White matter hyperintensities and patterns of atrophy in early onset Alzheimer's disease with causative gene mutations.

Abstract Objective White matter hyperintensities could be found in many degenerative dementias including Alzheimer’s disease (AD). Pathogenesis of white matter hyperintensities in AD is complicated. We aim to identify the features of white matter hyperintensities and the atrophy pattern in early onset Alzheimer’s disease with causative gene mutations. Methods 7 AD dementia patients with causative mutations were included and the clinical history, neuropsychology, neuroimaging,APOE genotype and whole-genome sequencing (WGS) were analyzed. Axial T1-weighted images and Fluid attenuated inversion recovery (FLAIR) were analyzed with visual rating scale to examine cortical atrophy and white matter hyperintensities. Results 5 female and 2 male patients with 4PSEN1, 2PSEN2 and 1APP mutation were included. The average age of onset was 46.7y/o (44–52) and the duration of disease was 28.6 months (8−60). Clinical phenotype included memory loss (100 %), visual/spatial disorder (100 %), executive dysfunction (100 %), calculation disorder (85.7 %), disorientation (85.7 %), language problem (57.1 %), personality change (28.6 %) and movement disorder (14.3 %). The grading of posterior cortex atrophy was higher than medial temporal lobe atrophy. Periventricular hyperintensities surrounding occipital and frontal horn of ventricle and sub-ventricular bands were most common, while small foci of lesions were also detected in deep white matter, sub-cortical and juxta-cortical area. Mutations carriers in the APP gene or PSEN1 gene postcodon 200 had more severe white matter hyperintensities than other mutations. Conclusion White matter hyperintensities were found in early onset AD with causative mutations. The severity was related to genotypes and spatial distributions. Axon degeneration following neuronal loss and ischemic injury might be the pathogenesis of white matter damage. Severer atrophy in the posterior cortex than medial temporal lobe can present in early onset AD.