Early‐onset Alzheimer’s disease is related to differential spatial patterns of tau pathology and cognitive impairment

Background Early‐onset Alzheimer’s disease (AD) dementia is characterized by a heterogeneous cognitive profile consisting of language and visuo‐spatial impairment. Spatial patterns of tau pathology measured with [18F]flortaucipir may help to explain the heterogeneity within early‐onset AD. Method Seventy‐one patients with Alzheimer’s disease dementia patients (n=28 early‐onset age=58, MMSE=22; n=43 late‐onset age=71, MMSE=23), of whom 6 patients with posterior cortical atrophy, 2 behavioral of AD (bvAD). All patients had available 130 minutes [18F]flortaucipir PET scans and extensive neuropsychological assessment. We generated parametric images and non‐displaceable binding potentials (BPnd) were extracted using receptor parametric mapping in the following brain regions; frontal, occipital, parietal, medial and lateral temporal cortex. We performed principal component analyses to reduce 12 cognitive tests into latent variables which reflect (uncorrelated) cognitive functions. ANOVA and linear regressions were performed to investigate between [18F]flortaucipir group differences and associations with cognition functions. Result Early‐onset AD dementia patients showed increased [18F]flortaucipir BPnd in occipital, parietal and frontal cortex (all p<0.001) compared to late‐onset AD. Across all AD patients, adjusted for education, sex and age, frontal [18F]flortaucipir BPnd was associated with attention (p=0.003), occipital [18F]flortaucipir BPnd with visual scanning and memory (both p=0.01), parietal [18F]flortaucipir BPnd with attention and visual scanning (p=0.002 and p=0.02 respectively). Lateral temporal [18F]flortaucipir BPnd was associated with attention (p=0.006) and medial temporal [18F]flortaucipir BPnd with memory (p=0.01). Interaction effects were found for occipital and parietal [18F]flortaucipir BPnd and visual scanning for early‐onset AD, and parietal [18F]flortaucipir BPnd and attention for late‐onset. Frontal [18F]flortaucipir BPnd was associated with visual scanning in late‐onset AD. In an exploratory analysis, we found higher [18F]flortaucipir BPnd in parieto‐occipital cortices in PCA compared early‐ and late‐onset AD (both p<0.001). Conclusion Differential spatial patterns of tau pathology were found depending on age‐of‐onset. Tau pathology may help to explain the clinical phenotype of early and late‐onset AD.