Clinical and biological underpinnings of longitudinal atrophy pattern progression in Alzheimer's disease
Pilar M. Ferraro, Laura Filippi, Marta Ponzano, Alessio Signori, Beatrice Orso, Federico Massa, Dario Arnaldi, Stefano Caneva, Lucia Argenti, Mattia Losa, Lorenzo Lombardo, Pietro Mattioli, Mauro Costagli, Lorenzo Gualco, Martina Pulze, Domenico Plantone, Andrea Brugnolo, Nicola Girtler, Andrea Diociasi, Sara Garbarino, Flavio Villani, Maria Pia Sormani, Antonio Uccelli, Luca Roccatagliata, Matteo Pardini,Background
Magnetic resonance imaging (MRI) has recently enabled to identify four distinct Alzheimer's disease (AD) subtypes: hippocampal sparing (HpSp), typical AD (tAD), limbic predominant (Lp), and minimal atrophy (MinAtr). To date, however, the natural history of these subtypes, especially regarding the presence of subjects switching to other MRI patterns and their clinical and biological differences, remains poorly understood.
Objective
To investigate the clinical and biological underpinnings of longitudinal atrophy pattern progression in AD.
Methods
251 AD patients (16 with significant memory concern, 66 with early mild cognitive impairment (MCI), 125 with late MCI, and 44 with AD dementia) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were assigned to their baseline MRI atrophy subtype using Freesurfer-derived cortical:hippocampal volumes ratio. Switching to other MRI patterns was investigated on longitudinal scans, and patients were accordingly classified as “ switching” and “ stable”. Logistic regression models were applied to identify predictors of switching to other MRI patterns.
Results
40% of Lp, 26% of HpSp, and 35% of MinAtr cases switched to other MRI patterns, with tAD representing the destination subtype of all switching HpSp and Lp, and the majority of MinAtr. At baseline significant clinical, cognitive and biomarkers differences were observed across the four subtypes. Only clinical and cognitive variables, however, were significantly associated with switch to other MRI patterns.
Conclusions
Our results suggest convergent directions of disease progression across atypical and typical AD forms, at least in a subset of AD subjects, and highlight the importance of deep-phenotyping approaches to understand AD heterogeneity.