Longitudinal decline in autopsy-defined frontotemporal lobar degeneration

Grossman, Murray; Xie, Sharon X.; Libon, David J.; Wang, X.; Massimo, Lauren; Moore, Peachie; Vesely, Luisa; Berkowitz, Richard L.; Chatterjee, Anjan; Coslett, H. Branch; Hurtig, Howard I.; Forman, Mark S.; Lee, V. M.-Y.; Trojanowski, John Q.

doi:10.1212/01.wnl.0000303816.25065.bc

Cited by 76 publications

(103 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…function than patients with CBS was mostly supported ( (table 2). This finding corroborates previous studies which found that tauϩ patients with frontotemporal lobar degeneration (including patients with CBD) had greater visuospatial deficits than tau-patients with frontotemporal lobar degeneration (a group that did not include patients with CBD), 8,9 and likely reflects the greater involvement of brain areas involved in motor and visuospatial function in CBS than in FTD.…”

Section: Principal Components Analysissupporting

confidence: 91%

“…This could be because these areas selectively contribute to executive function in CBS, or, more likely, because the patients with CBS's motor and visuospatial deficits interfere with the assessment of executive function (especially on the Trail Making test, which has significant motor and visuospatial components). 8,9 The patients with FTD show regionally specific associations: Verbal Fluency (with a significant language component) was associated with left frontal perisylvian cortex, Sorting with dorsolateral prefrontal cortex, and Twenty Questions, a reasoning task, with left anterior frontal cortex. These findings fit well with a large previous literature on the neuroanatomic localization of these specific executive functions.…”

Section: Principal Components Analysismentioning

confidence: 99%

See 1 more Smart Citation

Executive dysfunction in frontotemporal dementia and corticobasal syndrome

et al. 2009

View full text Add to dashboard Cite

Objective: To determine the pattern of executive dysfunction in frontotemporal dementia (FTD) and corticobasal syndrome (CBS) and to determine the brain areas associated with executive dysfunction in these illnesses. Method:We administered the Delis-Kaplan Executive Function System (D-KEFS), a collection of standardized executive function tests, to 51 patients with behavioral-variant FTD and 50 patients with CBS. We also performed a discriminant analysis on the D-KEFS to determine which executive function tests best distinguished the clinical diagnoses of FTD and CBS. Finally, we used voxel-based morphometry (VBM) to determine regional gray matter volume loss associated with executive dysfunction. Results:Patients with FTD and patients with CBS showed executive dysfunction greater than memory dysfunction. Executive function was better preserved in the patients with CBS than the patients with FTD with the exception of tests that required motor, visuospatial ability, or both. In patients with CBS, dorsal frontal and parietal and temporal-parietal cortex was associated with executive function. In FTD, tests with a language component (Verbal Fluency) were associated with left perisylvian cortex, sorting with the left dorsolateral prefrontal cortex, and reasoning (the Twenty Questions task) with the left anterior frontal cortex. The Twenty Questions test best distinguished the clinical diagnoses of CBS and FTD. Frontotemporal dementia (FTD) is a progressive neurodegenerative disease that primarily affects the frontal and anterior temporal lobes, resulting in changes in behavior, language, and cognition. Conclusions:1 Corticobasal syndrome (CBS) is a disorder characterized by progressive asymmetric apraxia and rigidity with other findings of cortical (e.g., alien limb, cortical sensory loss, myoclonus) and basal ganglia (e.g., bradykinesia and increased resistance to passive movement) dysfunction.2,3 Both disorders can be associated with pathologic tau aggregation.

show abstract

Section: Principal Components Analysissupporting

confidence: 91%

Section: Principal Components Analysismentioning

confidence: 99%

Executive dysfunction in frontotemporal dementia and corticobasal syndrome

et al. 2009

View full text Add to dashboard Cite

show abstract

“…By comparison, among 23 patients with neuropathologic information, 12 of 14 patients predicted to have TDP-43 pathology had FTLD-TDP, and 7 of 9 patients predicted to have tau pathology had FTLD-tau. As relative performance in certain neuropsychological tests can reflect differential brain region involvement associated with underlying FTLD pathology, 6 we analyzed the neuropsychological profiles of patients in the living cohort. A total of 56 patients underwent testing for both category naming fluency and confrontational naming, and a Z score difference (category naming fluency Ϫ confrontation naming) was calculated for each patient with a more…”

Section: Resultsmentioning

confidence: 99%

“…4,35 This could be due to the higher sensitivity at the cost of specificity observed in the autopsy cohort, or bias associated with referral or research participation. At the same time, the pattern of relative performance in category naming fluency and confrontational naming in autopsy-confirmed cases of FTLD-TDP 6 was also noted among patients with bv-FTD, which is the most prevalent phenotype. While this pattern of relative neuropsychological performance was not observed in other phenotypes, the limited power within each non-bv-FTD phenotype may mask any such trend in two tasks.…”

mentioning

confidence: 77%

“…For neuropsychological analysis, Z score was calculated for each neuropsychological subtest according to cognitively normal control subjects. According to previously observed patterns in subjects with autopsy-confirmed FTLD, 6 a relative performance score was calculated between confrontational naming and category naming fluency (⌬Z ϭ Z score of category naming fluency Ϫ Z score of confrontational naming). A positive relative performance score was taken as suggestive of predicted FTLD-TDP.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Novel CSF biomarkers for frontotemporal lobar degenerations

Chen‐Plotkin

Grossman³

et al. 2010

Neurology

Self Cite

View full text Add to dashboard Cite

Objective: To identify antemortem CSF diagnostic biomarkers that can potentially distinguish between the 2 main causes of frontotemporal lobar degeneration (FTLD), i.e., FTLD with TDP-43 pathology (FTLD-TDP) and FTLD with tau pathology (FTLD-tau).Methods: CSF samples were collected antemortem from 23 patients with FTLD with known pathology to form a autopsy cohort as part of a comparative biomarker study that additionally included 33 living cognitively normal subjects and 66 patients with autopsy-confirmed Alzheimer disease (AD). CSF samples were also collected from 80 living patients clinically diagnosed with frontotemporal dementia (FTD). Levels of 151 novel analytes were measured via a targeted multiplex panel enriched in neuropeptides, cytokines, and growth factors, along with levels of CSF biomarkers for AD.Results: CSF levels of multiple analytes differed between FTLD-TDP and FTLD-tau, including Fas, neuropeptides (agouti-related peptide and adrenocorticotropic hormone), and chemokines (IL-23, IL-17). Classification by random forest analysis achieved high sensitivity for FTLD-TDP (86%) with modest specificity (78%) in the autopsy cohort. When the classification algorithm was applied to a living FTD cohort, semantic dementia was the phenotype with the highest predicted proportion of FTLD-TDP. When living patients with behavioral variant FTD were examined in detail, those predicted to have FTLD-TDP demonstrated neuropsychological differences vs those predicted to have FTLD-tau in a pattern consistent with previously reported trends in autopsy-confirmed cases. Conclusions:Clinical cases with FTLD-TDP and FTLD-tau pathology can be potentially identified antemortem by assaying levels of specific analytes that are well-known and readily measurable in CSF. Neurology ® 2010;75:2079-2086 GLOSSARY AD ϭ Alzheimer disease; AgRP ϭ Aguti-related protein; ANG-2 ϭ angiopoietin-2; ACTH ϭ adrenocorticotropic hormone; ALS ϭ amyotrophic lateral sclerosis; ApoB ϭ apolipoprotein B; bv-FTD ϭ behavioral variant FTD; CBS ϭ corticobasal syndrome; FTD ϭ frontotemporal dementia; FTLD ϭ frontotemporal lobar degeneration; FTLD-tau ϭ frontotemporal lobar degeneration with tau pathology; FTLD-TDP ϭ frontotemporal lobar degeneration with TDP-43 pathology; IL ϭ interleukin; MDC ϭ macrophage-derived chemokine; PNFA ϭ progressive nonfluent aphasia; PPA ϭ primary progressive aphasia; PSP ϭ progressive supranuclear palsy; S100b ϭ S100 calcium binding protein b; SemD ϭ semantic dementia; TRAIL-R3 ϭ tumor necrosis factor-related apoptosis-inducing ligand receptor 3.Frontotemporal lobar degeneration (FTLD) includes neurodegenerative disorders which lead to progressive behavioral or language abnormalities.1-3 There are 2 major forms of FTLD: FTLD-TDP with neuronal and glial inclusions immunoreactive to TAR DNA binding protein of ϳ43 kD (TDP-43), and FTLD-tau containing fibrillar and hyperphosphorylated tau inclusions.2,3 The main FTLD lesions likely reflect distinct disease mechanisms, 2 although antemortem diagnosis of the underlying path...

show abstract