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. 2018 Dec 19;10(1):122.
doi: 10.1186/s13195-018-0455-y.

Heterogeneity of Alzheimer's disease: consequence for drug trials?

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Heterogeneity of Alzheimer's disease: consequence for drug trials?

Gayatri Devi et al. Alzheimers Res Ther. .

Abstract

Background: Alzheimer's disease is a heterogenous disorder with multiple phenotypes and genotypes, although they eventually converge to a final common clinicopathological endpoint. However, Alzheimer's disease drug trials do not account for the heterogeneity of the disease in trial design, impeding development of effective drugs.

Discussion: Alzheimer's disease drug trials commonly have wide inclusion criteria that subsume multiple subtypes of the condition, with varying genotypes, phenotypes, and clinical courses. The outcome variables used in many trials may not be sensitive for the particular disease subtype and trials may not follow patients for the appropriate length of time necessary for the subtype of disease. Methods of stratifying treatment trial design to account for disease heterogeneity using algorithms incorporating demographics, neuroimaging, genetics, and clinical phenotypes, as well as more tailored outcome measures, are proposed to allow for personalized, precision medicine in Alzheimer's disease therapeutics development. Approaching Alzheimer's disease as a heterogenous disorder will likely improve yield in the search for effective treatments for the condition.

Keywords: Alzheimer’s; Clinical trials; Heterogeneity; Precision medicine.

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The authors declare that they have no competing interests.

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References

    1. Friedland R, Koss E, Haxby J, et al. NIH conference. Alzheimer disease: clinical and biological heterogeneity. Ann Intern Med. 1988;109(4):298–311. doi: 10.7326/0003-4819-109-4-298. - DOI - PubMed
    1. Scheltens P, Vermersch P, Leys D. Heterogeneity of Alzheimer’s disease. Review. French. Rev Neurol (Paris) 1993;149(1):14–25. - PubMed
    1. Murray M, Graff-Radford N, Ross O, Petersen R, Duara R, Dickson D. Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: A retrospective study. Lancet Neurol. 2011;10(9):785–796. doi: 10.1016/S1474-4422(11)70156-9. - DOI - PMC - PubMed
    1. Ferreira D, Verhagen C, Hernandez-Cabrera J, et al. Distinct subtypes of Alzheimer's disease based on patterns of brain atrophy: longitudinal trajectories and clinical applications. Sci Rep. 2017;7:46263. doi: 10.1038/srep46263. - DOI - PMC - PubMed
    1. Scheltens N, Galindo-Garre F, Pijnenburg Y, et al. The identtification of cognitive subtypes in Alzheimer's disease dementia using latent class analysis. J Neurol Neurosurg Psychiatry. 2016;87:235–243. doi: 10.1136/jnnp-2014-309582. - DOI - PubMed