Cognitive Reserve Modulates Brain Structure and Cortical Architecture in the Alzheimer’s Disease

Abstract

Background: Cognitive reserve (CR) explains the individual resilience to neurodegeneration. Objective: The present study investigated the effect of CR in modulating brain cortical architecture. Methods: 278 individuals [110 Alzheimer’s disease (AD), 104 amnestic mild cognitive impairment (aMCI) due to AD, 64 healthy subjects (HS)] underwent a neuropsychological evaluation and 3T-MRI. Cortical thickness (CTh) and fractal dimension (FD) were assessed. Years of formal education were used as an index of CR by which participants were divided into high and low CR (HCR and LCR). Within-group differences in cortical architecture were assessed as a function of CR. Associations between cognitive scores and cortical measures were also evaluated. Results: aMCI-HCR compared to aMCI-LCR patients showed significant decrease of CTh in the right temporal and in the left prefrontal lobe. Moreover, they showed increased FD in the right temporal and in the left temporo-parietal lobes. Patients with AD-HCR showed reduced CTh in several brain areas and reduced FD in the left temporal cortices when compared with AD-LCR subjects. HS-HCR showed a significant increase of CTh in prefrontal areas bilaterally, and in the right parieto-occipital cortices. Finally, aMCI-HCR showed significant positive associations between brain measures and memory and executive performance. Conclusion: CR modulates the cortical architecture at pre-dementia stage only. Indeed, only patients with aMCI showed both atrophy (likely due to neurodegeneration) alongside richer brain folding (likely due to reserve mechanisms) in temporo-parietal areas. This opposite trend was not observed in AD and HS. Our data confirm the existence of a limited time-window for CR modulation at the aMCI stage.

Effect of cognitive reserve on physiological measures of cognitive workload in older adults with cognitive impairments

“…The copyright holder for this preprint this version posted September 9, 2022. ; https://doi.org/10.1101/2022.09.08.22279748 doi: medRxiv preprint the left prefrontal lobe, and increased fractional dimension in the right temporal and in the left temporo-parietal lobes compared to those with lower reserve [43]. Future studies combining the spatial accuracy of MRI and the temporal dynamics of EEG may elucidate the mediating effects of cognitive reserve between localized brain compensatory activity and neural efficiency across the cognitive aging spectrum.…”

“…The higher rectified area P3 amplitudes in the central and frontal channels compared to the parietal channels support this hypothesis. However, the time window for modulation of cognitive reserve on brain reserve may be limited to individuals with MCI [43]. Higher cognitive reserve in older adults with amnestic MCI was associated with lower macromolecular tissue volume across major white tracts, whereas no such relationship was observed in individuals with AD [44].…”

“…Higher cognitive reserve in older adults with amnestic MCI was associated with lower macromolecular tissue volume across major white tracts, whereas no such relationship was observed in individuals with AD [44]. Likewise, older adults with MCI and high cognitive reserve manifested decreased cortical thickness in the right temporal and in the left prefrontal lobe, and increased fractional dimension in the right temporal and in the left temporo-parietal lobes compared to those with lower reserve [43]. Future studies combining the spatial accuracy of MRI and the temporal dynamics of EEG may elucidate the mediating effects of cognitive reserve between localized brain compensatory activity and neural efficiency across the cognitive aging spectrum.…”

Cognitive resilience/reserve: Myth or reality? A review of definitions and measurement methods

“…82 A structural MRI study reported that lower grey matter volumes in presymptomatic carriers of genetic mutations for frontotemporal dementia (FTD) were influenced by both genetic factors and CR proxies, including educational attainments. 83,84 Another study utilized voxel-based morphometry to measure regional gray matter volume at a voxel scale in MRI to evaluate the effect of formal education on the brain tissue of patients with aMCI or fully developed AD. The groups were divided into high and low levels of formal education.…”

Moderating effect of education on glymphatic function and cognitive performance in mild cognitive impairment

“…Neuroimaging researches have indicated that CR is linked to enhanced connectivity within cognitive control networks, particularly between the left frontal cortex and the dorsal attentional network in MCI ( Franzmeier et al, 2017a , b ). Additionally, it has been demonstrated that CR could modify cortical architecture and WM macromolecular volume, enhance cerebral blood flow, which may alleviate cognitive decline in MCI ( Fingerhut et al, 2022 ; Serra et al, 2022 ; Brenner et al, 2023 ; Zhou et al, 2024 ).…”