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Perivascular space and white matter hyperintensities in Alzheimer’s disease: associations with disease progression and cognitive function

淋巴系统 磁共振弥散成像 高强度 医学 痴呆 血管周围间隙 白质 病理 阿尔茨海默病 神经学 脑脊液 生物标志物 心脏病学 内科学 疾病 磁共振成像 放射科 生物 精神科 生物化学
作者
Philine Schirge,Robert Perneczky,Toshiaki Taoka,Adriana L. Ruiz‐Rizzo,Ersin Ersoezlue,Robert Forbrig,Selim Guersel,Carolin Kurz,Matthias Brendel,Julian Hellmann‐Regen,Josef Priller,Anja Schneider,Frank Jessen,Emrah Düzel,Katharina Büerger,Stefan Teipel,Christoph Laske,Oliver Peters,Eike J. Spruth,Klaus Fließbach
出处
期刊:Alzheimer's Research & Therapy [BioMed Central]
卷期号:17 (1)
标识
DOI:10.1186/s13195-025-01707-9
摘要

Alzheimer's disease (AD) is the leading cause of dementia, characterized by the accumulation of amyloid-beta (Aβ) and neurofibrillary tangles. Recent studies emphasize the role of vascular factors, including the glymphatic system, in AD pathogenesis, particularly in Aβ clearance. The diffusion tensor image analysis along the perivascular space (DTI-ALPS; ALPS-Index) has emerged as a novel, non-invasive method to evaluate the glymphatic system in vivo, showing glymphatic insufficiency in AD. This study aimed to investigate alterations in the function of the glymphatic system in individuals with AD versus healthy controls (HC), and to explore its association with Aβ, cerebrovascular disease (CVD), white matter hyperintensities (WMH), and cognitive function. DTI MRI data from three independent study cohorts (ActiGliA: AD n = 16, Controls n = 18; DELCODE: AD n = 54, Controls n = 67; ADNI: AD n = 43, Controls n = 49) were used to evaluate the perivascular space (PVS) integrity; a potential biomarker for glymphatic activity. The DTI-Along the Perivascular Space technique was used to measure water diffusion along PVS providing an index to assess the efficiency of the glymphatic system's waste clearance function. WMH load was quantified in FLAIR MRI using the lesion segmentation tool. We quantified WMHs volume within our defined region of interest (ROI) and excluded participants with any WMHs to avoid confounding the ALPS-Index. Associations with cerebrospinal fluid (CSF) AD hallmark biomarkers, cognitive performance (MMSE) and clinical severity (CDR) were assessed. AD patients had a significantly lower ALPS-Index vs. healthy controls (ActiGliA: AD: mean = 1.22, SD = 0.12; Controls: mean = 1.36, SD = 0.14, p = 0.004; DELCODE: AD: mean = 1.26, SD = 0.18; Controls: mean = 1.34, SD = 0.2, p = 0.035; ADNI: AD: mean = 1.08, SD = 0.24; Controls: mean = 1.19, SD = 0.13, p = 0.008). The ALPS-Index was associated with CSF Aβ concentration, WMH number and MMSE and CDR. WMH, found in the ROIs correlated negatively with the ALPS-Index. This study highlights the potential of the DTI-ALPS-Index as a biomarker for glymphatic dysfunction in AD. It underscores the importance of considering vascular factors and the glymphatic system in the pathogenesis and diagnosis of AD as WMHs in the ROI could cause disturbances and inaccurate indices.
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