Network-Based Substrate of Cognitive Reserve in Alzheimer’s Disease

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".

Evidence of Neuroplasticity Due to Acupuncture: An fNIRS Study

“…Additionally, the classi cation accuracy decreased, supporting the aforementioned hypothesis. These results indicate improvements in the patients and are in accordance with the literature [27,44].…”

Rethinking the Reserve with a Translational Approach: Novel Ideas on the Construct and the Interventions

“…Instead, CR can play a protective role during the early stages of dementia. By using the graph theory [69,70], Serra and co-workers [26] showed connectivity differences only in a-MCI patients with high or low CR, confirming the hypothesis that CR impacts on neurodegenerative processes only in the early phase of AD. More recently, this hypothesis has been confirmed also by other studies highlighting a specific disease stage for the CR action [29,104].…”

“…Very recently, by using the graph theory approach that allows a whole brain network investigation without an a-priori hypothesis [69,70], Serra and co-workers [26] showed functional connectivity changes only in a-MCI patients categorized according to their CR level.…”

“…In humans, schooling is usually considered the most relevant factor impacting on brain resilience [4,24]. Indeed, schooling may induce an increase of synaptic density in the neocortex promoting neural connectivity [25,26]. Moreover, schooling appears to be an important environmental factor to drive the engagement in further cognitively stimulating activities during the lifespan [27] and to delay the AD symptom onset [25].…”

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“…Lesser cognitive reserve such as low education has been recognized as a risk factor for AD and greater cognitive reserve indicated a protective effect for neurodegeneration [57–62]. Including blunted senses such as taste deficit, auditory and olfactory impairment chronically accumulated effects of DD may create a significant deficit of physiological cognitive reserve, worsening the aging process and amplifying the possibility of neurodegeneration, including AD.…”