Abstract
Alzheimer’s disease (AD) is the most common form of dementia, with no means of cure or prevention. The presence of abnormal disease-related proteins in the population is, in turn, much more common than the incidence of dementia. In this context, the cognitive reserve (CR) hypothesis has been proposed to explain the discontinuity between pathophysiological and clinical expression of AD, suggesting that CR mitigates the effects of pathology on clinical expression and cognition. fMRI studies of the human connectome have recently reported that AD patients present diminished functional efficiency in resting-state networks, leading to a loss in information flow and cognitive processing. No study has investigated, however, whether CR modifies the effects of the pathology in functional network efficiency in AD patients. We analyzed the relationship between CR, pathophysiology and network efficiency, and whether CR modifies the relationship between them. Fourteen mild AD, 28 amnestic mild cognitive impairment (aMCI) due to AD, and 28 controls were enrolled. We used education to measure CR, cerebrospinal fluid (CSF) biomarkers to evaluate pathophysiology, and graph metrics to measure network efficiency. We found no relationship between CR and CSF biomarkers; CR was related to higher network efficiency in all groups; and abnormal levels of CSF protein biomarkers were related to more efficient networks in the AD group. Education modified the effects of tau-related pathology in the aMCI and mild AD groups. Although higher CR might not protect individuals from developing AD pathophysiology, AD patients with higher CR are better able to cope with the effects of pathology—presenting more efficient networks despite pathology burden. The present study highlights that interventions focusing on cognitive stimulation might be useful to slow age-related cognitive decline or dementia and lengthen healthy aging.
Highlights
In 2014, the movie ‘‘Still Alice,’’ interpreted by the actress Julianne Moore, brought to the public the dramatic experience of someone living with Alzheimer’s disease (AD), the most common form of dementia worldwide
Controls were younger than AD patients (p = 0.009), and this variable was included as a confounding factor throughout the analysis
An interaction term between cerebrospinal fluid (CSF) proteins and education was added to the models, and when significant, the interaction term indicated an interplay between pathophysiological level and cognitive reserve (CR) on network topology
Summary
In 2014, the movie ‘‘Still Alice,’’ interpreted by the actress Julianne Moore, brought to the public the dramatic experience of someone living with Alzheimer’s disease (AD), the most common form of dementia worldwide (and yet with no means of cure or even prevention). Studies involving fMRI analysis (Solé-Padullés et al, 2009; Bosch et al, 2010; ArenazaUrquijo et al, 2013a; Bozzali et al, 2015; Marques et al, 2015; Serra et al, 2017), in turn, found that healthy elders, mild cognitive impairment (MCI) and AD patients with higher CR present more activation/connectivity in brain regions than the individuals with lower CR These interesting results have shed some light onto the issue, proposing that the healthy elderly with higher education level present increased brain efficiency, while AD patients are able to recruit compensatory mechanisms to maintain cognitive function. Because of the lack of pathophysiological data for the subjects, these results only support the CR hypothesis, and preclude any further assumptions on it
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