Temporal Variant Frontotemporal Dementia Research Articles

Observing conversational laughter in frontotemporal dementia

BackgroundWe performed an observational study of laughter during seminaturalistic conversations between patients with dementia and familial caregivers. Patients were diagnosed with (1) behavioural variant frontotemporal dementia (bvFTD), (2) right temporal...

The clinical, neuroanatomical, and neuropathologic phenotype of TBK1-associated frontotemporal dementia: A longitudinal case report

IntroductionMutations in the TANK-binding kinase 1 (TBK1) gene have recently been shown to cause frontotemporal dementia (FTD). However, the phenotype of TBK1-associated FTD is currently unclear. MethodsWe performed a single case longitudinal study of a patient who was subsequently found to have a novel A705fs mutation in the TBK1 gene. He was assessed annually over a 7-year period with a series of clinical, cognitive, and magnetic resonance imaging assessments. His brain underwent pathological examination at postmortem. ResultsThe patient presented at the age of 64 years with an 18-month history of personality change including increased rigidity and obsessiveness, apathy, loss of empathy, and development of a sweet tooth. His mother had developed progressive behavioral and cognitive impairment from the age of 57 years. Neuropsychometry revealed intact cognition at first assessment. Magnetic resonance imaging showed focal right temporal lobe atrophy. Over the next few years his behavioral problems progressed and he developed cognitive impairment, initially with anomia and prosopagnosia. Neurological examination remained normal throughout without any features of motor neurone disease. He died at the age of 72 years and postmortem showed TDP-43 type A pathology but with an unusual novel feature of numerous TAR DNA-binding protein 43 (TDP-43)–positive neuritic structures at the cerebral cortex/subcortical white matter junction. There was also associated argyrophilic grain disease not previously reported in other TBK1 mutation cases. DiscussionTBK1-associated FTD can be associated with right temporal variant FTD with progressive behavioral change and relatively intact cognition initially. The case further highlights the benefits of next-generation sequencing technologies in the diagnosis of neurodegenerative disorders and the importance of detailed neuropathologic analysis.

Right Temporal Variant of Frontotemporal Dementia: A Clinical Introduction

Frontotemporal dementia (FTD) is a progressive, neurodegenerative syndrome that results in changes in personality, behavior, and language. The right temporal variant, a relatively under-studied and perhaps under-diagnosed clinical subtype of FTD, manifests as behavioral changes, loss of person-specific knowledge, and eventual deficits in word-finding and semantic knowledge. Thorough assessment is necessary in order to distinguish right temporal variant FTD from other dementias. Speech-language pathologists (SLPs) play an essential role in accurate diagnosis, provision of appropriate resources and referrals, and administration of effective treatments.

Cognitive and Affective Theory of Mind Ability in the Behavioral and Temporal Variant of Frontotemporal Dementia (P03.085)

Cognitive and Affective Theory of Mind Ability in the Behavioral and Temporal Variant of Frontotemporal Dementia (P03.085)

Episodic memory and the medial temporal lobe: not all it seems. Evidence from the temporal variants of frontotemporal dementia

BackgroundDisproportionate medial temporal lobe atrophy (MTA) is an early finding in Alzheimer's disease (AD). Episodic memory impairment in AD is associated with the degree of MTA. Episodic memory impairment and...

Right temporal variant frontotemporal dementia with motor neuron disease

Patterns of atrophy in frontotemporal dementia (FTD) correlate with the clinical subtypes of behavioral variant FTD (bvFTD), semantic dementia, progressive non-fluent aphasia (PNFA) and FTD with motor neuron disease (FTD-MND). Right temporal variant FTD is associated with behavioral dyscontrol and semantic impairment, with tau abnormalities more common in right temporal bvFTD and TDP-43 accumulation in right temporal semantic dementia. However, no clinical and anatomical correlation has been described for patients with predominant right temporal atrophy and FTD-MND. Therefore, we performed a database screen for all patients diagnosed with FTD-MND at Mayo Clinic and reviewed their MRI scans to identify those with striking, dominant, right temporal lobe atrophy. For cases with volumetric MRI we performed voxel based morphometry and for those with brain tissue we performed pathological examination. Of three such patients identified, each patient had different presenting behavioral and/or aphasic characteristics. MRI, including diffusion tensor imaging in one patient, and FDG positron emission tomography revealed striking and dominant right temporal lobe atrophy, right corticospinal tract degeneration, and right temporal hypometabolism. Archived brain tissue was available in two patients; both demonstrating TDP-43 type 3 pathology (Mackenzie scheme) with predominant neuronal cytoplasmic inclusions. In one case, neurofibrillary tangles (Braak V) and neuritic plaques were also present in keeping with a diagnosis of Alzheimer’s disease. There appears to be an association between FTD-MND and severe right temporal lobe atrophy. Until further characterization of such cases are determined, they may be best classified as right temporal variant FTD-MND.

The Word Processing Deficit in Semantic Dementia: All Categories Are Equal, but Some Categories Are More Equal than Others

It has been claimed that semantic dementia (SD), the temporal variant of fronto-temporal dementia, is characterized by an across-the-board deficit affecting all types of conceptual knowledge. We here confirm this generalized deficit but also report differential degrees of impairment in processing specific semantic word categories in a case series of SD patients (N = 11). Within the domain of words with strong visually grounded meaning, the patients' lexical decision accuracy was more impaired for color-related than for form-related words. Likewise, within the domain of action verbs, the patients' performance was worse for words referring to face movements and speech acts than for words semantically linked to actions performed with the hand and arm. Psycholinguistic properties were matched between the stimulus groups entering these contrasts; an explanation for the differential degrees of impairment must therefore involve semantic features of the words in the different conditions. Furthermore, this specific pattern of deficits cannot be captured by classic category distinctions such as nouns versus verbs or living versus nonliving things. Evidence from previous neuroimaging research indicates that color- and face/speech-related words, respectively, draw most heavily on anterior-temporal and inferior-frontal areas, the structures most affected in SD. Our account combines (a) the notion of an anterior-temporal amodal semantic "hub" to explain the profound across-the-board deficit in SD word processing, with (b) a semantic topography model of category-specific circuits whose cortical distributions reflect semantic features of the words and concepts represented.

Two distinct subtypes of right temporal variant frontotemporal dementia

Right temporal frontotemporal dementia (FTD) is an anatomic variant of FTD associated with relatively distinct behavioral and cognitive symptoms. We aimed to determine whether right temporal FTD is a homogeneous clinical, imaging, and pathologic/genetic entity. In this case-control study, 101 subjects with FTD were identified. Atlas-based parcellation generated temporal, frontal, and parietal grey matter volumes which were used to identify subjects with a right temporal dominant atrophy pattern. Clinical, neuropsychological, genetic, and neuropathologic features were reviewed. The subjects with right temporal FTD were grouped by initial clinical diagnosis and voxel-based morphometry was used to assess grey matter loss in the different groups, compared to controls, and each other. We identified 20 subjects with right temporal FTD. Twelve had been initially diagnosed with behavioral variant FTD (bvFTD), and the other 8 with semantic dementia (SMD). Personality change and inappropriate behaviors were more frequent in the bvFTD group, while prosopagnosia, word-finding difficulties, comprehension problems, and topographagnosia were more frequent in the SMD group. The bvFTD group showed greater loss in frontal lobes than the SMD group. The SMD group showed greater fusiform loss than the bvFTD group. All 8 bvFTD subjects with pathologic/genetic diagnosis showed abnormalities in tau protein (7 with tau mutations), while all three SMD subjects with pathology showed abnormalities in TDP-43 (p = 0.006). We have identified 2 subtypes of right temporal variant frontotemporal dementia (FTD) allowing further differentiation of FTD subjects with underlying tau pathology from those with TDP-43 pathology.

Démence sémantique : réflexions d’un groupe de travail pour des critères de diagnostic en français et la constitution d’une cohorte de patients

Semantic dementia (SD) is a syndrome of progressive loss of semantic knowledge for objects and people. International criteria propose that SD be included in the frontotemporal lobar degeneration syndromes, with progressive non-fluent aphasia and frontotemporal dementia (FTD). However, several related syndromes have been defined that clinically and conceptually share both similarities and differences with SD: fluent progressive aphasia, progressive prosopagnosia, temporal variant of FTD. In order to establish a French consensus for the diagnosis and modalities of evaluation and follow-up of SD, a working group, composed of neurologists, neuropsychologists and speech-therapists, was established by the Groupe de réflexion sur les évaluations cognitives (GRECO). New criteria were elaborated, based on clinical, neuropsychological, and imaging data. They define typical and atypical forms of SD. A diagnosis of typical SD relies on an isolated and progressive loss of semantic knowledge, attested by a deficit of word comprehension and a deficit of objects and/or people identification, with imaging showing temporal atrophy and/or hypometabolism. SD is atypical if the deficit of semantic knowledge is present only within a single modality (verbal versus visual), or if non-semantic deficits (mild and not present at onset) and/or neurological signs, are associated with the semantic loss.

The natural history of temporal variant frontotemporal dementia

The temporal variant of frontotemporal dementia (tvFTD) features asymmetric anterior temporal/amygdala degeneration as well as ventromedial frontal, insular, and inferoposterior temporal involvement. Left temporal atrophy has been linked to loss of semantic knowledge, whereas behavioral symptoms dominate the right temporal variant. To investigate the first symptoms and the timing of subsequent symptoms in patients with left versus right tvFTD. Twenty-six patients with tvFTD were identified. Six had right > left temporal atrophy (right temporal lobe variant [RTLV]) and were matched with six having comparable left > right temporal atrophy (left temporal lobe variant [LTLV]). Clinical records were reviewed to generate individualized symptom chronologies. In all patients, first symptoms involved semantics (4/6 LTLV, 1/6 RTLV), behavior (4/6 RTLV, 1/6 LTLV), or both (1 LTLV, 1 RTLV). Semantic loss began with anomia, word-finding difficulties, and repetitive speech, whereas the early behavioral syndrome was characterized by emotional distance, irritability, and disruption of physiologic drives (sleep, appetite, libido). After an average of 3 years, patients developed whichever of the two initial syndromes--semantic or behavioral--that they lacked at onset. A third stage, 5 to 7 years from onset, saw the emergence of disinhibition, compulsions, impaired face recognition, altered food preference, and weight gain. Compulsions in LTLV were directed toward visual, nonverbal stimuli, whereas patients with RTLV were drawn to games with words and symbols. The temporal variant of frontotemporal dementia follows a characteristic cognitive and behavioral progression that suggests early spread from one anterior temporal lobe to the other. Later symptoms implicate ventromedial frontal, insular, and inferoposterior temporal regions, but their precise anatomic correlates await confirmation.

Recognition of Emotion in the Frontal and Temporal Variants of Frontotemporal Dementia

Recent studies have suggested that the frontal and temporal variants of frontotemporal dementia (fvFTD and tvFTD) are both associated with impairments in emotional processing. However, the degree and type of emotional processing deficits in the two syndromes have not been previously compared. We used the Florida Affect Battery to examine recognition of facial expressions of emotion in fvFTD and tvFTD patients who have no evidence of visual perceptual difficulties for faces. In general, both groups were impaired at recognizing emotions compared with age-matched controls. In tvFTD, this deficit was limited to emotions with a negative valence (sadness, anger, fear), while fvFTD patients showed impairment for positive valence (happiness) as well. These results suggest that damage to frontal lobe regions in FTD may lead to more profound impairment in recognition of emotion than when damage is more limited to the temporal lobe.

A study of stereotypic behaviours in Alzheimer’s disease and frontal and temporal variant frontotemporal dementia

Objective: To document the prevalence and pattern of stereotypic behaviour in patients with Alzheimer’s dementia and frontal and temporal variants of frontotemporal dementia. Secondly, to examine the relationship between stereotypic...

SEMANTIC DEMENTIA WITH CATEGORY SPECIFICITY:ACOMPARATIVE CASE-SERIES STUDY

Patients with semantic dementia, the temporal variant of frontotemporal dementia, are relevant to both the neuroanatomical and neuropsychological debates in the category-specific literature. These patients present with a selective and progressive semantic deficit consequent on circumscribed atrophy of the inferolateral polar temporal lobes bilaterally, including the inferotemporal gyrus. In this study, a patient KH with a significant advantage for artefacts over living things was compared to five other semantic dementia patients with commensurate levels of semantic impairment. KH demonstrated a consistent category difference in favour of artefacts across all the expressive and receptive semantic tests. This difference was reliable even when familiarity, frequency, and other potential confounding factors were controlled. While KH demonstrated an association between poor knowledge of sensory attributes and a consistently greater impairment on living things than artefacts, the other patients did not. As observed in a number of previous studies, all five of the patients, contrasted to KH, exhibited an advantage for functional/associative over sensory attributes but without demonstrating the category-specific deficit that the sensory-functional theory (and the locus of their atrophy) might predict. The results of this and other studies are discussed in relation to four accounts of category specificity: the sensory-functional theory, domain-specific knowledge systems, intercorrelated features, and individual differences.

Recollection-based memory in frontotemporal dementia: implications for theories of long-term memory.

It has been convincingly demonstrated that patients with semantic dementia (the temporal variant of frontotemporal dementia) can show intact recognition memory for pictorial stimuli. As yet, the contribution made by recollective processes to this ability and the status of associated neural regions have not been investigated in the disease. Here, we used both a source monitoring paradigm and an associative memory test to evaluate the ability of patients with semantic dementia to use recollection-based memory processes, and a volumetric MRI technique to assess the extent of atrophy in the hippocampus. Although some patients showed impaired source and associative memory, many performed as well as control participants. Importantly, status of semantic knowledge, as measured by tests of comprehension and production, did not predict recollection-based memory ability. There was no significant positive correlation between recollection and volume of the hippocampus; instead, both source discrimination and associative memory correlated highly with performance on a battery of frontal lobe tests. Consistent with the view that damage to the prefrontal cortex might influence recollection performance, patients with the frontal variant of frontotemporal dementia, with atrophy largely confined to the frontal lobes, all performed at floor level on source discrimination. These results provide further compelling evidence in favour of the multiple input model of long-term memory and highlight the role of frontal lobe systems in recollection-based memory.

Rates of global and regional cerebral atrophy in AD and frontotemporal dementia.

Serial registered MRI provides a reproducible technique for detecting progressive cerebral atrophy in vivo and was used to determine if there were differences between the rates of cerebral atrophy in AD and frontotemporal dementia (FTD). Eighty-four patients with dementia (54 AD and 30 FTD) and 27 age-matched control subjects each had at least two volumetric MR scans. Serial scans were positionally matched (registered), and brain volume loss was determined by calculation of the brain boundary shift integral. There was a difference between the rates of whole-brain atrophy in patients (mean annual volume loss 2.7% of total brain volume) and in control subjects (mean annual volume loss 0.5%). AD and FTD were associated with different rates of atrophy (mean annual losses 2.4 and 3.2%). The range of atrophy rates in the FTD group (0.3 to 8.0%) greatly exceeded that in the AD group (0.5 to 4.7%). Frontal-variant FTD was associated with a wider range of atrophy rates than temporal-variant FTD. Analysis of regional brain atrophy rates revealed that there was widespread symmetrically distributed cerebral volume loss in AD, whereas in frontal FTD there was greater atrophy anteriorly and in temporal FTD the atrophy rate was greatest in the left anterior cerebral cortex. Both AD and FTD patients had increased rates of brain atrophy. Whereas the patients with AD were associated with a relatively restricted spread of atrophy rates, the greater spread of rates observed in the patients with FTD may reflect the heterogeneity of disease in FTD, with differences observed between frontal and temporal FTD. Increased rates of whole-brain atrophy did not discriminate AD from FTD, but analysis of regional atrophy rates revealed marked differences between patient groups.

Differing patterns of temporal atrophy in Alzheimer's disease and semantic dementia.

To characterize and quantify the patterns of temporal lobe atrophy in AD vs semantic dementia and to relate the findings to the cognitive profiles. Medial temporal lobe atrophy is well described in AD. In temporal variant frontotemporal dementia (semantic dementia), clinical studies suggest polar and inferolateral temporal atrophy with hippocampal sparing, but quantification is largely lacking. A volumetric method for quantifying multiple temporal structures was applied to 26 patients with probable AD, 18 patients with semantic dementia, and 21 matched control subjects. The authors confirmed the expected bilateral hippocampal atrophy in AD relative to controls, with involvement of the amygdala bilaterally and the right parahippocampal gyrus. Contrary to expectations, patients with semantic dementia had asymmetric hippocampal atrophy, more extensive than AD on the left. As predicted, the semantic dementia group showed more severe involvement of the temporal pole bilaterally and the left amygdala, parahippocampal gyrus (including the entorhinal cortex), fusiform gyrus, and the inferior and middle temporal gyri. Performance on semantic association tasks correlated with the size of the left fusiform gyrus, whereas naming appeared to depend upon a wider left temporal network. Episodic memory measures, with the exception of recognition memory for faces, did not correlate with temporal measures. Hippocampal atrophy is not specific for AD but is also seen in semantic dementia. Distinguishing the patients with semantic dementia was the severe global but asymmetric (left > right) atrophy of the amygdala, temporal pole, and fusiform and inferolateral temporal gyri. These findings have implications for diagnosis and understanding of the cognitive deficits in AD and semantic dementia.

Hemispheric Dominance for Emotions, Empathy and Social Behaviour: Evidence from Right and Left Handers with Frontotemporal Dementia.

Although evidence from primates suggests an important role for the anterior temporal cortex in social behaviour, human research has to date concentrated almost solely on the orbitofrontal cortex and amygdala. By describing four cases of the temporal variant of frontotemporal dementia we show how this degenerative condition provides an excellent model for investigating the role of the anterior temporal lobe, especially the right, in emotions, empathy and social behaviour. Assessments of semantic memory, processing of emotional facial expression and emotional prosody were made, empathy was measured, and facial expressions of emotion were coded. Of the two right handers described, one subject with predominantly left temporal lobe atrophy had severe semantic impairment but normal performance on all emotional tasks. In contrast, the subject with right temporal lobe atrophy showed severely impaired recognition of emotion from faces and voices that was not due to semantic or perceptual difficulties. Empathy was lost, interpersonal skills were severely affected and facial expression of emotion was characterized by a fixed expression that was unresponsive to situations. Additionally, two left handers with right temporal lobe atrophy are described. One demonstrated the same pattern of hemispheric lateralization as the right handers and had emotional impairment. The other left hander showed the opposite pattern of deficits, suggesting a novel presentation of anomalous dominance with reversed hemispheric specialization of semantic memory and emotional processing.

Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer's disease?

OBJECTIVESTo investigate the prevalence of changes in mood, personality, and behaviour in frontotemporal dementia (FTD) and Alzheimer's disease (AD) and hence, which features reliably distinguish between them. To establish whether...

Episodic memory: new insights from the study of semantic dementia

The study of patients with semantic dementia, the temporal variant of frontotemporal dementia, has provided new insights into the interaction between episodic and semantic memory, and the different roles played by various structures in the temporal lobe. Recent findings indicate that the syndrome of semantic dementia can inform us about the organisation of long-term memory and the relationship between semantic memory and other cognitive systems.