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Standard explanations address symptoms rather than structural causes. I argue that Alzheimer's disease research is caught in a Dual Diversity Crisis: the simultaneous neglect of population diversity and individual neurobiological heterogeneity as compounding validity threats. The first dimension concerns the systematic over-reliance on Western, young, healthy, and university-affiliated (WYHU) research samples, from which biomarker normative standards are derived and then applied universally to a demographically distinct clinical population. The second concerns the erasure, through group-level analysis, of the substantial neurobiological heterogeneity that exists within any sample regardless of its demographic composition. The critical structural insight is that these two problems do not add; they multiply. A WYHU-derived group average is doubly unrepresentative: it misrepresents the target population demographically and conceals the individual variance that exists even within that already-unrepresentative sample. FDG-PET evidence demonstrates that biological sex accounts for approximately 30 times more metabolic variance than diagnostic category in patients with equivalent symptom profiles, directly challenging the construct validity of threshold-based trial inclusion. Correcting the Dual Diversity Crisis requires treating demographic diversity and individual neurobiological characterization as primary design parameters, not post-hoc corrections. Until this reconceptualization occurs, translational failure in Alzheimer's disease research remains the structurally expected outcome.<\/jats:p>","DOI":"10.1007\/s11357-026-02400-x","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T21:07:34Z","timestamp":1783372054000},"page":"6431-6436","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The dual diversity crisis in alzheimer's disease research: why neuroimaging biomarkers and clinical trials keep failing"],"prefix":"10.1007","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2057-7793","authenticated-orcid":false,"given":"Thorsten","family":"Rudroff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"issue":"4","key":"2400_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/alzrt269","volume":"6","author":"JL Cummings","year":"2014","unstructured":"Cummings JL, Morstorf T, Zhong K. 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