Subtypes Of Frontotemporal Dementia Research Articles

Clinical characteristics of parkinsonism in frontotemporal dementia according to subtypes

BackgroundWe investigated the prevalence of parkinsonism in frontotemporal dementia (FTD) subtypes and the cognitive and behavioral differences between FTD with and without parkinsonism in a well-structured, prospective cohort. MethodsOne hundred and ninety-one FTD patients were enrolled and all patients underwent comprehensive neurological evaluations, neuropsychological tests, and the Unified Parkinson's Disease Rating Scale. ResultsThe prevalence of parkinsonism was 38.7% (74 patients), and included 33 (46.5%) behavioral variant FTD (bvFTD), 16 (24.2%) semantic dementia (SD), 19 (45.2%) progressive nonfluent aphasia (PNFA), and 6 (50%) FTD associated with motor neuron disease (FTD-MND). SD patients with parkinsonism had higher CDR sum of boxes scores (9.7±4.5 vs 6.2±4.5, p=0.024), frontal behavioral inventory total score (33.7±20.5 vs 24.3±14.5, p=0.045), and executive function score of frontal executive dysfunction, disinhibition, and apathy (28.9±13.7 vs 19.2±12.9, p=0.021) than those without parkinsonism. Seoul Instrumental Activities of Daily Living score (bvFTD: 23.5±11.7 vs 17.3±11.3, p=0.031, SD: 23.1±11.1 vs 11.3±9.3, p=0.005) was higher for bvFTD and SD with parkinsonism than for those without parkinsonism. ConclusionsParkinsonism is found to be more common in patients with bvFTD, PNFA, and FTD-MND patients than those with SD. Behavioral disturbances were more prominent in SD with parkinsonism than without. Additional studies are needed to determine the pathomechanism and optimal treatment of parkinsonism in different FTD subtypes.

Prion-like propagation as a pathogenic principle in frontotemporal dementia.

Frontotemporal dementia is a devastating neurodegenerative disease causing stark alterations in personality and language. Characterized by severe atrophy of the frontal and temporal brain lobes, frontotemporal dementia (FTD) shows extreme heterogeneity in clinical presentation, genetic causes, and pathological findings. Like most neurodegenerative diseases, the initial symptoms of FTD are subtle, but increase in severity over time, as the disease progresses. Clinical progression is paralleled by exacerbation of pathological findings and the involvement of broader brain regions, which currently lack mechanistic explanation. Yet, a flurry of studies indicate that protein aggregates accumulating in neurodegenerative diseases can act as propagating entities, amplifying their pathogenic conformation, in a way similar to infectious prions. In this prion‐centric view, FTD can be divided into three subtypes, TDP‐43 or FUS proteinopathy and tauopathy. Here, we review the current evidence that FTD‐linked pathology propagates in a prion‐like manner and discuss the implications of these findings for disease progression and heterogeneity. Frontotemporal dementia (FTD) is a progressive neurodegenerative disease causing severe personality dysfunctions, characterized by profound heterogeneity. Accumulation of tau, TDP‐43 or FUS cytoplasmic aggregates characterize molecularly distinct and non‐overlapping FTD subtypes. Here, we discuss the current evidence suggesting that prion‐like propagation and cell‐to‐cell spread of each of these cytoplasmic aggregates may underlie disease progression and heterogeneity. This article is part of the Frontotemporal Dementia special issue.

Detection and Differentiation of Frontotemporal Dementia and Related Disorders From Alzheimer Disease Using the Montreal Cognitive Assessment.

The Montreal Cognitive Assessment (MoCA) is a cognitive screening tool used by practitioners worldwide. The efficacy of the MoCA for screening frontotemporal dementia (FTD) and related disorders is unknown. The objectives were: (1) to determine whether the MoCA detects cognitive impairment (CI) in FTD subjects; (2) to determine whether Alzheimer disease (AD) and FTD subtypes and related disorders can be parsed using the MoCA; and (3) describe longitudinal MoCA performance by subtype. We extracted demographic and testing data from a database of patients referred to a cognitive neurology clinic who met criteria for probable AD or FTD (N=192). Logistic regression was used to determine whether dementia subtypes were associated with overall scores, subscores, or combinations of subscores on the MoCA. Initial MoCA results demonstrated CI in the majority of FTD subjects (87%). FTD subjects (N=94) performed better than AD subjects (N=98) on the MoCA (mean scores: 18.1 vs. 16.3; P=0.02). Subscores parsed many, but not all subtypes. FTD subjects had a larger decline on the MoCA within 13 to 36 months than AD subjects (P=0.02). The results indicate that the MoCA is a useful tool to identify and track progression of CI in FTD. Further, the data informs future research on scoring models for the MoCA to enhance cognitive screening and detection of FTD patients.

Frontotemporal Dementias.

This article reviews the common behavioral and cognitive features of frontotemporal dementia (FTD) and related disorders as well as the distinguishing clinical, genetic, and pathologic features of the most common subtypes. Advances in clinical phenotyping, genetics, and biomarkers have enabled improved predictions of the specific underlying molecular pathology associated with different presentations of FTD. Evaluation of large international cohorts has led to recent refinements in diagnostic criteria for several of the FTD subtypes. The FTDs are a group of neurodegenerative disorders featuring progressive deterioration of behavior or language and associated pathology in the frontal or temporal lobes. Based on anatomic, genetic, and neuropathologic categorizations, the six clinical subtypes of FTD or related disorders are: (1) behavioral variant of FTD, (2) semantic variant primary progressive aphasia, (3) nonfluent agrammatic variant primary progressive aphasia, (4) corticobasal syndrome, (5) progressive supranuclear palsy, and (6) FTD associated with motor neuron disease. Recognition and accurate diagnoses of FTD subtypes will aid the neurologist in the management of patients with FTD.

Amyloid deposition in semantic dementia: a positron emission tomography study.

BackgroundPittsburgh compound B ([11C]‐PIB) identifies amyloid‐β (Aβ) deposition in vivo. Asymptomatic Aβ deposition has been reported consistently in some healthy older subjects. Of patients with frontotemporal dementia, those who have later onset have a higher potential for Aβ deposition.ObjectiveComparison of Aβ deposition in Alzheimer's disease (AD), healthy older controls, and patients with early‐ and late‐onset semantic dementia (SD), a subtype of frontotemporal dementia.MethodsSubjects were recruited from tertiary academic care centers specializing in assessment and management of patients with neurodegenerative disease. We used the radiotracer [11C]‐PIB in a high‐resolution positron emission tomography scanner to evaluate 11 participants with SD (six with onset before age 65 and five with later onset), 9 with probable AD, and 10 controls over age 60. The main outcome measures were frontal, temporal, parietal, and total [11C]‐PIB standardized uptake value ratios to establish PIB‐positive (PIB+) cutoff.ResultsThe five patients with late‐onset SD were PIB‐negative. Two of six with early‐onset SD, seven of nine with AD, and 1 of 10 controls were PIB+. The SD participants who were PIB+ did not have memory or visuospatial deficits that are typical in AD.ConclusionsAβ deposition does not seem to be associated with late‐onset SD. Future larger studies might confirm whether a significant minority of early‐onset SD patients exhibit Aβ deposition. Copyright © 2016 John Wiley & Sons, Ltd.

Novel diagnostic cerebrospinal fluid biomarkers for pathologic subtypes of frontotemporal dementia identified by proteomics

IntroductionReliable cerebrospinal fluid (CSF) biomarkers enabling identification of frontotemporal dementia (FTD) and its pathologic subtypes are lacking. MethodsUnbiased high-resolution mass spectrometry–based proteomics was applied on CSF of FTD patients with TAR DNA-binding protein 43 (TDP-43, FTD-TDP, n = 12) or tau pathology (FTD-tau, n = 8), and individuals with subjective memory complaints (SMC, n = 10). Validation was performed by applying enzyme-linked immunosorbent assay (ELISA) or enzymatic assays, when available, in a larger cohort (FTLD-TDP, n = 21, FTLD-tau, n = 10, SMC, n = 23) and in Alzheimer's disease (n = 20), dementia with Lewy bodies (DLB, n = 20), and vascular dementia (VaD, n = 18). ResultsOf 1914 identified CSF proteins, 56 proteins were differentially regulated (fold change >1.2, P < .05) between the different patient groups: either between the two pathologic subtypes (10 proteins), or between at least one of these FTD subtypes and SMC (47 proteins). We confirmed the differential expression of YKL-40 by ELISA in a partly independent cohort. Furthermore, enzyme activity of catalase was decreased in FTD subtypes compared with SMC. Further validation in a larger cohort showed that the level of YKL-40 was twofold increased in both FTD pathologic subtypes compared with SMC and that the levels in FTLD-tau were higher compared to Alzheimer's dementia (AD), DLB, and VaD patients. Clinical validation furthermore showed that the catalase enzyme activity was decreased in the FTD subtypes compared to SMC, AD and DLB. DiscussionWe identified promising CSF biomarkers for both FTD differential diagnosis and pathologic subtyping. YKL-40 and catalase enzyme activity should be validated further in similar pathology defined patient cohorts for their use for FTD diagnosis or treatment development.

The Evolution of Caregiver Burden inFrontotemporal Dementia with and without Amyotrophic Lateral Sclerosis.

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) represent a disease spectrum. Caregiver burden in subtypes of FTD has not yet been directly compared with those patients who have co-existent FTD and ALS (ALSFTD). Perceived caregiver burden was evaluated using the short Zarit Burden Interview (ZBI) in patients with behavioral-variant FTD (bvFTD, n = 21), semantic dementia (SD, n = 18), and ALSFTD (n = 15) at the initial clinical presentation and follow-up assessments. The Mini-Addenbrooke's Cognitive Examination (M-ACE) and the Motor Neuron Disease Behaviour Scale (MiND-B) were also used. Linear mixed effects models examined longitudinal changes on the ZBI, M-ACE, and MiND-B across groups. Burden at baseline was highest for the bvFTD group. Longitudinally, perceived burden increased for the SD and ALSFTD groups whereas in bvFTD, the level of burden which was high at baseline and remained high with disease progression. The severity of abnormal behaviors at baseline, as assessed by the MiND-B, correlated with baseline levels of caregiver burden and further accounted for 23% of the variance in caregiver burden at clinical follow-up. The trajectory of perceived burden differs across the FTD-ALS spectrum, with SD and ALSFTD caregivers demonstrating an increased burden that develops over time, compared to a persistently high level for bvFTD caregivers, evident throughout the disease course. The evolution of burden in these three syndromes likely reflects the initial presentation and clinical characterization that develops with time. Psycho-education programs for caregivers, which provide better coping strategies for challenging behaviors, may reduce levels of burden experienced with disease progression.

Discriminative and prognostic potential of cerebrospinal fluid phosphoTau/tau ratio and neurofilaments for frontotemporal dementia subtypes

IntroductionA decreased cerebrospinal fluid (CSF) p-Tau181 to total tau ratio (p/t-tau) is a biomarker for frontotemporal lobar degeneration with TDP43 inclusions (FTLD-TDP) and for amyotrophic lateral sclerosis (ALS). CSF light chain neurofilaments (NfL) are increased in ALS. We examined whether CSF p/t-tau and NfL are related to ALS status in FTLD-TDP. MethodsWe compared CSF p/t-tau and NfL levels between patients with FTLD-TDP with ALS (n = 15), FTLD-TDP without ALS (n = 17), FTLD-Tau (n = 6), Alzheimer's disease (AD; n = 25), and subjective memory complaints (SMC, n = 24). ResultsApart from FTLD-Tau, all groups differed significantly with increasing p/t-tau ratios from FTLD-TDP with ALS to FTLD-TDP without ALS to AD and SMC. CSF NfL was very high in FTLD-TDP with ALS followed by FTLD-TDP without ALS, AD, and SMC. Both biomarkers correlated with survival. DiscussionCSF p/t-tau ratio and NfL levels are strongly driven by ALS status. These markers, therefore, appear to be more of prognostic than diagnostic significance.

Substance use history in behavioral-variant frontotemporal dementia versus primary progressive aphasia

ABSTRACTAs older adults are prone to cognitive disorders, the interaction of the fields of substance use and misuse and cognitive neuroscience is an emerging area of research. Substance use has been reported in some subtypes of frontotemporal dementia, such as behavioral variant frontotemporal dementia. However, characterization of substance use in other subtypes of frontotemporal dementia, such as primary progressive aphasia, is unknown. The objective of this baseline analysis was to explore whether any measures of substance use history differed significantly among behavioral variant frontotemporal dementia (n = 842) and primary progressive aphasia (n = 526) in a large national dataset. The National Alzheimer's Coordinating Center's Uniform Data Set study is a national dataset that collects data on patients with various cognitive disorders and includes some questions on substance use. Each substance use variable was used as the outcome and the frontotemporal dementia subtype as the predictor. Total years smoked cigarettes, age when last smoked cigarettes, average number of packs/day smoked when participants smoked, and any recent, remote, or combined recent/remote history of alcohol abuse or drug abuse did not significantly differ between the behavioral variant frontotemporal dementia and primary progressive aphasia subtypes (all p-values > .001). A significantly greater percentage of participants smoked in the last 30 days in the behavioral variant frontotemporal dementia subtype (10.4%, n = 834) compared to the primary progressive aphasia subtype (3.3%, n = 517; p < .001). Clinical providers in both the dementia and substance use fields are encouraged to screen for and monitor substance use in all frontotemporal dementia subtypes.

Genetics of frontotemporal dementia in Asia: Advancing knowledge through collaboration.

Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder characterized by selective involvement of the frontal and temporal lobes, where non-Alzheimer disease (AD) pathology is expected. FTD encompasses 3 distinct clinical syndromes including behavioral variant FTD (bvFTD) characterized by prominent behavioral abnormalities, and 2 language variants (semantic variant and nonfluent variant) collectively known as primary progressive aphasia (PPA). The most common FTD subtype, bvFTD, may manifest with disinhibition, compulsive/perseverative behavior, overeating, apathy, and emotional blunting. FTD is known in Western populations to be the second most common cause of dementia in those younger than 65 years.1 In Asian populations, FTD appears to be far less common, being the third most common cause of young-onset dementia in some cohorts behind AD and vascular dementia.2 The proportion of Asian patients with FTD who have a positive family history ranges from 9.5% to 20%,2–4 considerably lower than the 30% to 50% seen in Caucasian populations.5

Primer progressive aphasia: a case report

Background: Primaryprogressive aphasia (PPA) is known as subtype of frontotemporal dementia with evident language impairment. There is a progressive disorder in finding and understanding words at least for two years. Mental functions like memory, visuospatial functions, personality traits are generally preserved. Objective: We want to share a quite rare case, PPA by reporting a woman having difficulty in recognizing words and uttering long sentences. Patient and methods: A 65-year-old-woman was admitted to the hospital with complaints with difficult in speaking and fixing long sentences. She stated that she had gathered the sentences in her mind but was not able to find suitable words to express them. On the neurological examination , she could easily transfer her thoughts to writing as well as she could read long sentences, but there were pauses during her speech while using long sentences. She had difficulties in finding the right words to express her thoughts. Insight, judgement, personal care were preserved . In neuropsychological testing, the range of attention was slightly deteriorated and the complex attention was clearly deteriorated. Results: On brain MRI, there were atrophic changes in the perisylvian regions bilaterally. In brain PET hypoperfusion was observed particularly in the left temporal and frontal lobes. She was given donepezil and escitalopram treatment for 6 months and there were no changes on control examination. Conclusion: PPA may not be diagnosed for many years due to the insidious progressive loss of language functions. Neuropsychological testing and neuroimaging is important to diagnose. PPA seemed worth presenting since it was a rare case.

Frontotemporal dementia-associated N279K tau mutant disrupts subcellular vesicle trafficking and induces cellular stress in iPSC-derived neural stem cells.

BackgroundPallido-ponto-nigral degeneration (PPND), a major subtype of frontotemporal dementia with parkinsonism related to chromosome 17 (FTDP-17), is a progressive and terminal neurodegenerative disease caused by c.837 T > G mutation in the MAPT gene encoding microtubule-associated protein tau (rs63750756; N279K). This MAPT mutation induces alternative splicing of exon 10, resulting in a modification of microtubule-binding region of tau. Although mutations in the MAPT gene have been linked to multiple tauopathies including Alzheimer’s disease, frontotemporal dementia and progressive supranuclear palsy, knowledge regarding how tau N279K mutation causes PPND/FTDP-17 is limited.ResultsWe investigated the underlying disease mechanism associated with the N279K tau mutation using PPND/FTDP-17 patient-derived induced pluripotent stem cells (iPSCs) and autopsy brains. In iPSC-derived neural stem cells (NSCs), the N279K tau mutation induced an increased ratio of 4-repeat to 3-repeat tau and accumulation of stress granules indicating elevated cellular stress. More significant, NSCs derived from patients with the N279K tau mutation displayed impaired endocytic trafficking as evidenced by accumulation of endosomes and exosomes, and a reduction of lysosomes. Since there were no significant differences in cellular stress and distribution of subcellular organelles between control and N279K skin fibroblasts, N279K-related vesicle trafficking defects are likely specific to the neuronal lineage. Consistently, the levels of intracellular/luminal vesicle and exosome marker flotillin-1 were significantly increased in frontal and temporal cortices of PPND/FTDP-17 patients with the N279K tau mutation, events that were not seen in the occipital cortex which is the most spared cortical region in the patients.ConclusionTogether, our results demonstrate that alterations of intracellular vesicle trafficking in NSCs/neurons likely contribute to neurodegeneration as an important disease mechanism underlying the N279K tau mutation in PPND/FTDP-17.

Regional cerebral blood flow single photon emission computed tomography for detection of Frontotemporal dementia in people with suspected dementia.

Regional cerebral blood flow single photon emission computed tomography for detection of Frontotemporal dementia in people with suspected dementia.

Clinical and Neuropsychological Comparisons of Early-Onset Versus Late-Onset Frontotemporal Dementia: A CREDOS-FTD Study.

Cognitive performance changes with chronological aging. Previous studies investigating clinical heterogeneity in frontotemporal dementia (FTD) according to the age of symptom onset did not consider the effect of chronological aging on cognition. We compared cognitive and behavioral symptoms in patients with early-onset (EO) and late-onset (LO) FTD with consideration of chronological aging effect. A total of 166 FTD patients were enrolled consecutively from multi-center memory clinics using a nationwide FTD register. To control for the effects of chronological aging on neuropsychological scores, seven hundred and two subjects with normal cognition were also enrolled and regression models were set up. Neuropsychological scores that were detrended with the regression models and the behavioral symptoms of the EO-FTD and LO-FTD groups were compared. Subgroup analyses were performed for three main subtypes of FTD, behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), and progressive non-fluent aphasia (PNFA). Among 166 FTD patients, there were 76 bvFTD, 57 SD, and 33 PNFA patients who met new diagnostic criteria for bvFTD or primary progressive aphasia, respectively. LO-FTD (48.2%) was more common than previously thought and the proportions of EO and LO groups differed across FTD subtypes. EO-FTD patients had lower memory and frontal/executive scores and more prominent frontal/behavioral symptoms than LO-FTD patients. Our study suggested that FTD could be heterogeneous with respect the age of symptom onset. After controlling for the effects of chronological aging, EO-FTD patients exhibited more profound memory and frontal/executive dysfunction and more behavioral symptoms than LO-FTD patients.

Commentary on: Psychotic symptoms in frontotemporal dementia: a diagnostic dilemma?

Frontotemporal dementia is clearly a very important condition, not only because alongside Alzheimer's disease, vascular dementia, and Lewy body dementia it is one of the four most common causes of dementia, but because its broad symptom profile and younger age of onset makes it a particularly challenging condition to diagnose and manage. In recent years, great progress has been made in understanding genetic and pathological underpinnings of frontotemporal dementias, and in characterizing specific pathological causes. In particular, three major subtypes can be delineated: those associated pathologically with tau; transactive responsive DNA binding protein (TDP-43); or fused in sarcoma (FUS). Of these, tau and TDP-43 are by far the two most common subtypes of frontotemporal dementia. In addition, there have been important genetic advances and several autosomal dominant mutations have been described, for example associated with MAPT, progranulin, and C9ORF72. However, despite these important advances regarding pathophysiological heterogeneity, relatively little is known about the frequency, nature, and correlates of psychotic symptoms in the disorder. It is therefore very timely that in this month's Paper of the Month, Waldo and colleagues (Waldo et al., 2015) describe a very detailed description of a cohort of 97 consecutive subjects seen in Lund who received a neuropathological diagnosis of frontotemporal lobar degeneration.

Quantifying the Eating Abnormalities in Frontotemporal Dementia

Presence of eating abnormalities is one of the core criteria for the diagnosis of behavioral variant frontotemporal dementia (bvFTD), yet their occurrence in other subtypes of frontotemporal dementia (FTD) and effect on metabolic health is not known. To define and quantify patterns of eating behavior and energy, sugar, carbohydrate, protein, and fat intake, as well as indices of metabolic health in patients with bvFTD and semantic dementia (SD) compared with patients with Alzheimer disease (AD) and healthy control participants. Prospective case-controlled study involving patient and caregiver completion of surveys. Seventy-five participants with dementia (21 with bvFTD, 26 with SD, and 28 with AD) and 18 age- and education-matched healthy controls were recruited from FRONTIER, the FTD research clinic at Neuroscience Research Australia in Sydney. Caregivers of patients with FTD and AD completed validated questionnaires on appetite, eating behaviors, energy consumption, and dietary macronutrient composition. All participants completed surveys on hunger and satiety. Body mass index and weight measurements were prospectively collected. The bvFTD group had significant abnormalities in the domains of appetite (U = 111.0, z = 2.7, P = .007), eating habits (U = 69.5, z = 3.8, P = .001), food preferences (U = 57.0, z = 4.1, P = .001), swallowing (U = 109.0, z = 3.0, P = .003), and other oral behaviors (U = 141.0, z = 2.6, P = .009) compared with the AD group. The bvFTD and SD groups tended to have increased energy consumption. Compared with controls, the bvFTD group had significantly increased carbohydrate intake (251 vs 170 g/d; P = .05) and the SD group had significantly increased sugar intake (114 vs 76 g/d; P = .049). No significant differences in total fat or protein intake between the groups were found. Despite similar energy intake, the SD group had lower hunger and satiety scores compared with the bvFTD group. In contrast, hunger and satiety scores did not differ between the bvFTD group and controls. The abnormal eating behavior was found in the 2 groups (bvFTD and SD) with the highest body mass index (F = 4.2, P = .008) and waist circumference (F = 6.4, P = .001). Abnormal eating behaviors are prominent in patients with bvFTD and those with SD and are not limited to increased appetite. The observed higher intake of sugar and carbohydrates was found in patients with the FTD subtypes and those with higher body mass index and waist circumference and was not explained simply by increased hunger or lower satiety.

Brain Perfusion SPECT with Brodmann Areas Analysis in Differentiating Frontotemporal Dementia Subtypes

Despite the known validity of clinical diagnostic criteria, significant overlap of clinical symptoms between Frontotemporal dementia (FTD) subtypes exists in several cases, resulting in great uncertainty of the diagnostic boundaries. We evaluated the perfusion between FTD subtypes using brain perfusion (99m)Tc-HMPAO SPECT with Brodmann areas (BA) mapping. NeuroGam software was applied on single photon emission computed tomographic (SPECT) studies for the semi-quantitative evaluation of perfusion in BA and the comparison with the software's normal database. We studied 91 consecutive FTD patients: 21 with behavioural variants (bvFTD), 39 with language variants (lvFTD) [12 with progressive non-fluent aphasia (PNFA), 27 with semantic dementia (SD)], and 31 patients with progressive supranuclear palsy (PSP)/corticobasal degeneration (CBD). Stepwise logistic regression analyses showed that the BA 28L and 32R could independently differentiate bvFTD from lvFTD, while the BA 8R and 25R could discriminate bvFTD from SD and PNFA, respectively. Additionally, BA 7R and 32R were found to discriminate bvFTD from CBD/PSP. The only BA that could differentiate SD from PNFA was 6L. BA 6R and 20L were found to independently differentiate CBD/PSP from lvFTD. Moreover, BA 20L and 22R could discriminate CBD/PSP from PNFA, while BA 6R, 20L and 45R were found to independently discriminate CBD/PSP from SD. Brain perfusion SPECT with BA mapping can be a useful additional tool in differentiating FTD variants by improving the definition of brain areas that are specifically implicated, resulting in a more accurate differential diagnosis in atypical or uncertain forms of FTD.

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.

RELEARNING IN SEMANTIC DEMENTIA

Relearning in semantic dementia Semantic dementia is a subtype of frontotemporal dementia, primarily affecting the anterior temporal lobes. The most distinct and early detectable symptom of semantic dementia is anomia, but semantic dementia is not just a problem of naming objects, it implies a deeper degradation of conceptual knowledge across modalities. In the early stages of semantic dementia episodic memory and other cognitive abilities are most often relatively spared, and recent studies have demonstrated that patients with semantic dementia can relearn names of objects through cognitive training. However, it has not been clearly demonstrated if any method of cognitivetraining can lead to both improved naming and relearning of semantic knowledge. We wanted to explore whether extensive multimodal cognitive training could improve both naming and enhance semantic knowledge in semantic dementia. Three patients completed at 3 weeks individualized training program, which implied naming and knowledge training in a clinical setting and at-home training. Two methods of cognitive training were compared within subjects: extensive multimodal cognitive training and simple picture-word association training. Patients were assessed pre- and post-intervention on naming and knowledge of individualized items, presented as pictures. Results showed that the training programme did improve naming and semantic knowledge of items. However there were no significant differences between the two methods of cognitive training. Unexpectedly we also found improvement in naming of some control-items, which were not trained. This indicates a possibility of a more generalized effect of cognitive training in semantic dementia. This study supported the possible benefits of cognitive training in semantic dementia. More research is needed to develop methods which can improve both naming and semantic knowledge in patients with semantic dementia.

Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes

Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17–14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology.