For many people in the United States, the end-of-year holidays mean a trip back home, and the possibility of noticing cognitive changes in aging family members they do not see regularly. Observing cognitive decline in a relative also can raise uncomfortable questions about the heritability of dementia and the potential that younger family members will be similarly affected in the future.
The number of people in the United States who suffer from dementia has been growing over time as life expectancy has risen and the ability of healthcare providers to diagnose cognitive changes in earlier stages has grown.1 For years, scientists predicted a significant rise in cases of dementia and a significant public health impact when the baby boom generation reached older adulthood.2 Although the number of patients with dementia in the United States has grown as the population ages, recent research is beginning to show that the likelihood of a patient being diagnosed with dementia is decreasing.3,4
Unfortunately, pharmacologic treatment for dementia is only modestly effective in preventing further cognitive decline.5,6 Despite substantial investment by pharmaceutical companies over the last 2 decades, no substantial breakthroughs for treating dementia have been achieved.7 In January 2018, Pfizer announced that it would no longer pursue research for treatments for dementia. Other pharmaceutical companies also are considering whether they wish to continue to work in this field.8 Although many supplement manufacturers sell products that they promote as beneficial for mental alertness, concentration, or alertness, none of these claims have a strong scientific basis or clear role in dementia treatment.
Not all the news in dementia research is discouraging, however. Recent research from multiple countries using multiple approaches has begun to demonstrate that cognitive loss due to Alzheimer disease and vascular dementia is more preventable than previously thought.9 Evidence is getting stronger for behavioral approaches that can lower the risk of ever getting dementia or at least delaying the onset of a dementia that impairs daily function.10 Unfortunately, the general public is unaware of these ways to reduce the likelihood of developing dementia.11 This lack of knowledge is an opportunity for physician assistants (PAs) to intervene, both with prevention-oriented medical care and with education for patients and their families.
Preventing or slowing the onset of dementia is thought to be based on the idea of maximizing and preserving cognitive reserve, or the ability to maintain normal cognitive function despite brain deterioration or injury. People with greater cognitive reserve can sustain greater neuronal injury before beginning to demonstrate cognitive loss. The goal is for patients to develop as much cognitive reserve in youth and middle age as they can before brain deterioration begins or injury occurs.12
Dementia is the result of heterogeneous disease processes that often manifest with similar symptoms. The most common type of dementia is Alzheimer disease, followed by vascular dementia, dementia with Lewy bodies, and Parkinson disease–associated dementia. Less common types of dementia include frontotemporal dementia, Alzheimer disease in patients with Down syndrome, and Creutzfeldt-Jakob disease. This review will focus on risk-reduction strategies for the two most common types of dementia: Alzheimer disease and vascular dementia. Although they have different pathophysiologic mechanisms, effective risk-reduction strategies are very similar for these two diseases.
All of the relationships described in the literature on the topic of dementia are correlational. Strong correlations between an individual factor and a disease suggest causation but cannot definitively prove it. To prove causation, investigators would need to randomize subjects on variables such as diet, exercise, smoking, diabetes, and history of head injury. This type of study would not only be grossly impractical, it would be unethical. However, when multiple studies across many years and many countries demonstrate similar observations, we believe this evidence to be powerful enough to change our approach to patient care.
The risk factors for developing dementias have been very well characterized through population-based observational studies around the world over the last 40 years. Risk factors can be divided into three groups: nonmodifiable, modifiable primarily during childhood, and modifiable in adulthood (Table 1). This article focuses on modifiable risk factors that represent opportunities to help patients avoid, or at least delay, the onset of dementia.
NONMODIFIABLE RISK FACTORS FOR DEMENTIA
The most important risk factor for all dementias is age. In developing and developed countries, the prevalence of dementia has increased as life expectancy has increased.13 In the United States, Alzheimer disease affects about 13% of patients over age 65 years and 45% of those older than age 85 years.14 Although a focus on improving the general health of older adults is important, age itself is a predictor of development of dementia and cannot be changed.
Genetics also are a strong predictor for the development of Alzheimer disease and vascular dementia. Having a parent with dementia has been understood as a risk factor for development of dementia for many years before the scientific basis for this relationship was established. Epidemiologic studies over the past 20 years have demonstrated that patients who have a parent with dementia are about 2.5 times as likely as those who have parents who do not have dementia to receive a dementia diagnosis.15,16 Specific genes, chiefly the APOE epsilon 4 gene, predispose patients to development of Alzheimer disease and vascular dementia. The importance of the APOE epsilon 4 gene in the development of Alzheimer disease was established in the early 1990s; the link between this gene and risk for vascular dementia was established in the late 1990s.17,18 Research has shown that presence of the APOE epsilon 4 gene can confer an increased risk of Alzheimer disease by between 3 and 30 times that of a person who does not carry the gene.19 Presence of the gene also is associated with a lower age of onset of Alzheimer disease and faster disease progression.20,21
RISK FACTORS FOR DEMENTIA THAT ARE MODIFIABLE IN CHILDHOOD
Although some risk factors for dementia are modifiable throughout the lifespan, some are primarily modifiable before adulthood. PAs who treat children may wish to consider which interventions to take with these patients and their families that may enable them to preserve cognitive function over the lifespan.
- Low educational attainment. In epidemiologic assessments of dementia, low educational attainment is consistently associated with development of dementia. Increased education is associated with increased cognitive reserve capacity.22 Patients with greater cognitive reserve can lose more before symptoms of dementia appear.23 Studies around the world typically have compared patients who have participated in secondary education with those who have not. No large studies have demonstrated a linear relationship between education after primary school and reduced rates of dementia. Regardless, increased educational attainment has been correlated with good health overall, so clinicians should be working with patients and their families to ensure that children stay in school and obtain the highest level of education possible.24
- Head injury. The long-term consequences of head injuries in childhood have been increasingly in the news over the past decade. Repetitive head injuries sustained during childhood have been associated with cognitive decline, vertigo, depression, and other neuropsychiatric symptoms.25-28 Patients with traumatic brain injuries in adulthood have been found to be more likely to have Parkinson disease and dementia with Lewy bodies.29 Evidence for a direct relationship between childhood head trauma and Alzheimer disease in older adulthood is lacking, in part because the definitive studies of this research question will take decades to perform. However, the evidence seems clear that even mild head trauma is not good for brain health. In response, the CDC has begun working with youth sports leagues, state health organizations, and school districts to develop approaches for minimizing childhood head trauma.30 More information on this initiative, the Heads Up program, is available on the CDC website (www.cdc.gov). This site is an excellent resource to share with parents and community leaders who are concerned about this issue.
- Low-quality diet. The contribution of a low-quality diet to the development of dementia is not limited to childhood, but eating patterns and taste preferences often are established in childhood and persist into adulthood.31 Children who have greater exposure to fruits and vegetables and less exposure to sweetened beverages and candies are more likely to find healthful foods palatable and to maintain these dietary patterns into adulthood.31 Although improving the quality of a patient's diet is likely beneficial at any point in the patient's lifespan, efforts to help parents feed their children well have particularly long-lasting health benefits. Obesity, diabetes, and hypertension are strong risk factors for Alzheimer disease and vascular dementia.12 Dietary approaches that prevent the development of these diseases will prevent many different types of morbidity in addition to dementia, including stroke, myocardial infarction, osteoarthritis, renal failure, and blindness.
- Physical inactivity. This risk factor for vascular disease and dementia can be modified at any age. However, like diet, habits and preferences about physical activity that are established in childhood often carry over into adulthood. Adolescents who engage in moderate to vigorous physical activity are more likely than those who do not to continue regular exercise 5 and 10 years later.32 Lack of physical activity also is strongly associated with the development of obesity, diabetes, and hypertension. In part because of the increasing popularity and availability of personal electronic devices, recent studies show that children and adolescents are less likely than ever to be physically active on a daily basis and are more likely to be overweight or obese.33-35 Preventing childhood obesity by promoting daily moderate to vigorous physical activity is much easier than treating obesity in childhood. PAs should routinely engage with families about potential opportunities to exercise as a family.
RISK FACTORS FOR DEMENTIA THAT ARE MODIFIABLE IN ADULTHOOD
- Hearing loss. Surprisingly, one of the risk factors demonstrated to contribute most to progression of dementia also is one of the most treatable. Hearing loss has only been recognized as a substantial contributor to cognitive loss in the past 15 years. Cohort studies are showing that even typical, mild, age-related hearing loss is associated with an increased likelihood of development of dementia in those who were hearing impaired but cognitively intact at entry to the study.36,37 Based on these findings, investigators are beginning the rigorous studies needed to determine if correcting hearing loss with hearing aids or cochlear implants can slow dementia onset or progression.38 Small studies have already shown that patients who use hearing aids perform slightly better on the Mini Mental State Examination than those with hearing loss who do not use hearing aids.39 Researchers do not know if hearing loss is associated with cognitive decline because of the lack of auditory stimulation to the brain or because patients with hearing loss often become increasingly socially isolated. Social isolation is itself an independent risk factor for dementia. Although the answer to these questions is unknown, recommending hearing protection and hearing correction to patients is ethical.
- Smoking. Both the vascular damage caused by smoking and the neurotoxins contained in cigarettes damage the brain.12 Smoking is one of the strongest risk factors for stroke.40 In turn, strokes (detected or undetected) are one of the primary causes of vascular dementia.41 Smoking clearly is a modifiable behavior, although smoking cessation is notoriously difficult. A number of potentially synergistic strategies, including medications, nicotine replacement therapies, support groups, quit lines, and individual support, provided to the patient by the provider are available. Even patients who have smoked for decades can reduce their cardiovascular risks in a meaningful way through smoking cessation.42 Some patients may respond to an informed discussion about smoking as a risk factor for dementia, particularly if they have a family member with dementia and have expressed a wish to avoid dementia themselves.
- Depression. This common condition has strong links to dementia. Patients with early dementia often have depression although whether depression is a symptom of dementia onset or a cause of dementia is unclear. Studies have shown that patients who have more episodes of depression throughout their lives are at increased risk for developing mild cognitive impairment and dementia.43 Patients with a history of major depression are more likely to have higher levels of amyloid-beta deposition in their brains compared with patients without depression. Increased amyloid-beta deposition is associated with increased likelihood of Alzheimer disease.44 Early studies are beginning to suggest that treatment of depression with some selective serotonin reuptake inhibitors may decrease amyloid-beta deposition in the brain.45 In addition to treating depression aggressively to rid patients of a frustrating disease, clinicians should treat depression before making a diagnosis of dementia. Sometimes the apathy, poverty of speech, and forgetfulness that clinicians view as indicating dementia are simply symptoms of depression. When the depression is treated, these symptoms lift and the diagnostic dilemma of depression versus dementia is resolved.
- Physical inactivity. As discussed above, lack of physical activity at any age is a risk factor for dementia. One very large meta-analysis of data from 12 cohort studies and more than 33,000 participants who entered the study without dementia found that regular exercise was a significant protective factor for development of cognitive decline.46 The direct mechanism for how exercise protects the brain from cognitive loss is unknown. Researchers are actively looking into these mechanisms, which potentially include angiogenesis in central nervous system tissue, decreased production of free radicals in the hippocampus, and increased production of a number of neuroprotectant enzymes.47 Exercise may help protect the brain from dementia by preventing other conditions that are risk factors for development of dementia, including hypertension, diabetes, and obesity. In addition, many people exercise with others. Exercising with others on a regular basis can help reduce social isolation and loneliness. Finally, patients may reap synergistic benefits from the biologic, social, and physical consequences of engaging in regular exercise. Although studies have established that more exercise generally is better for preventing death in older adults, even modest increases in the amounts of exercise produce benefits.48 A reasonable approach is to attempt to get each patient to exercise just a bit more than he or she already does, and to continue to encourage patients to exercise more over the years.
- Social isolation and loneliness. People are socially isolated when they lack a sense of belonging to a group, lack meaningful engagement with others, and have a small number of quality relationships. People are lonely when they feel distressed about the discrepancy between their desired and actual social relationships.49 Some studies have shown that social isolation itself is a risk factor for dementia; other studies have found that only those who feel lonely are at increased risk for dementia.50 Patients with hearing loss and those who are depressed often remove themselves from their social networks because of difficulties interacting with others. These patients may increase their risk for dementia by adding loneliness to their existing dementia risk factors. Because people can sometimes be ashamed of their social isolation and loneliness, clinicians may find it challenging to get patients to tell the truth about their social situation. Encourage older patients to enhance their social networks and reduce loneliness by becoming involved in a religious community, taking on volunteer work, joining a club for those with similar interests, or signing up for an exercise class, for example. Each one of these at least provides the potential for the development of deeper friendships. If appropriate, refer the patient to a community social worker or a senior center. A specific referral of this sort may increase the likelihood that the patient and their family members may follow through.
- Lack of intellectual activity. Anyone who has ever watched late-night television can testify to the number of advertisements for “brain training” programs that purport to prevent or slow cognitive loss. These programs typically are online word, number, or spatial relationship puzzles. The makers of these programs try to demonstrate their effectiveness by showing that those who work the puzzles improve their scores over time. These data, however, do not really tell us whether the puzzles help strengthen cognitive reserve or simply enable people to become better at working a specific type of puzzle. A recent large meta-analysis found that patients who do puzzles get better at doing puzzles.51 However, the researchers found no evidence that doing the puzzles improved patient function in other cognitive domains.51 Based on multiple epidemiologic studies, engaging in a wide range of intellectual activities such as reading, doing puzzles, gardening, taking care of the home, visiting museums, and listening to music will do patients no harm and may improve their cognitive reserve.52,53 However, no evidence shows that intellectual activity helps patients who have already developed dementia.
- Hypertension. Long recognized as a significant contributor to the development of stroke and vascular dementia, hypertension now has been found likely to contribute to the development of Alzheimer disease.54,55 Given that nearly 30% of American adults have hypertension, the contribution of this risk factor to the development of dementia cannot be ignored.56 Hypertension also is one of the most modifiable of the dementia risk factors. Due to the wide variety in mechanisms of action of antihypertensive drugs, a suitable medication can be found for nearly every patient. A systematic review by Rouch and colleagues found that of the 11 longitudinal studies evaluated, eight demonstrated clear cognitive protective benefit from initiation of antihypertensive medication.57 This review found that calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers were particularly useful for slowing progression to dementia. Fortunately, all three of these classes of medication are well tolerated and all have at least one drug in the class that is reasonably priced.
- Obesity or type 2 diabetes. Although obesity and type 2 diabetes are not synonymous, both are associated with insulin resistance and both are risk factors for vasculopathies. The data on obesity and diabetes and their relationship to Alzheimer disease is unclear. Like hypertension, diabetes and obesity are risk factors for stroke. Some large longitudinal studies have found a relationship between mid-life obesity and subsequent development of dementia.58 Others have not been able to detect this relationship.59 One issue in the study of patients with significant obesity or diabetes is that patients with these diseases often die relatively young of other causes, such as myocardial infarction (MI) or cancer, and do not live long enough to develop dementia. Obesity (but not diabetes) in later life also may provide some protection from recurrent stroke.60 The mechanism of this protective effect is unknown. Encouraging patients to lose even 10% to 15% of body weight can provide significant reductions in the likelihood of early death from MI or stroke.61 In addition to potentially reducing the risk for dementia, weight loss is associated with a host of other positive outcomes for patients, including reduced joint pain, depression, and fatty liver disease.
Research has shown that patients are concerned about developing dementia but are unaware that proven risk-reduction measures exist. Most dementia risk-reduction measures are not only beneficial for preventing cognitive loss but are also beneficial to the patient's overall health if implemented. For some patients, the goal of preventing dementia may be the impetus they need to adopt health behaviors that will benefit them in several different ways.
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