Evaluation of Glymphatic System Activity Using Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) in Alzheimer’s Disease

Abstract

Aim: The glymphatic system is a recently discovered waste drainage system that facilitates the movement of cerebrospinal fluid through the brain's perivascular spaces and aids in removing soluble proteins. The Diffusion Tensor Imaging (DTI-ALPS) index analysis is a modern method used to evaluate the movement of water molecules in these spaces by measuring the diffusion coefficient. This study aimed to examine glymphatic system function in Alzheimer's disease (AD) patients compared to healthy controls (HC) using the DTI-ALPS method and to analyze its relationship with cognitive disorders. Methods:DTI data from 59 AD patients and 59 HC were obtained by downloading medical data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) platform. Using DSI Studio software, the diffusivities of the DTI data were extracted, and DTI-ALPS indices were calculated. Correlation analysis evaluated the relationship between the DTI-ALPS index and clinical features. Results:The findings indicated that the DTI-ALPS index was significantly lower in AD patients compared to HC (p = 0.042). Furthermore, the DTI-ALPS index showed a significant correlation with the Functional Activities Questionnaire (FAQ) (r = -0.214, p = 0.020) and the Mini-Mental State Examination (MMSE) (r = 0.225, p = 0.014) Conclusions:The study demonstrated that AD individuals have impaired glymphatic system function, as indicated by the DTI-ALPS index, which correlates with worse cognitive performance. These findings support early diagnosis methods for AD. A better understanding of glymphatic system function may provide new perspectives for monitoring AD progression.

Keywords

• Alzheimer
• Brain Perivascular Space
• Diffusion Tensor Imaging
• G-lymphatic System
• G-lymphatic Clearance System

Ethical Statement

The ethics committee approval has been obtained from Uskudar University Non Interventional Research Ethics Committee report number of 61351342/MAY 2023-12 (29 May 2023).

Thanks

Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. I would like to express my gratitude to Üsküdar University for their invaluable support during the preparation of my doctoral thesis, from which this study originates.

Alzheimer Hastalığında Perivasküler Alan Boyunca Difüzyon Tensor Görüntüleme Analizi (DTI-ALPS) Kullanılarak G-lenfatik Sistem Aktivitesinin Değerlendirilmesi

Abstract

Amaç: G-lenfatik sistem, beyin perivasküler boşlukları boyunca beyin omurilik sıvısının hareketini kolaylaştıran ve çözünür proteinlerin uzaklaştırılmasına yardımcı olan, yakın zamanda keşfedilmiş bir atık drenaj sistemidir. Difüzyon Tensör Görüntüleme (DTI-ALPS) indeks analizi, bu boşluklardaki su moleküllerinin hareketini difüzyon katsayısını ölçerek değerlendirmede kullanılan modern bir yöntemdir. Bu çalışma, DTI-ALPS yöntemi kullanılarak Alzheimer hastalığı (AH) olan bireylerde g-lenfatik sistem fonksiyonunu sağlıklı kontrollerle (SK) karşılaştırmayı ve bilişsel bozukluklarla olan ilişkisini incelemeyi amaçlamıştır. Yöntem: 59 AH hastasına ve 59 sağlıklı kontrole ait DTI verileri, Alzheimer Hastalığı Nörogörüntüleme Girişimi (ADNI) platformundan indirilen tıbbi veriler kullanılarak elde edilmiştir. DSI Studio yazılımı kullanılarak DTI verilerinin difüziviteleri çıkarılmış ve DTI-ALPS indeksleri hesaplanmıştır. Korelasyon analizi, DTI-ALPS indeksi ile klinik özellikler arasındaki ilişkiyi değerlendirmek için uygulanmıştır. Bulgular: Bulgular, AH hastalarında DTI-ALPS indeksinin sağlıklı kontrollere kıyasla anlamlı derecede düşük olduğunu göstermiştir (p = 0.042). Ayrıca DTI-ALPS indeksi, Fonksiyonel Aktivite Anketi (FAQ) (r = -0.214, p = 0.020) ve Mini Mental Durum Değerlendirmesi (MMSE) (r = 0.225, p = 0.014) ile anlamlı korelasyon göstermiştir. Sonuç: Bu çalışma, DTI-ALPS indeksiyle gösterildiği üzere Alzheimer hastalarında g-lenfatik sistem fonksiyonunun bozulduğunu ve bunun daha kötü bilişsel performansla ilişkili olduğunu ortaya koymuştur. Bu bulgular, Alzheimer hastalığının erken tanısına yönelik yöntemleri desteklemekte olup, g-lenfatik sistem fonksiyonunun daha iyi anlaşılması hastalığın ilerlemesinin izlenmesinde yeni bakış açıları sağlayabilir.

Keywords

• Alzheimer Hastalığı
• Beyin Perivasküler Alanı
• Difüzyon Tensör Görüntüleme
• G-lenfatik Sistem

Ethical Statement

Etik kurul onayı, Üsküdar Üniversitesi Girişimsel Olmayan Araştırmalar Etik Kurulu’ndan 61351342/MAY 2023-12 (29 Mayıs 2023) rapor numarası ile alınmıştır.

Thanks

Bu araştırmanın veri toplama ve paylaşımı, Alzheimer’s Disease Neuroimaging Initiative (ADNI) (Ulusal Sağlık Enstitüleri Hibe U01 AG024904) ve DOD ADNI (Savunma Bakanlığı ödül numarası W81XWH-12-2-0012) tarafından finanse edilmiştir. ADNI, Ulusal Yaşlanma Enstitüsü, Ulusal Biyomedikal Görüntüleme ve Biyomühendislik Enstitüsü tarafından ve aşağıdaki kuruluşların cömert katkılarıyla desteklenmektedir: AbbVie, Alzheimer Derneği; Alzheimer İlaç Keşif Vakfı; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd ve bağlı şirketi Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; ve Transition Therapeutics. Kanada’daki ADNI klinik merkezlerini desteklemek için Canadian Institutes of Health Research fon sağlamaktadır. Özel sektör katkıları, Ulusal Sağlık Enstitüleri Vakfı (www.fnih.org ) aracılığıyla kolaylaştırılmaktadır. Hibe alan kuruluş Northern California Institute for Research and Education olup, çalışma University of Southern California’daki Alzheimer’s Therapeutic Research Institute tarafından koordine edilmektedir. ADNI verileri, University of Southern California’daki Laboratory for Neuro Imaging tarafından dağıtılmaktadır. Bu çalışmanın kaynağı olan doktora tezimin hazırlanması sürecinde verdikleri değerli destek için Üsküdar Üniversitesi’ne şükranlarımı sunarım.

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