Reducing the prevalence of seven dementia risk factors by 10% to 25% could help as many as 184,000 to 492,000 Americans avoid Alzheimer disease, according to study findings published in Lancet Neurology.

Diabetes, midlife hypertension, midlife obesity, smoking, depression, lack of mental stimulation and physical inactivity are cumulatively responsible for 54.1% of U.S. AD cases and will account for 2.9 million new cases in the next 40 years, according to Deborah Barnes, PhD, and Kristine Yaffe, MD, of the University of California San Francisco.

Using Cochrane meta-analysis for diabetes and hypertension and pooled data from other published reports, Barnes and Yaffe calculated the projected effect of each of these seven risk factors on the prevalence of AD in the U.S. and worldwide.

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They found that among U.S. residents physical inactivity was the leading preventable cause of AD, responsible for 21% or 1.1 million cases.  

Physical inactivity is known to contribute to the development of cardiovascular risks factors that may also contribute to dementia, the researchers noted, including diabetes, hypertension and obesity.

“Because physical inactivity is associated with most of the other AD risk factors identified […] public health initiatives to increase physical activity levels throughout life could potentially have a dramatic effect on [U.S.] AD and dementia prevalence over time,” the researchers wrote.

The other six risk factors contributed to U.S. AD incidence as follows:

  • Depression: 14.7%; 781,000 U.S. cases
  • Smoking: 10.8%; 574,000 U.S. cases
  • Midlife hypertension: 8.0%; 425,000 cases
  • Midlife obesity: 7.3%; 386,000 cases
  • Low education and mental activity: 7.3%; 386,000 cases.

In the rest of the world, public education campaigns and smoking cessation initiatives have the greatest potential to reduce AD prevalence, according to the researchers – as 19% or 6.5 million cases worldwide were attributable to low education, and 14% or 4.7 million cases were attributable to smoking.

The researchers emphasized that “AD is a multifactorial disease,” and that many of the risk factors are interrelated.

Furthermore, they pointed out that the identified risk factors were associative and not causative, so the true effect of risk factor modification on disease incidence remains unknown.

“Randomized controlled trials (RTCs) of multimodal risk factor reduction strategies to prevent AD are crucially needed, and public health campaigns targeted at AD risk factor modification should be developed,” Barnes and Yaffe wrote.

In an accompanying editorial, Laura Fratiglioni, MD, PhD, and Chengxuan Qiu, MD, PhD, of the Karolinska Institute in Stockholm, noted that methodological aspects of studies included in the meta-analysis may also limit the reliability of Barnes’ and Yaffe’s calculations.

However, they agreed that the potential to reduce dementia cases by risk factor modification “is highly relevant for both individuals and society,” due to increasing rates of AD-specific disability and institutionalization among elderly adults.

“Large-scale multidomain intervention projects that could be undertaken in high-risk populations, as done with cardiovascular disease, should now be implemented,” Fratiglioni and Qui wrote.

Several age-related cognitive impairment RTCs are currently ongoing in Finland, France and the United States that are expected to provide more insight into the effects of risk factor modification on developing AD and other forms of dementia.

Barnes D, et al. Lancet Neurol. 2011;doi:10.1016/S1474-4422(11)70072-2.

Fratigilioni L, et al. Lancet Neurol 2011;doi:10.1016/S1474-4422(11)70145-0.