Atrophy of hippocampal subfields and amygdala nuclei in subjects with mild cognitive impairment progressing to Alzheimer's disease
Miriam Punzi,
Carlo Sestieri,
Eleonora Picerni,
Antonio Maria Chiarelli,
Caterina Padulo,
Andrea Delli Pizzi,
Maria Giulia Tullo,
Annalisa Tosoni,
Alberto Granzotto,
Stefania Della Penna,
Marco Onofrj,
Antonio Ferretti,
Stefano Delli Pizzi,
Stefano L. Sensi
Affiliations
Miriam Punzi
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Molecular Neurology Unit, Center for Advanced Studies and Technology (CAST), University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy
Carlo Sestieri
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Institute for Advanced Biomedical Technologies (ITAB), “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy
Eleonora Picerni
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy
Antonio Maria Chiarelli
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy
Caterina Padulo
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Department of Humanities, University of Naples Federico II, Naples, 80133, Italy
Andrea Delli Pizzi
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy
Maria Giulia Tullo
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy
Annalisa Tosoni
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy
Alberto Granzotto
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Molecular Neurology Unit, Center for Advanced Studies and Technology (CAST), University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy
Stefania Della Penna
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Institute for Advanced Biomedical Technologies (ITAB), “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy
Marco Onofrj
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy
Antonio Ferretti
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Institute for Advanced Biomedical Technologies (ITAB), “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; UdA-TechLab, Research Center, University “G. D’Annunzio” of Chieti-Pescara, 66100, Chieti, Italy
Stefano Delli Pizzi
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Institute for Advanced Biomedical Technologies (ITAB), “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Molecular Neurology Unit, Center for Advanced Studies and Technology (CAST), University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Corresponding author. Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy.
Stefano L. Sensi
Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Institute for Advanced Biomedical Technologies (ITAB), “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Molecular Neurology Unit, Center for Advanced Studies and Technology (CAST), University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy; Corresponding author. Department of Neuroscience, Imaging, and Clinical Sciences, University “G. D'Annunzio of Chieti-Pescara”, Chieti, 66100, Italy.
The hippocampus and amygdala are the first brain regions to show early signs of Alzheimer's Disease (AD) pathology. AD is preceded by a prodromal stage known as Mild Cognitive Impairment (MCI), a crucial crossroad in the clinical progression of the disease. The topographical development of AD has been the subject of extended investigation. However, it is still largely unknown how the transition from MCI to AD affects specific hippocampal and amygdala subregions. The present study is set to answer that question. We analyzed data from 223 subjects: 75 healthy controls, 52 individuals with MCI, and 96 AD patients obtained from the ADNI. The MCI group was further divided into two subgroups depending on whether individuals in the 48 months following the diagnosis either remained stable (N = 21) or progressed to AD (N = 31). A MANCOVA test evaluated group differences in the volume of distinct amygdala and hippocampal subregions obtained from magnetic resonance images. Subsequently, a stepwise linear discriminant analysis (LDA) determined which combination of magnetic resonance imaging parameters was most effective in predicting the conversion from MCI to AD. The predictive performance was assessed through a Receiver Operating Characteristic analysis. AD patients displayed widespread subregional atrophy. MCI individuals who progressed to AD showed selective atrophy of the hippocampal subiculum and tail compared to stable MCI individuals, who were undistinguishable from healthy controls. Converter MCI showed atrophy of the amygdala's accessory basal, central, and cortical nuclei. The LDA identified the hippocampal subiculum and the amygdala's lateral and accessory basal nuclei as significant predictors of MCI conversion to AD. The analysis returned a sensitivity value of 0.78 and a specificity value of 0.62. These findings highlight the importance of targeted assessments of distinct amygdala and hippocampus subregions to help dissect the clinical and pathophysiological development of the MCI to AD transition.
