Effect of Cholinergic Pathway Disruption on Cortical and Subcortical Volumes in Subcortical Vascular Cognitive Impairment

Jae-Sung Lim, Hyung-Min Kwon, Young-Seok Lee

Research output: Contribution to journalArticleResearchpeer-review

Abstract

BACKGROUND: The brain's cholinergic network has various interconnections with the cortical and subcortical structures. Disruption of cholinergic pathways by white matter hyperintensities (WMH) may cause pathologic changes within brain regions. Thus, WMH may represent an important pathological contributor of subcortical vascular cognitive impairment (scVCI). We aim to investigate associations between the magnitude of WMH and volumetric changes in cortical and subcortical regions innervated by cholinergic neurons in patients with scVCI.

METHODS: We enrolled patients with scVCI, defined as moderate to severe WMH or multiple (> 2) lacunar infarcts outside the brainstem. Cholinergic Pathway HyperIntensities Scale (CHIPS) scores were used to quantify the magnitude of cholinergic pathway disruptions by WMH. We measured cortical thickness and subcortical volumes of 11 brain regions innervated by cholinergic neurons. Partial correlation of brain region volumes with total CHIPS scores were obtained using multiple linear regression.

RESULTS: In total, 80 patients were enrolled. The mean age was 78.4±6.5 years, median mini-mental state examination score was 17 (interquartile range 13-20), and median CHIPS score was 11 points (interquartile range 7-17). CHIPS were positively correlated with subcortical volumes of the putamen (r'= 0.46, p=0.002) and pallidum (r'=0.45, p=0.002); and was negatively associated with inferior temporal (r'=-0.35, p=0.002) and medial orbitofrontal cortical thickness (r'=-0.32, p=0.002).

CONCLUSION: Our study suggests that WMH in cholinergic pathways may contribute to volumetric structural changes in cortical and subcortical structures innervated by cholinergic neurons. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalEuropean Journal of Neurology
DOIs
StateE-pub ahead of print - 24 Aug 2019

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Cholinergic Agents
Blood Vessels
Cholinergic Neurons
Brain
Lacunar Stroke
Globus Pallidus
Cognitive Dysfunction
Putamen
Brain Stem
White Matter
Linear Models

Cite this

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title = "Effect of Cholinergic Pathway Disruption on Cortical and Subcortical Volumes in Subcortical Vascular Cognitive Impairment",
abstract = "BACKGROUND: The brain's cholinergic network has various interconnections with the cortical and subcortical structures. Disruption of cholinergic pathways by white matter hyperintensities (WMH) may cause pathologic changes within brain regions. Thus, WMH may represent an important pathological contributor of subcortical vascular cognitive impairment (scVCI). We aim to investigate associations between the magnitude of WMH and volumetric changes in cortical and subcortical regions innervated by cholinergic neurons in patients with scVCI.METHODS: We enrolled patients with scVCI, defined as moderate to severe WMH or multiple (> 2) lacunar infarcts outside the brainstem. Cholinergic Pathway HyperIntensities Scale (CHIPS) scores were used to quantify the magnitude of cholinergic pathway disruptions by WMH. We measured cortical thickness and subcortical volumes of 11 brain regions innervated by cholinergic neurons. Partial correlation of brain region volumes with total CHIPS scores were obtained using multiple linear regression.RESULTS: In total, 80 patients were enrolled. The mean age was 78.4±6.5 years, median mini-mental state examination score was 17 (interquartile range 13-20), and median CHIPS score was 11 points (interquartile range 7-17). CHIPS were positively correlated with subcortical volumes of the putamen (r'= 0.46, p=0.002) and pallidum (r'=0.45, p=0.002); and was negatively associated with inferior temporal (r'=-0.35, p=0.002) and medial orbitofrontal cortical thickness (r'=-0.32, p=0.002).CONCLUSION: Our study suggests that WMH in cholinergic pathways may contribute to volumetric structural changes in cortical and subcortical structures innervated by cholinergic neurons. This article is protected by copyright. All rights reserved.",
author = "Jae-Sung Lim and Hyung-Min Kwon and Young-Seok Lee",
note = "This article is protected by copyright. All rights reserved.",
year = "2019",
month = "8",
day = "24",
doi = "10.1111/ene.14073",
language = "English",
journal = "European Journal of Neurology",
issn = "1351-5101",
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Effect of Cholinergic Pathway Disruption on Cortical and Subcortical Volumes in Subcortical Vascular Cognitive Impairment. / Lim, Jae-Sung; Kwon, Hyung-Min; Lee, Young-Seok.

In: European Journal of Neurology, 24.08.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effect of Cholinergic Pathway Disruption on Cortical and Subcortical Volumes in Subcortical Vascular Cognitive Impairment

AU - Lim, Jae-Sung

AU - Kwon, Hyung-Min

AU - Lee, Young-Seok

N1 - This article is protected by copyright. All rights reserved.

PY - 2019/8/24

Y1 - 2019/8/24

N2 - BACKGROUND: The brain's cholinergic network has various interconnections with the cortical and subcortical structures. Disruption of cholinergic pathways by white matter hyperintensities (WMH) may cause pathologic changes within brain regions. Thus, WMH may represent an important pathological contributor of subcortical vascular cognitive impairment (scVCI). We aim to investigate associations between the magnitude of WMH and volumetric changes in cortical and subcortical regions innervated by cholinergic neurons in patients with scVCI.METHODS: We enrolled patients with scVCI, defined as moderate to severe WMH or multiple (> 2) lacunar infarcts outside the brainstem. Cholinergic Pathway HyperIntensities Scale (CHIPS) scores were used to quantify the magnitude of cholinergic pathway disruptions by WMH. We measured cortical thickness and subcortical volumes of 11 brain regions innervated by cholinergic neurons. Partial correlation of brain region volumes with total CHIPS scores were obtained using multiple linear regression.RESULTS: In total, 80 patients were enrolled. The mean age was 78.4±6.5 years, median mini-mental state examination score was 17 (interquartile range 13-20), and median CHIPS score was 11 points (interquartile range 7-17). CHIPS were positively correlated with subcortical volumes of the putamen (r'= 0.46, p=0.002) and pallidum (r'=0.45, p=0.002); and was negatively associated with inferior temporal (r'=-0.35, p=0.002) and medial orbitofrontal cortical thickness (r'=-0.32, p=0.002).CONCLUSION: Our study suggests that WMH in cholinergic pathways may contribute to volumetric structural changes in cortical and subcortical structures innervated by cholinergic neurons. This article is protected by copyright. All rights reserved.

AB - BACKGROUND: The brain's cholinergic network has various interconnections with the cortical and subcortical structures. Disruption of cholinergic pathways by white matter hyperintensities (WMH) may cause pathologic changes within brain regions. Thus, WMH may represent an important pathological contributor of subcortical vascular cognitive impairment (scVCI). We aim to investigate associations between the magnitude of WMH and volumetric changes in cortical and subcortical regions innervated by cholinergic neurons in patients with scVCI.METHODS: We enrolled patients with scVCI, defined as moderate to severe WMH or multiple (> 2) lacunar infarcts outside the brainstem. Cholinergic Pathway HyperIntensities Scale (CHIPS) scores were used to quantify the magnitude of cholinergic pathway disruptions by WMH. We measured cortical thickness and subcortical volumes of 11 brain regions innervated by cholinergic neurons. Partial correlation of brain region volumes with total CHIPS scores were obtained using multiple linear regression.RESULTS: In total, 80 patients were enrolled. The mean age was 78.4±6.5 years, median mini-mental state examination score was 17 (interquartile range 13-20), and median CHIPS score was 11 points (interquartile range 7-17). CHIPS were positively correlated with subcortical volumes of the putamen (r'= 0.46, p=0.002) and pallidum (r'=0.45, p=0.002); and was negatively associated with inferior temporal (r'=-0.35, p=0.002) and medial orbitofrontal cortical thickness (r'=-0.32, p=0.002).CONCLUSION: Our study suggests that WMH in cholinergic pathways may contribute to volumetric structural changes in cortical and subcortical structures innervated by cholinergic neurons. This article is protected by copyright. All rights reserved.

U2 - 10.1111/ene.14073

DO - 10.1111/ene.14073

M3 - Article

JO - European Journal of Neurology

JF - European Journal of Neurology

SN - 1351-5101

ER -