Several Modifiable Risk Factors for Alzheimer’s Disease Identified

Jin-Tai Yu MD, PhD Memory and Aging Center, Department of Neurology University of California San Francisco San Francisco, CA 94158 Interview with:
Jin-Tai Yu MD, PhD
Memory and Aging Center,
Department of Neurology
University of California San Francisco
San Francisco, CA 94158

Medical Research: What is the background for this study? What are the main findings?

Response: The number of dementia cases in the whole world was estimated to be 35.6 million in 2010 and this number was expected to almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050. The global prevalence of dementia was 5-7% and Alzheimer’s disease accounts for roughly 60%. This data means that we are facing an increasing number of global populations of this specific neurodegenerative disease and also the heavy burden brought by it.

Data from the website of global clinical trials ( showed that a total of 1,732 clinical trials for Alzheimer’s disease were under way. However, the previous results are not so optimistic, possibly due to the complex etiological mechanisms. In one word, we had currently no effective drugs for this disease. Figuring out how to effectively prevent its occurrence is increasingly attracting people’s attentions.Therefore, we have done the most extensive and comprehensive systematic review and meta-analysis to date, which employs a full-scale search of observational studies to calculate effect sizes and grade the evidence strength of various modifiable risk factors for this disease. We hope these results will be informative and instructive.

We systematically searched PubMed and the Cochrane Database of Systematic Reviews from inception to July 2014, and the references of retrieved relevant articles. We included prospective cohort studies and retrospective case–control studies. 16,.906 articles were identified of which 323 with 93 factors met the inclusion criteria for meta-analysis. In addition, we assigned three grades of evidence in support of the conclusion according to two elements including the pooled sample size and heterogeneity: ‘grade I evidence’ was defined as both pooled population >5000 and lower heterogeneity (I2<50%); ‘grade II-A evidence’ was defined as pooled population >5000 but with higher heterogeneity (I2≥50%); ‘grade II-B evidence’ was defined as lower heterogeneity (I2≥50%) but with pooled population <5000; ‘grade III evidence’ was defined as both pooled population <5000 and higher heterogeneity.

Eleven risk factors with grade I evidence included heavy smoking, low DBP, high BMI in midlife, carotid atherosclerosis, DM-2 in Asian population, low BMI,  low educational attainment, high tHcy level, depression, SBP > 160mmHg and frailty; and 2 risk factors with grade II-A evidence included current smoking in Asian population and neuroticism. Our study also found that 23 protective factors for Alzheimer’s Disease (Grade I evidence: coffee/caffeine drinking, high folate intake, cognitive activity, high vitamin E intake, high vitamin C intake, current statin use, arthritis, light-to-moderate drinking, ever use of estrogens, anti-hypertensive medications, NASIDs use, high BMI in late-life, et al.; Grad II-A evidence: healthy dietary pattern, fish consumption, high education and physical activity). Given that most of the studies included in the meta-analysis are case-control studies, what is seen here is an association rather than a direct cause and effect relationship between any one factor and Alzheimer’s risk.

Medical Research: What should clinicians and patients take away from your report?

Response: Our study found that individuals would benefit from addressing the related potentially modifiable factors. Effective interventions in diet, medications, biochemical exposures, psychological condition, preexisting disease and lifestyle might decrease new incidence of Alzheimer’s Disease.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: Given that, as yet, there is no cure forAlzheimer’s Disease. Our study indicates that Alzheimer’s Disease might be preventable by effectively addressing the identified modifiable factors. More prospective cohort studies are necessary for clearing the exact direct relationship between the related modifiable risk factors and Alzheimer’s risk and exploring the possibility of preventing Alzheimer’s Disease by effectively addressing the identified modifiable factors.


J Neurol Neurosurg Psychiatry. 2015 Aug 20. pii: jnnp-2015-310548. doi: 10.1136/jnnp-2015-310548. [Epub ahead of print]

Meta-analysis of modifiable risk factors for Alzheimer’s disease.

Xu W1Tan L2Wang HF3Jiang T3Tan MS1Tan L4Zhao QF1Li JQ1Wang J1Yu JT5.
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Jin-Tai Yu MD, PhD (2015). Several Modifiable Risk Factors for Alzheimer’s Disease 

Last Updated on August 22, 2015 by Marie Benz MD FAAD