| Title: |
Perivascular space and white matter hyperintensities in Alzheimer's disease: associations with disease progression and cognitive function |
| Authors: |
Schirge, P.M.; Perneczky, R.; Taoka, T.; Ruiz-Rizzo, A.L.; Ersoezlue, E.; Forbrig, R.; Guersel, S.; Kurz, C.; Brendel, M.; Hellmann-Regen, J.; Priller, J.; Schneider, A.; Jessen, F.; Düzel, E.; Buerger, K.; Teipel, S.; Laske, C.; Peters, O.; Spruth, E.; Fliessbach, K.; Rostamzadeh, A.; Glanz, W.; Janowitz, D.; Kilimann, I.; Sodenkamp, S.; Ewers, M.; Rauchmann, B.S. |
| Publisher Information: |
BioMed Central |
| Publication Year: |
2025 |
| Collection: |
Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository |
| Subject Terms: |
Function and Dysfunction of the Nervous System; Topic 3: Integrative Biomedicine |
| Description: |
BACKGROUND: 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. METHODS: 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. RESULTS: 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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf; application/msword |
| Language: |
English |
| Relation: |
https://edoc.mdc-berlin.de/id/eprint/25224/1/25224oa.pdf; https://edoc.mdc-berlin.de/id/eprint/25224/2/25224suppl.docx; Perivascular space and white matter hyperintensities in Alzheimer's disease: associations with disease progression and cognitive function. Schirge, P.M., Perneczky, R., Taoka, T., Ruiz-Rizzo, A.L., Ersoezlue, E., Forbrig, R., Guersel, S., Kurz, C., Brendel, M., Hellmann-Regen, J., Priller, J., Schneider, A., Jessen, F., Düzel, E., Buerger, K., Teipel, S., Laske, C., Peters, O., Spruth, E., Fliessbach, K., Rostamzadeh, A., Glanz, W., Janowitz, D., Kilimann, I., Sodenkamp, S., Ewers, M. and Rauchmann, B.S. Alzheimer's Research & Therapy 17 (1): 62. 18 March 2025; PMID:40098158; https://doi.org/10.1186/s13195-025-01707-9 |
| DOI: |
10.1186/s13195-025-01707-9 |
| Availability: |
https://edoc.mdc-berlin.de/id/eprint/25224/; https://edoc.mdc-berlin.de/25224/; https://doi.org/10.1186/s13195-025-01707-9 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.1FE061C1 |
| Database: |
BASE |