Glymphatic function decline as a mediator of core memory-related brain structures atrophy in aging.

J Transl Int Med

Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders, Beijing 100191, China.

Published: February 2025


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Background And Objectives: This study aimed to elucidate the role of the glymphatic system-a crucial pathway for clearing waste in the brain-in the aging process and its contribution to cognitive decline. We specifically focused on the diffusion tensor imaging analysis along the perivascular space (ALPS) index as a noninvasive biomarker of glymphatic function.

Methods: Data were drawn from the Alzheimers Disease Neuroimaging Initiative (ADNI) database and a separate validation cohort to analyze the ALPS index in cognitively normal older adults. The relationships among the ALPS index, brain morphometry, and memory performance were examined.

Results: As a biomarker of glymphatic function, the ALPS index appeared to decline with age in both cohorts. According to the brain morphology analysis, the ALPS index was positively correlated with the thickness of the left entorhinal cortex ( = 0.258, = 2.96 × 10), and it played a mediating role between aging and left entorhinal cortex thinning. The independent cohort further validated the correlation between the ALPS index and the left entorhinal cortex thickness ( = 0.414, = 0.042). Additionally, in both the primary and validation cohorts, the ALPS index played a significant mediating role in the relationship between age and durable or delayed memory decline.

Conclusion: This study highlights the ALPS index as a promising biomarker for glymphatic function and links it to atrophy of the core memory brain regions during aging. Furthermore, these results suggest that targeting glymphatic dysfunction could represent a novel therapeutic approach to mitigate age-related memory decline.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921812PMC
http://dx.doi.org/10.1515/jtim-2025-0007DOI Listing

Publication Analysis

Top Keywords

glymphatic function
12
biomarker glymphatic
12
left entorhinal
12
entorhinal cortex
12
alps
8
played mediating
8
mediating role
8
glymphatic
6
decline
4
function decline
4

Similar Publications

Introduction: Dysfunction of the glymphatic system is thought to lead to build up of toxic proteins including β-amyloid and α-synuclein, and thus may be involved in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). The Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS) index has been proposed as a marker of glymphatic function.

Aims: To investigate DTI-ALPS in mild cognitive impairment (MCI) and dementia, and determine its relationship with cognitive decline, and biomarkers of neurodegeneration.

View Article and Find Full Text PDF

The therapeutic effects of vortioxetine on mood and cognition have been documented in major depressive disorder (MDD). This study aims to examine whether vortioxetine can improve brain glymphatic system function and connections among functional brain networks and to explore the underlying relationships among these changes. A total of 34 patients with MDD and 41 healthy controls (HCs) were recruited in the study.

View Article and Find Full Text PDF

Background: Blood pressure (BP) is not steady. It varies over intervals from months to consecutive cardiac cycles and this variation contains meaningful information beyond mean BP. Variability over multiple clinic visits (VVV-BP) and during 24-hour ambulatory monitoring (ABPV) is positively related to risk of stroke and coronary artery disease and negatively associated with cognitive performance.

View Article and Find Full Text PDF

Sleep disorders encompass a range of diseases and symptoms that disrupt individual sleep patterns, degrade sleep quality, and diminish sleep efficiency. Currently, the mechanisms governing sleep regulation and the etiology of sleep disorders remain unclear, leading to clinical treatments that are primarily symptomatic due to the absence of precise intervention methods. Recent studies suggest that glymphatic-meningeal lymphatic route is responsible for the clearance of macromolecular metabolites from the brain, thus playing a pivotal role in maintaining sleep homeostasis and circadian rhythm.

View Article and Find Full Text PDF