Association of Superficial White Matter Alterations with Cerebrospinal Fluid Biomarkers and Cognitive Decline in Neurodegenerative Dementia

Background: Superficial white matter (SWM) alterations correlated with cognitive decline have been described in Alzheimer's disease (AD). Objective: The study aims to extend the investigation of theSWMalterations toADand non-AD neurodegenerative dementia (ND) and explore the relationship with cerebrospinal fluid (CSF) biomarkers and clinical data. Methods: From a database of 323 suspected dementia cases, we retrospectively recruited 55 ND with abnormal amyloid-beta 42 (AD) and 38 ND with normal amyloid-beta 42 (non-AD) and collected clinical data, CSF biomarkers, and magnetic resonance images. Ten healthy controls (HC) were recruited for imaging and Mini-Mental State Examination (MMSE). Diffusion tensor imaging (DTI) measurements were performed in the lobar SWM regions and Kruskal Wallis tests were used for among-group comparison. Spearman's correlation tests were performed between DTI measures, CSF biomarkers, and clinical data. Results: AD and non-AD showed significant differences in the DTI measures across the SWM compared to HC. Significant differences between AD and non-AD were detected in the left parietal lobe. DTI measures correlated with amyloid-beta 42 and MMSE diffusely in the SWM, less extensively with total-tau and phosphorylated tau, and with disease duration in the parietal lobe bilaterally. Conclusion: Widespread SWM alterations occur in both AD and non-AD ND and AD shows appreciably more severe alterations in the parietal SWM. Notably, the alterations in the SWM are strongly linked not only to the cognitive decline but also to the diagnostic CSF biomarkers. Further studies are encouraged to evaluate the DTI measures in the SWM as in vivo non-invasive biomarkers in the preclinical phase.