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Review
. 2021 Dec 8;7(1):e12202.
doi: 10.1002/trc2.12202. eCollection 2021.

Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors

Ruth Peters  1   2 , John Breitner  3 , Sarah James  4 , Gregory A Jicha  5 , Pierre-Francois Meyer  6 , Marcus Richards  4 , A David Smith  7 , Hussein N Yassine  8 , Erin Abner  5 , Atticus H Hainsworth  9   10 , Patrick G Kehoe  11 , Nigel Beckett  12 , Christopher Weber  13 , Craig Anderson  14 , Kaarin J Anstey  1   2 , Hiroko H Dodge  15
Affiliations
Review

Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors

Ruth Peters et al. Alzheimers Dement (N Y). .

Abstract

Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need for more targeted sample selection in clinical trials, a better understanding of interventions, and deeper analysis of existing data.

Keywords: anti‐hypertensives; anti‐inflammatories; blood pressure; cholesterol; dementia; diabetes mellitus; homocysteine; hormone therapy; hypertension; inflammation; omega‐3 fatty acids.

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Figures

FIGURE 1
FIGURE 1
Confounds that have plagued clinical trials of statin therapy
FIGURE 2
FIGURE 2
Directed acyclic graph analysis of B vitamin treatment and consequential changes in brain structure and function in mild cognitive impairment (MCI). The mediating pathway shows the optimal Bayesian network that explains the findings from the VITACOG trial Abbreviations: CDR, Clinical Dementia Rating scale; MMSE, Mini‐mental state examination; tHcy, total homocysteine.
FIGURE 3
FIGURE 3
Common areas of discrepancy identified by expert review for each of the seven risk factors
See this image and copyright information in PMC

References

    1. Xu W, Tan L, Wang H‐F, et al. Meta‐analysis of modifiable risk factors for Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2015;86(12):1299‐1306. - PubMed
    1. Prince M, Albanese E, Guerchet M, Prina M, World Alzheimer Report 2014 Dementia and Risk Reduction AN ANALYSIS OF PROTECTIVE AND MODIFIABLE FACTORS. 2014: Alzheimer's Disease International.
    1. Smith AD, Yaffe K. Dementia (including Alzheimer's disease) can be prevented: statement supported by international experts. J Alzheimers Dis. 2014;38(4):699‐703. - PubMed
    1. Anstey KJ, Ee N, Eramudugolla R, Jagger C, Peters R. A Systematic Review of Meta‐Analyses that Evaluate Risk Factors for Dementia to Evaluate the Quantity, Quality, and Global Representativeness of Evidence. J Alzheimers Dis. 2019;70(s1):S165‐S186. - PMC - PubMed
    1. Peters R, Ee N, Peters J, et al. Common risk factors for major noncommunicable disease, a systematic overview of reviews and commentary: the implied potential for targeted risk reduction. Ther Adv Chronic Dis. 2019;10:204062231988039. - PMC - PubMed

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