Biomarker‐based stability in limbic‐predominant amnestic mild cognitive impairment. (10th December 2020) - Tondo, Giacomo
Abstract: Background: The amnestic presentation of mild cognitive impairment (aMCI) represents the most common prodromal stage of Alzheimer's disease (AD) dementia. There is, however, some evidence of aMCI with typical amnestic syndrome but showing long‐term clinical stability. The ability to predict stability or progression to dementia in the aMCI condition is important, particularly for the selection of candidates in clinical trials. We aimed to establish the role of in vivo biomarkers, as assessed by cerebrospinal fluid (CSF) measures and [ 18 F]fluorodeoxyglucose (FDG)‐positron emission tomography (PET) imaging, in predicting prognosis in a large aMCI cohort. Methods: We conducted a retrospective study, including 142 aMCI subjects who had a long follow‐up (4–19 years), baseline CSF data and [ 18 F]FDG‐PET scans individually assessed by validated voxel‐based procedures, classifying subjects into either limbic‐predominant or AD‐like hypometabolism patterns. Results: The two aMCI cohorts were clinically comparable at baseline. At follow‐up, the aMCI group with a limbic‐predominant [ 18 F]FDG‐PET pattern showed clinical stability over a very long follow‐up (8.20 ± 3.30 years), no decline in Mini‐Mental State Examination score, and only 7% conversion to dementia. Conversely, the aMCI group with an AD‐like [ 18 F]FDG‐PET pattern had a high rate of dementia progression (86%) over a shorter follow‐up (6.47 ± 2.07 years). Individual [ 18 F]FDG‐PET hypometabolism patterns predicted stability or conversion with high accuracy (area under the curve = 0.89), sensitivity (0.90) and specificity (0.89). In the limbic‐predominant aMCI cohort, CSF biomarkers showed large variability and no prognostic value. Conclusions: In a large series of clinically comparable subjects with aMCI at baseline, the specific [ 18 F]FDG‐PET limbic‐predominant hypometabolism pattern was associated with clinical stability, making progression to AD very unlikely. The identification of a biomarker‐based benign course in aMCI subjects has important implications for prognosis and in planning clinical trials. Abstract : This biomarker‐based study assessed the clinical outcome with a long follow‐up in a large population of amnestic mild cognitive impairment with baseline CSF and [ 18 F]FDG‐PET evaluations. The single‐subject [ 18 F]FDG‐PET analysis classified subjects either in the limbic‐predominant or in the Alzheimer's disease hypometabolism patterns. At follow‐up, the group with limbic‐predominant hypometabolism showed clinical stability and only 7% conversion to dementia, while the group with Alzheimer's disease hypometabolism pattern presented with a high rate of dementia progression (86%). CSF measures did not predict stability in the limbic‐predominant group. Thus the specific [ 18 F]FDG‐PET limbic‐predominant hypometabolism pattern predicts clinical stability in aMCI subjects, representing a biomarker of benign course with important implications for prognosis and planning clinical trials.