Cortical Tau Aggregation Patterns Associated With Apraxia in Patients With Alzheimer Disease

Apraxia is a frequently observed symptom in Alzheimer disease (AD), but the causal pathomechanism underlying this dysfunction is not well understood. Previous studies have demonstrated associations between various cognitive dysfunctions in AD and cortical tau deposition in specific brain areas, suggesting a causal relationship. Thus, we hypothesized that specific regional patterns of tau pathology in praxis-related brain regions may be associated with apraxic deficits in AD. For this purpose, we performed PET imaging with the second-generation tau-PET tracer [18F]PI-2620 in a well-defined group of patients with AD (N = 33) who had been systematically assessed for apraxia.

Patients with a biomarker-confirmed diagnosis of AD were recruited in addition to a sample of cognitively unimpaired (CU₁) control participants. Both groups underwent apraxia assessments with the Dementia Apraxia Screening Test. In addition, PET imaging with [18F]PI-2620 was performed to assess tau pathology in the patients with AD. To specifically investigate the association of apraxia severity with regional tau pathology, we compared the PET data from this group with an independent sample of amyloid-negative cognitively intact participants (CU₂) by generation of z-score deviation maps and submitted these maps to a voxel-based multiple regression analysis.

A total of 120 participants (39% female) with a mean age of 67.9 (9.2) years were included in the study (AD = 33; CU₁; N = 33; CU₂; N = 54). We identified a significant correlation between circumscribed clusters of tau aggregation in praxis-related brain regions (including parietal (angular gyrus), temporal, and occipital regions) and severity of apraxia in patients with AD. By contrast, no significant correlations between tau tracer uptake in primary motor cortex or subcortical brain regions and apraxia were observed.

These results suggest that tau deposition in specific cortical praxis-related brain regions may induce local neuronal dysfunction leading to a dose-dependent functional decline in praxis performance in AD. The awareness of this relationship could further refine a differentiated individual diagnostic characterization and classification of patients with AD.