Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing

When adults with high reserve eventually show cognitive decline, they decline at a rapid rate.

“However, it has been observed that when adults with high levels of reserve, as indicated by one or more reserve proxies, do eventually display cognitive decline, they do so at a rapid rate 69.”

• cites [69] Reed, B. R. et al. Measuring cognitive reserve based on the decomposition of episodic memory variance. Brain 133, 2196–2209 (2010). sourceDisputed

  The Hypothesis 4 results report that higher baseline reserve predicted slower, not faster, decline in executive function. The Discussion likewise says higher reserve was associated with less decline. The paper does not report a separate analysis of decline after its onset that would support the citing sentence's qualification. (LLM, conf=0.81)

  Checked by a reasoning model — may be wrong.

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Proxy measures of reserve may engage different neural mechanisms, each important for a different aspect of reserve, such as neural capacity or neural efficiency.

“In addition, it is likely that proxy measures of reserve may engage different neural mechanisms, each important for a different aspect reserve, such neural capacity (the total amount of neural resources available for cognition) or neural efficiency (using less neural resources—often operationalized as neural activity—to perform a cognitive task).54,56”

• cites [54] Ghisletta, P., Rabbitt, P., Lunn, M. & Lindenberger, U. Two thirds of the age-based changes in fluid and crystallized intelligence, perceptual speed, and memory in adulthood are shared. Intelligence 40, 260–268 (2012). sourceCould not verify

  The Discussion considers shared and domain-specific mechanisms of age-related cognitive decline, but does not discuss proxy measures of reserve or distinguish neural capacity from neural efficiency. Searches for those terms and for cognitive-reserve proxies found no passage addressing the attributed claim; the Conclusions also say the behavioral evidence cannot establish the nature of the underlying factors. Page numbers were not available in our copy. (LLM, conf=0.74)

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• cites [56] Piras, F., Cherubini, A., Caltagirone, C. & Spalletta, G. Education mediates microstructural changes in bilateral hippocampus. Hum. Brain Mapp. 32, 282–289 (2011). sourcePartly supported

  The Introduction (page not specified) distinguishes reserve capacity in a threshold model from more efficient use of brain networks in an active model. It also identifies education as a reserve proxy, but does not say that different proxy measures engage different neural mechanisms or correspond to different aspects of reserve. (LLM, conf=0.82)

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Diffusion MRI indicates age-related changes in white matter connectivity between prefrontal and posterior cortical regions and within posterior sensory cortices.

“Diffusion MRI methods have shown age-related changes in white matter connectivity between prefrontal and posterior cortical regions, and within posterior sensory cortices.25–27”

• cites [25] Musiek, E. S. & Holtzman, D. M. Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science 354, 1004–1008 (2016). sourceCould not verify

  The Sleep and Neurodegeneration section discusses sleep, synaptic function, and medial prefrontal amyloid pathology, while the Circadian function and neurodegeneration section discusses age-related circadian changes. Neither addresses diffusion MRI or the specified age-related white matter connectivity changes. Searches for diffusion MRI and for connectivity in posterior sensory cortices found no supporting passage in our copy; page numbers were unavailable. (LLM, conf=0.76)

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• cites [26] Hullinger, R. & Puglielli, L. Molecular and cellular aspects of age-related cognitive decline and Alzheimer’s disease. Behav. Brain Res. 322, 191–205 (2017). sourceCould not verify

  The Introduction and §5.1 discuss age-related brain and synaptic changes, but not diffusion MRI findings about the specified cortical connections. Searches for diffusion MRI, white matter, and prefrontal-to-posterior or posterior sensory connectivity found no passage addressing the claim. Page numbers are not available in our copy. (LLM, conf=0.76)

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• cites [27] Mattson, M. P. & Arumugam, T. V. Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell Metab. 27, 1176–1199 (2018). sourcePartly supported

  The 'Aberrant Neuronal Network Activity' section says white matter integrity is compromised during normal aging and describes age-related changes in functional connectivity. It does not say that diffusion MRI showed changes specifically between prefrontal and posterior cortical regions or within posterior sensory cortices. No page number is available in our copy. (LLM, conf=0.86)

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Development of expertise is associated with richer and more differentiated conceptual representations, which can attenuate age-related decline in the domain of expertise.

“The development of expertise is associated with the presence of richer and more differentiated conceptual representations, which can attenuate age-related decline in the domain of expertise.54,65–67”

• cites [54] Ghisletta, P., Rabbitt, P., Lunn, M. & Lindenberger, U. Two thirds of the age-based changes in fluid and crystallized intelligence, perceptual speed, and memory in adulthood are shared. Intelligence 40, 260–268 (2012). sourceCould not verify

  The Abstract reports age-related cognitive decline, and the Discussion notes that some variation in decline is domain-specific. Neither passage addresses whether expertise produces richer conceptual representations or attenuates decline in an expert domain. Searches for expertise and domain-specific protection found no supporting passage in our copy. (LLM, conf=0.76)

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• cites [65] Alladi, S. et al. Bilingualism delays age at onset of dementia, independent of education and immigration status. Neurology 81, 1938–1944 (2013). sourceNot checked — no full text of the source
• cites [66] Anthony, M. & Lin, F. A. Systematic review for functional neuroimaging studies of cognitive reserve across the cognitive aging spectrum. Arch. Clin. Neuropsychol. https://doi.org/10.1093/arclin/acx125 (2017). sourcePartly supported

  The Introduction (page not available) says cognitive reserve may help people tolerate or compensate for the effects of aging and discusses delaying cognitive decline. It does not address expertise, richer and more differentiated conceptual representations, or protection specifically within a domain of expertise. (LLM, conf=0.78)

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• cites [67] Reed, B. R. et al. Cognitive activities during adulthood are more important than education in building reserve. J. Int. Neuropsychol. Soc. 17, 615–624 (2011). sourcePartly supported

  The Discussion (page not provided) links midlife cognitive activity to greater semantic-memory reserve and suggests that abilities may be maintained to different degrees in the face of dementia. It does not examine expertise or say that developing expertise produces richer, more differentiated conceptual representations; nor does it demonstrate reduced age-related decline specifically within a domain of expertise. (LLM, conf=0.79)

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Education improves neural resources during childhood and young adulthood, possibly by increasing synaptic density.

“A good example of a factor that promotes reserve is education, which improves neural resources during childhood and young adulthood, possibly by enhancing synaptic density 50”

• cites [50] Trahan, L. H., Stuebing, K. K., Fletcher, J. M. & Hiscock, M. The Flynn effect: a meta-analysis. Psychol. Bull. 140, 1332–1360 (2014). sourceCould not verify

  The “What is Rising?” section discusses formal education as a possible contributor to rising IQ scores, not as a means of improving neural resources. A search of our copy for neural resources, cognitive reserve, and synaptic density found no passage addressing the claimed mechanism during childhood or young adulthood. (LLM, conf=0.76)

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Greater cognitive reserve, measured using IQ and education-occupation as proxies, is associated with lower activity during cognitive processing, suggesting more effective use of cerebral networks.

“For instance, one study found that greater cognitive reserve, as measured using IQ and education-occupation as proxies, was associated with lower activity during cognitive processing, suggesting more effective use of cerebral networks.30”

• cites [30] Sampedro-Piquero, P., Alvarez-Suarez, P. & Begega, A. Coping with stress during aging: the importance of a resilient brain. Curr. Neuropharmacol. 16, 284–296 (2018). sourcePartly supported

  In “Effects on Neurobiological Resilient Mechanisms” (page unavailable), the paper reports lower metabolic activity in aged, enriched rats performing a spatial-learning task. It does not link that activity to cognitive reserve measured by IQ or education–occupation, and it proposes better stress coping rather than more effective use of cerebral networks. (LLM, conf=0.84)

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Cross-sectional designs can be affected by birth cohort effects, including inter-generational IQ increases known as the Flynn Effect.

“Also, cross-sectional designs can be contaminated by birth cohort effects, including inter-generational IQ increases (the ‘Flynn Effect’).43,44”

• cites [43] Giorgio, A. et al. Age-related changes in grey and white matter structure throughout adulthood. Neuroimage 51, 943–951 (2010). sourcePartly supported

  The Discussion (page unavailable) says the study’s cross-sectional design compares different cohorts across age groups and may be less sensitive to lifespan brain changes than a longitudinal design. This supports the general concern about cohort effects, but our copy does not mention inter-generational IQ increases or the Flynn Effect. (LLM, conf=0.88)

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• cites [44] Madden, D. J. et al. Adult age differences in functional connectivity during executive control. Neuroimage 52, 643–657 (2010). sourcePartly supported

  The Discussion’s Limitations section says cross-sectional age-group differences reflect cohort differences as well as chronological age. It does not mention inter-generational IQ increases or the Flynn Effect; searches for those terms found no supporting passage. Page numbers were not provided in our copy. (LLM, conf=0.87)

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Genetic and environmental factors, including longer education, greater physical activity, demanding leisure activities, and bilingualism, affect individual differences in reserve.

“Genetic55 and environmental factors,54,56 including longer education,32 greater physical activity,57 active participation in demanding leisure activities58 and bilingualism59,60 impact individual differences in reserve.”

• cites [55] Stern, Y., Gazes, Y., Razlighi, Q., Steffener, J. & Habeck, C. A task-invariant cognitive reserve network. Neuroimage 178, 36–45 (2018). sourceSupported
• cites [54] Ghisletta, P., Rabbitt, P., Lunn, M. & Lindenberger, U. Two thirds of the age-based changes in fluid and crystallized intelligence, perceptual speed, and memory in adulthood are shared. Intelligence 40, 260–268 (2012). sourcePartly supported

  The Discussion (page not provided) suggests that lifestyle and common genetic variation may contribute to individual differences in rates of cognitive decline. It does not establish that these factors affect individual differences in reserve. The specific examples in the sentence have separate citations and are not attributed to this paper. (LLM, conf=0.83)

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• cites [56] Piras, F., Cherubini, A., Caltagirone, C. & Spalletta, G. Education mediates microstructural changes in bilateral hippocampus. Hum. Brain Mapp. 32, 282–289 (2011). sourceSupported
• cites [32] Morgan, D. G. The dopamine and serotonin systems during aging in human and rodent brain. A brief review. Prog. Neuropsychopharmacol. Biol. Psychiatry 11, 153–157 (1987). sourceNot checked — no full text of the source

At some level, the burden of pathology becomes great enough to overcome the protective mechanism of reserve, resulting in rapid cognitive decline.

“Possibly, at some level, the burden of pathology becomes great enough to overcome this protective mechanism, resulting in rapid cognitive decline31,53.”

• cites [31] Rosario, E. R., Chang, L., Head, E. H., Stanczyk, F. Z. & Pike, C. J. Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer’s disease. Neurobiol. Aging 32, 604–613 (2011). sourceCould not verify

  The Discussion describes a possible protective role for sex hormones against Alzheimer’s pathology, but does not discuss cognitive reserve, a pathology threshold that overcomes it, or rapid cognitive decline. Searches for reserve and pathology-threshold language found no passage addressing that proposed sequence. (LLM, conf=0.77)

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• cites [53] Raz, N. et al. Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb. Cortex 15, 1676–1689 (2005). sourceCould not verify

  The Discussion says the study found no support for the brain reserve hypothesis, while noting that its cognitive measures were too narrow to settle the question. It discusses pathology and brain shrinkage, but does not address whether a threshold of pathology overcomes reserve and causes rapid cognitive decline (searched: pathology burden, reserve, protective mechanism, rapid cognitive decline). (LLM, conf=0.76)

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Increased neural capacity is associated with a proxy measure of reserve, as shown by the effect of education on synaptic density.

“One example of how increased capacity is associated with a proxy measure of reserve is the aforementioned effect of education on synaptic density.50”

• cites [50] Trahan, L. H., Stuebing, K. K., Fletcher, J. M. & Hiscock, M. The Flynn effect: a meta-analysis. Psychol. Bull. 140, 1332–1360 (2014). sourceCould not verify

  The “What is Rising?” section discusses education as a possible contributor to rising IQ scores, not its effect on synaptic density. Searches for synaptic density, neural capacity, and reserve found no passage in our copy addressing the claimed association. (LLM, conf=0.76)

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As task difficulty increases, neural activity, particularly in frontal regions, tends to increase up to a certain level, beyond which activation asymptotes and ultimately declines.

“As task difficulty increases, neural activity (particularly in frontal regions) tends to increase up to a certain level33, beyond which activation asymptotes and ultimately declines (FIG. 3–A)36,37.”

• cites [33] Freeman, G. B. & Gibson, G. E. Dopamine, acetylcholine, and glutamate interactions in aging. Behavioral and neurochemical correlates. Ann. N. Y. Acad. Sci. 515, 191–202 (1988). sourceNot checked — no full text of the source
• cites [36] Sperling, R. Potential of functional MRI as a biomarker in early Alzheimer’s disease. Neurobiol. Aging 32 (Suppl. 1), S37–S43 (2011). sourceCould not verify

  The Abstract (page unavailable) reports increased prefrontal activity during task performance in people with Alzheimer’s dementia, but does not relate that activity to increasing task difficulty. The cited paper’s copy does not establish the graded increase or threshold attributed to citation 33; searches for task difficulty, load, and increasing demands found no such passage. (LLM, conf=0.76)

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• cites [37] Grady, C. L. The cognitive neuroscience of ageing. Nat. Rev. Neurosci. 13, 491–505 (2012). sourceNot checked — no full text of the source

• AssumptionThe authors state this as an assumption: The asymptote in neural activity reflects available neural resources, and the final decline reflects breakdown in cognitive performance when those resources are exceeded.

In aging, reorganization could explain the finding that older adults often have more bilateral brain activity than younger adults.

“In the case of aging, reorganization could underlie the well-established finding that older adults often show more bilateral patterns of brain activity than younger adults43–45”

• cites [43] Giorgio, A. et al. Age-related changes in grey and white matter structure throughout adulthood. Neuroimage 51, 943–951 (2010). sourceCould not verify

  The Results section on age-subgroup comparisons reports bilateral differences in grey-matter volume, not bilateral patterns of brain activity. Searches for reorganization, compensation, and bilateral activation found no passage in our copy addressing the claimed functional pattern in older versus younger adults. (LLM, conf=0.76)

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• cites [44] Madden, D. J. et al. Adult age differences in functional connectivity during executive control. Neuroimage 52, 643–657 (2010). sourcePartly supported

  The Abstract describes greater frontoparietal activation in older adults across several executive-control studies and suggests compensatory recruitment. The Discussion section on event-related and sustained activation also reports greater activation in several prefrontal regions in older adults. Neither passage establishes the specific finding that older adults often show more bilateral activity than younger adults; the proposed explanation by reorganization is the citing authors’ framing. (LLM, conf=0.78)

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• cites [45] Craik, F. I. M. & Salthouse, T. A. The Handbook of Aging and Cognition (Lawrence Erlbaum Associates, Mahwah, NJ, 2000).Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Maintenance mechanisms are ideally studied with longitudinal data, because only within-person assessments can truly quantify change or lack of change.

“This is because maintenance mechanisms are ideally investigated using longitudinal data, as only within-person assessments can truly quantify change, or, in case of maintenance, lack thereof.74”

• cites [74] Li, Y. et al. Sound credit scores and financial decisions despite cognitive aging. Proc. Natl Acad. Sci. USA 112, 65–69 (2015). sourceCould not verify

  The Discussion (page unavailable) describes the study as cross-sectional and recommends examining the interplay of cognitive abilities and knowledge rather than age alone. It does not say that longitudinal, within-person assessments are necessary to quantify change or maintenance; searches for those methodological terms found no supporting passage. (LLM, conf=0.75)

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Compensatory upregulation could explain the frequent finding that at least some age-related activity increases occur within the same brain regions that younger adults recruit during the same task.

“Compensatory upregulation could explain the frequent finding that at least some age-related activity increases are evident within the same brain regions that younger adults recruit during the same task.81”

• cites [81] Persson, J. et al. Longitudinal structure–function correlates in elderly reveal MTL dysfunction with cognitive decline. Cereb. Cortex 22, 2297–2304 (2012). sourcePartly supported

  The Discussion suggests that increased parahippocampal activity in older adults with declining memory performance might be attempted functional compensation. It does not establish the claimed frequent finding that age-related increases occur in the same regions younger adults recruit during the same task; this study follows older adults over time rather than making that comparison. (LLM, conf=0.84)

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In a longitudinal structural MRI study from the Swedish Betula project, individuals aged 65 or older with little or no episodic memory decline over 15 years showed less hippocampal atrophy over 4 years than those with substantial memory decline.

“For example, a longitudinal structural MRI study from the Swedish Betula project71 found that individuals aged 65 years or older, with little or no episodic memory decline over a 15-year period, showed less hippocampal atrophy over 4 years than individuals with substantial memory decline”

• cites [71] Adamson, M. M. et al. Higher landing accuracy in expert pilots is associated with lower activity in the caudate nucleus. PLOS ONE 9, e112607 (2014). sourceCould not verify

  The Materials and Methods section describes MRI acquisition and processing for a study of pilots, while the Results section reports brain activity during a landing-decision task. Searches for the Swedish Betula project, episodic-memory decline, and longitudinal hippocampal atrophy found no passage addressing the claimed comparison. (LLM, conf=0.76)

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In a longitudinal fMRI study, hippocampal activity during an episodic memory task was significantly higher in people whose memory was stable over two decades than in people whose memory declined over that period.

“Similarly, in a longitudinal fMRI study73 hippocampal activity during an episodic memory task was significantly higher in people whose memory function was stable over two decades than in people whose memory abilities declined over this period”

• cites [73] Kozasa, E. H. et al. Effects of a 7-day meditation retreat on the brain function of meditators and non-meditators during an attention task. Front. Hum. Neurosci. 12, 222 (2018). sourceCould not verify

  The Materials and Methods (Image Processing; page unavailable) describe a pre- and post-retreat Stroop attention task, and the Results (Stroop Task Imaging Results; page unavailable) compare meditators with non-meditators. Searches for an episodic-memory task and a two-decade comparison of stable versus declining memory found no passage reporting the claimed hippocampal result. (LLM, conf=0.78)

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Older adults often show more bilateral brain activity patterns than younger adults.

“the well-established finding that older adults often show more bilateral patterns of brain activity than younger adults43–45”

• cites [43] Giorgio, A. et al. Age-related changes in grey and white matter structure throughout adulthood. Neuroimage 51, 943–951 (2010). sourceCould not verify

  The Abstract describes age-related changes in brain structure, and the Results section on age-subgroup comparisons reports bilateral differences in grey-matter volume—not brain activity. Searches for bilateral brain activity and functional activation found no passage in our copy addressing whether older adults show more bilateral activity than younger adults. Page numbers were not provided. (LLM, conf=0.77)

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• cites [44] Madden, D. J. et al. Adult age differences in functional connectivity during executive control. Neuroimage 52, 643–657 (2010). sourcePartly supported

  The Results (Target-related activation; page unavailable) report greater activation for older than younger adults in the prefrontal cortex bilaterally. This supports an example of bilateral age-related activation, but the paper does not establish the broader claim that older adults often have more bilateral activity patterns across tasks. (LLM, conf=0.78)

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• cites [45] Craik, F. I. M. & Salthouse, T. A. The Handbook of Aging and Cognition (Lawrence Erlbaum Associates, Mahwah, NJ, 2000).Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Highly educated individuals may show different activation patterns than less educated individuals because greater reserve allows more effective compensatory processes.

“For example, highly educated individuals may show different activation patterns than individuals with lower educational attainment because their greater reserve allows them to deploy more effective compensatory processes.”

Individual differences in age-related cognitive decline reflect a complex interaction of genetic and environmental factors, partly mediated by reserve, maintenance, and compensation.

“Individual differences in age-related cognitive decline undoubtedly reflect a complex interaction between genetic and environmental factors, whose actions could be partly mediated by three interacting mechanisms known as reserve, maintenance, and compensation (FIG. 1–A).”

Education attenuates age-related cognitive decline.

“and then attenuates age-related cognitive decline. 51,52”

• cites [51] Deary, I. J., Whiteman, M. C., Starr, J. M., Whalley, L. J. & Fox, H. C. The impact of childhood intelligence on later life: following up the Scottish mental surveys of 1932 and 1947. J. Pers Soc. Psychol. 86, 130–147 (2004). sourceNot checked — no full text of the source
• cites [52] Nyberg, L., Pudas, S. & Lundquist, A. in Cogntiive Neuroscience of Aging 2nd edn (eds Cabeza, R., Nyberg, L. & Park, D. C.) (Oxford Univ. Press, 2016).Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Reserve and the capacity for compensation may interact.

“Complicating the distinction, reserve and the capacity for compensation may interact.”

Development of expertise in a domain through training is an example of increased neural efficiency.

“An example of an increase in neural efficiency is the development of expertise in a particular domain through training.”

Some 80-year-olds perform as well as or better than some 40-year-olds, including on episodic memory, a function generally impaired by aging.

“In fact, some 80-year olds can perform as well as or better than some 40-year olds, even when considering functions generally impaired by aging such as episodic memory.42”

• cites [42] Salat, D. H. et al. Age-related changes in prefrontal white matter measured by diffusion tensor imaging. Ann. N. Y. Acad. Sci. 1064, 37–49 (2005). sourceNot checked — no full text of the source

For compensation, heightened cognitive demands from task difficulty and age-related decline are counteracted by recruiting additional neural resources, including those established by neural enhancement.

“In the case of compensation (FIG. 1–D), heightened cognitive demands due to the combined effects of task difficulty and age-related cognitive decline are counteracted by recruiting additional neural resources, including those established by neural enhancement.”

Cross-sectional designs cannot separate age-invariant differences from age-related differences.

“Moreover, cross-sectional designs cannot distinguish between age-invariant and age-related differences, which is important as a large proportion of variance in cognitive performance among older adults existed already when they were children.45”

• cites [45] Craik, F. I. M. & Salthouse, T. A. The Handbook of Aging and Cognition (Lawrence Erlbaum Associates, Mahwah, NJ, 2000).Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Cognitive aging shows striking variability between individuals.

“Inter-individual variability in cognitive aging is striking.”

Cross-sectional designs have several limitations compared with longitudinal designs when studying individual differences among older adults.

“When investigating individual differences among older adults, however, cross-sectional designs have several limitations compared to longitudinal designs.”

One study decomposed variance in episodic memory performance into components predicted by demographics, pathology measured by structural MRI, and a residual reserve component, which moderated cognitive decline.

“For example, one study decomposed variance in episodic memory performance into a component predicted by demographics, a component predicted by pathology (as measured by structural MRI), and a residual “reserve” component, which was then shown to moderate cognitive decline.64”

• cites [64] Bialystok, E., Craik, F. I. M. & Freedman, M. Bilingualism as a protection against the onset of symptoms of dementia. Neuropsychologia 45, 459–464 (2007). sourceNot checked — no full text of the source

Age-related declines in brain structure and function are linked to cognitive decline across multiple domains.

“These age-related declines in brain structure and function are associated with cognitive decline in a variety of domains.28,29”

• cites [28] Santoro, A. et al. Innate immunity and cellular senescence: the good and the bad in the developmental and aged brain. J. Leukoc. Biol. 103, 509–524 (2018). sourceNot checked — no full text of the source
• cites [29] Backman, L., Lindenberger, U., Li, S. C. & Nyberg, L. Linking cognitive aging to alterations in dopamine neurotransmitter functioning: recent data and future avenues. Neurosci. Biobehav. Rev. 34, 670–677 (2010). sourceNot checked — no full text of the source

Compensation by selection requires a qualitative change in the cognitive operations that older and younger people use.

“Unlike compensation by upregulation, compensation by selection involves a qualitative difference in the cognitive processes engaged by older and younger individuals”

To attribute greater activity or connectivity to compensation, evidence should show that the activation is directly or indirectly related to an insufficiency or gap between available neural resources and task demands.

“First, it is not just “compensation” but “compensation for”, and hence, evidence should be available that the activation is directly or indirectly related to some insufficiency or gap between available neural resources (“supply”) and task demands (supply-demand gap)76,79.”

• cites [76] Morrow, D., Leirer, V., Altieri, P. & Fitzsimmons, C. When expertise reduces age-differences in performance. Psychol. Aging 9, 134–148 (1994). sourceNot checked — no full text of the source
• cites [79] Ten Brinke, L. F. et al. Aerobic exercise increases cortical white matter volume in older adults with vascular cognitive impairment: a 6-month randomized controlled trial. Alzheimers Dement. 11, 606 (2015). sourceNot checked — no full text of the source

Recovery from aphasia after left-hemisphere stroke involves recruitment of right-hemisphere regions that do not support language in the normal brain.

“For example, there is evidence that recovery from aphasia following a left-hemisphere stroke is associated with the recruitment of right hemispheric regions that do not support language processes in the normal brain83.”

• cites [83] Miller, E. K. & Cohen, J. D. An integrative theory of prefrontal cortex function. Annu. Rev. Neurosci. 24, 167–202 (2001). sourceNot checked — no full text of the source

In compensation by upregulation, older adults recruit the same processes as younger adults, but to a greater extent.

“In such cases, the processes recruited by older adults would be the same as those engaged by younger adults, with the primary difference being quantitative: older adults would engage the process to a greater extent than younger adults.”

Cross-sectional brain data can still be informative about maintenance.

“Critically, this does not imply that cross-sectional brain data cannot be informative.”

Compensation by selection is likely to recruit different brain areas, not the same area with different activity levels.

“and hence it is likely to be associated with the recruitment of different brain regions, rather than recruitment of the same region with differential levels of activity (as in upregulation).”

If task demands are not parametrically varied, over-activation in older adults can be wrongly attributed to selection instead of upregulation.

“Note that without a parametric manipulation of task demands, one could mistakenly attribute an over-activation in older adults to selection rather than upregulation.”

Compensation by selection is linked to individual differences in reserve, since some older adults may possess a larger set of alternative neural implementations of a behavior, reflecting greater accumulated reserve.

“Finally, we note that this form of compensation is related to individual differences in reserve because some older adults may have a larger repertoire of alternative neural implementation of a given behavior than others, reflecting differences in accumulated reserve.”

The high covariance among changes in different cognitive abilities suggests that maintenance in one functional domain is likely related to maintenance in another domain.

“At the same time, the high degree of covariance among changes in different cognitive abilities suggests that maintenance in one functional domain is likely to be related to maintenance in another domain48.”

• cites [48] Habib, R., Nyberg, L. & Nilsson, L. G. Cognitive and non-cognitive factors contributing to the longitudinal identification of successful older adults in the Betula study. Aging Neuropsychol. Cogn. 14, 257–273 (2007). sourceNot checked — no full text of the source

In cross-sectional studies, some differences between young and older adults could be due to cohort effects such as early life influences, not aging itself.

“However, when considering cross-sectional studies it is important to remember that some differences between young and older adults could be due to cohort effects, such as early life influences, and not aging per se, as such effects have been noted in the brain75.”

• cites [75] Lindenberger, U., Kliegl, R. & Baltes, P. B. Professional expertise does not eliminate age-differences in imagery-based memory performance during adulthood. Psychol. Aging 7, 585–593 (1992). sourceNot checked — no full text of the source

Adults who maintain stable cognitive performance as they age tend to show minimal brain decline or pathology.

“The notion of maintenance is consistent with evidence that adults who display stable cognitive performance as they age tend to show minimal brain decline or pathology.33”

• cites [33] Freeman, G. B. & Gibson, G. E. Dopamine, acetylcholine, and glutamate interactions in aging. Behavioral and neurochemical correlates. Ann. N. Y. Acad. Sci. 515, 191–202 (1988). sourceNot checked — no full text of the source

Behavioral genetic studies suggest that genetic and environmental contributions to maintenance become increasingly correlated with advancing age.

“Behavioral genetic studies suggest that genetic and environmental contributions to maintenance become increasingly correlated with advancing age.77”

• cites [77] Vaci, N., Gula, B. & Bilalic, M. Is age really cruel to experts? Compensatory effects of activity. Psychol. Aging 30, 740–754 (2015). sourceNot checked — no full text of the source

Successful maintenance could explain cross-sectional findings that high-performing older adults' brains resemble young brains in anatomy and physiology, whereas low-performing older adults' brains differ from young brains.

“For example, successful maintenance could explain cross-sectional findings that the brains of high-performing older adults look similar in anatomy and physiology to young brains, whereas the brains of low-performing older adults look different to young brains.33”

• cites [33] Freeman, G. B. & Gibson, G. E. Dopamine, acetylcholine, and glutamate interactions in aging. Behavioral and neurochemical correlates. Ann. N. Y. Acad. Sci. 515, 191–202 (1988). sourceNot checked — no full text of the source

The efficacy of maintenance depends on both the magnitude of decline and the efficacy of repair.

“Thus, the efficacy of maintenance depends both on the magnitude of decline and the efficacy of repair.”

If regions newly engaged by older adults are also recruited by younger adults in similar or harder conditions, that finding would better support compensation by selection.

“If the new regions engaged by older adults are sometimes recruited by younger adults in other similar or more difficult conditions, then the finding would be more consistent with compensation by selection.”

It is not sufficient to build and maintain reserve; one must also deploy those resources during tasks in response to demands, which is compensation.

“Likewise, it is not enough to accumulate reserve and maintain it, it is also necessary to deploy these resources during task performance in response to task demands, that is to engage in compensation.”

If education increases reserve by raising synaptic density, it can reduce age-related cognitive decline only when the new synapses are maintained.

“For example, if education augments reserve by increasing synaptic density, this can only go on to attenuate age-related cognitive decline if the new synapses are preserved via maintenance.”