Evidence of demyelination in mild cognitive impairment and dementia using a direct and specific magnetic resonance imaging measure of myelin content

Bouhrara, Mustapha; Reiter, David A.; Bergeron, Christopher M.; Zukley, Linda; Ferrucci, Luigi; Resnick, Susan M.; Spencer, Richard G.

doi:10.1016/j.jalz.2018.03.007

Cited by 123 publications

(112 citation statements)

References 59 publications

(86 reference statements)

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“…We have previously used mcDESPOT MCR to characterize the spatiotemporal pattern of human brain myelination as reflected by MWF Deoni et al, 2016), and to explore the crosssectional relationships between MWF and cognitive development O'Muircheartaigh et al, 2014). In addition to pediatric applications, mcDESPOT has also been used to investigate myelin change in known white matter demyelinating and dysmyelinating disorders, for example, multiple sclerosis (Kitzler et al, 2012;Kolind et al, 2012;Kolind et al, 2013), Alzheimer's disease , and dementia (Bouhrara et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Longitudinal associations between white matter maturation and cognitive development across early childhood

Dai

Hadjipantelis

Wang

et al. 2019

Human Brain Mapping

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From birth to 5 years of age, brain structure matures and evolves alongside emerging cognitive and behavioral abilities. In relating concurrent cognitive functioning and measures of brain structure, a major challenge that has impeded prior investigation of their time‐dynamic relationships is the sparse and irregular nature of most longitudinal neuroimaging data. We demonstrate how this problem can be addressed by applying functional concurrent regression models (FCRMs) to longitudinal cognitive and neuroimaging data. The application of FCRM in neuroimaging is illustrated with longitudinal neuroimaging and cognitive data acquired from a large cohort (n = 210) of healthy children, 2–48 months of age. Quantifying white matter myelination by using myelin water fraction (MWF) as imaging metric derived from MRI scans, application of this methodology reveals an early period (200–500 days) during which whole brain and regional white matter structure, as quantified by MWF, is positively associated with cognitive ability, while we found no such association for whole brain white matter volume. Adjusting for baseline covariates including socioeconomic status as measured by maternal education (SES‐ME), infant feeding practice, gender, and birth weight further reveals an increasing association between SES‐ME and cognitive development with child age. These results shed new light on the emerging patterns of brain and cognitive development, indicating that FCRM provides a useful tool for investigating these evolving relationships.

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Section: Introductionmentioning

confidence: 99%

Longitudinal associations between white matter maturation and cognitive development across early childhood

Dai

Hadjipantelis

Wang

et al. 2019

Human Brain Mapping

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“…The reasons why NYT can improve apathy remain to be clarified. Recent reports have revealed that myelin loss is an important factor in the pathology of MCI, as well as both degenerative and vascular dementia [9,10]. The association between demyelination and apathy has also been reported in multiple sclerosis patients [11,12].…”

Section: Discussionmentioning

confidence: 93%

Ninjin'yoeito (Tsumura) Extract; a Kampo (traditional herbal medicine) Improved Apathy in a Mild Cognitive Impairment Patient

Sato

Tamura²,

Takahashi

et al. 2018

CNPT

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Apathy, characterized by lack of motivation and loss of initiative, is a common symptom with all forms of dementia. The traditional Japanese medicine: Ninjin'yoeito (NYT) has been reported to improve anemia, fatigue, loss of appetite, and anorexia in patients with Alzheimer's disease. We reported here the case of a 71year-old female with mild cognitive impairment (MCI) and apathy. NYT improved her apathy symptoms effectively, without any adverse effects, including cognitive decline. Our findings suggest that apathy symptoms in MCI patients can be improved without prescribing cholinesterase inhibitors.

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“…In humans, partial loss of myelin, axons and oligodendroglial cells have been observed histologically in early AD (Brun and Englund, 1986;Englund et al, 1988;Kobayashi et al, 2002;Roher et al, 2002;Svennerholm and Gottfries, 1994). Recent non-invasive MRI methods including diffusion MRI and relaxometry also provide evidence for demyelination in mild cognitive impairment and early AD (Bouhrara et al, 2018;Dong et al, 2020). Current theories further suggest a two-step demyelination process, with initial oligodendrocyte degeneration releasing iron, which promotes amyloid plaques, which in turn further destroy myelin until the neurodegenerative stage (Bartzokis, 2011(Bartzokis, , 2004.…”

Section: Discussionmentioning

confidence: 99%

Synchronous nonmonotonic changes in functional connectivity and white matter integrity in a rat model of sporadic Alzheimer’s disease

Diao²,

Poitry‐Yamate

et al. 2020

Preprint

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Impaired brain glucose metabolism has been singled out as an important contributor and possibly main trigger to the development of Alzheimer's disease. Intracerebroventricular injections of streptozotocin (icv-STZ) precisely cause brain glucose hypometabolism without systemic diabetes and are a valuable tool for evaluating ensuing neurodegeneration. Here, a first-time comprehensive longitudinal study of brain glucose metabolism, functional connectivity and white matter microstructure was performed in icv-STZ rats using FDG-PET, resting-state fMRI and diffusion MRI, respectively. STZ rats displayed altered functional connectivity and white matter degeneration in brain regions typically involved in AD, in a temporal pattern of acute injury, transient recovery and chronic degeneration, which did not match the temporal pattern of glucose hypometabolism. This finding supports the hypothesis that a compensatory mechanism, possibly recruiting ketone bodies, can restore normal brain structure and function up to a certain level of pathological severity. This study further highlights the dynamics of how brain insulin resistance affects structure and function and identifies potent MRI-derived biomarkers to track neurodegeneration in human AD and diabetic populations.

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Evidence of demyelination in mild cognitive impairment and dementia using a direct and specific magnetic resonance imaging measure of myelin content

Cited by 123 publications

References 59 publications

Longitudinal associations between white matter maturation and cognitive development across early childhood

Longitudinal associations between white matter maturation and cognitive development across early childhood

Ninjin'yoeito (Tsumura) Extract; a Kampo (traditional herbal medicine) Improved Apathy in a Mild Cognitive Impairment Patient

Synchronous nonmonotonic changes in functional connectivity and white matter integrity in a rat model of sporadic Alzheimer’s disease

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