White matter hyperintensities in the corpus callosum are associated with beta‐amyloid, neurodegeneration and cognitive performance.

Background: WMH in the corpus callosum (CC), as previously related to AD pathology(1) and lower cognition in AD patients(2), are suggested to play an important role in AD. The Aim of this study was to substantiate the associations between WMH location, biomarkers of AD pathophysiology, and cognitive performance in the DELCODE study. Method: 429 participants were included (HC: 126, SCD: 165, MCI: 87, AD: 51). WMH volumes were segmented from FLAIR images. WMH volumes were adjusted for total intracranial volume and log‐transformed. Beta‐Amyloid and total Tau (Aß42 and tTau, measured in CSF) and neurodegeneration (ND, measured by hippocampal volume) were log‐transformed and used as surrogate markers for AD pathophysiology. Cognitive performance was assessed by a global cognitive composite. Path modelling, adjusted for age, sex and education, was performed to estimate direct and indirect associations between regional WMH volumes (in the CC splenium, body, genu and the frontal lobe as possible control region), AD biomarkers and cognition. Results: The correlation matrix (Figure 1) showed the highest correlation of Aß42 and tTau with WMH volume the splenium CC. Greater WMH volume in the splenium CC was directly associated with lower global cognition (Figure 2a, ß = ‐0.10, p = 0.01) and indirectly through Aß42 (ß = ‐0.10, p = 0.001) and ND (Figure 2b, ß = ‐0.05, p = 0.001). The same indirect association was statistically significant regarding tTau (ß = ‐0.03, p < 0.001). Model outcomes were similar for the body and genu of the CC. For frontal WMH volume, the direct association with global cognition was not statistically significant (ß = ‐0.002, p = 0.96), only through indirect associations with Aß42 (ß = ‐0.05, p = 0.003) and ND (ß = ‐0.02, p = 0.05). Conclusion: WMH in the CC are associated with lower cognitive performance through direct and indirect associations with Aß42 and neurodegeneration. Similar associations were seen for frontal WMH. However, a direct association between frontal WMH volume and cognition was not noticed, when considering AD biomarkers. Our study substantiates the clinical relevance and impact of WMH in the CC, in particular the splenium, in AD. 1)Gaubert et al.,2021 2)Garnier‐Crussard et al.,2021 [ABSTRACT FROM AUTHOR]