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Abstract Details

Different Rates of Lobar Atrophy Between Symptomatic and Asymptomatic MAPT Mutation Carriers
Aging, Dementia, and Behavioral Neurology
S9 - Aging and Dementia: Clinical Trials and Novel Therapies (3:41 PM-3:52 PM)
002

It is important to characterize the longitudinal imaging features in f-FTD in mutation carriers in order to plan for future disease-modifying trials.

To characterize the longitudinal volumetric changes in familial frontotemporal dementia (f-FTD).

Using MRI we compared rates of atrophy between 4 microtubule associated protein tau (MAPT) mutation carriers (N279K mutation) who transitioned from asymptomatic to symptomatic (converter) to 8 asymptomatic (asym) and 8 non-mutation carrier family controls (noncarrier). MRI was analyzed using the TBM-SyN methodology to quantify lobar volumes at baseline and longitudinally.

There were no differences between the 3 groups at baseline based on sex, education, age at initial MRI scan and cognitive scores. Baseline temporal (P=0.01) and parietal (P=0.02) lobe volumes were less in the converter group compared to asym and noncarrier groups. Using mixed effect models with the noncarriers as the reference, the annual change estimates (95% CI) were greatest in the temporal lobes [converter x age at MRI= -1.26 (-1.83, -0.69), P<0.001, and asym x age at MRI= -0.73 (-1.21, -0.26), P=0.003].  The annual change estimates in the frontal and parietal lobes were lower but still significant [frontal: converter x age at MRI= -0.76 (-1.33, -0.18), P=0.01, and parietal: converter x age at MRI= -0.19 (-0.35, -0.03), P=0.02]. The annual changes for frontotemporal lobe volume compared to non-carrier were: converter x age at MRI= -2.02 (-3.06, -0.97), P<0.001, and asym x age at MRI= -1.20 (-2.08, -0.32), P=0.008.

These findings suggest that among this cohort of MAPT mutation carriers, a) the temporal lobe volumes decline earliest (asymptomatic phase) and the changes are most dramatic during the symptomatic phase, b) frontal and parietal lobe volumes also decline during the early symptomatic phase, and c) the composite frontotemporal volume appears to show the most robust change in the asymptomatic as well as symptomatic phases.

Authors/Disclosures
Bradley F. Boeve, MD, FAAN (Mayo Clinic)
PRESENTER
Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from EIP Pharma. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care.
No disclosure on file
Matthew Senjem (Mayo Clinic) Matthew Senjem has received stock or an ownership interest from Align Technology, Inc.. Matthew Senjem has received stock or an ownership interest from Inovio Biomedical Corp.. Matthew Senjem has received stock or an ownership interest from Johnson & Johnson. Matthew Senjem has received stock or an ownership interest from Mesa Laboratories, Inc.. Matthew Senjem has received stock or an ownership interest from Nvidia Inc.. Matthew Senjem has received stock or an ownership interest from LHC Group, Inc.. Matthew Senjem has received stock or an ownership interest from Natus Medical Incorporated. Matthew Senjem has received stock or an ownership interest from Varex Imaging Corporation. Matthew Senjem has received personal compensation in the range of $100,000-$499,999 for serving as a IT Technical Specialist II with Mayo Clinic.
Timothy Lesnick No disclosure on file
Scott Przybelski Scott Przybelski has nothing to disclose.
Nirubol Tosakulwong Nirubol Tosakulwong has nothing to disclose.
No disclosure on file
Julie A. Fields, PhD (Mayo Clinic) The institution of Dr. Fields has received research support from National Institutes of Health. The institution of Dr. Fields has received research support from Patient-Centered Outcomes Research Institute.
Leah K. Forsberg, PhD (Mayo Clinic) Ms. Forsberg has nothing to disclose.
Ralitza H. Gavrilova, MD (Mayo Clinic) Dr. Gavrilova has nothing to disclose.
Jonathan Graff-Radford, MD, FAAN Dr. Graff-Radford has received personal compensation for serving as an employee of Mayo Clinic. Dr. Graff-Radford has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NINDS/NIH. The institution of Dr. Graff-Radford has received research support from NIH. The institution of Dr. Graff-Radford has received research support from Eisai. The institution of Dr. Graff-Radford has received research support from Cognition therapeutics.
Neill R. Graff-Radford, MD, FAAN (Mayo Clinic Jacksonville) The institution of Dr. Graff-Radford has received research support from Biogen. The institution of Dr. Graff-Radford has received research support from Lilly. The institution of Dr. Graff-Radford has received research support from Eisai. The institution of Dr. Graff-Radford has received research support from Biogen. Dr. Graff-Radford has received publishing royalties from a publication relating to health care.
David T. Jones, MD (Mayo Clinic) Dr. Jones has received intellectual property interests from a discovery or technology relating to health care.
David S. Knopman, MD, FAAN (Mayo Clinic) Dr. Knopman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for DIAN TU study. The institution of Dr. Knopman has received research support from NIH.
Walter Kremers The institution of Walter Kremers has received research support from NIH. The institution of an immediate family member of Walter Kremers has received research support from NIH.
Jeremy Syrjanen No disclosure on file
Adam L. Boxer, MD, PhD (University of California, San Francisco) An immediate family member of Dr. Boxer has received personal compensation for serving as an employee of Kaiser Permanente. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Oscotec. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arrowhead. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Switch. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvinas. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alector. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Transposon. Dr. Boxer has stock in Alector. Dr. Boxer has stock in Arvinas. Dr. Boxer has stock in Neurovanda. The institution of Dr. Boxer has received research support from Biogen. The institution of Dr. Boxer has received research support from Eisai. The institution of Dr. Boxer has received research support from Regeneron. The institution of Dr. Boxer has received research support from NIH. The institution of Dr. Boxer has received research support from Bluefield Project. Dr. Boxer has received research support from Rainwater Charitable Foundation.
Howard J. Rosen, MD (UCSF) Dr. Rosen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Pharmaceuticals. Dr. Rosen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. The institution of Dr. Rosen has received research support from NIH. The institution of Dr. Rosen has received research support from State of CA. Dr. Rosen has a non-compensated relationship as a Consultant with Alector that is relevant to AAN interests or activities. Dr. Rosen has a non-compensated relationship as a Consultant with Prevail Therapeutics that is relevant to AAN interests or activities. Dr. Rosen has a non-compensated relationship as a consultant with Alchemab that is relevant to AAN interests or activities.
Zbigniew K. Wszolek, MD, FAAN (Mayo Clinic- Jacksonville) Dr. Wszolek has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Polish Neurological Society/Via Medica.
Kejal Kantarci, MD (Mayo Clinic) The institution of Dr. Kantarci has received research support from Eli Lilly. The institution of Dr. Kantarci has received research support from NIH. The institution of Dr. Kantarci has received research support from ADDF.