Clinical and neuroimaging predictors of Alzheimer’s Dementia Conversion in patients with mild cognitive impairment using 18F‐Florapronol amyloid PET by quantitative analysis over 2 years

Abstract

AbstractBackgroundPatients with mild cognitive impairment(MCI) are a clinically important group because of the increased risk for the progression to Alzheimer’s dementia(AD). Amyloid positron emission tomography(PET) was useful as a predictor for identifying AD pathology in the pre‐dementia stage. We determined the rates of conversion to AD in MCI patients based on amyloid positivity by visual and quantitative analysis over 2 years. We also investigated the clinical and neuroimaging predictors for conversion to AD.MethodIndividuals aged 50 and above with MCI according to Petersen’s criteria were eligible. Subjects underwent laboratory tests including APOE genotyping, neuropsychological tests, brain magnetic resonance imaging(MRI), and amyloid PET assessed by 18F‐FC119S. Amyloid positivity was determined in each lobe of the brain and quantitatively analyzed. The follow‐up period was at least 2 years. Cox regression analysis was performed to identify prognostic factors which are independently related to time to AD conversion.ResultWe recruited 50 patients and 39 subjects were enrolled. 5 patients dropped out at 2 years, so 34 subjects were finally included. 13 of 34(38.2%) by visual analysis and 12 of 34(35.3%) by quantitative analysis of 18F‐FC119S PET showed amyloid positive. The basic demographics were not significantly different between the groups except for Korea‐Instrumental Activities of Daily Living(K‐IADL) at baseline(p = 0.004) and 1 year(p = 0.001), Mini‐mental State Examination(MMSE) at 2 years(p = 0.047) and Global Deterioration Scale(GDS) at 2 years(p = 0.029). 4 of 13(30.8%) by visual analysis, 4 of 12(66.7%) by quantitative analysis amyloid‐positive MCI patients converted to AD. Amyloid positive in posterior cingulate was marginally significant(p = 0.066). AD conversion group had a higher Clinical Dementia Rating‐Sum of box(CDR‐SOB) at baseline(p = 0.002) compared with remained MCI group. In multivariate cox regression, CDR‐SOB at baseline, MMSE at 1 year and K‐IADL at 2 years were included.ConclusionAmyloid‐positive MCI group was more likely to progress to AD. But long‐term follow‐up was required. By quantitative analysis of 18F‐FC119S PET, amyloid deposition in posterior cingulate was highly associated with the AD conversion group. CDR‐SOB at baseline, MMSE at 1 year and K‐IADL at 2 years were considered as clinically valuable prognostic predictors of disease progression. Especially, CDR‐SOB is important as a predictive biomarker in the pre‐dementia stage.