The Myelin Water Fraction Serves as a Marker for Age-Related Myelin Alterations in the Cerebral White Matter – A Multiparametric MRI Aging Study

Background: Cerebrovascular pathologies and hypertension could play a vital role in Alzheimer disease (AD) progression. However, whether cerebrovascular pathologies and hypertension accelerate the AD progression through an independent or interaction effect is unknown. Objective: To investigate the effect of the interactions of cerebrovascular pathologies and hypertension on AD progression. Method: A retrospective longitudinal study was conducted to compare AD courses in patients with different severities of cerebral White Matter Changes (WMCs) in relation to hypertension. Annual comprehensive psychometrics were performed. WMCs were rated using a rating scale for Age-related WMCs (ARWMC). Results: In total, 278 patients with sporadic AD were enrolled in this study. The mean age of the patients was 76.6 ± 7.4 years, and 166 patients had hypertension. Among AD patients with hypertension, those with deterioration in clinical dementia rating-sum of box (CDR-SB) and CDR had significantly severe baseline ARWMC scales in total (CDR-SB: 5.8 vs. 3.6, adjusted P = 0.04; CDR: 6.4 vs. 4.4, adjusted P = 0.04) and frontal area (CDR-SB: 2.4 vs. 1.2, adjusted P = 0.01; CDR: 2.4 vs. 1.7, adjusted P < 0.01) compared with those with no deterioration in psychometrics after adjustment for confounders. By contrast, among AD patients without hypertension, no significant differences in ARWMC scales were observed between patients with and without deterioration. Conclusion: The effect of cerebrovascular pathologies on AD progression between those with and without hypertension might differ. An interaction but not independent effect of hypertension and WMCs on the progression of AD is possible.

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Development and validation of morphological segmentation of age-related cerebral white matter hyperintensities

NeuroImage ◽

10.1016/j.neuroimage.2009.03.055 ◽

2009 ◽

Vol 47 (1) ◽

pp. 199-203 ◽

Cited By ~ 31

Author(s):

Richard Beare ◽

Velandai Srikanth ◽

Jian Chen ◽

Thanh G. Phan ◽

Jennifer Stapleton ◽

...

Keyword(s):

White Matter ◽

White Matter Hyperintensities ◽

Cerebral White Matter ◽

Morphological Segmentation ◽

Age Related ◽

Development And Validation

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Myelin Water Fraction Imaging Reveals Hemispheric Asymmetries in Human White Matter That Are Associated with Genetic Variation in PLP1

Molecular Neurobiology ◽

10.1007/s12035-018-1351-y ◽

2018 ◽

Vol 56 (6) ◽

pp. 3999-4012 ◽

Cited By ~ 4

Author(s):

Sebastian Ocklenburg ◽

Catrona Anderson ◽

Wanda M. Gerding ◽

Christoph Fraenz ◽

Caroline Schlüter ◽

...

Keyword(s):

Genetic Variation ◽

White Matter ◽

Hemispheric Asymmetries ◽

Water Fraction ◽

Myelin Water Fraction

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Multiple indicators of age-related differences in cerebral white matter and the modifying effects of hypertension

NeuroImage ◽

10.1016/j.neuroimage.2009.10.035 ◽

2010 ◽

Vol 49 (3) ◽

pp. 2083-2093 ◽

Cited By ~ 56

Author(s):

S. Burgmans ◽

M.P.J. van Boxtel ◽

E.H.B.M. Gronenschild ◽

E.F.P.M. Vuurman ◽

P. Hofman ◽

...

Keyword(s):

White Matter ◽

Cerebral White Matter ◽

Multiple Indicators ◽

Age Related

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Pathophysiology of Age-Related Cerebral White Matter Changes

Cerebrovascular Diseases ◽

10.1159/000049143 ◽

2002 ◽

Vol 13 (2) ◽

pp. 7-10 ◽

Cited By ~ 131

Author(s):

Leonardo Pantoni

Keyword(s):

White Matter ◽

Cerebral White Matter ◽

White Matter Changes ◽

Age Related

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Disconnected aging: Cerebral white matter integrity and age-related differences in cognition

Neuroscience ◽

10.1016/j.neuroscience.2013.11.026 ◽

2014 ◽

Vol 276 ◽

pp. 187-205 ◽

Cited By ~ 190

Author(s):

I.J. Bennett ◽

D.J. Madden

Keyword(s):

White Matter ◽

White Matter Integrity ◽

Cerebral White Matter ◽

Age Related

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A High Burden of Cerebral white Matter Lesion: Evidences from 9 Asian Cities

10.21203/rs.3.rs-124194/v1 ◽

2020 ◽

Author(s):

Bonnie Yin Ka Lam ◽

Brian Yiu ◽

Encarnita Ampil ◽

Christopher Li-Hsian Chen ◽

Yustiani Dikot ◽

...

Keyword(s):

Risk Factors ◽

White Matter ◽

Cognitive Performance ◽

Small Vessel Disease ◽

White Matter Lesion ◽

Large Population ◽

Significant Risk ◽

Cerebral White Matter ◽

Age Related ◽

Asian Cities

Abstract Background Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Methods Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5,701) and classified into i) stroke/transient ischemic attack (TIA), ii) Alzheimer’s disease (AD)/mild cognitive impairment (MCI), or iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. ResultsThe prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3 %). Bandang Indonesia showed the highest prevalence of WML, adjusted for age, sex, education and disease groups. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. ConclusionsWML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.

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LIFESPAN AGE-RELATED DIFFERENCES IN THE REGIONAL WHITE MATTER MICROSTRUCTURE OF THE HUMAN CORPUS CALLOSUM

Innovation in Aging ◽

10.1093/geroni/igz038.3435 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S945-S945

Author(s):

John Lynn ◽

Chaitali Anand ◽

Muzamil Arshad ◽

Dalal Khatib ◽

Jeffrey Stanley ◽

...

Keyword(s):

White Matter ◽

Corpus Callosum ◽

Geometric Mean ◽

Age Groups ◽

Fiber Density ◽

Linear Effect ◽

Water Fraction ◽

General Linear Model Analysis ◽

Age Related ◽

Axonal Density

Abstract The corpus callosum (CC) connects homologous cortical structures across hemispheres and is the largest white matter tract in the human brain. Post-mortem studies suggest that CC myelination begins in infancy, reaches a plateau in the middle age, and declines in the later years. The latter is accompanied by myelin disruption and reduction in fiber density and diameter, i.e. changes in intra-/extracellular water space. We used multi-echo T2 imaging to estimate, via multi-exponential T2 relaxation of water, the myelin water fraction (MWF), a direct proxy for myelin content, and geometric mean T2 (geomT2IEW) that reflects water in the intra-/extracellular space, to investigate age differences in five CC regions covering its anterior to posterior span in 395 healthy individuals (7-85 years; 161M+235F). The general linear model analysis of MWF showed main effects of age and age-squared conditioned on interactions by CC region. Univariate polynomial regressions on three age groups (7-29, 30-59, and 60-85 years) revealed the overall quadratic association between age and MWF as mainly driven by the positive linear relationship in the youngest group and minimal differences in the remainder of the lifespan, save for two weak negative linear associations in the anterior/middle CC body. With geomT2, a main linear effect of age, and significant interactions between age and age-squared by region were observed. The positive linear association was especially prominent in the regions with greater fiber density. The results are consistent with CC myelination into adulthood and decreased axonal density and diameter but not prominent myelin degeneration in elderly individuals.

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Pathological basis of diffusely abnormal white matter: insights from magnetic resonance imaging and histology

Multiple Sclerosis Journal ◽

10.1177/1352458510384008 ◽

2010 ◽

Vol 17 (2) ◽

pp. 144-150 ◽

Cited By ~ 46

Author(s):

Cornelia Laule ◽

Irene M Vavasour ◽

Esther Leung ◽

David KB Li ◽

Piotr Kozlowski ◽

...

Keyword(s):

White Matter ◽

Magnetization Transfer ◽

Selective Reduction ◽

Myelin Proteins ◽

Water Fraction ◽

Normal Appearing White Matter ◽

Three Samples ◽

Disability Status ◽

Myelin Water Fraction

Background: The pathological basis of diffusely abnormal white matter (DAWM) in multiple sclerosis (MS) has not been elucidated in detail, but may be an important element in disability and clinical progression. Methods: Fifty-three subjects with MS were examined with T1, multi-echo T2 and magnetization transfer (MT). Twenty-three samples of formalin-fixed MS brain tissue were examined with multi-echo T2 and subsequently stained for myelin phospholipids using luxol fast blue, for axons using Bielschowsky, immunohistochemically for the myelin proteins myelin basic protein (MBP) and 2′,3′-cyclic nucleotide 3′ phosphohydrolase (CNP) and for astrocytes using glial fibrillary acidic protein (GFAP). Regions of interest in DAWM were compared with normal appearing white matter. Results: Fourteen of 53 subjects with MS in the in vivo study showed the presence of DAWM. Subjects with DAWM were found to have a significantly lower Expanded Disability Status Scale (EDSS) and shorter disease duration (DD) when compared with subjects without DAWM (EDSS: 1.5 versus 3.0, p = 0.031; DD: 5.4 versus 10.3 years, p = 0.045). DAWM in vivo had reduced myelin water and MT ratio, and increased T2 and water content. Histological analysis suggests DAWM, which shows a reduction of the myelin water fraction, is characterized by selective reduction of myelin phospholipids, but with a relative preservation of myelin proteins and axons. Conclusions: These findings suggest that the primary abnormality in DAWM is a reduction or perturbation of myelin phospholipids that correlates with a reduction of the myelin water fraction.

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