[P1–006]: TAU PATHOLOGY BURDEN ASSOCIATED WITH LEVEL OF COGNITIVE RESERVE IN ALZHEIMER's DISEASE

Abstract

PET studies have demonstrated that higher educated patients with Alzheimer's disease (AD) display greater levels of beta amyloid pathology than lower educated patients with equal symptom severity, supporting the concept of cognitive reserve. Whether similar associations exist for in vivo tau pathology remains elusive, although closer relations between tau-deposition and cognitive decline have been reported. Therefore, this study examined differences in tau pathology load and spread in higher versus lower educated AD patients using [¹⁸F]AV-1451-PET imaging.

24 patients with typical AD were grouped into a higher (HEAD) and lower educated (LEAD) group. The two groups were matched for age and cognition measured by the Mini Mental State Examination. Additionally, a group of 14 age-matched healthy controls was included. [¹⁸F]AV-1451-PET scans were acquired to assess cerebral tau-burden. Regional tau ratios (reference region: cerebellum) were determined in a set of regions of interest (ROIs) which were defined according to the pathological disease stages by Braak & Braak. The obtained tau ratios were then compared between the groups. Furthermore, whole brain voxel-wise comparisons were conducted using Statistical Parametric Mapping to determine differences in tau-distribution between each AD-group and the healthy controls, respectively, as well as between the two AD-groups.

The ROI analysis yielded tau pathology in regions corresponding to more advanced Braak stages exclusively in the HEAD group, whereas tau pathology in the LEAD group was still confined to lower Braak stages. These results were confirmed by voxel-wise comparisons revealing higher tau levels in dorsomedial fronto-parietal cortical areas in the HEAD group when compared to the LEAD group.

Highly educated AD patients seem to be able to tolerate more tau tangle pathology than lower educated patients with comparable cognitive impairment in support of the cognitive reserve hypothesis. These cognitive reserve-related differences in disease manifestation have crucial implications for early detection of AD, prognosis and assessment of disease progression and the monitoring of drug treatments.