Human cognitive aging:
            <i>Corriger la fortune?</i>

Lindenberger, Ulman

doi:10.1126/science.1254403

Cited by 323 publications

(276 citation statements)

References 115 publications

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“…Concurrent with substantia nigra and ventral tegmental DA neuron loss, D 1 and D 2 receptor densities reduce notably from early to late adulthood across various subcortical and cortical regions (9)(10)(11). However, it is not yet known whether DA affects brain signal variability in relation to age and performance.…”

mentioning

confidence: 99%

Amphetamine modulates brain signal variability and working memory in younger and older adults

Garrett

Nagel

Preuschhof

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

106

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Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD BOLD ) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD BOLD levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD BOLD and reaction time means (RT mean ) and SDs (RT SD ). Older adults who received AMPH in the first session tended to improve in RT mean and RT SD when SD BOLD was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD BOLD decreased (for RT mean ) or no effect at all (for RT SD ). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state-and practice-dependent neurochemical basis of human brain dynamics.brain signal variability | dopamine | aging | working memory | fMRI H uman brain signals are characteristically variable and dynamic, at a variety of timescales and levels of analysis (1, 2). For decades, age-related cognitive deficits have been conceptualized as due to various forms of "noisy," inefficient neural processing (3, 4). However, the preponderance of available neuroimaging work on brain signal variability and aging indicates that healthy, higher performing, younger adults typically express more signal variability across trials and time in a variety of cortical regions relative to older, poorer performers (2, 5-7). Theoretical and computational explanations of this finding include notions such as flexibility/adaptability, dynamic range, Bayesian optimality, and multistability (2), but empirically supported mechanisms for age and performance-graded differences in human brain signal dynamics are not yet available. Dopamine (DA) neuromodulation may provide one such mechanism.DA neuromodulation is a leading mechanistic candidate for age-related cognitive losses (8-10). Concurrent with substantia nigra and ventral tegmental DA neuron loss, D 1 and D 2 receptor densities reduce notably from early to late adulthood acro...

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mentioning

confidence: 99%

Amphetamine modulates brain signal variability and working memory in younger and older adults

Garrett

Nagel

Preuschhof

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

106

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“…Our results provide novel evidence for stability in brain-cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course. development | aging | cortical change I t is well-established that both brain and cognition change with age, and that although there are early gains, older age brings with it decrements in aspects of both (1,2). Much focus has been on age-specific mechanisms of neural foundations of cognition and their change (3,4).…”

mentioning

confidence: 99%

Neurodevelopmental origins of lifespan changes in brain and cognition

Walhovd

Krogsrud

Amlien

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

185

182

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Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4-88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother-Child Cohort study were identified as such early factors of possible lifelong influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain-cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course. development | aging | cortical change I t is well-established that both brain and cognition change with age, and that although there are early gains, older age brings with it decrements in aspects of both (1, 2). Much focus has been on age-specific mechanisms of neural foundations of cognition and their change (3, 4). In contrast, neurodevelopmental origins of functional variation in older age are now increasingly being acknowledged (5-8), but identification of how early factors may impact human brain and cognition throughout the lifespan has remained challenging.General cognitive ability (GCA) is essential to human beings, relates to a multitude of health and social outcomes (9), and necessarily originates in characteristics of the central nervous system at all ages. Paradoxically, even though GCA is highly vulnerable to the influence of aging, there is a remarkable stability in individuals' GCA relative to their same-age peers (10, 11). It has even been shown that childhood GCA can account for GCA-cortical thickness associations in old age (12). Cortical thickness is known to decrease with age monotonously from relatively early childhood through the entire lifespan (6,13,14). This thinning, albeit continuous, signifies different neurobiological events at different stages of life (15, 16), and does not have a stable functional correla...

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“…Age-related degenerative processes often contribute to various diseases (1)(2)(3)(4)(5)(6). Depending on factors such as genetic background, environmental exposure, and diet, the rate of pathologic changes can differ among individuals, but the major contributor to the progression of disease is age itself (7)(8)(9).…”

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confidence: 99%

Serum levels of lipid metabolites in age‐related macular degeneration

et al. 2015

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Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4 2/2 Rdh8 2/2 mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decreased as compared with the eyes of control dark-adapted C57BL/6J mice. In addition, exposure to intense light correlated with higher levels of prostaglandin G2 in the eyes of Abca4 2/2 Rdh8 2/2 mice. Intense light exposure also lowered DHA levels in the eyes of wild-type C57BL/6J mice without discernible retinal degeneration. Analysis of human serum from patients with AMD recapitulated these dysregulated DHA levels and revealed dysregulation of arachidonic acid (AA) levels as well (∼32% increase in patients with AMD compared with average levels in healthy individuals). From these observations, we then built a statistical model that included levels of DHA and AA from human serum. This model had a 74% probability of correctly identifying patients with AMD from controls. Addition of a genetic analysis for one of the most prevalent amino acid substitutions in the age-related maculopathy susceptibility 2 gene linked to AMD, Ala 69 →Ser, did not improve the statistical model. Thus, we have characterized a reliable method with the potential to detect AMD without a genetic component, paving the way for a larger-scale clinical evaluation. Our studies on mouse models along with the analysis of human serum suggest that our small molecule-based model may serve as an effective tool to estimate the risk of developing AMD.-Orban, T., Johnson, W. M., Dong, Z., Maeda, T., Maeda, A., Sakai, T., Tsuneoka, H., Mieyal, J. J., Palczewski, K. Serum levels of lipid metabolites in age-related macular degeneration. FASEB J. 29, 4579-4588 (2015). www.fasebj.org

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Human cognitive aging: Corriger la fortune?

Cited by 323 publications

References 115 publications

Amphetamine modulates brain signal variability and working memory in younger and older adults

Amphetamine modulates brain signal variability and working memory in younger and older adults

Neurodevelopmental origins of lifespan changes in brain and cognition

Serum levels of lipid metabolites in age‐related macular degeneration

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