Cognitive reserve impacts on inter-individual variability in resting-state cerebral metabolism in normal aging

Abstract

There is a great deal of heterogeneity in the impact of aging on cognition and cerebral functioning. One potential factor contributing to individual differences among the elders is the cognitive reserve, which designates the partial protection from the deleterious effects of aging that lifetime experience provides. Neuroimaging studies examining task-related activation in elderly people suggested that cognitive reserve takes the form of more efficient use of brain networks and/or greater ability to recruit alternative networks to compensate for age-related cerebral changes. In this multicentre study, we examined the relationships between cognitive reserve, as measured by education and verbal intelligence, and cerebral metabolism at rest (FDG-PET) in a sample of 74 healthy older participants. Higher degree of education and verbal intelligence was associated with less metabolic activity in the right posterior temporoparietal cortex and the left anterior intraparietal sulcus. Functional connectivity analyses of resting-state fMRI images in a subset of 41 participants indicated that these regions belong to the default mode network and the dorsal attention network respectively. Lower metabolism in the temporoparietal cortex was also associated with better memory abilities. The findings provide evidence for an inverse relationship between cognitive reserve and resting-state activity in key regions of two functional networks respectively involved in internal mentation and goaldirected attention.Liège, the 11 th of June 2012Ref. Dear Pr. Lustig, Please find attached the revision of our manuscript entitled "Cognitive reserve impacts on interindividual variability in resting-state cerebral metabolism in normal aging" that we submit for publication in NeuroImage.We thank you for giving us the opportunity to revise our manuscript. We are also grateful to the Reviewers for their useful suggestions that have all been taken into account in this revised version. Changes to the text appear in bold in the manuscript. Highlights-Variability in cerebral metabolism is related to cognitive reserve in older people.-The correlated regions were part of the default mode and dorsal attention networks.-Higher cognitive reserve might refer to optimized resting-state brain functioning. Response to Reviews Dear Pr. Lustig, dear Reviewers, We thank you for giving us the opportunity to revise our manuscript. We are also grateful to the Reviewers for their useful suggestions that have all been taken into account in this revised version. Changes to the text appear in bold in the manuscript. Please find below detailed answers to each comment.Reviewer #11. Reviewer 1 underlines the lack of clarity of the introduction with respect to the meaning of cerebral differences associated with cognitive reserve. We agree that decreased metabolic activity is not necessarily a positive outcome and that increased and decreased fMRI activity in aging may refer to beneficial or detrimental mechanisms depending on how this correlates with performance. ...

Metabolic and structural connectivity within the default mode network relates to working memory performance in young healthy adults

“…Yet, additional analyses with vocabulary as proxy of verbal intelligence (Baddeley et al, 1993;Bastin et al, 2012) did not reveal any significant relationships (data not shown). Finally, we cannot exclude that the differences in data acquisition protocols between two centers have influenced our PET findings.…”

Relationships between years of education and gray matter volume, metabolism and functional connectivity in healthy elders

“…This is important yet to highlight the relative contribution of education to cognitive and brain reserve as well as to provide a further understanding of the role of this factor in healthy brain aging. In a previous study, we failed to evidence positive relationships between a reserve proxy (combining verbal intelligence and education) and FDG-PET or resting state functional connectivity while inverse relationships were found (Bastin et al, 2012). We hypothesize that the selection of a 6 population of healthy elders based on strict criteria including amyloid imaging to exclude preclinical Alzheimer"s disease cases would allow highlighting positive relationships.…”

“…Thirty-nine right-handed healthy elders (mean age (±SD): 67.14 (±5.45), range 60-80; mean MMSE (±SD): 29.33 (±0.96), range 27-30; 24 women) were recruited after detailed clinical and neuropsychological examinations, part of which (25/39) were also included in Bastin et al (2012). Neuropsychological testing included memory, language, executive functions, visuo-spatial functioning and praxis.…”

“…From a structural point of view, although negative relationships Bastin et al, 2012;Coffey et al, 1999;Querbes et al, 2009) or null findings (Christensen et al, 2009;Seo et al, 2011) have also been reported, several neuroimaging studies in cognitively healthy elders highlighted positive relationships between brain 5 measures and education. Thus, greater gray matter volume and cortical thickness in temporoparietal areas (Foubert-Samier et al, 2012, Liu et al, 2012, larger cortical thickness in orbitofrontal lobe (Liu et al, 2012) as well as greater white matter volume in regions connecting these latter areas (Foubert-Samier et al, 2012) and decreased mean diffusivity in the bilateral hippocampus (Piras et al, 2011) have been found in elderly with greater education.…”

“…Studies investigating cerebral metabolism at rest showed a negative association between a proxy of reserve combining education and intelligence and metabolic activity in temporoparietal areas (Bastin et al, 2012) or failed to show any influence of education (Perneczky et al, 2006, Scarmeas et al, 2003a. By contrast, functional studies during memory tasks showed functional reorganization of brain networks (compensation) in healthy elders with higher education compared to young individuals (Scarmeas et al, 2003b;Springer et al, 2005), and more efficient or optimal patterns of brain activation in elders with higher reserve proxies compared to elders with lower reserve proxies (Bosch et al, 2010;Solé-Padullés et al, 2009).…”