High expression of Alzheimer’s disease‐related metabolic brain pattern is predictive of conversion to mild cognitive impairment or dementia and faster cognitive decline

Abstract

AbstractBackgroundAlzheimer’s disease‐related pattern (ADRP) is a metabolic brain biomarker of Alzheimer’s disease (AD), which was previously identified and validated. Its utility for differential diagnosis is known. Here, we aimed to explore its predictive value for conversion from cognitively normal (CN) to mild cognitive impairment (MCI), from MCI to dementia and for the rate of cognitive decline.MethodWe analysed 609 participants followed for up to 15 years and their FDG PET scans from ADNI database (CN = 133, MCI = 352, dementia due to AD = 124) and 56 participants from University Medical centre Ljubljana (MCI = 22, AD = 34). ADRP expression was calculated from pre‐processed FDG PET scans. CN and MCI participants were stratified according to their conversion status and cerebrospinal fluid biomarkers. Amyloid positivity (A+) was defined as Aß42 < 880 pg/mL and tau positivity (T+) as pTau > 21.8 pg/mL. AD patients were stratified into slow (< 2 points/per year decline on mini mental state examination (MMSE)) and fast (> 2 points/per year decline on MMSE) progressors.ResultA+T+ cCN had higher baseline ADRP expression than A–T– (p<0.001), A+T– (p = 0.003) and A+T+ (p = 0.01) stable CN corrected for age, while the groups did not differ in gender, education or baseline MMSE scores. A+T+ cMCI had higher baseline ADRP expression than A–T– (p<0.001), A+T– (p = 0.001) and A+T+ (p<0.001) stable MCI, corrected for baseline age and MMSE. A+T– stable MCI had higher baseline ADRP expression than A–T– stable MCI (p = 0.02). ADRP was a predictor of conversion to dementia in survival analysis (HR = 4.5[2.4‐8.7]). Similarly, in the UMCL dataset A+T+ cMCI had higher baseline ADRP expression than A–T– stable MCI (p = 0.03). Fast progressing AD patients had higher baseline ADRP expression than slowly progressing AD patients (p<0.001). Similarly, in the UMCL dataset fast progressing AD patients had higher baseline ADRP expression than slowly progressing AD patients (p = 0.02). In neither dataset, AD groups differed in age, sex or baseline MMSE scores.ConclusionADRP expression levels can be used to predict conversion from CN to MCI and from MCI to dementia in A+T+ individuals. AD patients with high ADRP expression are at an elevated risk for faster progression of cognitive decline.