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Pattern of progression in MAPT‐related frontotemporal dementia: Results from the GENFI study
Author(s) -
Todd Emily G,
Peakman Georgia,
Cash David M,
Convery Rhian S,
Russell Lucy L,
Thomas David L,
van Swieten John C,
Jiskoot Lize C.,
Seelaar Harro,
Borroni Barbara,
Galimberti Daniela,
SanchezValle Raquel,
Laforce Robert,
Moreno Fermin,
Synofzik Matthis,
Graff Caroline,
Masellis Mario,
Tartaglia Maria Carmela,
Rowe James B,
Vandenberghe Rik,
Finger Elizabeth,
Tagliavini Fabrizio,
de Mendonca Alexandre,
Santana Isabel,
Butler Christopher,
Ducharme Simon,
Gerhard Alexander,
Danek Adrian,
Levin Johannes,
Otto Markus,
Sorbi Sandro,
Le Ber Isabelle,
Pasquier Florence,
Rohrer Jonathan D,
Bocchetta Martina
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.052265
Subject(s) - frontotemporal dementia , orbitofrontal cortex , amygdala , hippocampus , entorhinal cortex , temporal cortex , psychology , nucleus accumbens , medicine , dementia , pathology , oncology , neuroscience , prefrontal cortex , central nervous system , cognition , disease
Background Mutations in MAPT are associated with frontotemporal dementia (FTD), but little is known about the progression in its early stages. We aimed at identifying the presence of early brain changes in MAPT mutation carriers. Method We included 3T MRIs from 84 MAPT carriers [27 symptomatic: mean(SD) age 58(8) years; 57 presymptomatic: 40(11) years] from the Genetic FTD Initiative (GENFI) and from 77 age‐matched non‐carrier healthy controls (44(14) years). Based on their expected years to symptom onset (EYO), we divided the presymptomatic carriers into early (n=35, <‐10 years) and late (n=22, >‐10 years) groups. First, we performed voxel‐based morphometry (VBM) comparing 24 symptomatic carriers with 32 controls to identify the regions of interest (ROIs) which were atrophic in the symptomatic stage of MAPT . We then used automated and manual segmentations to extract these ROI volumes in all carriers. To remove the effect of age, gender, total intracranial volume and scanner type, we transformed the volumes into w‐scores, considering the controls as the reference group. A w‐score of <‐1.28 (corresponding to the 10 th percentile) was considered abnormal. Result From the VBM we identified seven structures significantly atrophic in symptomatic carriers: the nucleus accumbens, amygdala, hippocampus, orbitofrontal cortex, temporal pole, anterior insula and hypothalamus. The percentage of early presymptomatic carriers with abnormal w‐scores was 14% for nucleus accumbens and hippocampus, and 20% orbitofrontal cortex. In the late group, 36% showed abnormal amygdala and temporal pole, 27% abnormal hippocampus, 32% abnormal anterior insula and 9% abnormal hypothalamus. In the symptomatic group, the percentages were higher: nucleus accumbens (41%), amygdala, hippocampus and temporal pole (85%), orbitofrontal cortex (56%), anterior insula (93%) and hypothalamus (48%). Conclusion Abnormal limbic regions are a frequent feature in presymptomatic MAPT carriers, showing early structural changes before symptom onset. Further investigations on the associated cognitive and white matter changes are ongoing.