White matter hyperintensities in the splenium of the corpus callosum predict cognitive decline in memory clinic outpatients

AbstractBackgroundWhite matter hyperintensities (WMH) are very frequent in ageing and related to worse cognition. Recent studies suggest that WMH in the corpus callosum (CC) are particularly relevant in neurocognitive disorders, as they are strongly associated with lower cognitive performance, as well as amyloid and neurodegeneration biomarkers. This study examined whether WMH in subregions of the CC (genu, body, splenium) affect cross‐sectional and long‐term longitudinal (up to 5 years) cognitive performance in patients recruited from a memory clinic.MethodThis study included memory clinic outpatients from the MEMORA cohort who had a brain MRI (T1 and FLAIR scans) within 6 months of the baseline visit. QyScore® software was used for the automatic segmentation of WMH in the CC and hippocampal volumes (HP). The cross‐sectional and longitudinal relationships between regional WMH in the CC and cognitive performance, as measured with the mini‐mental state examination (MMSE), were assessed using multivariable linear regressions and mixed models.ResultAmong 236 patients included (mean age 76.2±8.8 years old; mean MMSE 23.6±4.9), 111 were diagnosed with probable Alzheimer’s disease (AD), 20 with vascular cognitive impairment (VCI), 22 with mixed AD‐VCI, 18 with another neurological disease and 65 with a subjective cognitive complaint. Cross‐sectional analyses disclosed that higher WMH in the splenium of the CC were associated with reduced MMSE (p=0.03, n=199) after adjustment for diagnosis and education. The relationship did not remain significant after adjustment for HP and total WMH. Longitudinal analyses with a follow‐up up to 5 years showed that the MMSE declined faster in patients with higher WMH in the splenium of the CC (p<0.001, n=143) after adjustment for education, diagnosis, HP and total WMH (Figure). WMH in the genu and in the body of the CC were not associated with MMSE decline (respectively p=0.92 and p=0.23, n=124, Figure).ConclusionWMH in the splenium of the CC were associated with cognitive decline, whereas WMH in the genu and the body were not. This study highlights the clinical relevance of posterior CC WMH in a memory clinic population.