期刊
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
卷 8, 期 1, 页码 95-110出版社
WILEY
DOI: 10.1002/acn3.51249
关键词
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资金
- Tau Consortium
- National Institutes of Health [K23AG039414, R01 AG058233, P50 AG023501, P01 AG019724, U54 NS092089, AG035610, R01 AG26938, R35 NS097261, UG3 NS103870, R01 NS076837, U01 AG045390, U54NS092089, 2R01AG038791, K24 AG045333, R01 AG032306, P01AG019724, P50AG23501, P41EB015922, AG023501, AG19724, K12 HD001459, K01 AG049152, K08 AG052648, K23NS088341, P01AG017586, U01AG052943, 5P50AG005131-33, 2R01AG038791-06A, U01NS090259, 1U54 NS 092089, U01NS100610, U01NS80818, R25NS098999, P20GM109025, R01EB022055, R01CA132870, U01AG045390]
- John Douglas French Alzheimer's Foundation
- National Institute on Aging (NIA) [U24AG21886]
- LEFFTDS Consortium (National Institute on Aging) [U01 AG045390]
- LEFFTDS Consortium (National Institute of Neurological Diseases and Stroke) [U01 AG045390]
- ARTFL Consortium (National Institute of Neurological Diseases and Stroke) [U54 NS092089]
- ARTFL Consortium (National Center for Advancing Translational Sciences) [U54 NS092089]
- Mayo Clinic Center for Regenerative Medicine
- Haworth Family Professorship in Neurodegenerative Diseases fund
- Albertson Parkinson's Research Foundation
- Canadian Institutes of Health Research [74580]
- Dioraphte Foundation [09-02-00]
- Association for Frontotemporal Dementias Research Grant 2009
- Netherlands Organization for Scientific Research (NWO) [HCMI 056-13-018]
- ZonMw Memorabel [733050813, 733050103]
- Alzheimer Nederland
- JPND PreFrontAls consortium
- Bluefield Project
- Parkinson Study Group
- Michael J. Fox Foundation
- Lewy Body Association
- AVID Pharmaceuticals
- Abbvie
- Biogen
- Roche
This study found that a subset of presymptomatic MAPT mutation carriers exhibited low volumes in the mesial temporal lobe, a region commonly atrophied in all symptomatic carriers. With increasing age, a higher percentage of presymptomatic carriers showed low mesial temporal volume, suggesting early neurodegeneration.
Objective: MAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach. Methods: We studied 22 symptomatic carriers (age 54.7 +/- 9.1, 13 female) and 43 presymptomatic carriers (age 39.2 +/- 10.4, 21 female). Symptomatic carriers' clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson's disease (1), and mild cognitive impairment (1). We performed voxel-based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype. Results: Symptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volumes emerged in a subset of presymptomatic carriers as early as their thirties. Low white matter volumes arose infrequently among presymptomatic carriers. Interpretation: A subset of presymptomatic MAPT mutation carriers showed low volumes in mesial temporal lobe, the region ubiquitously atrophied in all symptomatic carriers. With each decade of age, an increasing percentage of presymptomatic carriers showed low mesial temporal volume, suggestive of early neurodegeneration.
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