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The following is a summary of “Risk factors and clinical significance of neurodegenerative co-pathologies in symptomatic cerebral small vessel disease,” published in the April 2025 issue of Journal of Neurology by Arndt et al. 

Cerebral small vessel disease (CSVD) often coexists with neurodegenerative pathologies, but their role in cognitive decline is unclear. 

Researchers conducted a retrospective study to assess the prevalence, risk factors, and cognitive effects of neurodegenerative pathologies in patients with deep perforator arteriopathy (DPA) or cerebral amyloid angiopathy (CAA) using the ATN classification. 

They conducted a cross-sectional study with 186 patients (median age 75 years, 41% females), including 111 with probable CAA and 75 with DPA. MRI analysis of CSVD severity and etiology, along with lumbar puncture for cerebrospinal fluid analysis (amyloid-β 42/40 ratio, phosphorylated-tau, total-tau, and neurofilament light), was performed. ATN profiles were correlated with clinical characteristics, MRI markers, and cognitive performance using multivariate regression models. 

The results showed 30% of patients with CSVD 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). AD pathology was linked to a severe lobar hemorrhagic phenotype and cognitive impairment, while non-AD changes were associated with CSVD severity, stroke history, and cognitive impairment. Both profiles were related to lower MMSE scores (A + T ± N ± : B = − 3.3, P = .006; A-T ± N + : B = − 2.7, P = .021). 

Investigators confirmed in vivo that CSVD frequently co-occurred with neurodegenerative pathologies. These co-occurrences exerted detrimental effects on cognitive health. 

Source: link.springer.com/article/10.1007/s00415-025-13087-z