Identifying a subtype of Alzheimer\u2019s disease characterised by predominant right focal cortical atrophy

Ko Woon Kim,Sang Won Seo,Soo Hyun Cho,Hee Jin Kim,Hyunjin Jo,Duk L Na,Seongbeom Park,Hyemin Jang,Yeshin Kim,Seung Joo Kim

doi:10.1038/s41598-020-64180-4

Abstract

We aimed to identify an Alzheimer’s disease (AD) subtype with right predominant focal atrophy. We recruited 17 amyloid PET positive logopenic variant primary progressive aphasia (lvPPA) and 226 amyloid PET positive AD patients. To identify AD with right focal atrophy (Rt-AD), we selected cortical areas that showed more atrophy in lvPPA than in AD and calculated an asymmetry index (AI) for this area in each individual. Using a receiver operating characteristic curve, we found that the optimal AI cut-off to discriminate lvPPA from AD was −3.1 (mean AI – 1.00 standard deviation) (sensitivity 88.2, specificity 89.8). We identified 32 Rt-AD patients whose AI was above mean AI + 1.00 standard deviation, 38 Lt-AD patients whose AI was lower than mean AI − 1.00 standard deviation, and 173 Symmetric-AD patients whose AI was within mean AI ± 1.00 standard deviation. We characterized clinical and cognitive profiles of Rt-AD patients by comparing with those of Lt-AD and Symmetric-AD patients. Compared to Symmetric-AD patients, Rt-AD patients had asymmetric focal atrophy in the right temporoparietal area and showed poor performance on visuospatial function testing (p = 0.009). Our findings suggested that there is an AD variant characterized by right focal atrophy and visuospatial dysfunction.

Highlights

Alzheimer’s disease (AD) patients typically have bilaterally symmetric atrophy in the temporoparietal area and present with memory impairment[1]
After we defined Rt-AD based on the asymmetry index (AI) of the superior temporal area, we evaluated the overall atrophy pattern of Rt-AD patients
The Rt-AD group had significant cortical thinning in the right temporoparietal area compared to Sym-AD patients (Fig. 1) (p < 1.0E-7, false discovery rate (FDR) corrected)

Summary

Introduction

Alzheimer’s disease (AD) patients typically have bilaterally symmetric atrophy in the temporoparietal area and present with memory impairment[1]. Three atypical AD variants are characterized by progressive focal atrophy in the anterior, posterior, and left cortex with symptoms matched to the affected area. Previous studies have suggested that an additional AD subtype with asymmetric atrophy on the right hemisphere might exist[5,6,7,8]. To identify an AD variant with right focal atrophy we used an anatomical approach because these patients may not be recognized by clinical phenotype alone. We assumed that the cortical atrophy pattern of this particular subtype would mirror the atrophy pattern of lvPPA, which has asymmetric atrophy in the left temporoparietal area[11]. We investigated whether an AD variant with right focal atrophy had clinical symptoms matched to the affected area

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Conclusion