Dataset Information

Cholinergic White Matter Lesions, AD-Signature Cortical Thickness, and Change in Cognition: The Northern Manhattan Study.

ABSTRACT:

Background

How cerebrovascular disease and neurodegeneration affect each other to impact cognition is not yet known. We aimed to test whether Alzheimer's disease-signature (AD) cortical thickness mediates the association between cholinergic white matter lesion load and change in domain-specific cognition.

Methods

Clinically stroke-free participants from the Northern Manhattan Study with both regional white matter hyperintensity volume (WMHV) and gray matter measurements were included (N = 894). Tract-specific WMHVs were quantified through FSL using the Johns Hopkins University white matter tract atlas. We used Freesurfer 5.1 to estimate regional cortical thickness. We fit structural equation models, including multiple indicator latent change score models, to examine associations between white matter hyperintensity volume (WMHV) in cholinergic tracts, AD-signature region cortical thickness (CT), and domain-specific cognition.

Results

Our sample (N = 894) had a mean (SD) age = 70 (9) years, years of education = 10 (5), 63% women, and 67% Hispanics/Latinos. Greater cholinergic WMHV was significantly related to worse processing speed at baseline (standardized ? = -0.17, SE = 0.05, p = .001) and over time (standardized ? = -0.28, SE = 0.09, p = .003), with a significant indirect effect of AD-signature region CT (baseline: standardized ? = -0.02, SE = 0.01, p = .023; change: standardized ? = -0.03, SE = 0.02, p = .040).

Conclusions

Cholinergic tract WMHV is associated with worse processing speed, both directly and indirectly through its effect on AD-signature region CT.

SUBMITTER: Caunca MR

PROVIDER: S-EPMC7457185 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Cholinergic White Matter Lesions, AD-Signature Cortical Thickness, and Change in Cognition: The Northern Manhattan Study.

Caunca Michelle R MR Siedlecki Karen K Cheung Ying Kuen YK Alperin Noam N Lee Sang H SH Elkind Mitchell S V MSV Sacco Ralph L RL Wright Clinton B CB Rundek Tatjana T

The journals of gerontology. Series A, Biological sciences and medical sciences 20200701 8

<h4>Background</h4>How cerebrovascular disease and neurodegeneration affect each other to impact cognition is not yet known. We aimed to test whether Alzheimer's disease-signature (AD) cortical thickness mediates the association between cholinergic white matter lesion load and change in domain-specific cognition.<h4>Methods</h4>Clinically stroke-free participants from the Northern Manhattan Study with both regional white matter hyperintensity volume (WMHV) and gray matter measurements were inclu ...[more]

PMID: 31944231

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Project description:Cerebral white matter lesions (WML) encompass axonal loss and demyelination and are assumed to be associated with small vessel disease (SVD)-related ischaemia. However, our previous study in the parietal lobe white matter revealed that WML in Alzheimer's disease (AD) are linked with degenerative axonal loss secondary to the deposition of cortical AD pathology. Furthermore, neuroimaging data suggest that pathomechanisms for the development of WML differ between anterior and posterior lobes with AD-associated degenerative mechanism driving posterior white matter disruption, and both AD-associated degenerative and vascular mechanisms contributed to anterior matter disruption. In this pilot study, we used human post-mortem brain tissue to investigate the composition and aetiology of frontal WML from AD and non-demented controls to determine if frontal WML are SVD-associated and to reveal any regional differences in the pathogenesis of WML. Frontal WML tissue sections from 40 human post-mortem brains (AD, n = 19; controls, n = 21) were quantitatively assessed for demyelination, axonal loss, cortical hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ) burden, and arteriolosclerosis as a measure of SVD. Biochemical assessment included Wallerian degeneration-associated protease calpain and the myelin-associated glycoprotein to proteolipid protein ratio as a measure of ante-mortem ischaemia. Arteriolosclerosis severity was found to be associated with and a significant predictor of frontal WML severity in both AD and non-demented controls. Interesting, frontal axonal loss was also associated with HPτ and calpain levels were associated with increasing Aβ burden in the AD group, suggestive of an additional degenerative influence. To conclude, this pilot data suggest that frontal WML in AD may result from both increased arteriolosclerosis and AD-associated degenerative changes. These preliminary findings in combination with previously published data tentatively indicate regional differences in the aetiology of WML in AD, which should be considered in the clinical diagnosis of dementia subtypes: posterior WML maybe associated with degenerative mechanisms secondary to AD pathology, while anterior WML could be associated with both SVD-associated and degenerative mechanisms.

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Dataset Information

Cholinergic White Matter Lesions, AD-Signature Cortical Thickness, and Change in Cognition: The Northern Manhattan Study.

Background

Methods

Results

Conclusions

Publications

Cholinergic White Matter Lesions, AD-Signature Cortical Thickness, and Change in Cognition: The Northern Manhattan Study.

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