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Review
. 2022 Apr 24;11(5):650.
doi: 10.3390/biology11050650.

What Does the Brain Have to Keep Working at Its Best? Resilience Mechanisms Such as Antioxidants and Brain/Cognitive Reserve for Counteracting Alzheimer's Disease Degeneration

Davide Maria Cammisuli  1 , Ferdinando Franzoni  2 , Giorgia Scarfò  2 , Jonathan Fusi  2 , Marco Gesi  3 , Ubaldo Bonuccelli  2 , Simona Daniele  4 , Claudia Martini  4 , Gianluca Castelnuovo  1   5
Affiliations
Review

What Does the Brain Have to Keep Working at Its Best? Resilience Mechanisms Such as Antioxidants and Brain/Cognitive Reserve for Counteracting Alzheimer's Disease Degeneration

Davide Maria Cammisuli et al. Biology (Basel). .

Abstract

Here we performed a narrative review highlighting the effect of brain/cognitive reserve and natural/synthetic antioxidants in exerting a neuroprotective effect against cognitive deterioration during physiological and pathological aging. Particularly, we discussed pathogenesis of Alzheimer's disease, brain and cognitive reserve as means of resilience towards deterioration, and evidence from the literature about antioxidants' role in sustaining cognitive functioning in the preclinical phase of dementia. During aging, the effects of disease-related brain changes upon cognition are reduced in individuals with higher cognitive reserve, which might lose its potential with emerging cognitive symptoms in the transitional phase over the continuum normal aging-dementia (i.e., Mild Cognitive Impairment). Starting from this assumption, MCI should represent a potential target of intervention in which antioxidants effects may contribute-in part-to counteract a more severe brain deterioration (alongside to cognitive stimulation) causing a rightward shift in the trajectory of cognitive decline, leading patients to cross the threshold for clinical dementia later.

Keywords: Alzheimer’s disease; aging; antioxidants; brain reserve; cognitive reserve; mild cognitive impairment; rehabilitation; subjective cognitive decline.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A representation of physical activity effects on brain functioning. Notes: The figure shows how aerobic, endurance and resistance physical exercise promote an upregulation of endogenous antioxidants, such as glutathione peroxidase (GHS), superoxide dismutase and catalase (CAT) and increases Brain-derived Neurotrophic Factor (BDNF) levels. This is responsible for the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) which, once separated from Keap1, translocates into the nucleus and triggers promoter sequences called ‘ARE’. Such a process leads to a balance between the cellular antioxidant defences and the formation of free radicals (ROS) in order to obtain an improvement of cerebral performance and of synaptic neuroplasticity.
Figure 2
Figure 2
Trajectory of cognitive decline and resilience mechanisms.
See this image and copyright information in PMC

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