Journal Article

Risk factors and clinical significance of neurodegenerative co-pathologies in symptomatic cerebral small vessel disease

Müller, Patrick, Vielhaber, Stefan, Braun-Dullaeus, Rüdiger C., Neumann, Katja, Bernal, Jose, John, Anna-Charlotte, Arndt, Philipp, Perosa, Valentina, Jansen, Robin, Garz, Cornelia, Meuth, Sven G., Henneicke, Solveig, Nelke, Christopher, Schreiber, Stefanie, Pfister, Malte, Gliem, Michael, Mattern, Hendrik, Dörner, Marc, Kokott, Alma

2025

Overview

Background Cerebral small vessel disease (CSVD) often coexists with neurodegenerative pathologies, yet their role remains underexplored. This study aims to determine their prevalence, risk factors, and cognitive effects in patients with deep perforator arteriopathy (DPA) or cerebral amyloid angiopathy (CAA) using the biomarker-based ATN classification. Methods In this cross-sectional study 186 patients (median age 75 years, 41% females, 111 with probable CAA, 75 with DPA) underwent MRI for analysis of CSVD severity and etiology, and lumbar puncture for analysis of cerebrospinal fluid amyloid-β 42/40 ratio, phosphorylated-tau, total-tau and neurofilament light. ATN profiles were related to clinical characteristics, MRI markers and cognitive performance in multivariate regression models. Results Among CSVD patients, 30% had normal biomarkers (A-T-N-), 33% were within the AD pathology continuum (A + T ± N ± : 47% in CAA vs. 13% in DPA, p < .001), and 37% showed non-AD pathological changes (A-T ± N + : 53% in DPA vs. 25% in CAA, p < .001). The AD pathology continuum was associated with a severe lobar hemorrhagic phenotype and cognitive impairment, while non-AD pathological change was related to CSVD severity, history of stroke and similarly cognitive impairment. Both pathological ATN profiles were further related to lower MMSE scores (A + T ± N ± : B = − 3.3, p = .006; A-T ± N + : B = − 2.7, p = .021). Conclusions Using biomarkers, this study confirms in vivo that CSVD frequently co-occurs with neurodegenerative pathologies, exerting detrimental effects on cognitive health.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Aged / Aged, 80 and over / Alzheimer's disease / Amyloid beta-Peptides - cerebrospinal fluid / Biomarkers / Biomarkers - cerebrospinal fluid / Cerebral amyloid angiopathy / Cerebral Amyloid Angiopathy - cerebrospinal fluid / Cerebral Amyloid Angiopathy - complications / Cerebral Amyloid Angiopathy - diagnostic imaging / Cerebral Amyloid Angiopathy - epidemiology / Cerebral Amyloid Angiopathy - pathology / Cerebral Small Vessel Diseases - cerebrospinal fluid / Cerebral Small Vessel Diseases - complications / Cerebral Small Vessel Diseases - diagnostic imaging / Cerebral Small Vessel Diseases - epidemiology / Cerebral Small Vessel Diseases - pathology / Cerebrospinal fluid / Clinical Relevance / Cognitive ability / Cognitive Dysfunction - epidemiology / Cross-Sectional Studies / Female / Health risks / Humans / Magnetic Resonance Imaging / Male / Medicine / Medicine & Public Health / Middle Aged / Neurodegenerative Diseases - cerebrospinal fluid / Neurodegenerative Diseases - epidemiology / Neurodegenerative Diseases - pathology / Neurofilament Proteins - cerebrospinal fluid / Neurology / Neuroradiology / Neurosciences / Original Communication / Pathology / Phenotypes / Regression analysis / Risk Factors / Tau protein / tau Proteins - cerebrospinal fluid / Vascular diseases / β-Amyloid