Longitudinal outcomes of amyloid positive versus negative amnestic mild cognitive impairments: a three-year longitudinal study

Byoung Seok Ye,Juyoun Lee,Hee Jin Kim,Jacob W Vogel,Yeo Jin Kim,Na-Yeon Jung,Duk L Na,Jin San Lee,Sang Won Seo,Young Kyoung Jang,Jong-Min Lee,Jin-Ju Yang

doi:10.1038/s41598-018-23676-w

Abstract

We aimed to compare the longitudinal outcome of amnestic mild cognitive impairment (aMCI) patients with significant Pittsburgh Compound B uptake [PiB(+) aMCI] and those without [PiB(−) aMCI]. Cerebral β-amyloid was measured in 47 patients with aMCI using PiB-positron emission tomography (PET) (31 PiB(+) aMCI and 16 PiB(−) aMCI). Clinical (N = 47) and neuropsychological follow-up (N = 37), and follow-up with brain magnetic resonance imaging (N = 38) and PiB-PET (N = 30) were performed for three years. PiB(+) aMCI had a higher risk of progression to dementia (hazard ratio = 3.74, 95% CI = 1.21–11.58) and faster rate of cortical thinning in the bilateral precuneus and right medial and lateral temporal cortices compared to PiB(−) aMCI. Among six PiB(−) aMCI patients who had regional PiB uptake ratio >1.5 in the posterior cingulate cortex (PCC), three (50.0%) progressed to dementia, and two of them had global PiB uptake ratio >1.5 at the follow-up PiB-PET. Our findings suggest that amyloid imaging is important for predicting the prognosis of aMCI patients, and that it is necessary to pay more attention to PiB(−) aMCI with increased regional PiB uptake in the PCC.

Highlights

Cerebral β-amyloidosis is a key requirement for development of Alzheimer’s disease (AD) according to the amyloid cascade hypothesis[1,2]
Cox regression models showed that PiB(+) amnestic mild cognitive impairment (aMCI) had a higher risk of progression to dementia [hazard ratio (HR) = 3.74, 95% CI = 1.21–11.58] after controlling for age, sex, and education
All PiB(+) aMCI patients who progressed to dementia were diagnosed as probable AD, while PiB(−) aMCI patients progressed to various causes of dementia including probable AD (1), progressive supranuclear palsy syndrome (PSPS) (2) and subcortical vascular dementia (1)

Summary

Introduction

Cerebral β-amyloidosis is a key requirement for development of Alzheimer’s disease (AD) according to the amyloid cascade hypothesis[1,2]. Previous studies have shown that about 40–70% of aMCI patients showed measurable fibrillar β-amyloidosis using Pittsburgh Compound B positron emission tomography (PiB-PET)[6,7,8]. Several heterogeneous possibilities have been proposed as underlying causes for PiB-negative [PiB(−)] aMCI patients including cognitive impairment related to depression, accelerated brain aging as indicated by abnormality in vascular markers[9,10], and other pathologies such as cerebrovascular disease[3], hippocampal sclerosis[11] and argyrophilic grain disease[12]. Previous studies have shown that β-amyloidosis in aMCI is predictive of future progression to dementia[8,13,14,15]. We followed aMCI patients included in the previous cross-sectional study[9] up for three years and aimed to investigate the longitudinal outcome of β-amyloidosis in a prospectively recruited cohort of aMCI patients. We hypothesized that (1) PiB(+) aMCI patients have greater risk of progression to dementia compared to PiB(−) aMCI patients; and (2) there could be certain features predicting progression to dementia in PiB(−) aMCI patients

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Conclusion