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01. Evidence-Based Prevention of Alzheimer’s Disease: Systematic Review and Meta-Analysis of 243 Observational Prospective Studies and 153 Randomised Controlled Trials

Published on February 1, 2021 Expired on April 1, 2024

James Phelps, M.D.

Research Editor - Psychopharmacology Institute

Key Points

  • In this new meta-analysis, 19 risk factors are identified and rank-ordered. This compendium is a useful reminder of things to look for in your patients to help them understand their long-term risks of this very common end-of-life disaster.

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If you’re young, you may be interested in this Quick Take because you have patients at risk of or developing Alzheimer’s dementia. If you’re older, like me, you might also be interested because you know that if you’re lucky enough not to get early heart disease or cancer, then you face a substantial risk of Alzheimer’s disease yourself.

Hi! Jim Phelps here for the Psychopharmacology Institute. Let’s look at a recent meta-analysis of studies examining Alzheimer’s dementia risk and preventive factors. Ranking the evidence from observational studies and randomized trials, authors Jin-Tai Yu and colleagues identified 19 factors we should all be aware of—10 with very good evidence for their role in Alzheimer’s disease and another 9 with weaker but still substantial evidence. One of the most interesting results in this analysis is the authors’ ranking of all the factors by their relative risk. So, what’s at the top? What’s the biggest risk?

After you toss out the really obvious ones, like a history of cerebral bleed or low cerebral perfusion—hey look, there’s “a high level of depressive symptoms.” I take that to mean that we psychiatric providers are in a position to lower Alzheimer’s dementia risk through our regular practice with patients, which for most of us includes decreasing depressive symptoms among them.

Not surprisingly, near the top of the list are cardiovascular risk factors, particularly diabetes, smoking, and the usual suspects, such as hypertension, being overweight, and physical inactivity.

But here’s an interesting one also near the top of the list—sleep disturbance. It’s right up there with diabetes. The evidence base for sleep disturbance as a risk factor for Alzheimer’s dementia is in the weaker group, but 1 of the recommendations that emerges is pretty simple. We practitioners should routinely assess sleep quality and quantity amongst our patients. It might be a modifiable Alzheimer’s risk factor, particularly if we can identify sleep apnea.

What’s most strongly associated with lowering the risk of Alzheimer’s? Interestingly, 1 of the most studied factors, one that lowers risk by about 50%, is getting a lot of education when you’re young. This is perhaps somewhat reassuring for us overeducated healthcare providers.

So, the 19 factors identified in this analysis generally parallel 12 that were identified in the Lancet Commission report. Of particular importance to psychiatric providers are those which we can routinely identify—obvious ones like smoking, obesity, physical inactivity, and diabetes but also sleep disturbance, hearing impairment, and low social contact—and 1 we can routinely treat, depression.

In summary, this article reminds us that, for Alzheimer’s dementia, the risk is modifiable, and we can help patients recognize their risk when there’s still time to do something about it.

For more on all this, we have linked here the article so that you can take a glance at Dr. Yu and colleagues’ Figure 3A for that ranking of factors by relative risk. In the center graph, you will see that the number of studies examined is superimposed on the relative risk and the confidence intervals. It’s like a forest plot visualization. It’s nice.

Abstract

Evidence-Based Prevention of Alzheimer’s Disease: Systematic Review and Meta-Analysis of 243 Observational Prospective Studies and 153 Randomised Controlled Trials

Jin-Tai Yu, Wei Xu, Chen-Chen Tan, Sandrine Andrieu, John Suckling, Evangelos Evangelou, An Pan, Can Zhang, Jianping Jia, Lei Feng, Ee-Heok Kua, Yan-Jiang Wang, Hui-Fu Wang, Meng-Shan Tan, Jie-Qiong Li, Xiao-He Hou, Yu Wan, Lin Tan, Vincent Mok, Lan Tan, Qiang Dong, Jacques Touchon, Serge Gauthier, Paul S Aisen, Bruno Vellas

Background: Evidence on preventing Alzheimer’s disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention.

Methods: Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised.

Results: A total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B).

Interpretation: Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.

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Reference

Yu, J., Xu, W., Tan, C., Andrieu, S., Suckling, J., Evangelou, E., Pan, A., Zhang, C., Jia, J., Feng, L., Kua, E., Wang, Y., Wang, H., Tan, M., Li, J., Hou, X., Wan, Y., Tan, L., Mok, V., … Vellas, B. (2020). 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, 91(11), 1201-1209.

Table of Contents

Learning Objectives:

After completing this activity, the learner will be able to:

  1. Review the current understanding of Alzheimer's dementia risk and protective factors using a new meta-analysis, which rank-orders factors by relative risk.
  2. Assess the evidence for claims of superior efficacy of selected antidepressants for the treatment of cognitive impairment in the context of major depressive disorder.
  3. Review the evidence for treatment options for severe neuroleptic malignant syndrome.
  4. Analyze a recent review and meta-analysis of depression relapse rates upon antidepressant discontinuation during pregnancy.
  5. Assess the value of transcranial magnetic stimulation for patients with treatment-resistant obsessive-compulsive disorder.

Original Release Date: 02/01/2021

Review Date: 03/01/2024

Expiration Date: 04/01/2024

Relevant Financial Disclosures:

The following planners, faculty, and reviewers have the following relevant financial relationships with commercial interests to disclose:

Dr. Phelps has disclosed the following relationships:

  • McGraw-Hill: book on bipolar disorder
  • W.W. Norton & Co.: books on bipolar disorder

All of the relevant financial relationships listed for these individuals have been mitigated.

Contact Information: For questions regarding the content or access to this activity, contact us at support@psychopharmacologyinstitute.com

Instructions for Participation and Credit:

Participants must complete the activity online during the valid credit period that is noted above.

Follow these steps to earn CME credit:

  1. View the required educational content provided on this course page.
  2. Complete the Post Activity Evaluation for providing the necessary feedback for continuing accreditation purposes and for the development of future activities. NOTE: Completing the Post Activity Evaluation after the quiz is required to receive the earned credit.
  3. Download your certificate.
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