Thalamic nuclei atrophy at high and heterogenous rates during cognitively unimpaired human aging.
NeuroImage. 2022-11-01; 262: 119584
DOI: 10.1016/j.neuroimage.2022.119584
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Choi EY(1), Tian L(2), Su JH(3), Radovan MT(4), Tourdias T(5), Tran TT(6), Trelle AN(6), Mormino E(7), Wagner AD(8), Rutt BK(9).
Author information:
(1)Department of Neurosurgery, Stanford University, 300 Pasteur Drive, MC5327,
Stanford, CA 94305, USA.
(2)Department of Biomedical Data Science, 1265 Welch Road, MC5464, Stanford, CA
94305, USA.
(3)Department of Radiology, Stanford University, 300 Pasteur Drive, MC5488,
Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford
University, 350 Jane Stanford Way, MC9505, Stanford, CA 94305, USA.
(4)Department of Computer Science, Stanford University, 353 Jane Stanford Way,
MC9025, Stanford, CA 94305, USA.
(5)Department of Neuroradiology, Bordeaux University Hospital, Bordeaux, France;
INSERM U1215, Neurocentre Magendie, University of Bordeaux, France.
(6)Department of Psychology, Stanford University, Building 420, MC2130,
Stanford, CA 94305, USA.
(7)Department of Neurology and Neurological Sciences, Stanford, University, 300
Pasteur Drive, MC5235, Stanford, CA 94305, USA; Wu Tsai Neurosciences Institute,
Stanford University, 290 Jane Stanford Way, Stanford, CA 94305, USA.
(8)Department of Psychology, Stanford University, Building 420, MC2130,
Stanford, CA 94305, USA; Wu Tsai Neurosciences Institute, Stanford University,
290 Jane Stanford Way, Stanford, CA 94305, USA.
(9)Department of Radiology, Stanford University, 300 Pasteur Drive, MC5488,
Stanford, CA 94305, USA; Wu Tsai Neurosciences Institute, Stanford University,
290 Jane Stanford Way, Stanford, CA 94305, USA. Electronic address:
.
The thalamus is a central integration structure in the brain, receiving and
distributing information among the cerebral cortex, subcortical structures, and
the peripheral nervous system. Prior studies clearly show that the thalamus
atrophies in cognitively unimpaired aging. However, the thalamus is comprised of
multiple nuclei involved in a wide range of functions, and the age-related
atrophy of individual thalamic nuclei remains unknown. Using a recently
developed automated method of identifying thalamic nuclei (3T or 7T MRI with
white-matter-nulled MPRAGE contrast and THOMAS segmentation) and a
cross-sectional design, we evaluated the age-related atrophy rate for 10
thalamic nuclei (AV, CM, VA, VLA, VLP, VPL, pulvinar, LGN, MGN, MD) and an
epithalamic nucleus (habenula). We also used T1-weighted images with the
FreeSurfer SAMSEG segmentation method to identify and measure age-related
atrophy for 11 extra-thalamic structures (cerebral cortex, cerebral white
matter, cerebellar cortex, cerebellar white matter, amygdala, hippocampus,
caudate, putamen, nucleus accumbens, pallidum, and lateral ventricle). In 198
cognitively unimpaired participants with ages spanning 20-88 years, we found
that the whole thalamus atrophied at a rate of 0.45% per year, and that thalamic
nuclei had widely varying age-related atrophy rates, ranging from 0.06% to 1.18%
per year. A functional grouping analysis revealed that the thalamic nuclei
involved in cognitive (AV, MD; 0.53% atrophy per year), visual (LGN, pulvinar;
0.62% atrophy per year), and auditory/vestibular (MGN; 0.64% atrophy per year)
functions atrophied at significantly higher rates than those involved in motor
(VA, VLA, VLP, and CM; 0.37% atrophy per year) and somatosensory (VPL; 0.32%
atrophy per year) functions. A proximity-to-CSF analysis showed that the group
of thalamic nuclei situated immediately adjacent to CSF atrophied at a
significantly greater atrophy rate (0.59% atrophy per year) than that of the
group of nuclei located farther from CSF (0.36% atrophy per year), supporting a
growing hypothesis that CSF-mediated factors contribute to neurodegeneration. We
did not find any significant hemispheric differences in these rates of change
for thalamic nuclei. Only the CM thalamic nucleus showed a sex-specific
difference in atrophy rates, atrophying at a greater rate in male versus female
participants. Roughly half of the thalamic nuclei showed greater atrophy than
all extra-thalamic structures examined (0% to 0.54% per year). These results
show the value of white-matter-nulled MPRAGE imaging and THOMAS segmentation for
measuring distinct thalamic nuclei and for characterizing the high and
heterogeneous atrophy rates of the thalamus and its nuclei across the adult
lifespan. Collectively, these methods and results advance our understanding of
the role of thalamic substructures in neurocognitive and disease-related changes
that occur with aging.
Copyright © 2022. Published by Elsevier Inc.
DOI: 10.1016/j.neuroimage.2022.119584
PMCID: PMC9787236
PMID: 36007822 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of Competing Interest None