Cognitive reserve, maintenance, and compensation - tips for neurologist's practice

Highlights:

• Age-related cognitive decline depends on both genetic and environmental factors
• To fight age-related changes brain incorporates mechanisms of reserve, maintenance, and compensation
• Environmental and lifestyle changes can prolong neural healthspan and longevity

Introduction

With age, the brain undergoes a series of detrimental transformations, including gray and white matter atrophy, degeneration of synapses, reduced blood flow, and neurochemical changes. Due to that, older adults perform more poorly than young adults in various cognitive tasks, including perception, attention, and memory. Rapid aging of the population requires addressing the public problem of age-associated cognitive impairment. Fortunately, there is much evidence for behavioral interventions that can prevent or delay the onset of dementia. Due to that, growing public interest in the concept of brain health: maintenance of optimal cognitive, emotional, psychological, and behavioral function throughout life.

Cognitive neuroscience of healthy aging

Magnetic resonance imaging (MRI) methods gave us a significantly advanced understanding of how the brain's anatomy and function change with age. MRI studies have shown that normal aging is associated with gray matter volume reductions and functional changes in regions necessary for higher cognitive function: prefrontal, medial temporal, and parietal cortices. Age-related changes also presented themselves in a decreased white matter connectivity between prefrontal and posterior cortical regions and within posterior sensory cortices, all of which lead to cognitive decline.

The cognitive neuroscience of aging researches the multilevel neural mechanisms of age-related cognitive decline and those of healthy aging. Individual differences in age-related cognitive degeneration reflect a complex interaction between genetic and environmental factors, whose actions could be to some extent mediated by mechanisms known as cognitive reserve, maintenance, and compensation (1, 2). While some elders show a pronounced cognitive decline, others perform the same or better than young adults due to those mechanisms. We will describe in detail all three mechanisms and suggest tips that you could offer to your patients to keep their cognitive abilities sharp as long as possible.

How to gain the cognitive reserve?

This mechanism refers to a cumulative improvement in neural resources due to genetic and environmental factors that mitigate the effects of neural decline caused by aging or age-related diseases. Reserve is hypothesized to accumulate before neural resources demonstrate age-related decreases over a period of years. Possibly, reserve accumulates during childhood and young adulthood the most, but it may also develop in older age, which arguably highlights the importance of intellectual engagement throughout the lifespan. One of the factors proven to promote reserve is education (3), which improves neural resources at a younger age, possibly by enhancing synaptic density and then delays age-related cognitive decline. Genetic and environmental factors such as longer education (4), regular physical activity (5), participation in demanding leisure activities (6), and knowledge of more than one language  (7), impact individual differences in reserve.

Engagement in leisure activities of intellectual nature (such as playing a musical instrument, handicrafts) and social nature (i.e., volunteering) might lead to functionally more efficient cognitive networks providing cognitive reserve. It is also scientifically proven to be associated with slower cognitive decline in healthy elderly and dementia and Alzheimer's disease prevention. On the other hand, lower educational and occupational attainment is associated with an increased risk for incident dementia. Similarly, lower childhood linguistic and mental ability scores are strong predictors of poor cognitive function and dementia in late life (6).

Another example of an increase in neural efficiency is the development of expertise in a particular domain through training. This idea can perhaps explain why older individuals can remain highly effective in their specific fields of professional expertise (8). However, it is observed that when adults with high levels of cognitive reserve start to display cognitive decline such as Alzheimer's disease, eventually, they do it rapidly (6, 9, 10). Possibly, the burden of pathology becomes significant enough to overcome the reserve protective mechanism, resulting in quick cognitive decline (2).

Cognitive maintenance of the brain

Cognitive maintenance is the conservation of neural resources, which involves ongoing repair of the brain. This mechanism happens throughout life but could be critical in elders as neural deterioration becomes more severe in old age. In the ideal case, repair processes fully counteract decline, but in reality, repair processes do not entirely reverse the neural decline, leading to a gradual process of age-related deterioration. It  can refer to different aspects of the brain, such as gray and white matter, neurotransmitter functions, or, more generally, to different brain regions.  

 The efficacy of maintenance depends on the level of the decline and the effectiveness of the repair. The concepts of reserve and maintenance are related, but the reserve is about enhancing and extending resources, whereas maintenance is about their preservation. The reserve impacts future maintenance while the accumulated reserve needs maintenance. 

Neural maintenance is a dynamic process that engages cellular repair mechanisms and possibly overlaps with mechanisms of brain plasticity in adulthood. Similarly to reserve, it is suggested to have both genetic and environmental origins, such as diet, exercise, and cognitive and social engagement (5, 11-13). There is a known link between exercise and white-matter integrity (14), suggesting that people who exercise regularly maintain white-matter integrity better than other aspects of the brain. Adults who pursue stable cognitive performance tend to show lower brain decline or pathology with age (11), less hippocampal atrophy (15), and higher hippocampal activity (16). Successful maintenance could explain the findings that the brains of high-performing older adults look similar in anatomy and physiology to those of younger adults. In contrast, the brains of low-performing older adults look different from young ones.

Neural compensation and its strategies

Recruiting neural resources to enhance cognition in response to relatively high cognitive demand is known as compensation. Compensation is directly linked to changes in cognitive needs and can occur in a matter of seconds. The compensation process can occur in a few different ways:

• Compensation by upregulation – enhancing cognitive performance by boosting a neural process in response to task demands. Here the cognitive processes initiated by older adults would be the same as those in younger adults, with a quantitative difference: older adults would engage the process to a larger extent than younger adults (1, 17, 18).
• Compensation by selection – occurs when older adults start using neural regions that were previously not utilized for the same cognitive task. An example would be the increased use of frontal lobes or cortical medial-temporal lobe during memory-related tasks in elders with reduced hippocampal activity (18).
• Compensation by reorganization – occurs when elders use an alternative neural mechanism to respond to aging-induced cognitive decline, unavailable to younger individuals (1, 18). An example could be the development of new neural mechanisms following brain damage (19).

There are many compensatory strategies, especially for those who suffer from age-related cognitive impairment. Those strategies empower patients to adapt to the impairments inflicted by their illness. The team of M.C Greenway developed a Memory Support System to help patients with memory loss (20). The system consists of a small calendar and note-taking system for patients to log appointments, task lists, and write a journal. The method implemented after correct training improved functional ability, memory self-efficacy, and mood in patients with mild cognitive impairment (21). Another known strategy is Goal Management Training. It is a metacognitive rehabilitation program teaching patients to stop what they are doing periodically, think about task goals, and evaluate their performance (22, 23).

Connections between reserve, maintenance, and compensation

Mechanisms of cognitive reserve, maintenance can operate concurrently and affect each other. While education boosts reserve by increasing synaptic density, it needs new synapses preservation via maintenance for full function. It is also not enough to only accumulate reserve and maintain it. It is also necessary to use these resources in response to task demands, which means engaging in compensation. Mechanisms of reserve, maintenance, and compensation implemented in age-related disease management can also be used during child development, acute brain injury, neurodegeneration, and psychiatric illness. Patients with neurological conditions may compensate for their disorder-related deficit in ways similar to those for healthy older adults (2). An example could be the full recovery of children after hemispherectomy.

Conclusions and the missing pieces of the cognitive aging puzzle

Despite remarkable advances in neuroscience, there are still many challenges in understanding the mechanisms of cognitive decline, brain aging, and preserving cognitive abilities (2). To date, most studies of cognitive aging were limited to testing samples of high functioning, highly educated, primarily Caucasian healthy older adults. The inclusion criteria to cover individuals from diverse backgrounds need to be altered to develop more representative cognitive and brain, aging models. Extensive, ideally longitudinal studies are required to combine longitudinal observations with intervention studies to gauge the long-term effects of physical exercise, cognitive training, and other variables. Such studies will lead to a better understanding of age-related changes in brain and cognition in biological aging and variations in environmental and genetic factors influence. They will start the particular trends in health, education, and technology, determining the aging journey of the future generations (2).

Recommendations for your practice:

• Suggest participation in intellectual, social, and physical activities and cognitive tasks as a way of brain maintenance.
• Suggest the engagement in leisure activities (traveling, doing odd jobs such as house repairs, gardening, knitting) as it is proven to affect the incident dementia (5, 6,24).
• Empower your patients to pursue education in every stage of life. It supports cognitive reserve (3, 4), improves neural resources, enhances synaptic density, and attenuates age-related cognitive decline.
• Suggest learning or improving language skills. Bilingualism actively delays the onset of dementia. Learning language also supports social circle building (7).
• Underline the importance of social engagement (family, friends, group memberships) and productive activities such as helping others with daily tasks, paid work, and volunteer work due to its inverse association with the risk of incident dementia.
• Connect your patient with a nutritionist or health coach - neuroprotective mechanisms are supported by dietary modifications such as caloric restriction and methylfolate and antioxidant supplementation (13).

References:

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2.            Cabeza R, Albert M, Belleville S, Craik FIM, Duarte A, Grady CL, et al. Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing. Nature reviews Neuroscience. 2018;19(11):701-10.

3.            Piras F, Cherubini A, Caltagirone C, Spalletta G. Education mediates microstructural changes in bilateral hippocampus. Human brain mapping. 2011;32(2):282-9.

4.            Arenaza-Urquijo EM, Bejanin A, Gonneaud J, Wirth M, La Joie R, Mutlu J, et al. Association between educational attainment and amyloid deposition across the spectrum from normal cognition to dementia: neuroimaging evidence for protection and compensation. Neurobiology of aging. 2017;59:72-9.

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17.          Spreng RN, Wojtowicz M, Grady CL. Reliable differences in brain activity between young and old adults: a quantitative meta-analysis across multiple cognitive domains. Neuroscience & Biobehavioral Reviews. 2010;34(8):1178-94.

18.          Dennis NA, Kim H, Cabeza R. Age-related differences in brain activity during true and false memory retrieval. Journal of cognitive neuroscience. 2008;20(8):1390-402.

19.          Hope TM, Leff AP, Prejawa S, Bruce R, Haigh Z, Lim L, et al. Right hemisphere structural adaptation and changing language skills years after left hemisphere stroke. Brain. 2017;140(6):1718-28.

20.          Greenaway MC, Hanna SM, Lepore SW, Smith GE. A Behavioral Rehabilitation Intervention for Amnestic Mild Cognitive Impairment. American Journal of Alzheimer's Disease & Other Dementias®. 2008;23(5):451-61.

21.          Greenaway MC, Duncan NL, Smith GE. The memory support system for mild cognitive impairment: randomized trial of a cognitive rehabilitation intervention. International journal of geriatric psychiatry. 2013;28(4):402-9.

22.          Stamenova V, Levine B. Effectiveness of goal management training(R) in improving executive functions: A meta-analysis. Neuropsychol Rehabil. 2019;29(10):1569-99.

23.          Liou H, Stonnington CM, Shah AA, Buckner-Petty SA, Locke DEC. Compensatory and Lifestyle-Based Brain Health Program for Subjective Cognitive Decline: Self-Implementation versus Coaching. Brain Sci. 2021;11(10).

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