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Measures of amyloid-β (Aβ) and phosphorylated tau (p-tau) concentrations in cerebrospinal fluid are extensively used for diagnostic and research purposes in Alzheimer's disease (AD) as correlates of cortical thinning and cognitive outcomes. The present study investigated the relationship of Aβ and p-tau with hippocampal subfield volumes Cornu Ammonis (CA) 1-4, dentate gyrus (DG), and subiculum. Subfields were segmented from T1-weighted images from the ADNI-population using FreeSurfer v6. Linear and polynomial regression models revealed distinct associations of Aβ and p-tau with subfield volumes. Aβ had a quadratic relationship with all hippocampal subfield volumes and the inflection point was higher than the validated cut-off for Aβ. For p-tau the relationships were linear, except for CA3, in which it was quadratic. For the CA1 and CA3, these quadratic relationships with Aβ were only observed when p-tau was low. Amyloid and p-tau contributed equally to the explained variance in CA4 and DG volume. Subicular volume was best explained by Aβ alone. These biomarker relationships with hippocampal subfield volumes seem to mirror the hippocampal-specific topography of Aβ and tau reported in neuropathological staging models. In addition, using continuous values of Aβ reveals positive patterns with imaging markers for individuals around the positivity threshold that would be masked when using dichotomized biomarker groups, which can be important for early detection and accurate inclusion of potential participants at risk for AD in clinical trials. [ABSTRACT FROM AUTHOR]

White matter hyperintensities are associated with an increased risk of Alzheimer's disease (AD). White matter hyperintensities are believed to disconnect brain areas. We examined the topographical association between white matter hyperintensities and cortical thickness in controls, mild cognitive impairment (MCI), and AD patients. We examined associations between white matter hyperintensities and cortical thickness among 18 older cognitively healthy participants, 18 amnestic MCI, and 17 mild AD patients. These associations were cluster-size corrected for multiple comparisons. In controls, a positive association between white matter hyperintensities and cortical thickness was found in lateral temporal gyri. In MCI patients, white matter hyperintensities were positively related to cortical thickness in frontal, temporal, and parietal areas. Positive associations between white matter hyperintensities and cortical thickness in AD patients were confined to parietal areas. The results of the interaction group by white matter hyperintensities on cortical thickness were consistent with the findings of positive associations in the parietal lobe for MCI and AD patients separately. In the frontal areas, controls and AD patients showed inverse associations between white matter hyperintensities and cortical thickness, while MCI patients still showed a positive association. These results suggest that a paradoxical relationship between white matter hyperintensities and cortical thickness could be a consequence of neuroinflammatory processes induced by AD-pathology and white matter hyperintensities. Alternatively, it might reflect a region-specific and disease-stage dependent compensatory hypertrophy in response to a compromised network. [ABSTRACT FROM AUTHOR]