A multivariate MRI model of Alzheimer’s disease risk is associated with clinical diagnosis, PET imaging, and plasma biomarkers in a mixed dementia sample

Abstract

AbstractBackgroundWe sought to validate two structural MRI‐based brain health models: Spatial Pattern of Atrophy for REcognition of Alzheimer’s disease (SPARE‐AD) and SPARE‐Brain Age Gap (SPARE‐BAG), which estimates the discrepancy between biological brain age and chronological age. These models' generalization to non‐amnestic AD (naAD) syndromes and associations with positron emission tomography (PET) and plasma biomarkers remain underinvestigated. We hypothesized that SPARE‐AD scores in naAD would be lower (less abnormal) than in amnestic AD (aAD) but elevated (more abnormal) relative to controls; and that SPARE‐AD but not SPARE‐BAG scores would be associated with PET and plasma biomarkers of AD.MethodSPARE‐AD and SPARE‐BAG scores were estimated for each of 1607 MRI scans from 277 cognitively normal adults (62.8% female; mean age = 69.5 years) and 902 clinical participants (54.2% female; mean age = 73.1 years), including 585 with amnestic mild cognitive impairment (aMCI) or aAD; 56 with naAD syndromes; 28 with vascular disease; 28 with Lewy body disorders (LBD); 18 with suspected frontotemporal lobar degeneration (FTLD); 56 with non‐amnestic MCI of uncertain etiology; and 131 with other clinical diagnoses. We used mixed effects models adjusting for age, sex, and global cognition to test group differences in SPARE‐AD and SPARE‐BAG. Additionally, we assessed associations with tau (n = 122) and amyloid‐beta (n = 199) PET imaging and plasma‐based phosphorylated tau‐181 (p‐tau181) and glial fibrillary acidic protein (GFAP) (n = 358).ResultSPARE‐AD scores were elevated vs. controls in aMCI/aAD, naAD, vascular disease, FTLD, and naMCI (all p<0.003) but not in LBD or other diagnoses (p>0.1). NaAD patients had lower SPARE‐AD (p<0.02) but higher SPARE‐BAG scores (p<0.02) than aMCI/aAD patients. SPARE‐AD scores were positively associated with mean cortical tau PET uptake, amyloid PET positivity, and plasma p‐tau181 and GFAP (all p<0.001). In contrast, SPARE‐BAG scores were not associated with PET or plasma biomarkers (all p>0.05).ConclusionSPARE‐AD values for naAD syndromes were intermediate between those of controls and aMCI/AD patients, likely reflecting divergent, partially overlapping cortical atrophy relative to aAD. PET and plasma biomarkers of AD neuropathologic change were associated with SPARE‐AD but not with SPARE‐BAG scores, suggesting SPARE‐BAG reflects age‐related atrophy that is largely independent of AD.