Individual Subject Classification of Mixed Dementia from Pure Subcortical Vascular Dementia Based on Subcortical Shape Analysis

Hee Jin Kim,Chang-Hun Kim,Byoung Seok Ye,Cindy W Yoon,Jae Seung Kim,Yearn Seong Choe,Jae Hong Lee,Sang Won Seo,Hanna Cho,Young Noh,Geon Ha Kim,Duk L Na,Joon-Kyung Seong,Kyung-Han Lee,Jeonghun Kim,Michael W Weiner,Yong Fan

doi:10.1371/journal.pone.0075602

Abstract

Subcortical vascular dementia (SVaD), one of common causes of dementia, has concomitant Alzheimer's disease (AD) pathology in over 30%, termed “mixed dementia”. Identifying mixed dementia from SVaD is important because potential amyloid-targeted therapies may be effective for treatment in mixed dementia. The purpose of this study was to discriminate mixed dementia from pure SVaD using magnetic resonance imaging (MRI). We measured brain amyloid deposition using the 11C-Pittsburgh compound B positron emission tomography (PiB-PET) in 68 patients with SVaD. A PiB retention ratio greater than 1.5 was considered PiB(+). Hippocampal and amygdalar shape were used in the incremental learning method to discriminate mixed dementia from pure SVaD because these structures are known to be prominently involved by AD pathologies. Among 68 patients, 23 (33.8%) patients were positive for PiB binding. With use of hippocampal shape analysis alone, PiB(+) SVaD could be discriminated from PiB(-) SVaD with 77.9% accuracy (95.7% sensitivity and 68.9% specificity). With use of amygdalar shape, the discrimination accuracy was 75.0% (87.0% sensitivity and 68.9% specificity). When hippocampal and amygdalar shape were analyzed together, accuracy increased to 82.4% (95.7% sensitivity and 75.6% specificity). An incremental learning method using hippocampal and amygdalar shape distinguishes mixed dementia from pure SVaD. Furthermore, our results suggest that amyloid pathology and vascular pathology have different effects on the shape of the hippocampus and amygdala.

Highlights

Subcortical vascular dementia (SVaD) is one of common causes of dementia [1], and is characterized by extensive white matter hyperintensities (WMH) and multiple lacunes
Pathological studies have demonstrated that some patients who have been clinically diagnosed with SVaD have co-associated Alzheimer’s disease (AD) pathologies [2,3]
There is considerable overlap, mixed dementia and pure SVaD differ in terms of clinical phenotype and treatment

Summary

Introduction

Subcortical vascular dementia (SVaD) is one of common causes of dementia [1], and is characterized by extensive white matter hyperintensities (WMH) and multiple lacunes. Pathological studies have demonstrated that some patients who have been clinically diagnosed with SVaD have co-associated Alzheimer’s disease (AD) pathologies [2,3]. Of patients who have been clinically diagnosed with SVaD present with significant amyloid burden, indicating that these patients have mixed dementia [5]. There is considerable overlap, mixed dementia and pure SVaD differ in terms of clinical phenotype and treatment. A previous study indicated that, clinically, patients with mixed dementia were older and performed worse on memory tests than those with pure SVaD [5].

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Conclusion