Hostname: page-component-78c5997874-lj6df Total loading time: 0 Render date: 2024-11-04T21:08:38.142Z Has data issue: false hasContentIssue false

Cognitive Indicators of Preclinical Behavioral Variant Frontotemporal Dementia in MAPT Carriers

Published online by Cambridge University Press:  21 November 2018

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]

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)

Type
Regular Research
Copyright
Copyright © The International Neuropsychological Society 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alberici, A., Gobbo, C., Panzacchi, A., Nicosia, F., Ghidoni, R., Benussi, L., … Binetti, G. (2004). Frontotemporal dementia: Impact of P301L tau mutation on a healthy carrier. Journal of Neurology, Neurosurgery, and Psychiatry, 75(11), 16071610. doi:10.1136/jnnp.2003.021295 Google Scholar
Beekly, D., Monsell, S., Besser, L., Robichaud, E., Knopman, D., & Kukull, W. (2012). The NACC FTLD Module Data. Dementia and Geriatric Cognitive Disorders, 33, 109110.Google Scholar
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society . Series B (Methodological), 289300.Google Scholar
Beyer, M.K., Bronnick, K.S., Hwang, K.S., Bergsland, N., Tysnes, O.B., Larsen, J.P., … Apostolova, L.G. (2013). Verbal memory is associated with structural hippocampal changes in newly diagnosed Parkinson’s disease. Journal of Neurology, Neurosurgery, and Psychiatry, 84(1), 2328.Google Scholar
Bird, T.D., Nochlin, D., Poorkaj, P., Cherrier, M., Kaye, J., Payami, H., … Schellenberg, G.D. (1999). A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L). Brain, 122(Pt 4), 741756.Google Scholar
Boeve, B.F., & Hutton, M. (2008). Refining frontotemporal dementia with parkinsonism linked to chromosome 17: Introducing FTDP-17 (MAPT) and FTDP-17 (PGRN). Archives of Neurology, 65(4), 460464.Google Scholar
Boxer, A.L., & Miller, B.L. (2005). Clinical features of frontotemporal dementia. Alzheimer Disease and Associated Disorders, 19(Suppl 1), S3S6.Google Scholar
Brandt, R., Hundelt, M., & Shahani, N. (2005). Tau alteration and neuronal degeneration in tauopathies: Mechanisms and models. Biochimica et Biophysica Acta, 1739(2), 331354.Google Scholar
Buschke, H. (1973). Selective reminding for analysis of memory and learning. Journal of Verbal Learning and Verbal Behavior, 12(5), 543550.Google Scholar
Carver, C.S., & White, T.L. (1994). Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: The BIS/BAS Scales. Journal of Personality and Social Psychology, 67(2), 319.Google Scholar
Davis, M.H. (1980). Interpersonal reactivity index: Lewiston, NY: Edwin Mellen Press.Google Scholar
Delis, D.C., Kaplan, E., & Kramer, J.H. (2001). Delis-Kaplan executive function system (D-KEFS). Lutz, FL: Psychological Corporation.Google Scholar
Deweer, B., Lehericy, S., Pillon, B., Baulac, M., Chiras, J., Marsault, C., … Dubois, B. (1995). Memory disorders in probable Alzheimer’s disease: The role of hippocampal atrophy as shown with MRI. Journal of Neurology, Neurosurgery, and Psychiatry, 58(5), 590597.Google Scholar
Dubois, B., Slachevsky, A., Litvan, I., & Pillon, B. (2000). The FAB A frontal assessment battery at bedside. Neurology, 55(11), 16211626.Google Scholar
Ferman, T.J., McRae, C., Arvanitakis, Z., Tsuboi, Y., Vo, A., & Wszolek, Z.K. (2003). Early and pre-symptomatic neuropsychological dysfunction in the PPND family with the N279K tau mutation. Parkinsonism & Related Disorders, 9(5), 265270.Google Scholar
Ghetti, B., Oblak, A.L., Boeve, B.F., Johnson, K.A., Dickerson, B.C., & Goedert, M. (2015). Invited review: Frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: A chameleon for neuropathology and neuroimaging. Neuropathology and Applied Neurobiology, 41(1), 2446. doi:10.1111/nan.12213 Google Scholar
Glosser, G., & Goodglass, H. (1990). Disorders in executive control functions among aphasic and other brain-damaged patients. Journal of Clinical and Experimental Neuropsychology, 12(4), 485501.Google Scholar
Goedert, M., Crowther, R.A., & Spillantini, M.G. (1998). Tau mutations cause frontotemporal dementias. Neuron, 21(5), 955958.Google Scholar
Hodges, J.R. (2001). Frontotemporal dementia (Pick’s disease): Clinical features and assessment. Neurology, 56(Suppl 4), S6S10.Google Scholar
Hornberger, M., Piguet, O., Graham, A., Nestor, P., & Hodges, J. (2010). How preserved is episodic memory in behavioral variant frontotemporal dementia? Neurology, 74(6), 472479.Google Scholar
Hughes, C.P., Berg, L., Danziger, W.L., Coben, L.A., & Martin, R. (1982). A new clinical scale for the staging of dementia. The British journal of psychiatry, 140(6), 566572.Google Scholar
Jiskoot, L.C., Dopper, E.G., den Heijer, T., Timman, R., van Minkelen, R., van Swieten, J.C., & Papma, J.M. (2016). Presymptomatic cognitive decline in familial frontotemporal dementia: A longitudinal study. Neurology, 87(4), 384391.Google Scholar
Lennox, R.D., & Wolfe, R.N. (1984). Revision of the self-monitoring scale. Journal of Personality and Social Psychology, 46(6), 13491364 Google Scholar
Lough, S., Kipps, C.M., Treise, C., Watson, P., Blair, J.R., & Hodges, J.R. (2006). Social reasoning, emotion and empathy in frontotemporal dementia. Neuropsychologia, 44(6), 950958.Google Scholar
Lynch, T., Sano, M., Marder, K., Bell, K., Foster, N., Defending, R., … Fahn, S. (1994). Clinical characteristics of a family with chromosome 17-linked disinhibition-dementia-parkinsonism-amyotrophy complex. Neurology, 44(10), 1878.Google Scholar
Manns, J.R., Hopkins, R.O., & Squire, L.R. (2003). Semantic memory and the human hippocampus. Neuron, 38(1), 127133.Google Scholar
McCarthy, A., Lonergan, R., Olszewska, D.A., O’Dowd, S., Cummins, G., Magennis, B., … Lynch, T. (2015). Closing the tau loop: The missing tau mutation. Brain, 138(Pt 10), 31003109. doi:10.1093/brain/awv234 Google Scholar
Miyoshi, M., Shinotoh, H., Wszolek, Z.K., Strongosky, A.J., Shimada, H., Arakawa, R., … Fukushi, K. (2010). In vivo detection of neuropathologic changes in presymptomatic MAPT mutation carriers: A PET and MRI study. Parkinsonism & Related Disorders, 16(6), 404408.Google Scholar
Neary, D., Snowden, J., & Mann, D. (2005). Frontotemporal dementia. The Lancet Neurology, 4(11), 771780.Google Scholar
Neary, D., Snowden, J.S., Gustafson, L., Passant, U., Stuss, D., Black, S., … Benson, D.F. (1998). Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria. Neurology, 51(6), 15461554.Google Scholar
Rascovsky, K., Hodges, J.R., Kipps, C.M., Johnson, J.K., Seeley, W.W., Mendez, M.F., … Salmon, D.P. (2007). Diagnostic criteria for the behavioral variant of frontotemporal dementia (bvFTD): Current limitations and future directions. Alzheimer Disease & Associated Disorders, 21(4), S14S18.Google Scholar
Rascovsky, K., Hodges, J.R., Knopman, D., Mendez, M.F., Kramer, J.H., Neuhaus, J., … Onyike, C.U. (2011). Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain, 134(9), 24562477.Google Scholar
Rascovsky, K., Salmon, D.P., Hansen, L.A., Thal, L.J., & Galasko, D. (2007). Disparate letter and semantic category fluency deficits in autopsy-confirmed frontotemporal dementia and Alzheimer’s disease. Neuropsychology, 21(1), 20.Google Scholar
Rohrer, J.D., Nicholas, J.M., Cash, D.M., van Swieten, J., Dopper, E., Jiskoot, L., … Clegg, S. (2015). Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: A cross-sectional analysis. The Lancet Neurology, 14(3), 253262.Google Scholar
Rohrer, J.D., Ridgway, G.R., Modat, M., Ourselin, S., Mead, S., Fox, N.C., … Warren, J.D. (2010). Distinct profiles of brain atrophy in frontotemporal lobar degeneration caused by progranulin and tau mutations. Neuroimage, 53(3), 10701076. doi:10.1016/j.neuroimage.2009.12.088 Google Scholar
Seeley, W.W., Crawford, R., Rascovsky, K., Kramer, J.H., Weiner, M., Miller, B.L., & Gorno-Tempini, M.L. (2008). Frontal paralimbic network atrophy in very mild behavioral variant frontotemporal dementia. Archives of Neurology, 65(2), 249255.Google Scholar
Shirk, S.D., Mitchell, M.B., Shaughnessy, L.W., Sherman, J.C., Locascio, J.J., Weintraub, S., & Atri, A. (2011). A web-based normative calculator for the uniform data set (UDS) neuropsychological test battery. Alzheimer’s Research & Therapy, 3(6), 32.Google Scholar
Snowden, J.S., Neary, D., & Mann, D.M. (2002). Frontotemporal dementia. The British Journal of Psychiatry, 180(2), 140143.Google Scholar
Spillantini, M.G., Bird, T.D., & Ghetti, B. (1998). Frontotemporal dementia and Parkinsonism linked to chromosome 17: A new group of tauopathies. Brain Pathology, 8(2), 387402.Google Scholar
Van Swieten, J., Stevens, M., Rosso, S., Rizzu, P., Joosse, M., De Koning, I., … Niermeijer, M. (1999). Phenotypic variation in hereditary frontotemporal dementia with tau mutations. Annals of Neurology, 46(4), 617626.Google Scholar
Weintraub, S., Salmon, D., Mercaldo, N., Ferris, S., Graff-Radford, N.R., Chui, H., … Galasko, D. (2009). The Alzheimer’s disease centers’ uniform data set (UDS): The neuropsychological test battery. Alzheimer Disease and Sssociated Disorders, 23(2), 91.Google Scholar
Wittenberg, D., Possin, K.L., Rascovsky, K., Rankin, K.P., Miller, B.L., & Kramer, J.H. (2008). The early neuropsychological and behavioral characteristics of frontotemporal dementia. Neuropsychology Review, 18(1), 91102.Google Scholar