Ten major risk factors for Alzheimer's disease

Researchers have collated available scientific evidence on risk factors associated with Alzheimer's disease and come up with a list of ten important ones. The Chinese researchers led by Jin Tai-Yu from the Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China, published their findings in an article titled, "Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomized controlled trials," the latest issue of the Journal of Neurology, Neurosurgery & Psychiatry.

Alzheimer's disease (AD)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that forms around 60 to 70 percent of all cases of dementia around the world. According to the World Health Organization statistics, 50 million people around the world have dementia, with 10 million new cases added annually. Only around 10 to 15 percent of cases are genetic, and there are several risk factors. At present, the drugs available for the treatment of AD are at best symptomatic, and no cure is available. The disease typically begins with minor memory loss, and with time there is more severe cognitive damage and behavioral and motor degeneration that progress to death.

What was done for this study?

This was a systematic review and analysis of existing studies on risk factors and prevention of AD. For this, the team of researchers looked at the electronic databases and websites that contain evidence regarding AD up until 1st March 2019. They included both observational prospective studies (OPSs) and randomized controlled trials (RCTs), they wrote.

From all the information gathered, the team next analyzed the evidence using statistical tools to see which of the risk factors were strongly associated with AD. To reach their results they adjusted for other factors such as confounding variables, bias, and also adjusted for imprecision in the studies analyzed.

What was found?

The study included a total of 44,676 reports. There were 243 OPSs and 153 RCTs. The team found which were eligible for final analysis. From these studies, the team filtered out a total of 140 factors that could be associated with AD and could be modified therapeutically or behaviourally. A total of 11 interventions were found from the meta-analysis of studies.

Level A evidence from studies is considered to be robust. Of the total 19 factors found to be associated with AD, 10 were found to have Level A evidence. These include;

  1. Level of education
  2. Level of cognitive activity
  3. Presence of a high body mass index or obesity in late life
  4. Presence of hyperhomocysteinemia on lab studies
  5. Depression
  6. Stress
  7. Diabetes
  8. History of head trauma or injury
  9. Hypertension or high blood pressure in midlife
  10. Orthostatic hypotension or fall in blood pressure on changing body posture (such as standing up)

Level B evidence is weaker evidence. Of the 19 factors, 9 were found to have a Level B association with AD. These were;

  1. Presence of obesity in midlife
  2. Weight loss in late life
  3. Physical exercise or lack of it
  4. Smoking
  5. Sleep and sleep problems
  6. Cerebrovascular disease or stroke
  7. Frailty
  8. Atrial fibrillation or a type of abnormal heart rhythm
  9. Vitamin C consumption in the diet

From the results, the researchers suggested that two of the factors were not recommended as risk factors. These included "estrogen replacement therapy (Level A) and acetylcholinesterase inhibitors (Level B)." They added that six more factors had a weak association with AD and need to be confirmed in future studies. These included;

  1. Management of diastolic blood pressure
  2. NSAID use
  3. Social activity
  4. Diagnosis of osteoporosis
  5. Exposure to pesticides
  6. Exposure to silicon from drinking water

Implications and conclusions

The authors wrote, "Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD."

They concluded that two-thirds of the factors considered here are blood vessel-related factors such as high blood cholesterol and high blood pressure. Significant stress is to be laid upon lifestyle factors such as maintain body weight, reducing stress, being active physically as well as cognitively, smoking cessation, and sleep management. This remains one of the most comprehensive and extensive systematic reviews that look at all the risk factors associated with AD, the researchers said.

They wrote in conclusion, "This study provides an advanced and contemporary survey of the evidence, suggesting that more high-quality observational prospective studies and randomised controlled trials are urgently needed to strengthen the evidence base for uncovering more promising approaches to preventing Alzheimer's disease."

This study was funded by the National Key R&D Program of China, Shanghai Municipal Science and Technology Major Project, and Zhangjiang lab.

Journal reference:
  • Yu J, Xu W, Tan C, et al, Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials, Journal of Neurology, Neurosurgery & Psychiatry Published Online First: 20 July 2020. doi: 10.1136/jnnp-2019-321913, https://jnnp.bmj.com/content/early/2020/06/01/jnnp-2019-321913
Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.


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