Heterogeneity in mild cognitive impairment: Differences in neuropsychological profile and associated white matter lesion pathology

This study examined whether distinct neuropsychological profiles could be delineated in a sample with Mild Cognitive Impairment (MCI) and whether white matter lesion (WML) burden contributed to MCI group differences. A heterogeneous, clinical sample of 70 older adults diagnosed with MCI was assessed using cognitive scores, and WML was quantified using a semi-automated, volumetric approach on T₂- weighted fluid-attenuated inversion recovery (FLAIR) images. Using cluster and discriminant analyses, three distinct groups (Memory/ Language, Executive/Processing Speed, and Pure Memory) were empirically derived based on cognitive scores. Results also showed a dose dependent relationship of WML burden to MCI subgroup, with the Executive/ Processing Speed subgroup demonstrating significantly higher levels of WML pathology when compared to the other subgroups. In addition, there was a dissociation of lesion type by the two most impaired subgroups (Memory/Language and Executive/Processing Speed) such that the Memory/ Language subgroup showed higher periventricular lesion (PVL) and lower deep white matter lesion (DWML) volumes, whereas the Executive/ Processing Speed demonstrated higher DWML and lower PVL volumes. Results demonstrate that distinct MCI subgroups can be empirically derived and reliably differentiated from a heterogeneous MCI sample, and that these profiles differ according to WML burden. Overall, findings suggest different underlying pathologies within MCI and contribute to our understanding of MCI subtypes.