Affiliations: [a] Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy
| [b]
Department of Engineering University of Rome, “Roma Tre”, Italy
| [c] Brighton & Sussex Medical School, CISC, University of Sussex, Brighton, Falmer, UK
| [d] Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy
| [e] Stroke Unit, Department of Neuroscience, Tor Vergata Policlinic, Rome, Italy
| [f] Institute of Neurology, Catholic University, Rome, Italy
Correspondence:
[*]
Correspondence to: Dr. Marco Bozzali, Via Ardeatina 306, 00179 Rome, Italy. Tel.: +39 06 5150 1324; Fax: +39 06 5150 1213; E-mail: m.bozzali@hsantalucia.it.
Abstract: Cognitive reserve (CR) is known to modulate the clinical features of Alzheimer’s disease (AD). This concept may be critical for the development of non-pharmacological interventions able to slow down patients’ cognitive decline in the absence of disease-modifying treatments. We aimed at identifying the neurobiological substrates of CR (i.e., neural reserve) over the transition between normal aging and AD, by assessing the underlying brain networks and their topological properties. A cohort of 154 participants (n = 68 with AD, n = 61 with amnestic mild cognitive impairment (aMCI), and 25 healthy subjects) underwent resting-state functional MRI and neuropsychological testing. Within each group, participants were classified as having high or low CR, and functional connectivity measures were compared, within group, between high and low CR individuals. Network-based statistics and topological network properties derived from graph theory were explored. Connectivity differences between high and low CR were evident only for aMCI patients, with participants with high CR showing a significant increase of connectivity in a network involving mainly fronto-parietal nodes. Conversely, they showed significantly decreased connectivity in a network involving fronto-temporo-cerebellar nodes. Consistently, changes to topological measures were observed in either direction, and were associated with measures of global cognitive function. These findings support the hypothesis that CR impacts on neurodegenerative process in the early phase of AD only. In addition, they fit with the existence of a “neural reserve”, characterized by specific neural networks and their efficiency. It remains to be demonstrated whether interventions later in life can modulate this “neural reserve”.
