Search

Background: Pittsburgh 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., Objective: Comparison 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., Methods: Subjects 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., Results: The 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., Conclusions: Aβ 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., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objective: This study examines reading aloud in patients with amyotrophic lateral sclerosis (ALS) and those with frontotemporal dementia (FTD) in order to determine whether differences in patterns of speaking and pausing exist between patients with primary motor vs. primary cognitive-linguistic deficits, and in contrast to healthy controls., Design: 136 participants were included in the study: 33 controls, 85 patients with ALS, and 18 patients with either the behavioural variant of FTD (FTD-BV) or progressive nonfluent aphasia (FTD-PNFA). Participants with ALS were further divided into 4 non-overlapping subgroups--mild, respiratory, bulbar (with oral-motor deficit) and bulbar-respiratory--based on the presence and severity of motor bulbar or respiratory signs. All participants read a passage aloud. Custom-made software was used to perform speech and pause analyses, and this provided measures of speaking and articulatory rates, duration of speech, and number and duration of pauses. These measures were statistically compared in different subgroups of patients., Results: The results revealed clear differences between patient groups and healthy controls on the passage reading task. A speech-based motor function measure (i.e., articulatory rate) was able to distinguish patients with bulbar ALS or FTD-PNFA from those with respiratory ALS or FTD-BV. Distinguishing the disordered groups proved challenging based on the pausing measures., Conclusions and Relevance: This study demonstrated the use of speech measures in the identification of those with an oral-motor deficit, and showed the usefulness of performing a relatively simple reading test to assess speech versus pause behaviors across the ALS-FTD disease continuum. The findings also suggest that motor speech assessment should be performed as part of the diagnostic workup for patients with FTD.

Behavioral variant frontotemporal dementia (bvFTD) affects emotional evaluation, but less is known regarding the patients' ability to remember emotional stimuli. Here, bvFTD patients and age-matched controls studied positive, negative, and neutral pictures followed by a recognition memory test. Compared to controls, bvFTD patients showed a reduction in emotional evaluation of negative scenes, but not of positive or neutral scenes. Additionally, the patients showed an overall reduction in recognition memory accuracy, due to impaired recollection in the face of relatively preserved familiarity. These results show that bvFTD reduces the emotional evaluation of negative scenes and impairs overall recognition memory accuracy and recollection.

Mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal dementia. We used a comprehensive neuropsychological battery to investigate whether early cognitive changes could be detected in GRN mutation carriers before dementia onset. Twenty-four at-risk members from six families with known GRN mutations underwent detailed neuropsychological testing. Group differences were investigated by domains of attention, language, visuospatial function, verbal memory, non-verbal memory, working memory and executive function. There was a trend for mutation carriers (n=8) to perform more poorly than non-carriers (n=16) across neuropsychological domains, with significant between group differences for visuospatial function (p<.04; d=0.92) and working memory function (p<.02; d=1.10). Measurable cognitive differences exist before the development of frontotemporal dementia in subjects with GRN mutations. The neuropsychological profile of mutation carriers suggests early asymmetric, right hemisphere brain dysfunction that is consistent with recent functional imaging data from our research group and the broader literature.

Importance: Noninvasive measures of activity within intrinsic brain networks may be clinically relevant, providing a marker of neurodegenerative disease and predicting clinical behaviors., Objective: To correlate baseline resting-state measures within the salience network and changes in behavior among patients with frontotemporal dementia., Design: Baseline resting-state functional magnetic resonance imaging data and longitudinal clinical measures were obtained from prospectively accrued patients during 8 weeks., Setting: Tertiary academic care center specializing in the assessment and management of patients with neurodegenerative disease., Participants: Fifteen patients with clinically diagnosed frontotemporal dementia (5 behavioral variant and 10 semantic dementia)., Main Outcomes and Measures: Baseline resting-state functional magnetic resonance imaging data measured within regions of interest were regressed on serial behavioral measures from prospectively accrued patients with frontotemporal dementia to determine the ability of baseline resting-state activity to account for changes in behavior., Results: Low-frequency fluctuations in the left insula significantly predicted changes in Frontal Behavioral Inventory scores (standard β = 0.51, P = .049), accounting for 28% of the change variance. The trend was driven by changes in measures of apathy independent of dementia severity., Conclusion and Relevance: Baseline measures of salience network connectivity involving the left insula may predict behavioral changes in patients with frontotemporal dementia.

Introduction: Degraded social function, disinhibition, and stereotypy are defining characteristics of frontotemporal dementia (FTD), manifesting in both the behavioral variant of frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Recent neuroimaging research also associates FTD with alterations in the brain's intrinsic connectivity networks. The present study explored the relationship between neural network connectivity and specific behavioral symptoms in FTD., Methods: Resting-state functional magnetic resonance imaging was employed to investigate neural network changes in bvFTD and SD. We used independent components analysis (ICA) to examine changes in frontolimbic network connectivity, as well as several metrics of local network strength, such as the fractional amplitude of low-frequency fluctuations, regional homogeneity, and seed-based functional connectivity. For each analysis, we compared each FTD subgroup to healthy controls, characterizing general and subtype-unique network changes. The relationship between abnormal connectivity in FTD and behavior disturbances was explored., Results: Across multiple analytic approaches, both bvFTD and SD were associated with disrupted frontolimbic connectivity and elevated local connectivity within the prefrontal cortex. Even after controlling for structural atrophy, prefrontal hyperconnectivity was robustly associated with apathy scores. Frontolimbic disconnection was associated with lower disinhibition scores, suggesting that abnormal frontolimbic connectivity contributes to positive symptoms in dementia. Unique to bvFTD, stereotypy was associated with elevated default network connectivity in the right angular gyrus. The behavioral variant was also associated with marginally higher apathy scores and a more diffuse pattern of prefrontal hyperconnectivity than SD., Conclusions: The present findings support a theory of FTD as a disorder of frontolimbic disconnection leading to unconstrained prefrontal connectivity. Prefrontal hyperconnectivity may represent a compensatory response to the absence of affective feedback during the planning and execution of behavior. Increased reliance upon prefrontal processes in isolation from subcortical structures appears to be maladaptive and may drive behavioral withdrawal that is commonly observed in later phases of neurodegeneration., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The effect of early onset frontotemporal dementias (FTD) on spouses and children is profound, requiring different types of support services from pre-existing Alzheimer's disease interventions already in place. This article explores how the needs of families living with FTD resulted in three programme initiatives developed at Baycrest (an academic health sciences centre focused on ageing, in Toronto, Canada) to meet the needs of this population. These included an Internet-based videoconferencing support group for spouses, a website that provides support and counsel for children and their parents, and an adult day programme designed for FTD patients. The strength of these interventions is that services were developed with involvement of stakeholders in FTD care from the start, to deal with gaps in services in a sustainable way.

Objective: To study the effect of memantine on apathy, a common symptom of behavioral variant frontotemporal dementia (bvFTD)., Design: The patient underwent an off-label trial of memantine with behavioral inventories and [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans performed at baseline, 7 weeks and 6 months., Subject: The patient was a 66-year-old male whose main manifestation of bvFTD was affective, behavioral and cognitive apathy., Intervention: The patient began memantine at an oral dose of 5 mg per morning and titrated up by 5 mg per week to the maintenance dose of 10 mg PO bid., Results: Informants reported reduction of the apathy. The insula and cerebellum, both involved in the salience network, showed improved metabolism., Conclusion: Further study to correlate the effects of memantine on apathy and the salience network in bvFTD are warranted.

Objective: To learn more about the needs and experiences of young carers for patients of frontotemporal dementia (FTD) in order to create a relevant support website for young caregivers to dementia patients., Methods: Two focus groups were held with a total of fourteen young carers aged 11-18. The data corpus was collected through a semi-structured interview facilitated by a medical journalist who had prior experience as a caregiver to a patient with FTD. The transcripts were narrowed to a dataset for descriptive analysis using a coding scheme to reveal the main themes of their responses., Results: Seven overlapping theme areas were: emotional impact of living with a parent with FTD, caregiving, coping, symptoms, diagnosis, relationships, and support. Based on the participants' responses, a website was launched providing supportive information and counsel for young carers., Conclusion: Young carers saw the experience of caring for a parent with early-onset dementia as positive overall, but identified opportunities for professionals to assist them in overcoming stigma and the challenge of balancing childhood and adolescent development within this context.

Frontotemporal dementia (FTD) symptoms at the beginning of illness are in either the realm of behavioral disturbance or in language disruption, also known as aphasia. Based on specific constellations of behavioral change or characteristics of the aphasia, physicians can anticipate the type of protein that is abnormal in the brain. Family history rich with similar instances of illness can further guide the cause of illness in an individual. Knowing the type of protein abnormality (proteinopathy) from among the three most common in FTD (tau, TDP-43, or fused in sarcoma) can help treating clinicians to advise families on the future course of illness and future clinical drug trials that would be most applicable to each patient.

Objective: To guide development of public awareness and caregiver support resources for frontotemporal dementia (FTD) syndromes., Methods: We used an online survey to explore their needs. The survey was self-administered by self-identified, English-speaking caregivers for patients with FTD in several countries., Results: Of 79 caregiver respondents, approximately half were caring for patients with behavioural variant FTD or semantic dementia. The most common initial symptoms were Changes in Thinking and Judgment. Half of the respondents identified "failure to recognize the early stage of illness as a dementia" as the most troublesome aspect. Accordingly, over 40% of respondents had difficulty obtaining an accurate diagnosis for the patient. Caregivers prioritized family counseling and the public educational message that dementia can affect young people., Conclusion: The largest international survey of FTD caregivers to-date showed that support is needed for all family members adapting to the shock of early-onset dementia, and this may be most readily provided online.

Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.

Background/aims: We review the characteristics of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP) and determine prevalence of behavioral variant of frontotemporal dementia (bvFTD) features in ALSP., Methods: Clinical and pathological information was abstracted from histopathologically confirmed ALSP cases identified by a systematic literature search. A new case of ALSP presenting as bvFTD was also described., Results: We retrieved 51 ALSP cases. Mean age of onset was 42.2 years. Mean disease duration was 6.2 years, with 24 cases lasting 4 years or fewer. Fourteen cases had 3 or more of the 6 key bvFTD features. White matter hyperintensities on T(2)-weighted MRI, motor symptoms, seizures and amnesia were common., Conclusion: ALSP can underlie FTD syndrome, as well as rapidly progressive dementia., (Copyright © 2011 S. Karger AG, Basel.)

Objectives To follow up on the increases we reported in normalized metabolic activity in salience network hubs from a 2-month open-label study of memantine in frontotemporal dementia (FTD). Methods We repeated fluorodeoxyglucose positron emission tomography (FDG-PET) after 6 months of drug use and subjected the data to Statistical Parametrical Mapping (SPM) analysis to reveal clusters of significant change from baseline. We also sought correlations between changes in behavioral disturbances on the Frontal Behavioral Inventory (FBI) and the PET signal. Results Recruitment of one progressive nonfluent aphasia and one behavioral variant FTD precluded statistical analysis for any FTD subtype other than semantic dementia (SD). The baseline-to-6-month interval showed increased normalized metabolic activity in the left orbitofrontal cortex ( p < 0.002) for five participants with SD. The 2-6-month interval revealed a late increase in normalized metabolic activity in the left insula ( p < 0.013), right insula ( p < 0.009), and left anterior cingulate ( p < 0.005). The right anterior cingulate showed both an initial increase and a delayed further increase (2-6 months, p < 0.016). FBI scores worsened by 43.3%. One participant with SD opted not to continue memantine beyond 2 months yet showed similar FDG-PET increases. Conclusions Increases in normalized cortical metabolic activity in salience network hubs were sustained in SD over a 6-month period. Because one participant without medication also showed these changes, further investigation is recommended through a double-blind, placebo-controlled study with FDG-PET as an outcome measure. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Predicting the progression of dementia is a challenge for clinicians yet this information is highly valued by patients' families. An informally observed 4-stage model of dementia can be helpful in educating caregivers and preparing them for what lies ahead. In the behavioral variant of frontotemporal dementia (bvFTD), this model describes the evolution of behavioral disturbances and is characterized by an inflection point between stage 2 (progressively severe behavioral aberration) and stage 3 (increasing apathy and remission of behavior problems). In this study, we sought evidence for this model using a database of serial Neuropsychiatric Inventory (NPI) scores for 45 patients with FTD and 47 patients with Alzheimer's disease (AD). We transformed the NPI scores into a single variable for each participant that represented the yearly rate of change in total NPI score and used this as the dependent variable in a multivariate linear regression. Age at onset of dementia, NPI score at initial visit, and duration of illness at first NPI all contributed significantly to the regression model in the bvFTD group. Participants with an initial NPI acquired before 6 years of disease duration tended to have a more positive rate of change in NPI total score (representing worsening behavioral disturbances) than those with an initial NPI performed after 6 years. None of the aforementioned variables were significantly associated with yearly change in NPI total score in the AD group. These results support a crescendo-decrescendo trajectory of behavioral symptoms in bvFTD but do not suggest that there is a similar pattern in AD, and further longitudinal data collection is necessary. [ABSTRACT FROM AUTHOR]

Background/Aims: The clinical syndrome of the frontotemporal dementias (FTD) overlaps with frontal-subcortical circuit syndromes. We explored the extent to which subcortical atrophy on structural magnetic resonance imaging may indicate a subcortical contribution to the progression of FTD. Methods: This cross-sectional case-control study compared striatal and thalamic gray matter volumes and functional levels from 30 FTD cases and 30 age- and gender-matched controls. Results: The FTD group had significantly more atrophy in all gray matter subcortical regions, correlating with ipsilateral frontocortical atrophy. Subcortical atrophy was also associated with functional disability. Subcortical asymmetry was most marked in subjects with primary progressive aphasia. Conclusion: Subcortical gray matter atrophy may contribute as significantly to symptoms of FTD as cortical atrophy. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The clinical diagnostic criteria for frontotemporal degeneration (FTD) include relative preservation of memory and visuospatial function, in contradistinction to characteristics of Alzheimer’s disease (AD). The Mini-Mental State Examination (MMSE) contains items to assess these areas of cognition. In a retrospective case-control study of participants at two institutionally-based AD centers, we determined whether total MMSE and MMSE subscores would reflect the disease progression projected by the clinical criteria of FTD vs. AD. Participants were 44 subjects with FTD (7 pathologically confirmed) and 45 with pathologically confirmed AD. Each subject had at least two MMSEs with minimum inter-test intervals of 9 months. We compared annualized rates of change for total MMSE scores and cognitive domain subscores over time and between groups by two independent samples t-tests and proportion tests. The total MMSE score (p = 0.03) and language subscore (p = 0.02) showed a greater rate of decline for the FTD group than the AD group, although the constructional praxis item declined less rapidly in the FTD group (p = 0.018). Changes in MMSE subscores paralleled the clinical diagnostic criteria for FTD. The more rapid progression on the language subscore was observed in both language and behavioral variants of FTD. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This review of pharmacotherapy for frontotemporal lobar degeneration describes the chemical rationale for agents used and reports observed responses to psychotropic medications. Paroxetine addressed anxiety and repetitive, ritualistic behaviors. Depression was resistant to treatment. Valproic acid and quetiapine calmed agitated subjects without exacerbating Parkinsonism. Donepezil has not emerged as a beneficial medication for this group of subjects. Behavioral disturbances can be alleviated pharmacologically, but further research might determine guidelines for management of this non-Alzheimer's dementia syndrome that could decrease the frequency of adverse drug events. [ABSTRACT FROM PUBLISHER]

Objective: To determine whether basal ganglia atrophy, known to be associated with apathy in nondementia populations, was associated with presence of apathy in patients with frontotemporal dementia (FTD). Methods: A cross-sectional case study was conducted at two tertiary dementia care clinics in Toronto, Ontario, Canada. Striatal and thalamic gray matter volumes and apathy measures were collected from 21 subjects with FTD, 6 of whom did not show apathy on the Neuropsychiatric Inventory. Results: No significant differences in gray matter volumes were found between apathetic and nonapathetic groups for the striatum or the thalamus. Conclusions: Our findings imply that the etiology of apathy seen in patients with FTD differs from that of patients with apathy after acquired injuries to the basal ganglia. Further study is needed to determine whether posterior thalamic atrophy correlates with apathy in FTD or functional imaging techniques might successfully find a relationship between basal ganglia dysfunction and apathy. [ABSTRACT FROM AUTHOR]

Abstract: Frontotemporal lobar degeneration (FTLD) often presents with asymmetric atrophy. We assessed whether premorbid occupations in FTLD patients were associated with these hemispheric asymmetries. In a multi-center chart review of 588 patients, occupation information was related to location of tissue loss or dysfunction. Patients with atrophy lateralized to the right had professions more dependent on verbal abilities than patients with left-lateralized or symmetrical atrophy. In a subgroup of 96 well-characterized patients with quantified neuroimaging data, the lateralization effect was localized to the temporal lobes and included verbal and mathematical ability. Patients whose professions placed high demands on language and mathematics had relatively preserved left temporal relative to right temporal volumes. Thus, occupation selection occurring in early adulthood is related to lateralized brain asymmetry in patients who develop FTLD decades later in the relatively deficient hemisphere. The finding suggests that verbal and mathematical occupations may have been pursued due to developmental right-lateralized functional impairment that precedes the neurodegenerative process. Alternatively, long-term engagement of activities associated with these occupations contributed to left-lateralized reserve, right-lateralized dysfunction, or both. [ABSTRACT FROM AUTHOR]