Network-Based Substrate of Cognitive Reserve in Alzheimer's Disease.
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".
Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
Laura
L
Serra
Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.|Department of Engineering University of Rome, "Roma Tre", Italy.
Matteo
M
Mancini
Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.|Brighton & Sussex Medical School, CISC, University of Sussex, Brighton, Falmer, UK.
Mara
M
Cercignani
Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
Carlotta
C
Di Domenico
Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
Barbara
B
Spanò
Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
Giovanni
G
Giulietti
Non Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.|Stroke Unit, Department of Neuroscience, Tor Vergata Policlinic, Rome, Italy.
Giacomo
G
Koch
Institute of Neurology, Catholic University, Rome, Italy.
Camillo
C
Marra
Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
Marco
M
Bozzali
D000368:Aged; D000375:Aging / Q000502:physiology / Q000523:psychology; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000503:physiopathology*; D058245:Cognitive Reserve / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D009483:Neuropsychological Tests; D012146:Rest
Alzheimer’s disease; amnestic mild cognitive impairment; brain connectivity; cognitive reserve; compensatory network; neural reserve