Multicenter Tract-Based Analysis of Microstructural Lesions within the Alzheimer's Disease Spectrum: Association with Amyloid Pathology and Diagnostic Usefulness

摘要

Diffusion changes as determined by diffusion tensor imaging are potential indicators of microstructural lesions in people with mild cognitive impairment (MCI), prodromal Alzheimer's disease (AD), and AD dementia. Here we extended the scope of analysis toward subjective cognitive complaints as a pre-MCI at risk stage of AD. In a cohort of 271 participants of the prospective DELCODE study, including 93 healthy controls and 98 subjective cognitive decline (SCD), 45 MCI, and 35 AD dementia cases, we found reductions of fiber tract integrity in limbic and association fiber tracts in MCI and AD dementia compared with controls in a tract-based analysis (p < 0.05, family wise error corrected). In contrast, people with SCD showed spatially restricted white matter alterations only for the mode of anisotropy and only at an uncorrected level of significance. DTI parameters yielded a high cross-validated diagnostic accuracy of almost 80% for the clinical diagnosis of MCI and the discrimination of A beta positive MCI cases from A beta negative controls. In contrast, DTI parameters reached only random level accuracy for the discrimination between A beta positive SCD and control cases from A beta negative controls. These findings suggest that in prodromal stages of AD, such as in A beta positive MCI, multicenter DTI with prospectively harmonized acquisition parameters yields diagnostic accuracy meeting the criteria for a useful biomarker. In contrast, automated tractbased analysis of DTI parameters is not useful for the identification of preclinical AD, including A beta positive SCD and control cases.