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Reader response: Healthy lifestyle and the risk of Alzheimer dementia: Findings from 2 longitudinal studies

  • Jeroen F. Uleman, PhD Researcher, Dept Geriatrics, Radboudumc Alzheimer Center, Donders Institute of Medical Neurosciences, Radboud university medical center
  • Marcel G.M. Olde Rikkert, Principal investigator, Geriatrician, Dept Geriatrics, Radboudumc Alzheimer Center, Donders Institute of Medical Neurosciences, Radboud university medical center
Submitted July 21, 2020

The excellent work of Dhana et al.1 is another step forward in the recognition of lifestyle factors in AD prevention. The substantially reduced hazard ratio (HR) for better lifestyle scores is in line with other works2,3 as well as our own.4

That being said, this change in HR does not necessarily imply that interventions on these lifestyle factors will yield comparable reductions in AD incidence. Moreover, save the cited FINGER study, multidomain RCTs for AD prevention (MAPT, preDIVA) do not currently support such reductions yet.3 This lack of evidence for causality and reversibility is a serious limitation of predictive modeling.

To potentially improve the success rate of the long and costly RCTs needed to obtain such evidence, we need explanatory models that incorporate an understanding of AD’s multicausal etiology. For this purpose, causal loop diagrams (CLDs) can be developed to describe risk factors and their causal relationships to AD.4 These CLDs can be quantified as system dynamics models (SDMs). As previously demonstrated in cancer research5, such SDMs can be used to replicate RCT outcomes and test various intervention scenarios. Applying these methodologies to AD could be a next step toward unraveling the complex effect of lifestyle on AD.

Disclosure

The authors report no relevant disclosures. Contact journal@neurology.org for full disclosures.

References

  1. Dhana K, Evans DA, Rajan KB, Bennett DA, Morris MC. Healthy lifestyle and the risk of Alzheimer dementia: Findings from 2 longitudinal studies. Neurology 2020 Jun 17.
  2. Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet, 2017;390:2673–2734.
  3. Kivipelto M, Mangialasche F, Ngandu T. Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease. Nat Rev Neurol. 2018;14:653–666.
  4. Uleman JF, et al. Mapping the Complex Multicausality of Alzheimer’s Disease. Geroscience [in press].
  5. Darabi N, Hosseinichimeh N. (2020). System Dynamics Modeling in Health and Medicine: A Systematic Literature Review. System Dynamics Review 2020;36:29–73.

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Neurology | Print ISSN:0028-3878
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