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JNNP Online First, published on December 15, 2014 as 10.1136/jnnp-2014-309120 Neurodegeneration
RESEARCH PAPER
Differentiating between right-lateralised semantic dementia and behavioural-variant frontotemporal dementia: an examination of clinical characteristics and emotion processing Jody Kamminga,1,2 Fiona Kumfor,1,3,4 James R Burrell,1,3,4 Olivier Piguet,1,3,4 John R Hodges,1,3,4 Muireann Irish1,2,4 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ jnnp-2014-309120). 1
Neuroscience Research Australia, Sydney, New South Wales, Australia 2 School of Psychology, University of New South Wales, Sydney, New South Wales, Australia 3 School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia 4 Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, New South Wales, Australia Correspondence to Dr Muireann Irish, Neuroscience Research Australia, Barker Street, Randwick, Sydney, NSW 2031, Australia;
[email protected] JK and FK contributed equally to this study. Received 29 July 2014 Revised 12 November 2014 Accepted 15 November 2014
ABSTRACT Background and purpose Right-lateralised semantic dementia (right SD) and behavioural-variant frontotemporal dementia (bvFTD) appear clinically similar, despite different patterns of underlying brain changes. This study aimed to elucidate distinguishing clinical and cognitive features in right SD versus bvFTD, emphasising emotion processing and its associated neural correlates. Methods 12 patients with right SD and 19 patients with bvFTD were recruited. Clinical features were documented. All patients were assessed on standardised neuropsychological tests and a facial emotion processing battery. Performance was compared to 20 age-matched and education-matched controls. Grey matter intensity was related to emotion processing performance using whole-brain voxel-based morphometry analysis. Results Patients with right SD exhibited disproportionate language dysfunction, prosopagnosia and a suggestion of increased obsessive personality/ behavioural changes versus patients with bvFTD. In contrast, patients with bvFTD demonstrated pronounced deficits in attention/working memory, increased apathy and greater executive dysfunction, compared to patients with right SD. Decreased empathy, disinhibition and diet changes were common to both dementia subtypes. Emotion processing deficits were present in both FTD syndromes but were associated with divergent patterns of brain atrophy. In right SD, emotion processing dysfunction was associated with predominantly right medial and lateral temporal integrity, compared to mainly left temporal, inferior frontal and orbitofrontal and right frontal gyrus integrity in bvFTD. Conclusions This study demonstrates comparable deficits in facial emotion processing in right SD and bvFTD, in keeping with their similar clinical profiles. These deficits are attributable to divergent neural substrates in each patient group, namely, right lateralised regions in right SD, versus predominantly left lateralised regions in bvFTD.
INTRODUCTION To cite: Kamminga J, Kumfor F, Burrell JR, et al. J Neurol Neurosurg Psychiatry Published Online First: [ please include Day Month Year] doi:10.1136/ jnnp-2014-309120
Behavioural and emotional disturbances are common in frontotemporal dementia (FTD), particularly the semantic dementia (SD) and behavioural-variant FTD (bvFTD) subtypes.1–10 Characterised by severe left anterior temporal atrophy, SD, also referred to as semantic-variant
primary progressive aphasia (PPA), typically presents with a breakdown in word and object knowledge.11 Approximately 25% of SD cases, however, present atypically,12 with predominant right temporal lobe atrophy (right SD). In contrast to typical left SD cases, behavioural, emotional and interpersonal dysfunctions are prominent early symptoms in the right SD variant.1–8 These features are similar to those seen in bvFTD, which is associated with increased apathy and changes in personality and behaviour, together with a marked reduction in empathy.10 Furthermore, these features outweigh classic language difficulties,1 2 8 making clinical distinction from bvFTD difficult.8 Emotion processing dysfunction is well documented in right SD2 7 and bvFTD,13 however, direct comparisons between these syndromes are scant. Of relevance here, recent studies suggest that aspects of socioemotional processing are differentially affected in bvFTD compared with the non-fluent variant of PPA,14 suggesting that different profiles may also exist between bvFTD and right SD. Whether the observed emotion processing deficits in bvFTD and right SD are underpinned by pathological involvement of similar brain structures, remains unknown. While right anterior temporal and prefrontal cortical atrophy has been associated with socioemotional deficits in FTD,15–17 no study has directly contrasted the neural substrates of emotion processing difficulties in right SD versus bvFTD. Here, we aimed to explore the (1) clinical and cognitive features; (2) emotion processing profile; and (3) neural correlates underlying emotion processing in right SD compared to bvFTD. We hypothesised that significant overlap in clinical features would be evident between the patient groups. Similarly, for emotion processing, we expected to find significant deficits in both patient groups, although we predicted that emotion processing deficits may be attributable to divergent patterns of brain atrophy according to FTD subtype. In bvFTD, frontal regions are initially involved, however with disease evolution the temporal lobes become increasingly affected, whereas in right SD the converse pattern is observed. We therefore hypothesised that frontal regions would be predominantly implicated in emotion processing in bvFTD, whereas temporal regions would play a greater role in right SD.
Kamminga J, et al. J Neurol Neurosurg Psychiatry 2014;0:1–7. doi:10.1136/jnnp-2014-309120
Copyright Article author (or their employer) 2014. Produced by BMJ Publishing Group Ltd under licence.
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Neurodegeneration METHODS Participants Thirty-one patients with dementia (19 bvFTD, 12 right SD) from a consecutive series of referrals, and 20 age-matched and education-matched controls were recruited through FRONTIER, the FTD research clinic located at Neuroscience Research Australia, Sydney. Ethical approval was obtained from the South Eastern Sydney Local Health District and the University of New South Wales ethics committees. Informed consent was acquired in accordance with the Declaration of Helsinki. All participants had a structural 3T MRI at baseline with coronal images. Patients with bvFTD met International Consensus Criteria.10 In brief, individuals with bvFTD presented with behavioural disinhibition, reduced empathy, changes in appetite, perseverative behaviour and/or frontoexecutive dysfunction. Similar to previous methodology,8 patients with right SD were selected on the basis of a pattern of MRI changes typical of SD but with markedly greater right>left anterior temporal lobe atrophy on coronal sections on a 3T MRI as judged by the clinical team. The main presenting symptoms varied. Of the 12 right SD cases, 10 reported naming or word finding difficulties and fulfilled clinical diagnostic criteria for SD.11 Six presented with prosopagnosia as the principal symptom, although three cases had prosopagnosia in addition to other symptoms. No right SD cases presented with purely behavioural disturbance but 11 had behavioural changes and nine showed clinical features suggestive of possible bvFTD.10 For all participants, exclusion criteria included prior history of mental illness, significant head injury, movement disorders, cerebrovascular disease, alcohol/drug abuse, limited English proficiency and severe language disturbance that impeded sufficient understanding of tasks. The Frontotemporal Dementia Functional Rating Scale (FTDFRS18) evaluated functional decline. The Addenbrooke’s Cognitive Examination, Revised (ACE-R19), assessed general cognitive functioning. Controls scored >88/100 on the ACE-R.
Emotion processing All participants were assessed on a comprehensive emotion processing battery that included: 1. Face-Emotion Matching Task: Participants were presented with pairs of faces of different individuals and determined whether the two faces expressed the same or different emotions (happy, sad, anger, fear, disgust, surprise and neutral) across 42 trials, following four initial practice trials.26 2. Emotion Selection Task: Participants were presented with seven different emotional faces (anger, disgust, fear, sadness, surprise, happiness, neutral) and pointed to the face that matched the emotion label that was provided orally, across 42 trials. Prior to the task, the participants completed a practice trial to ensure they understood the task.26 3. Ekman 60 task: Recognition of facial expressions across six basic emotions (anger, disgust, fear, happiness, sadness, surprise) was assessed using stimuli from the Pictures of Facial Affect series.28 Across 60 trials, stimuli were presented one at a time, pseudorandomly for 5 s, and participants selected the label that best described the emotional expression. Participants completed six practice trials before the task started. Prior to each task, the researcher checked the participant could sufficiently understand the language demands of the task. Where any concerns about comprehension ability were raised, the participant was excluded from the study.
Behavioural statistical analyses
Clinical features All patients and carers underwent a structured interview by the senior neurologist ( JRH). This interview is designed to determine the presence/absence of clinical features including: memory impairment, language impairment, visuospatial difficulty, motor symptoms, as well as behavioural features such as disinhibition, apathy, loss of empathy, perseverative behaviour and neuropsychiatric features such as hallucinations and delusions. A neuropsychologist ( JK) reviewed the clinical file of each patient and abstracted these clinical features from the structured interview as well as other available clinical records (eg, referral letters, neuropsychological reports). Clinical features were recorded as either present or absent concentrating particularly on features defined in recent International Consensus Criteria for bvFTD and for variants of PPA.10 11
Cognition Participants completed a neuropsychological battery of tests to assess: visual episodic memory recognition (Doors A, Doors and People test20) and recall (Rey Complex Figure Test (RCFT) 3 min delay21), basic attention/working memory (Digit Span Total, Wechsler Adult Intelligence Scale, Third Edition22), psychomotor speed and mental flexibility (Trail Making Test23), letter fluency (F,A,S24), language (object Naming and word Comprehension; Sydney Language Battery25) and visuoconstruction (RCFT Copy21). Face processing was assessed via two subtests from the 2
Facial Affect and Identity Discrimination Task.26 In the Face-Perception task, participants view pairs of faces and must determine if the two images are identical or different (maximum score 40). In the Face-Matching task, participants view pairs of faces expressing different emotions and must determine if they belong to the same individual or not (maximum score 42). The Famous Faces task examines knowledge of well-known faces, whereby, over 20 trials, the participant points to the famous face (Recognition) and provides the corresponding name (Naming) of the famous face among three distractors.27
The suitability of variables for parametric analyses was determined using Kolmogorov-Smirnov tests and were found to be normally distributed. Between-group differences in categorical variables, including the presence or absence of clinical features, were assessed with χ2 tests. For continuous variables, analyses of variance with Sidak post hoc comparisons were used. To compare between patient groups, independent samples t tests were conducted. Unless otherwise reported, significance level was set at p
