COMMENTARY

Alzheimer's Prevention: A Summary of What We Know

Laurie L. Barclay, MD

Disclosures

August 23, 2017

Prevention of Alzheimer's Disease: Lessons Learned and Applied

Galvin JE
J Amer Geriatr Soc. 2017 Aug 2. [Epub ahead of print]

Summary

Alzheimer disease (AD) prevalence in the United States currently exceeds 5 million, and the Alzheimer's Association estimates a US prevalence of 16 million by the year 2050 unless an effective treatment is developed. Increasing age is still the leading risk factor for AD, with a prevalence of 42% by age 82 years. Other nonmodifiable risk factors include female sex, positive family history, and presence of the apolipoprotein E ε4 allele.

At present, only four FDA-approved medications are available for memory and behavioral AD symptoms. Disease-modifying treatment trials have been unsuccessful, although several new trials are underway and research continues. Prevention strategies are therefore essential and are now facilitated by advances in diagnostic criteria, biomarker development, and greater understanding of the biophysiologic underpinnings of AD.

Risk-factor prevention should target diabetes mellitus and insulin resistance, obesity, metabolic syndrome, hypertension, hypercholesterolemia, cerebrovascular disease, depression, psychological and physiologic stress, traumatic brain injury, sleep-disordered breathing, smoking, alcohol abuse, high blood pressure, renal disease, alcohol and tobacco use, high cholesterol, coronary heart disease, sedentary life style, and diet. These potentially modifiable risk factors, when combined, account for more than 50% of AD risk, based on observational studies, and many of these risk factors do not appear to affect amyloid or tau proteins. In sporadic and genetic forms of AD, pharmacologic trials of antiamyloid therapies are ongoing.

Modifiable factors appearing to protect against AD include cognitive reserve and mental activity, educational attainment and lifelong learning, cognitive leisure activities, physical activity and exercise, social engagement, mindfulness and wellness activities, optimism and purpose in life, healthy diet, and omega-3 intake. A review of 19 studies suggests that certain brain-stimulating activities may help reduce AD risks. These include crossword puzzles, card games, computer use, arts or crafts, taking classes, group discussions, and listening to music.

Depending on the type of exercise and its intensity, physical activity may lower AD risk by up to 65%. Underlying mechanisms may include reduction in blood vessel disease, better pulmonary function, increased cell survival, and anti-inflammatory effects.

Up to 30% of AD may be preventable by well-balanced, healthy lifestyle choices, including regular exercise, social engagement, and a healthy diet including recommended servings of fresh fruits and vegetables, whole grains, and lean proteins, and avoiding processed foods.

Viewpoint

Although clear explanations are lacking regarding why some people and not others develop AD as they age, targeting known risk factors may help prevent or forestall the disease. Healthy lifestyle modification including increased physical activity, healthy diet, social engagement, and mentally challenging activities may be effective.

Future research into AD prevention should concentrate on persons at increased risk because of genetic or other vulnerabilities, and on better management of chronic health conditions and lifestyle choices.

Conventional clinical trials require large-sample, long-duration, randomized designs and may therefore be difficult to conduct. By contrast, a precision-medicine approach using a single subject may more rapidly determine whether personalized prevention plans may optimize person-centered outcomes. Several different pathways may trigger AD, suggesting that several different strategies may prevent or forestall AD. Even if ineffective alone, these precision strategies can reduce comorbidities and thereby substantially increase the probability that amyloid- or tau-specific therapies will be effective. The usually slow, progressive course of AD suggests that patient-specific approaches may have a chance to be effective.

Abstract

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