Healthy Cognitive Aging

Introduction

The World Health Organization estimates that the number of individuals age 65 or more will increase from approximately 12% currently, to 22% in 2050.¹ It is estimated that at least 20% of older adults experience declines in cognitive skills that affect their abilities to complete daily living skills independently.² Given this trend, a growing area of research in recent years has been to identify methods for maintaining cognitive functioning, as well as to better understand structural and functional properties of the brain during aging (Figure 1).^2,3 This review highlights general findings regarding the most researched therapies that involve cognitive therapy/remediation (ie, “brain training”), the importance of cardiovascular fitness in the maintenance of thinking skills, and the influence of dietary factors on cognition.

There is limited evidence to support that commercially available cognitive-training programs result in real-world improvements in everyday functional cognitive abilities. Instead, there is stronger empirical support for the benefit of cardiovascular fitness on the maintenance of cognitive skills and brain functioning in the context of aging. Further, dietary patterns such as the Mediterranean diet have been identified as another well-supported strategy for maintaining cognitive abilities and the functional and structural properties of the brain during older adulthood. The final section of this review contains practical recommendations for both patients and physicians.

Cognition and Aging

Cognition has been defined as “the intellectual or mental process whereby an organism becomes aware of or obtains knowledge.”⁴ In a practical sense, cognition refers to the ability to functionally use thinking skills in everyday life. Increased age is associated with declines in aspects of cognition, including reduced speed of information processing, attention, working memory, executive functioning, initial learning, and memory retrieval.⁵ Notably, cognitive skills are not uniformly affected by aging, and some abilities are particularly resilient to the aging process. For example, verbal knowledge and emotional awareness are relatively unaffected by age.⁵

Functional and Structural Changes Associated With Aging

Normal aging results in structural and functional changes to the brain.⁵ Studies employing functional MRI (fMRI) show that older adults who experience decreased brain activity in specific areas typically experience greater cognitive impairments.⁵ The prefrontal cortex is particularly vulnerable to atrophy during the aging process, and that atrophy in this region is associated with impairments in attention, processing speed, and executive functioning.⁵ Prior studies have found that brain reorganization may occur in order to compensate for atrophy.⁵ Older adults may exhibit bilateral activation of the prefrontal cortex, whereas younger adults tend to have unilateral activation.⁵ Over the course of the aging process, brain atrophy tends to become more generalized and involvement of compensatory mechanisms declines.^6,7

Factors That Worsen Cognition

One of the most common age-related changes associated with decreased cognition involves the evolution of white matter, identified as hyperintensities on MRI. Studies have found that vascular risk factors such as hypertension, stroke, obesity, diabetes, and hyperlipidemia are strongly associated with white matter hyperintensity.^6,7 Hypertension has been described as the most common vascular risk factor, with a lifetime prevalence rate of up to 90%.⁸ Older adults with vascular risk factors such as hypertension are at an increased risk for white matter hyperintensity lesions, stroke, and cerebral atrophy.^6,7 Other lifestyle factors, such as heavy use of tobacco and alcohol, have been linked with more severe white matter hyperintensity and atrophy of frontal and prefrontal regions.^7,9

There is strong evidence that older adults with vascular risk factors are more susceptible to cognitive declines when compared with healthy age-matched peers.⁶ For example, individuals with more severe white matter hyperintensity due to vascular factors demonstrate reduced performance on measures of attention, processing speed, and executive functioning.⁶ More pronounced weaknesses in initial learning and memory retrieval are seen in individuals with more severe vascular-related changes in the brain.⁶

There is also evidence that psychologic factors, including depression and chronic stress, are linked to structural changes in the brain. A meta-analysis concluded that individuals with longstanding depression have reduced hippocampal volume.⁷ Individuals with greater levels of cardiovascular reactivity to psychologic stress were found to have reduced hippocampal and amygdala gray matter volume.⁹

The vast majority of older adults will experience a vascular and/or psychologic risk factor during their lives, and individuals who have more of these factors are at an increased risk for structural and functional changes to the brain during the aging process.^6,7,10 Older adults with a greater number of these factors are at an increased risk for cognitive and functional decline.

Factors That May Improve Cognition

In recent years, a strong research emphasis has been placed on examining effective methods for preventing or reducing age-related cognitive changes (Figure 2).^5,11,12

Cognitive-Training Programs

There has been a rise in the promotion and use of commercially available cognitive-training programs in recent years. The premise of these programs is that the use of repetitive cognitive exercises can improve neuroplasticity of the brain in older adults and that this will counteract the cognitive declines associated with aging.⁵ The most widely used cognitive training programs use domain-specific cognitive exercises completed on a computer.¹¹

Prior studies have yielded mixed findings regarding the utility of the commercially-available cognitive-training programs. One of the larger studies of a computer-administered therapy, the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE), involved administration of 10 sessions of brain-training programming to 2,800 elderly adults. In this study, subjects were randomly assigned to 1 of 4 groups that included a control group, and 3 cognitive-training groups that focused on memory, reasoning, or processing speed. Immediately after the completion of the training, individuals who completed the program demonstrated improved performance on laboratory tasks associated with their specific cognitive domain. The ACTIVE trial found that 5 years later, people who completed the cognitive intervention had fewer declines in independent living skills. For example, individuals who completed processing speed training were less likely to have stopped driving 5 years later.Notably, however, the individuals who demonstrated the fewest functional declines were those who had higher levels of education and better overall physical health.Thus, the role of moderator variables, such as education and health status, is unclear.¹²

Although the ACTIVE trial demonstrated promising results for these cognitive-training programs, the majority of studies have demonstrated limited efficacy.^5,10 A study with 11,000 participants, ages 18 to 60 years, randomly assigned subjects to 6 weeks of visuospatial/attention training or to an active control group. At the end of this study, no significant difference was found in neuropsychologic test performance for either group compared with baseline performance.¹²

Another limitation of cognitive-training studies is that they have failed to investigate whether these programs result in sustainable cognitive changes over time.¹¹ Given that working memory (ie, the ability to mentally manipulate information) underlies higher-order cognitive skills, including initial learning and memory retrieval, methods for expanding working memory capacity have been a considerable focus of these training programs.^12,13 A meta-analysis showed that prior studies have demonstrated that domain-specific training may improve working-memory capacity on a short-term basis.¹⁴ There has been a paucity of prior investigations into the maintenance of these cognitive changes over time, however.

There is also limited evidence to support that any benefits from cognitive-training programs will transfer into more meaningful activities of daily living in older adults.^12-14 Prior studies have found that there are greater transfer effects among younger, healthy subjects. There has been limited generalizability of laboratory findings to closely related functional activities in older adults, with 1 study concluding, “transfer effects are small, or nonexistent, in old age.”¹³ Although the potential benefits of cognitive-training programs remain unclear in general, they may be particularly less useful in older adult populations.

The efficacy of cognitive-training programs to improve real-world, everyday use of cognitive skills is unclear. The degree to which implementation of cognitive-training programs can influence neuroanatomic and neurophysiologic changes also is unclear. For example, individuals who completed working-memory training had increased activity in prefrontal brain regions and increased connectivity between the prefrontal and parietal cortices.¹⁵ In contrast, in a randomized controlled trial of young adults to determine whether executive functioning training affected decision-making abilities, there were no significant differences in neural activity during decision-making tasks in subjects who did or did not have executive-functioning training.¹¹ Overall, what little research does exist reveals inconsistent findings of whether cognitive-training programs result in structural or functional changes in the brain.

In summary, there has been limited but intriguing research suggesting that specific cognitive skills may improve with training. However, much of the evidence supporting the benefits of these programs cite an individual’s improvement on the tasks employed in the program itself. Because the goal is not to perform better on cognitive-training exercises, but to have the exercises result in real-world improvements in memory and other thinking skills, and current research does not strongly support the use of these tools as part of a healthy cognitive aging program.¹³ The evidence does not support a generalizable effect of these training programs on overall cognition. Moreover, commercially available cognitive-training programs can be expensive, whereas the less expensive and readily accessible activities reviewed below are likely to have similar or greater benefits.

Exercise

There is substantial empirical support demonstrating that physical activity can be a preventive mechanism for cognitive and physical decline.^16,17 Throughout the lifespan, regular cardiovascular exercise is linked to reduced occurrence of vascular risk factors, including diabetes, cardiac disease, and obesity.¹⁶ Studies show that engaging in regular cardiovascular exercise such as walking or water aerobics at least twice each week for as little as 10 weeks can result in improved physical functioning in older adults.¹⁷ Although the majority of studies have focused on the use of aerobic exercise as a strategy for maintaining physical and cognitive health, there is some evidence to support the positive impact of resistance training for physical functioning in older adults as well.¹⁶

In addition to the benefits of exercise on physical health, research has demonstrated that regular aerobic exercise in older adults can slow cognitive decline and may play a role in preventing neurodegenerative processes such as Alzheimer’s disease.¹⁷ Longitudinal studies have demonstrated that older adults with higher baseline levels of cardiovascular fitness demonstrate better performance on measures of speeded information processing, attention, working memory, and general cognitive abilities 6 years later.¹⁷ Exercise may also have indirect benefit on cognitive efficiency by decreasing stress and improving sleep quality.^16,17

In older adults, studies have consistently demonstrated that exercise may produce structural and functional changes in the brain. Specifically, older adults with higher levels of cardiovascular fitness were less likely to have gray and white matter loss in prefrontal, frontal, and temporal brain areas. Studies using fMRI show that better respiratory fitness is associated with greater activation in brain regions associated with attentional control. Aging adults who engaged in a regular aerobic exercise regimen for a 12-month period demonstrated increased connectivity in frontal regions.¹⁷ There are numerous benefits of regular physical exercise, including improved physical, cognitive, and neuroanatomical functioning.

Dietary Patterns

In addition to the likely preventative mechanisms of exercise, investigations into dietary patterns for maintaining cognitive health have promising findings. Research shows that diets with higher amounts of saturated fat and simple carbohydrates are associated with increased rates of cognitive impairment and neurodegenerative processes.¹⁸

In contrast, the Mediterranean diet, a “plant-based, antioxidant-rich dietary pattern,” that incorporates a variety of foods including fish, vegetables, fruit, nuts, olive oil, complex carbohydrates, and moderate levels of red wine, is associated with lower rates of cognitive decline during older adulthood, independent of vascular risk factors.¹⁸ A randomized controlled trial of subjects adhering to the Mediterranean diet for 5 years found that these individuals demonstrated better performance on measures of executive functioning and memory when compared to a control group.¹⁹ More recent findings have emerged to support that closely-related dietary patterns, including the MIND and DASH diets, may also be associated with lower rates of cognitive decline with aging.²⁰

There is also evidence to suggest that dietary patterns, such as the Mediterranean diet, may protect against age-related changes to the brain. Individuals with relatively better adherence to this diet had more preserved white matter structural connectivity after 9 years compared with subjects who did not adhere to this dietary pattern. Adherence to the Mediterranean diet has been associated with decreased risk for stroke in individuals with multiple vascular factors.²¹

Recent studies have also investigated the role of nutrient biomarkers in long-term cognitive outcomes.Individuals with a pattern of lower levels of vitamin D, carotenoids, and unsaturated fats, along with higher levels of saturated fat, were more likely to be diagnosed with dementia within 12 years.²² Developing a better understanding of nutrient biomarkers is likely to be a growing field of research.

Social Support and Learning New Skills

The relationship between social support and cognitive functioning during older adulthood is less understood. Prior studies have found that greater social activity is associated with higher levels of general cognitive functioning, executive functioning, working memory, visuospatial abilities, and processing speed. The mechanism underlying this finding is unclear, however, and is possibly freighted with the tautologies to which clinical research is vulnerable, (ie, individuals who experience cognitive decline may be less apt to engage in social activities, partly because of awareness of decline and consequent embarrassment, and individuals who are more cognitively intact may exhibit higher levels of social engagement).²³ At present, the notion of social support as a protective factor for maintaining cognitive functioning is an area in need of additional research.

There has been some support that learning a new skill (eg, a new language) can be beneficial for maintaining cognitive health during aging.²⁴

Conclusion

Considering the rising number of older adults worldwide, an extensive focus of research in recent years has been on identifying mechanisms for maintaining cognitive and neuroanatomical functioning within the context of aging.^1,2 As reviewed here, there is evidence for several positive interventions (Checklist).

Although research for cognitive-training programs has revealed promising findings at improving cognitive functioning on the activity for which the program is designed, there is little evidence that benefits from these programs transfer into more useful daily activities and thereby have a preventive effect on the cognitive deficits associated with aging. Instead, there is stronger support for the role of cardiovascular exercise and dietary patterns such as the Mediterranean diet on improving cognitive and neuroanatomical functioning during the aging process.

1. World Health Organization Fact Sheet, February 5, 2018. http://www.who.int/news-room/fact-sheets/detail/ageing-and-health.

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14. Kilmova B. Computer-based cognitive training in aging. Front Aging Neurosci. 2016;8.

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17. Bherer L, Erickson KI, Liu-Ambrose T. A review of the effects of physical activity and exercise on cognitive and brain functions in older adults. J Aging Res. 2013:1-8.

18. Knight A, Bryan J, Murphy K. Is the Mediterranean diet a feasible approach to preserving cognitive function and reducing risk of dementia for older adults in Western countries? New insights and future directions. Aging Res Rev. 2016;25:85-101.

19. Valls-Pedret C, Sala-Vila A, Serra-Mir M, et al. Mediterranean diet and age-related cognitive decline: a randomized clinical trial. JAMA Int Med. 2015;175:1094-1103.

20. Morris MC, Tangney CC, Wang Y, et al. MIND diet slows cognitive decline with aging. Alz Dement. 2015;11:1015-1022.

21. Pelletier A, Barul C, Feart C, et al. Mediterranean diet and preserved brain structural connectivity in older subjects. Alz Dement. 2015;11:1023-1031.

22. Amadieu C, Lefevre-Arbogast S, Delcourt C, et al. Nutrient biomarker patterns and long-term risk of dementia in older adults. Alz Dement. 2017;13:1125-1132.

23. Kelly ME, Duff H, Kelly S, et al. The impact of social activities, social networks, social support and social relationships on cognitive functioning of healthy older adults: a systematic review. Syst Rev. 2017;6:1-18.

24. Klimova, B. Learning a foreign language: a review on recent findings about its effect on enhancement of cognitive functions among healthy older individuals. Front Hum Neurosci. 2018;12:305.