Press and the authors. All rights reserved.

Our objective was to compare the cognitive and behavioural profile of patients with amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD), and to explore the continuum between these disorders according to neuropsychological and behavioural performance using novel methods of testing and analysis. Twenty patients with ALS, 20 bvFTD patients and 20 healthy controls completed a neuropsychiatric and neuropsychological assessment including cognitive screening, working memory, inhibitory control, decision making and emotion recognition. The resulting neuropsychological and behavioural data were analysed by Rasch analysis. ALS patients showed a similar profile to bvFTD patients on tests of working memory, inhibitory control and behavioural measures. Nine ALS patients (45%) had cognitive impairment and five (25%) met criteria for bvFTD. Even in a subset of MND patients with no impairment on the ACE-R, subtle impairment of inhibitory control together with moderate to severe apathy, were found. The Rasch analysis confirmed that all patients could be ranked on the same continuum, based on their neuropsychological performance and behaviour. Thus, the cognitive and behavioural profiles of ALS mirror those seen in bvFTD. Impaired inhibitory control and behavioural changes suggest subtle orbitofrontal dysfunction in ALS. The Rasch analysis revealed a clear overlap between bvFTD and ALS. © 2012 Informa Healthcare.

Primary progressive aphasia comprises a heterogeneous group of neurodegenerative conditions with diverse clinical profiles and underlying pathological substrates. A major development has been the publication of the recent International Consensus Criteria for the three major variants namely: semantic, non-fluent/agrammatic and logopenic. The logopenic variant is assumed to represent an atypical presentation of Alzheimer pathology although evidence for this is, at present, limited. The semantic and non-fluent/agrammatic variants are largely associated with frontotemporal lobar degeneration with TDP-43 and tau pathology, respectively. The applicability of the International Consensus Criteria to an unselected clinical sample is unknown and no agreed clinical evaluation scale on which to derive the diagnosis exists. We assessed 47 consecutive cases of primary progressive aphasic seen over a 3-year period in a specialist centre, using a newly developed progressive aphasia language scale. A subgroup of 30 cases underwent 11C-labelled Pittsburgh Compound B positron emission tomography imaging, a putative biomarker of Alzheimer's disease that detects ß-amyloid accumulation, and they were compared with an age-matched group (n=10) with typical, predominately amnestic Alzheimer's disease. The application of an algorithm based on four key speech and language variables (motor speech disorders, agrammatism, single-word comprehension and sentence repetition) classified 45 of 47 (96) of patients and showed high concordance with the gold standard expert clinical diagnosis based on the International Consensus Criteria. The level of neocortical ß-amyloid burden varied considerably across aphasic variants. Of 13 logopenic patients, 12 (92) had positive ß-amyloid uptake. In contrast, one of nine (11) semantic variant and two of eight (25) non-fluent/agrammatic cases were positive. The distribution of ß-amyloid across cortical regions of interest was identical in cases with the logopenic variant to that of patients with typical Alzheimer's disease although the total load was lower in the aphasic cases. Impairments of sentence repetition and sentence comprehension were positively correlated with neocortical burden of ß-amyloid, whereas impaired single-word comprehension showed a negative correlation. The International Consensus Criteria can be applied to the majority of cases with primary progressive aphasic using a simple speech and language assessment scale based upon four key variables. ß-amyloid imaging confirms the higher rate of Alzheimer pathology in the logopenic variant and, in turn, the low rates in the other two variants. The study offers insight into the biological basis of clinical manifestations of Alzheimer's disease, which appear topographically independent of ß-amyloid load. © 2011 The Author.

Background: Behavioral variant frontotemporal dementia (bvFTD) patients show prefrontal cortex dysfunction and atrophy. Methods: We investigated whether executive function in conjunction with prefrontal cortex atrophy discriminates bvFTD and Alzheimer's disease (AD) patients efficiently at presentation. Results: AD and bvFTD patients were distinguishable by 89.5% on their performance of 3 executive tasks: the Hayling Test of Inhibitory Control, Digit Span Backward and Letter Fluency. Similarly, scan ratings showed that orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex regions distinguish both patient groups. More importantly, employing the Hayling error score in conjunction with the OFC atrophy rating showed that 92% of patients can be correctly classified into bvFTD and AD. Conclusion: A combination of OFC and disinhibition measures appears to be a powerful diagnostic tool in differentiating bvFTD from AD patients in this preliminary study. Copyright © 2011 S. Karger AG, Basel.

Frontotemporal dementia (FTD) is a neurodegenerative brain disorder that affects the frontal and temporal lobes predominantly. Impaired emotion recognition has been reported in two FTD subtypes: behavioral-variant FTD (bvFTD) and semantic dementia (SD), but has not been investigated in the third subtype: progressive nonfluent aphasia (PNFA). Methods: Recognition of six basic facial emotions (anger, disgust, fear, sadness, surprise, and happiness) was investigated in 41 FTD patients (bvFTD = 16; SD = 12; PNFA = 13) and 37 age- and education-matched controls, using two tests. In one task, intensity of emotional expression was increased to identify cognitive components contributing to emotion recognition performance. Results: All patient groups demonstrated impaired overall facial emotion recognition compared to controls. Performance, however, improved with increased emotion intensity in bvFTD and PNFA groups, the effect of intensity on emotion recognition being particularly pronounced for negative emotions. In contrast, increased intensity of facial emotion did not change performance in SD. Conclusions: Patients with SD demonstrate a primary emotion processing impairment, whereas PNFA and bvFTD patients' emotional disturbance is in part mediated by attentional deficits. These findings indicate that a subset of FTD patients may benefit from enhanced emotional intensity that will facilitate facial emotion recognition. © 2011 Copyright 2011 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business.

Objective: We aimed to develop a novel tool capable of staging disease severity in frontotemporal dementia (FTD) based upon functional dependence and behavioral changes, and to assess change over time in the 3 main FTD variants (behavioral variant FTD [bvFTD]; progressive nonfluent aphasia [PNFA]; and semantic dementia [SemD]). Methods: The Frontotemporal Dementia Rating Scale (FRS) was developed in a validation cohort of 77 consecutive clinic attendees (bvFTD = 29; PNFA = 20; SemD = 28) and applied to an independent sample of 75 patients (bvFTD = 28; PNFA = 21; SemD = 26) to establish intergroup differences. Assessments from 42 patients followed up after 12 months were used to determine annual progression. Finally, a combined sample (n = 152) was used to determine length of symptoms in each severity category. Results: Six severity stages were identified and operationalized based upon a 30-item questionnaire (very mild to profound). The cross-sectional study revealed much greater levels of impairment in bvFTD than in the language variants, with limited correlation with general cognitive measures. Patients with SemD showed the closest association between length of symptoms and stage, taking, on average, 10 years to reach the severe stage. Patients with bvFTD appear to move most quickly between stages and patients with PNFA were intermediate. The FRS was capable of detecting functional deterioration in all 3 variants over 12 months. Conclusions: Disease progression differs across frontotemporal dementia (FTD) variants. Patients with behavioral variant FTD progress rapidly whereas those with semantic dementia progress more slowly. The Frontotemporal Dementia Rating Scale can aid in staging and determining disease progression. Length of symptoms and global cognitive assessments alone do not reflect disease severity and progression in FTD. Copyright © 2010 by AAN Enterprises, Inc.

Background: This paper examines the methodological quality of aphasia ther py research using the Psychological database for Brain Impairment Treatment Efficacy (www.psycbite.com). PsycBITE¿ includes five designs: Systematic Reviews (SR), Randomised Controlled Trials (RCT), non-RCTs (NRCT), Case Series (CS), and Single Subject Designs (SSD). Aim: To provide an overview of the types of research designs and levels of compliance used in aphasia treatment research studies, and assess the methodological quality of aphasia research. Methods & Procedures: Asearch was completed on 27 September 2007 of all papers in the target area Communication/Language/Speech on the PsycBITE¿ database. Papers were listed according to the methodology used and a mean methodological quality rating (MQR) score was determined for RCTs, and NRCTs based on the PEDro scale. Finally, the rate of compliance of RCTs and NRCTs for each of the criteria on the PEDro scale was analysed. Outcomes & Results: Of 339 studies indexed for aphasia: SR = 9 (3%); RCT = 23 (7%); NRCT = 18 (5%); CS = 51 (15%); and SSD = 238 (70%). Methodological quality ratings (MQR) using the PEDro scale (scored out of 10) were available for 21 RCTs (mean MQR = 4.4, SD = 1.7, range = 2-8), and 14 NRCTs (mean MQR = 2.6, SD = 1.0, range = 1-4). Conclusions: Methodological quality of current aphasia treatment studies is modest. The current examination of a small sample of RCTs and non-RCTs indicates that sources of bias are not sufficiently well controlled. These results have implications for aphasia therapy researchers in the design and report of their work. It is hoped that access to databases such as PsycBITETM and rating scales such as PEDro will facilitate this process.

Rating scales that assess methodological quality of clinical trials provide a means to critically appraise the literature. Scales are currently available to rate randomised and non-randomised controlled trials, but there are none that assess single-subject designs. The Single-Case Experimental Design (SCED) Scale was developed for this purpose and evaluated for reliability. Six clinical researchers who were trained and experienced in rating methodological quality of clinical trials developed the scale and participated in reliability studies. The SCED Scale is an 11-item rating scale for single-subject designs, of which 10 items are used to assess methodological quality and use of statistical analysis. The scale was developed and refined over a 3-year period. Content validity was addressed by identifying items to reduce the main sources of bias in single-case methodology as stipulated by authorities in the field, which were empirically tested against 85 published reports. Inter-rater reliability was assessed using a random sample of 20/312 single-subject reports archived in the Psychological Database of Brain Impairment Treatment Efficacy (PsycBITETM). Inter-rater reliability for the total score was excellent, both for individual raters (overall ICC = 0.84; 95% confidence interval 0.73-0.92) and for consensus ratings between pairs of raters (overall ICC = 0.88; 95% confidence interval 0.78-0.95). Item reliability was fair to excellent for consensus ratings between pairs of raters (range k = 0.48 to 1.00). The results were replicated with two independent novice raters who were trained in the use of the scale (ICC = 0.88, 95% confidence interval 0.73-0.95). The SCED Scale thus provides a brief and valid evaluation of methodological quality of single-subject designs, with the total score demonstrating excellent inter-rater reliability using both individual and consensus ratings. Items from the scale can also be used as a checklist in the design, reporting and critical appraisal of single-subject designs, thereby assisting to improve standards of single-case methodology. © 2008 Psychology Press.

Patients with frontotemporal dementia (both behavioural variant [bvFTD] and semantic dementia [SD]) as well as those with Alzheimer's disease (AD) show deficits on tests of face emotion processing, yet the mechanisms underlying these deficits have rarely been explored. We compared groups of patients with bvFTD (n=17), SD (n=12) or AD (n=20) to an age-and education-matched group of healthy control subjects (n=36) on three face emotion processing tasks (Ekman 60, Emotion Matching and Emotion Selection) and found that all three patient groups were similarly impaired. Analyses of covariance employed to partial out the influences of language and perceptual impairments, which frequently co-occur in these patients, provided evidence of different underlying cognitive mechanisms. These analyses revealed that language impairments explained the original poor scores obtained by the SD patients on the Ekman 60 and Emotion Selection tasks, which involve verbal labels. Perceptual deficits contributed to Emotion Matching performance in the bvFTD and AD patients. Importantly, all groups remained impaired on one task or more following these analyses, denoting a primary emotion processing disturbance in these dementia syndromes. These findings highlight the multifactorial nature of emotion processing deficits in patients with dementia. © 2012-IOS Press and the authors. All rights reserved.