Literature Review

Modifiable Risk Factors for Alzheimer’s Disease Point to Preventive Strategies



Interventions that target modifiable risk factors for Alzheimer’s disease hold promise for reducing the incidence of Alzheimer’s disease in the general population, according to a meta-analysis published in the December 2015 issue of Journal of Neurology, Neurosurgery and Psychiatry.

“Effective interventions in diet, medications, biochemical exposures, psychological condition, pre-existing disease, and lifestyle may decrease new incidence of Alzheimer’s disease,” said Jin-Tai Yu, MD, PhD, of the University of California San Francisco, and colleagues.

 Jin-Tai Yu, MD, PhD

Jin-Tai Yu, MD, PhD

The causes of Alzheimer’s disease remain poorly understood, but genetic and environmental factors are believed to play a role. A 2011 study by Barnes and Yaffe indicated that nearly half of worldwide Alzheimer’s disease cases might be associated with seven common, potentially modifiable risk factors. To evaluate the association between Alzheimer’s disease and modifiable risk factors, Dr. Yu and colleagues conducted a meta-analysis of studies published in English between 1968 and July 2014. They identified 16,906 studies of potential risk factors for Alzheimer’s disease. Of those articles, they found 323 articles examining 93 separate factors that had associations with Alzheimer’s disease that met inclusion criteria for their meta-analysis. They assessed the quality of the evidence for each risk factor based on the heterogeneity of the pooled analyses and whether the pooled analyses included more than 5,000 people.

Seven general categories of modifiable risk factors emerged from their literature search, which were consistent with those identified in prior studies: pre-existing disease status, biochemical exposure, dietary factors, medical exposure to drugs or therapy, lifestyle, psychological conditions, and occupational exposures.

In their primary meta-analysis, Dr. Yu and colleagues identified 13 risk factors, 28 protective factors, and 52 factors that showed no association with Alzheimer’s disease. Subsequent subgroup analysis reclassified seven factors from the neutral group as being positively associated with Alzheimer’s disease and four as negatively associated.

The investigators found grade I evidence that one environmental factor (ie, biochemical exposure to hyperhomocysteine) and one psychological factor (ie, depression) increased the risk of Alzheimer’s disease. Four medical exposures (ie, estrogen, statin, antihypertensive medication, and nonsteroidal anti-inflammatory therapy) and four dietary exposures (ie, folate, vitamin E, vitamin C, and coffee) were protective factors.

The meta-analysis also found grade I evidence that various medical conditions are associated with the risk of Alzheimer’s disease. Pre-existing conditions, including frailty, carotid atherosclerosis, hypertension, low diastolic blood pressure, and type II diabetes among Asians, increased risk, while previous history of arthritis, heart disease, metabolic syndrome, and cancer conferred protection.

Among lifestyle factors, low education, which has long been associated with a higher risk of Alzheimer’s disease, was identified as a risk factor. Other lifestyle factors such as smoking, alcohol consumption, and BMI influenced the risk of Alzheimer’s disease in contradictory ways at different ages. Those with high BMI at midlife only, and low BMI otherwise, had an increased risk of Alzheimer’s disease, while those with high BMI late in life had decreased risk. Current smoking, cognitive activity, stress, and light-to-moderate drinking were also associated with a decreased risk of Alzheimer’s disease. Interestingly, occupational exposures had little or no association with Alzheimer’s disease, the researchers noted.

Linda Peckel

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