May/June 2018

Brain Health and Dementia: Challenge or Opportunity?
By Krystal L. Culler, DBH, MA; Jeronimo Martin, MD; and Alejandra Guerrero, MD
Today's Geriatric Medicine
Vol. 11 No. 3 P. 26

Recent research findings present recommendations for lifestyle modifications aimed at dementia prevention. Providers can play a key role in promoting these protective modifications.

A public health approach to dementia could prevent up to 30% of worldwide dementia cases over the next 20 years.1 Various studies that call attention to modifiable lifestyle factors and their role in the manifestation of dementia symptoms are reporting decreasing prevalence rates of dementia.2-6 Dementia prevention is commonly discussed in terms of risk reduction in modifiable lifestyle factors such as the management of cardiovascular risks, diabetes management, and level of educational attainment, among others.

A natural decline in brain function comes with age; nonetheless, dementia is not a normal part of aging. This decline may be explained by the varying degrees of brain health and cognitive reserve, the capacity of the brain to maintain function despite age-related damage. The variation in cognitive reserve and the development of dementia can be attributed to different risk factors. Brain health is commonly attributed to 70% lifestyle and 30% genetics. Research is escalating to support minimizing individuals' risks for the development of dementia rather than searching for the silver bullet.

In 2015, the Institute of Medicine released a call for action to enable health care providers, family members, communities, and individuals to take actions in their daily lives that may ward off the impact of cognitive issues and dementia, thus leading to more independent lives.7 Since June 2017, there have been numerous publications that have addressed lifestyle factors that decrease individuals' risks for late-life cognitive decline and dementia. This article aims to summarize the findings of the recently published National Academy of Sciences, Engineering, and Medicine's report, "Preventing Cognitive Decline and Dementia: A Way Forward," and the Lancet Commissions' report, "Dementia Prevention, Intervention, and Care."8,9 The reports were published within one month of each other but put forth different recommendations for lifestyle modifications for dementia prevention, which will be outlined and discussed below.

National Academies of Sciences, Engineering, and Medicine
Published in June 2017, "Preventing Cognitive Decline and Dementia: A Way Forward" examined recent evidence that intervention can prevent or slow the progression of age-related cognitive decline, mild cognitive impairment, and clinical Alzheimer's type dementia.8 For inclusion in this report, only the gold standard of research, randomized controlled trials, were reviewed but were quite limited. Based on the research reviewed, the committee found no intervention that could definitely prevent cognitive decline or dementia. The committee identified the following three activities as encouraging but inconclusive: cognitive training, high blood pressure management, and increased physical activity.8

• Cognitive training is a broad term that is used to examine a general set of cognitive functions such as memory, speed of processing, and problem-solving, that may or may not be computer based. At this time there is no evidence that commercial computer-based cognitive training offers advantageous long-term cognitive effects. The effects appear to advance to short-term benefits that apply only to the cognitive skill or domain that was specifically targeted in the training. Further research in this area is warranted to investigate whether cognitive training can prevent or delay cognitive impairment or dementia.

• Blood pressure management for people with hypertension lacks sufficient evidence to determine how much impact it has on preventing dementia because neurocognitive effects appear after 10 or more years following the diagnosis of hypertension. Nonetheless, control of high blood pressure in middle age (ie, ages 35 to 65) when brain changes related to dementia begin to occur might have an impact in reducing dementia in later life.

• Increasing physical activity has numerous documented health benefits, and aerobic exercise and strength training were underlined in the report. A simple rule of thumb to guide behavior change is to strive to increase what an individual is currently doing with regard to physical exercise.

In sum, more longitudinal research is needed to understand how the aforementioned interventions (cognitive training, high blood pressure management, and increased physical activity) may benefit people across various ages and disease stages with a focus on cognitive decline, mild cognitive impairment, and dementia. Ultimately, the goal is to prevent cognitive decline to enable people to live longer, healthier lives. The report concludes, "There is good cause for hope that in the next several years much more will be known about how to prevent cognitive decline and dementia."8

Prevention Is Better Than a Cure
Published online in July 2017, the Lancet Commissions' report "Dementia Prevention, Intervention, and Care" identified nine potentially modifiable lifestyle factors that, if addressed across the life span, may prevent dementia.9 The report suggested that approximately 35% of dementia is attributed to the following nine risks factors: education, midlife hypertension, midlife obesity, hearing loss, late-life depression, diabetes, physical inactivity, smoking, and social isolation. On the other hand, eliminating the apolipoprotein E ε4 allele, commonly known as the major genetic risk factor associated with developing Alzheimer's disease, produced a 7% reduction in the incidence of dementia risk; thus, lifestyle factors are playing a greater role than genetics in dementia risk reduction.9 The committee concluded that it is important to be "ambitious about prevention," as this offers the potential to delay or prevent one-third of dementia cases. Each lifestyle risk factor identified by Livingston and colleagues will be explored below and real-world information will be offered for health care providers.9

• Education is the second most important modifiable risk factor; a lack of education is common among 40% of dementia patients. Lower levels of education are associated with a 59% increase in the risk of dementia and are directly related to up to 19.1% of cases of dementia. A low educational level results in greater vulnerability to cognitive decline because it results in less cognitive reserve, which is the capacity to maintain the brain functions despite brain pathology. Evidence is currently lacking to determine whether higher levels of education diminish the risk of dementia.

• Midlife hypertension increases the risk for dementia by 57.3%. If hypertension is controlled, approximately 2% to 5% of dementia cases in the general population could be avoided. Hypertension produces chronic endothelial damage, impairs cerebral blood flow regulation, and increases the risk for stroke and vascular dementia. It is also important to point out that adequate control of hypertension (<150/90 mm Hg) can reduce the progression of cognitive decline and incidence of dementia.

• Midlife obesity is one of the components of metabolic syndrome. Metabolic syndrome can produce insulin resistance and an increase in concentrations of insulin in the bloodstream. This can lead to diminished insulin levels in the brain, provoking decreased amyloid clearance and a greater risk of developing dementia. People with obesity also have higher blood glucose levels and higher inflammatory markers, both which have been proposed as pathways for cognitive decline. Obesity is present in 2% of all dementia cases.

• Hearing loss has only recently been established as a risk factor for dementia and is the main modifiable risk factor for dementia. Hearing loss has been associated with a 94% increase in the risk of dementia. Subsequently, among 100 dementia cases, up to 23 can be attributed to hearing loss, and hearing loss has a prevalence of 31.7% in patients with dementia. The mechanism underlying cognitive decline associated with peripheral hearing loss is not yet clear, and it has not been established whether correcting it can prevent or delay the onset of dementia. A recent systematic review and meta-analysis published online by Loughrey and colleagues in December 2017 further highlighted the relationship between hearing loss as a modifiable risk factor for cognitive decline, cognitive impairment, and dementia.10

• Debate continues about the direction of causation for depression: Is depression a prodromal symptom or an independent risk factor for dementia? It is reasonable that dementia risk increases due to depression's impact on stress hormones, neuronal growth factors, and hippocampal volume.

• As previously stated, higher blood glucose levels have been proposed as a possible pathway for cognitive decline. It has been determined that diabetes confers a 50% risk increase for developing dementia. Additionally, 6.4% of people with dementia suffer from diabetes. It is important to point out that diabetes is a risk factor for stroke and endothelial dysfunction, which, in turn, can contribute to developing dementia.

• Studies have reported that physical activity has a significant protective effect against cognitive decline, with a high level of exercise being the most protective factor, reducing the risk of dementia by 38%. In older people without dementia, physical exercise improves balance and reduces falls, improves mood, reduces mortality, and improves function.

• Smoking increases the risk of dementia by 60% but is an easily preventable risk factor. Smoking is present in 27.4% of all dementia cases, and if smoking cessation occurred, there would be a decrease in up to 13.9% of all dementia cases. It has been proven that smoking is related to cognitive impairment due to vascular pathology and the neurotoxins contained in cigarettes.

• Social isolation is a new risk factor identified by this report and may be a preclinical symptom of dementia. Individuals who are socially isolated are at an increased risk for hypertension, coronary heart disease, and depression. Additionally, social isolation can result in cognitive inactivity, which is associated with low mood and a more rapid decline in cognition.

Report Comparisons
The reports issued from the National Academies of Sciences, Engineering, and Medicine and Lancet Commissions offer different information regarding the levels of evidence on lifestyle factors and their potential impact on dementia. (It is important to note that each report had different criteria for research to be included for its committee review.) Both reports offer lifestyle factors that warrant further investigation to better understand their relationship with the prevention of cognitive decline and dementia.

Both reports call attention to physical activity and the management of high blood pressure. Both point out the importance of high blood pressure control during midlife to prevent vascular damage in brain blood vessels, diminish the risk of stroke, and decrease the risk of vascular dementia.

The Lancet Commissions' report puts forth two new factors for consideration: hearing loss and social isolation in comparison with similar previous studies.1,9,11 The inclusion of social isolation as a risk factor speaks to the World Health Organization's comprehensive definition of health as "a state of complete physical, mental, and social well-being, not merely the absence of disease or infirmity." These risk factors call for more research but may also be linked to other documented risks such as depression and/or loneliness; therefore, taking into consideration the social lives of adults in addition to their physical and mental health is noteworthy for health care professionals.9

As older adults express concern about their brain health, health care professionals are viewed as trusted sources of information. In addition to practitioners gaining an understanding of lifestyle factors that contribute to dementia risks, it is important for providers to be aware of existing networks and institutions that focus on diminishing the impact of dementia and provide accessible information to the public. The following are resources made readily available to providers.

Global Brain Health Institute
Launched in 2015, the Global Brain Health Institute (GBHI) is a leader in the global community dedicated to protecting the world's aging populations from threats to brain health. Located across two sites—the University of California, San Francisco and Trinity College Dublin—the GBHI works to reduce the scale and impact of dementia in three ways: by training and connecting the next generation of leaders in brain health through the Atlantic Fellows for Equity in Brain Health program; by collaborating in expanding preventions and interventions; and by sharing knowledge and engaging in advocacy.

GBHI brings together a powerful mix of disciplines, professions, backgrounds, skill sets, perspectives, and approaches to develop new solutions. GBHI strives to improve brain health for populations across the world, reaching into local communities and across its global network. By focusing on working compassionately with people in vulnerable and underserved populations to improve outcomes and promote dignity for all people, the Atlantic Fellows for Equity in Brain Health, based at GBHI, provides innovative training, networking, and support to emerging leaders who are focused on bringing transformative change to improve brain health and reduce the impact of dementia worldwide. It is one of six global Atlantic Fellows programs to advance fairer, healthier, and more inclusive societies. Health care professionals from a variety of disciplines are encouraged to engage with the GBHI training, collaboration, and expertise offered through its recognized leaders in a range of disciplines, fellows, and senior fellows. Connect with the GBHI at www.gbhi.org.

Global Council on Brain Health
Information regarding brain health and dementia is rapidly evolving as new research becomes available. Practitioners are challenged to stay up to date with relevant information to provide to their patients. The Global Council on Brain Health offers evidence-based recommendations for people to consider adopting into their daily lives. A collaborative of AARP, the council consists of scientists, health professionals, scholars, and policy experts from around the world working in broad areas of brain health. The intent of the council is to offer practical brain health advice to the public, health care providers, and policy makers based on the current research evidence from a consensus of interdisciplinary experts.

To date, the council has published reports on the following brain health topics: nutrition and brain health, cognitively stimulating activities, social engagement and brain health, sleep and brain health, and physical activity and brain health. The reports offer advice that older adults can utilize to adopt a brain healthy lifestyle. Full-length reports are available as resources for practitioners and brief reports can be distributed to patients interested in gaining practical up-to-date brain health recommendations. Additional information can be found at www.aarp.org/health/brain-health/global-council-on-brain-health. This information is beneficial for providers to be prepared to respond to patient queries related to brain health and dementia.

Conclusion
Dementia is commonly referred to as the public health challenge of the 21st century. Recent research is mounting to provide an opportunity—that changes in lifestyle earlier in life can have a profound impact on later life. Understanding the importance of prevention earlier in the disease progress (because it is known that changes occur for up to 20 years in the brain and body before an Alzheimer's disease diagnosis) is an initial first step emphasized by both reports highlighted in this article.

Additionally, nonpharmacological interventions such as cognitive brain training and socially based interventions may offer encouraging evidence toward the prevention of cognitive decline and dementia. The prospect for dementia prevention is growing across multiple disciplines, and a growing body of research will influence future decision making by health care providers and patients. For now, though, it's important to emphasize that it is possible to live a brain-healthy life with dementia. It is never too early nor too late to adopt healthy lifestyle modification(s) to maximize brain health and wellness.

— Krystal L. Culler, DBH, MA, is an Atlantic Fellow for Equity in Global Brain Health at Global Brain Health Institute, Trinity College Dublin. She is the Nathan and Lenore Oscar Family Director of Menorah Park Center for Brain Health, the first nonpharmacological, nonhospital-based brain health center located on a senior living campus in the United States (Center4BrainHealth.org).

— Jeronimo Martin, MD, is an emergency medicine specialist and an attending physician in Hospital General Dr. Gaudencio Gonzalez Garza CMN La Raza in Mexico City. He is an Atlantic Fellow in Equity in Brain Health at Global Brain Health Institute, Trinity College Dublin. His main clinical focus is stroke treatment and prevention, and neurovascular diseases in the emergency department setting.

— Alejandra Guerrero, MD, is a neurologist and an Atlantic Fellow for Equity in Brain Health at Global Brain Health Institute, Trinity College Dublin. Her clinical focus is on the care of patients with cognitive impairment and vulnerable populations.

References
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2. Langa KM, Larson EB, Crimmins EM, et al. A comparison of the prevalence of dementia in the United States in 2000 and 2012. JAMA Intern Med. 2017;177(1):51-58.

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5. Matthews FE, Arthur A, Barnes LE, et al. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet. 2013;382(9902):1405-1412.

6. Petersen RB, Lissemore FM, Appleby B, et al. From neurodegeneration to brain health: an integrated approach. J Alzheimers Dis. 2015;46(1):271-283.

7. Institute of Medicine. Cognitive Aging: Progress in Understanding and Opportunities for Action. Washington, D.C.: The National Academies Press; 2015.

8. National Academies of Sciences, Engineering, and Medicine. Preventing Cognitive Decline and Dementia: A Way Forward. Washington, D.C.: The National Academies Press; 2017.

9. Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673-2734.

10. Loughrey DG, Kelly ME, Kelley GA, Brennan S, Lawlor BA. Association of age-related hearing loss with cognitive function, cognitive impairment, and dementia: a systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg. 2018;144(2):115-126.

11. Barnes DE, Yaffe K. The projected impact of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 2011;10(9):819-828.