Multimodal Magnetic Resonance Imaging Assessment of White Matter Aging Trajectories Over the Lifespan of Healthy Individuals

Bartzokis, George; Lu, Po H.; Heydari, Panthea; Couvrette, Alexander; Lee, Grace J.; Kalashyan, Greta; Freeman, Frank N.; Grinstead, John; Villablanca, Pablo; Finn, J. Paul; Mintz, Jim; Alger, Jeffry R.; Altshuler, Lori L.

doi:10.1016/j.biopsych.2012.07.010

Cited by 143 publications

(149 citation statements)

References 64 publications

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“…In HD, these remyelination processes may successfully compensate during younger years, which usually correspond to the beginning of the pathology or to the years before onset (Pre-HD stage), but eventually begin failing in older years as brain myelin volume continues to grow and the maintenance of this expanding volume becomes increasingly difficult. This is similar to what happens in healthy older individuals (Bartzokis et al 2012).…”

Section: Discussionsupporting

confidence: 87%

The Corticospinal Tract in Huntington's Disease

Phillips¹,

Squitieri

Sánchez-Castañeda

et al. 2014

Cereb. Cortex

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Huntington's disease (HD) is characterized by progressive motor impairment. Therefore, the connectivity of the corticospinal tract (CST), which is the main white matter (WM) pathway that conducts motor impulses from the primary motor cortex to the spinal cord, merits particular attention. WM abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using magnetic resonance imaging (MRI). In the present study, we examined CST microstructure using diffusion tensor imaging (DTI)-based tractography in 30-direction DTI data collected from 100 subjects: Pre-HD subjects (n = 25), HD patients (n = 25) and control subjects (n = 50), and T 2 *-weighted (iron sensitive) imaging. Results show decreased fractional anisotropy (FA) and increased axial (AD), and radial diffusivity (RD) in the bilateral CST of HD patients. Pre-HD subjects had elevated iron in the left CST, regionally localized between the brainstem and thalamus. CAG repeat length in conjunction with age, as well as motor (UHDRS) assessment were correlated with CST FA, AD, and RD both in Pre-HD and HD. In the presymptomatic phase, increased iron in the inferior portion supports the "dying back" hypothesis that axonal damage advances in a retrograde fashion. Furthermore, early iron alteration may cause a high level of toxicity, which may contribute to further damage.

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Section: Discussionsupporting

confidence: 87%

The Corticospinal Tract in Huntington's Disease

Phillips¹,

Squitieri

Sánchez-Castañeda

et al. 2014

Cereb. Cortex

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show abstract

“…We observed a linear decline in tract integrity with age, in contrast to previous studies that observed higher order associations of age and DTI measures [15,16,18,19,44,45]. Yet, those studies invariably included subjects of young age and in young adulthood, and therefore also modeled (proximity of) the inflection point between net development of white matter and the degeneration observed with aging.…”

Section: Discussioncontrasting

confidence: 72%

Tract‐specific white matter degeneration in aging: The Rotterdam Study

Groot

Ikram

Akoudad

et al. 2014

Alzheimer's & Dementia

196

153

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“…Remarkably, the white matter myelination in the frontal lobe, as assessed using diffusion imaging and transverse relaxation rate, reveals a similar inverted-U relationship, peaking at a comparable age (41). It is therefore possible that what we observe here as a subtle effect in the gray matter (on top of the dominating loss of gray matter) relates to the myelination process of intracortical fibers (12).…”

Section: Discussionsupporting

confidence: 63%

A common brain network links development, aging, and vulnerability to disease

Douaud

Groves

Tamnes³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

300

263

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Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy agerelated brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely-but not only-transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.M any phylogenetic or ontogenetic models attempt to relate development and aging at genetic, molecular, or cognitive systems levels (1-4). In neuroscience, one of the most popular hypotheses in this respect postulates that the process of healthy age-related brain decline mirrors developmental maturation. This concept was first introduced in 1881 as a "loi de régression" (Ribot's law) when Théodule Ribot, a French philosopher, observed that the destruction of memories progresses in reverse order to that of their formation: from the unstable to the stable, from the newly formed memories to older "sensory, instinctive" memories (5). More generally, this hypothesis postulates that the sequence of events associated with brain decline should present itself in reverse order to the series of events related to brain development, with brain regions thought to develop relatively late-at both ontogenetic and phylogenetic levels-also degenerating relatively early (2, 6, 7).One way of tracking this hypothesized mirroring pattern of development and aging in the human brain is to use the information provided at a macroscopic level by structural MRI in large-scale, lifespan human populations. Although structural MRI does not distinguish between the various cellular mechanisms underpinning development and aging processes [e.g., de...

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Multimodal Magnetic Resonance Imaging Assessment of White Matter Aging Trajectories Over the Lifespan of Healthy Individuals

Cited by 143 publications

References 64 publications

The Corticospinal Tract in Huntington's Disease

The Corticospinal Tract in Huntington's Disease

Tract‐specific white matter degeneration in aging: The Rotterdam Study

A common brain network links development, aging, and vulnerability to disease

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