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␤ positive MCI cases from A␤ negative controls. In contrast, DTI parameters reached only random level accuracy for the discrimination between A␤ positive SCD and control cases from A␤ negative controls. These findings suggest that in prodromal stages of AD, such as in A␤ 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␤ positive SCD and control cases.

Figure 2. Proportion of subjects in each category (normal vs abnormal) at each EBM stage. Proportion of negative scans in dark blue and positive scans in green. Each EBM stage on the x-axis corresponds to the occurrence of a new regional transition event. Stage 0 corresponds to no events having occurred and stage 20 is when all events have occurred. Events are ordered by the maximum likelihood event sequence for the whole population as shown in Figure 1.

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