Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease

Jung Lung Hsu; Yi Chia Wei; Cheng Hong Toh; Ing Tsung Hsiao; Kun Ju Lin; Tzu Chen Yen; Ming Feng Liao; Long Sun Ro

doi:10.1002/ana.26516

Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease

Jung Lung Hsu, Yi Chia Wei, Cheng Hong Toh, Ing Tsung Hsiao, Kun Ju Lin, Tzu Chen Yen, Ming Feng Liao, Long Sun Ro^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

61 Scopus citations

Abstract

OBJECTIVE: The glymphatic system cleans amyloid and tau proteins from the brain in animal studies of Alzheimer disease (AD). However, there is no direct evidence showing this in humans.

METHODS: Participants (n = 50, 62.6 ± 5.4 years old, 36 women) with AD and normal controls underwent amyloid positron emission tomography (PET), tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS).

RESULTS: ALPS-indexes showed negative correlations with deposition of amyloid and tau on PET images and positive correlations with cognitive scores even after adjusting for age, sex, years of education, and APOE4 genotype covariates in multiple AD-related brain regions (all p < 0.05). Mediation analysis showed that ALPS-index acted as a significant mediator between regional standardized uptake value ratios of amyloid and tau images and cognitive dysfunction even after correcting for multiple covariates in AD-related brain regions. These regions are responsible for attention, memory, and executive function, which are vulnerable to sleep deprivation.

INTERPRETATION: Glymphatic system activity may act as a significant mediator in AD-related cognitive dysfunction even after adjusting for multiple covariates and gray matter volumes. ALPS-index may provide useful disease progression or treatment biomarkers for patients with AD as an indicator of modulation of glymphatic activity. ANN NEUROL 2023;93:164-174.

Original language	English
Pages (from-to)	164-174
Number of pages	11
Journal	Annals of Neurology
Volume	93
Issue number	1
DOIs	https://doi.org/10.1002/ana.26516
State	Published - 01 2023

Bibliographical note

Keywords

Aged
Female
Humans
Middle Aged
Alzheimer Disease/pathology
Amyloid/metabolism
Brain/pathology
Cognitive Dysfunction/pathology
Magnetic Resonance Imaging
Positron-Emission Tomography/methods
tau Proteins/metabolism
Male

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10.1002/ana.26516

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@article{f4fb80d425704ac58474c3232edd28d0,

title = "Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease",

abstract = "OBJECTIVE: The glymphatic system cleans amyloid and tau proteins from the brain in animal studies of Alzheimer disease (AD). However, there is no direct evidence showing this in humans.METHODS: Participants (n = 50, 62.6 ± 5.4 years old, 36 women) with AD and normal controls underwent amyloid positron emission tomography (PET), tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS).RESULTS: ALPS-indexes showed negative correlations with deposition of amyloid and tau on PET images and positive correlations with cognitive scores even after adjusting for age, sex, years of education, and APOE4 genotype covariates in multiple AD-related brain regions (all p < 0.05). Mediation analysis showed that ALPS-index acted as a significant mediator between regional standardized uptake value ratios of amyloid and tau images and cognitive dysfunction even after correcting for multiple covariates in AD-related brain regions. These regions are responsible for attention, memory, and executive function, which are vulnerable to sleep deprivation.INTERPRETATION: Glymphatic system activity may act as a significant mediator in AD-related cognitive dysfunction even after adjusting for multiple covariates and gray matter volumes. ALPS-index may provide useful disease progression or treatment biomarkers for patients with AD as an indicator of modulation of glymphatic activity. ANN NEUROL 2023;93:164-174.",

keywords = "Aged, Female, Humans, Middle Aged, Alzheimer Disease/pathology, Amyloid/metabolism, Brain/pathology, Cognitive Dysfunction/pathology, Magnetic Resonance Imaging, Positron-Emission Tomography/methods, tau Proteins/metabolism, Male",

author = "Hsu, {Jung Lung} and Wei, {Yi Chia} and Toh, {Cheng Hong} and Hsiao, {Ing Tsung} and Lin, {Kun Ju} and Yen, {Tzu Chen} and Liao, {Ming Feng} and Ro, {Long Sun}",

note = "{\textcopyright} 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",

year = "2023",

month = jan,

doi = "10.1002/ana.26516",

language = "英语",

volume = "93",

pages = "164--174",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley & Sons Inc.",

number = "1",

}

TY - JOUR

T1 - Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease

AU - Hsu, Jung Lung

AU - Wei, Yi Chia

AU - Toh, Cheng Hong

AU - Hsiao, Ing Tsung

AU - Lin, Kun Ju

AU - Yen, Tzu Chen

AU - Liao, Ming Feng

AU - Ro, Long Sun

PY - 2023/1

Y1 - 2023/1

N2 - OBJECTIVE: The glymphatic system cleans amyloid and tau proteins from the brain in animal studies of Alzheimer disease (AD). However, there is no direct evidence showing this in humans.METHODS: Participants (n = 50, 62.6 ± 5.4 years old, 36 women) with AD and normal controls underwent amyloid positron emission tomography (PET), tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS).RESULTS: ALPS-indexes showed negative correlations with deposition of amyloid and tau on PET images and positive correlations with cognitive scores even after adjusting for age, sex, years of education, and APOE4 genotype covariates in multiple AD-related brain regions (all p < 0.05). Mediation analysis showed that ALPS-index acted as a significant mediator between regional standardized uptake value ratios of amyloid and tau images and cognitive dysfunction even after correcting for multiple covariates in AD-related brain regions. These regions are responsible for attention, memory, and executive function, which are vulnerable to sleep deprivation.INTERPRETATION: Glymphatic system activity may act as a significant mediator in AD-related cognitive dysfunction even after adjusting for multiple covariates and gray matter volumes. ALPS-index may provide useful disease progression or treatment biomarkers for patients with AD as an indicator of modulation of glymphatic activity. ANN NEUROL 2023;93:164-174.

AB - OBJECTIVE: The glymphatic system cleans amyloid and tau proteins from the brain in animal studies of Alzheimer disease (AD). However, there is no direct evidence showing this in humans.METHODS: Participants (n = 50, 62.6 ± 5.4 years old, 36 women) with AD and normal controls underwent amyloid positron emission tomography (PET), tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS).RESULTS: ALPS-indexes showed negative correlations with deposition of amyloid and tau on PET images and positive correlations with cognitive scores even after adjusting for age, sex, years of education, and APOE4 genotype covariates in multiple AD-related brain regions (all p < 0.05). Mediation analysis showed that ALPS-index acted as a significant mediator between regional standardized uptake value ratios of amyloid and tau images and cognitive dysfunction even after correcting for multiple covariates in AD-related brain regions. These regions are responsible for attention, memory, and executive function, which are vulnerable to sleep deprivation.INTERPRETATION: Glymphatic system activity may act as a significant mediator in AD-related cognitive dysfunction even after adjusting for multiple covariates and gray matter volumes. ALPS-index may provide useful disease progression or treatment biomarkers for patients with AD as an indicator of modulation of glymphatic activity. ANN NEUROL 2023;93:164-174.

KW - Aged

KW - Female

KW - Humans

KW - Middle Aged

KW - Alzheimer Disease/pathology

KW - Amyloid/metabolism

KW - Brain/pathology

KW - Cognitive Dysfunction/pathology

KW - Magnetic Resonance Imaging

KW - Positron-Emission Tomography/methods

KW - tau Proteins/metabolism

KW - Male

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U2 - 10.1002/ana.26516

DO - 10.1002/ana.26516

M3 - 文章

C2 - 36214568

AN - SCOPUS:85140440709

SN - 0364-5134

VL - 93

SP - 164

EP - 174

JO - Annals of Neurology

JF - Annals of Neurology

IS - 1

ER -

Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease

Abstract

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