TY - JOUR
T1 - Neurite-based white matter alterations in MAPT mutation carriers
T2 - A multi-shell diffusion MRI study in the ALLFTD consortium
AU - Corriveau-Lecavalier, Nick
AU - Tosakulwong, Nirubol
AU - Lesnick, Timothy G.
AU - Fought, Angela J.
AU - Reid, Robert I.
AU - Schwarz, Christopher G.
AU - Senjem, Matthew L.
AU - Jack, Clifford R.
AU - Jones, David T.
AU - Vemuri, Prashanthi
AU - Rademakers, Rosa
AU - Ramos, Eliana Marisa
AU - Geschwind, Daniel H.
AU - Knopman, David S.
AU - Botha, Hugo
AU - Savica, Rodolfo
AU - Graff-Radford, Jonathan
AU - Ramanan, Vijay K.
AU - Fields, Julie A.
AU - Graff-Radford, Neill
AU - Wszolek, Zbigniew
AU - Forsberg, Leah K.
AU - Petersen, Ronald C.
AU - Heuer, Hilary W.
AU - Boxer, Adam L.
AU - Rosen, Howard J.
AU - Boeve, Bradley F.
AU - Kantarci, Kejal
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2024/2
Y1 - 2024/2
N2 - We assessed white matter (WM) integrity in MAPT mutation carriers (16 asymptomatic, 5 symptomatic) compared to 31 non-carrier family controls using diffusion tensor imaging (DTI) (fractional anisotropy; FA, mean diffusivity; MD) and neurite orientation dispersion and density imaging (NODDI) (neurite density index; NDI, orientation and dispersion index; ODI). Linear mixed-effects models accounting for age and family relatedness revealed alterations across DTI and NODDI metrics in all mutation carriers and in symptomatic carriers, with the most significant differences involving fronto-temporal WM tracts. Asymptomatic carriers showed higher entorhinal MD and lower cingulum FA and patterns of higher ODI mostly involving temporal areas and long association and projections fibers. Regression models between estimated time to or time from disease and DTI and NODDI metrics in key regions (amygdala, cingulum, entorhinal, inferior temporal, uncinate fasciculus) in all carriers showed increasing abnormalities with estimated time to or time from disease onset, with FA and NDI showing the strongest relationships. Neurite-based metrics, particularly ODI, appear to be particularly sensitive to early WM involvement in asymptomatic carriers.
AB - We assessed white matter (WM) integrity in MAPT mutation carriers (16 asymptomatic, 5 symptomatic) compared to 31 non-carrier family controls using diffusion tensor imaging (DTI) (fractional anisotropy; FA, mean diffusivity; MD) and neurite orientation dispersion and density imaging (NODDI) (neurite density index; NDI, orientation and dispersion index; ODI). Linear mixed-effects models accounting for age and family relatedness revealed alterations across DTI and NODDI metrics in all mutation carriers and in symptomatic carriers, with the most significant differences involving fronto-temporal WM tracts. Asymptomatic carriers showed higher entorhinal MD and lower cingulum FA and patterns of higher ODI mostly involving temporal areas and long association and projections fibers. Regression models between estimated time to or time from disease and DTI and NODDI metrics in key regions (amygdala, cingulum, entorhinal, inferior temporal, uncinate fasciculus) in all carriers showed increasing abnormalities with estimated time to or time from disease onset, with FA and NDI showing the strongest relationships. Neurite-based metrics, particularly ODI, appear to be particularly sensitive to early WM involvement in asymptomatic carriers.
KW - Diffusion magnetic resonance imaging
KW - Diffusion tensor imaging
KW - Frontotemporal dementia
KW - Microtubule-associated protein tau
KW - Neurite orientation dispersion and density imaging
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UR - http://www.scopus.com/inward/citedby.url?scp=85179805027&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2023.12.001
DO - 10.1016/j.neurobiolaging.2023.12.001
M3 - Article
C2 - 38091751
AN - SCOPUS:85179805027
SN - 0197-4580
VL - 134
SP - 135
EP - 145
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -