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Cognitive Indicators of Preclinical Behavioral Variant Frontotemporal Dementia in MAPT Carriers

Published online by Cambridge University Press:  21 November 2018

Gayathri Cheran ,
Liwen Wu ,
Seonjoo Lee ,
Masood Manoochehri ,
Sarah Cines ,
Emer Fallon ,
Timothy Lynch ,
Judith Heidebrink ,
Henry Paulson  and
Jill Goldman
...Show all authors
Gayathri Cheran
Affiliation:
Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, New York
Liwen Wu
Affiliation:
Columbia University, Department of Biostatistics, Mailman School of Public Health, New York, New York
Seonjoo Lee
Affiliation:
Columbia University, Department of Biostatistics, Mailman School of Public Health, New York, New York
Masood Manoochehri
Affiliation:
Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, New York
Sarah Cines
Affiliation:
Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, New York Fairleigh Dickinson University, Teaneck, New Jersey
Emer Fallon
Affiliation:
Dublin Neurological Institute, Dublin, Ireland
Timothy Lynch
Affiliation:
Dublin Neurological Institute, Dublin, Ireland
Judith Heidebrink
Affiliation:
The University of Michigan, Department of Neurology, Ann Arbor, Michigan
Henry Paulson
Affiliation:
The University of Michigan, Department of Neurology, Ann Arbor, Michigan
Jill Goldman
Affiliation:
Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, New York
Edward Huey
Affiliation:
Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, New York Columbia University, Department of Psychiatry & New York State Psychiatric Institute, New York, New York
Stephanie Cosentino*
Affiliation:
Columbia University, Cognitive Neuroscience Division of the Taub Institute, G.H. Sergievsky Center, Department of Neurology, New York, New York
*
Correspondence and reprint requests to: Stephanie Cosentino, 630 West 168th Street, P&S Box 16, New York, NY 10032. E-mail: [email protected]
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Abstract

Objectives: The cognitive indicators of preclinical behavioral variant Frontotemporal Dementia (bvFTD) have not been identified. To investigate these indicators, we compared cross-sectional performance on a range of cognitive measures in 12 carriers of pathogenic MAPT mutations not meeting diagnostic criteria for bvFTD (i.e., preclinical) versus 32 demographically-matched familial non-carriers (n = 44). Studying preclinical carriers offers a rare glimpse into emergent disease, environmentally and genetically contextualized through comparison to familial controls. Methods: Evaluating personnel blinded to carrier status administered a standardized neuropsychological battery assessing attention, speed, executive function, language, memory, spatial ability, and social cognition. Results from mixed effect modeling were corrected for multiplicity of comparison by the false discovery rate method, and results were considered significant at p < .05. To control for potential interfamilial variation arising from enrollment of six families, family was treated as a random effect, while carrier status, age, gender, and education were treated as fixed effects. Results: Group differences were detected in 17 of 31 cognitive scores and spanned all domains except spatial ability. As hypothesized, carriers performed worse on specific measures of executive function, and social cognition, but also on measures of attention, speed, semantic processing, and memory storage and retrieval. Conclusions: Most notably, group differences arose on measures of memory storage, challenging long-standing ideas about the absence of amnestic features on neuropsychological testing in early bvFTD. Current findings provide important and clinically relevant information about specific measures that may be sensitive to early bvFTD, and advance understanding of neurocognitive changes that occur early in the disease. (JINS, 2019, 25, 184–194)

Keywords

Frontotemporal dementiaMAPT proteinNeurodegenerative hereditary diseaseCognition disordersFrontotemporal lobar degenerationTauopathy
Type
Regular Research
Information
Journal of the International Neuropsychological Society , Volume 25 , Issue 2 , February 2019 , pp. 184 - 194
Copyright
Copyright © The International Neuropsychological Society 2018 

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