@article{ab52678175f3488bb28cd64ce884a6d6,
title = "Altered functional connectivity in asymptomatic MAPT subjects A comparison to bvFTD",
abstract = "Objective: To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD). Methods: In this case-control study, we identified 8 asymptomatic subjects with mutations in MAPT and 8 controls who screened negative for mutations in MAPT. Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and matched to 21 controls. All subjects had resting-state fMRI. In-phase functional connectivity was assessed between a precuneus seed in the default mode network (DMN) and a fronto-insular cortex seed in the salience network, and the rest of the brain. Atlas-based parcellation was used to assess functional connectivity and gray matter volume across specific regions of interest. Results: The asymptomatic MAPT subjects and subjects with bvFTD showed altered functional connectivity in the DMN, with reduced in-phase connectivity in lateral temporal lobes and medial prefrontal cortex, compared to controls. Increased in-phase connectivity was also observed in both groups in the medial parietal lobe. Only the bvFTD group showed altered functional connectivity in the salience network, with reduced connectivity in the fronto-insular cortex and anterior cingulate. Gray matter loss was observed across temporal, frontal, and parietal regions in bvFTD, but not in the asymptomatic MAPT subjects. Conclusions: Functional connectivity in the DMN is altered in MAPT subjects before the occurrence of both atrophy and clinical symptoms, suggesting that changes in functional connectivity are early features of the disease.",
author = "Whitwell, {J. L.} and Josephs, {K. A.} and R. Avula and N. Tosakulwong and Weigand, {S. D.} and Senjem, {M. L.} and P. Vemuri and Jones, {D. T.} and Gunter, {J. L.} and M. Baker and Wszolek, {Z. K.} and Knopman, {D. S.} and R. Rademakers and Petersen, {R. C.} and Boeve, {B. F.} and Jack, {C. R.}",
note = "Funding Information: Dr. Whitwell receives research support from the NIH (NIDCD, NIA) and the Dana Foundation. Dr. Josephs receives research support from the NIH (NIDCD, NIA) and the Dana Foundation. Dr. Avula serves as a consultant to Medical Imaging Solutions. N. Tosakulwong, S.D. Weigand, and M.L. Senjem report no disclosures. Dr. Vemuri receives support from the Robert H. Smith Family Foundation Research Fellowship and the NIH. Dr. Jones and Dr. Gunter report no disclosures. M. Baker holds patents re: Methods and materials for detecting and treating dementia. Dr. Wszolek serves as Co-Editor-in-Chief of Parkinsonism and Related Disorders, Regional Editor of the European Journal of Neurology, and on the editorial boards of Neurologia i Neurochirurgia Polska, Advances in Rehabilitation, the Medical Journal of the Rzeszow University, and Clinical and Experimental Medical Letters; holds and has contractual rights for receipt of future royalty payments from patents re: A novel polynucleotide involved in heritable Parkinson's disease; receives royalties from publishing Parkinsonism and Related Disorders (Elsevier, 2007, 2008, 2009) and the European Journal of Neurology (Wiley-Blackwell, 2007, 2008, 2009); and receives research support from Allergan, Inc., the NIH, the Pacific Alzheimer Research Foundation (Canada), the CIHR, the Mayo Clinic Florida Research Committee CR program, and a gift from Carl Edward Bolch, Jr., and Susan Bass Bolch. Dr. Knopman serves as Deputy Editor for Neurology{\textregistered}; has served on a data safety monitoring board for Eli Lilly and Company; has served as a consultant for Elan/Janssen AI; is an investigator in clinical trials sponsored by Elan/Janssen AI, Baxter International Inc., and Forest Laboratories, Inc.; and receives research support from the NIH. Dr. Rademakers holds patents re: Methods and materials for detecting and treating dementia and receives research support from the NIH, the Pacific Alzheimer Research Foundation (Canada), the Association for Frontotemporal Dementia, the Amyotrophic Lateral Sclerosis Association, CurePSP, and the Consortium for Frontotemporal Dementia. Dr. Petersen serves on scientific advisory boards for the Alzheimer's Association, the National Advisory Council on Aging (NIA), Elan/Janssen AI, Pfizer Inc (Wyeth), and GE Healthcare; receives royalties from publishing Mild Cognitive Impairment (Oxford University Press, 2003); serves as a consultant for Elan/Janssen AI and GE Healthcare; and receives research support from the NIH/NIA. Dr. Boeve has served as a consultant to GE Healthcare; receives publishing royalties for The Behavioral Neurology of Dementia (Cambridge University Press, 2009); and receives research support from Cephalon, Inc., Allon Therapeutics, Inc., the NIH/NIA, the Alzheimer's Association, and the Mangurian Foundation. Dr. Jack serves on scientific advisory boards for Elan/Janssen AI, Eli Lilly & Company, GE Healthcare, and Eisai Inc.; receives research support from Baxter International Inc., Allon Therapeutics, Inc., Pfizer Inc., the NIH/NIA, and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation; and holds stock/stock options in Johnson & Johnson. Funding Information: Study funding: Supported by NIH grants R01-DC010367, R01-AG037491, R21-AG38736, R01-AG11378, P50-AG16574, R01-NS065782, R01-AG02651, and P50-NS072187 , Dana Foundation, PPND Family Fund, Robert H. and Clarice Smith and Abigail Van Buren Alzheimer′s Disease Research Program of the Mayo Foundation, the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation, and the NIH Construction Grant ( NIH C06 RR018898 ). ",
year = "2011",
month = aug,
day = "30",
doi = "10.1212/WNL.0b013e31822c61f2",
language = "English (US)",
volume = "77",
pages = "866--874",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "9",
}