{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:31:22Z","timestamp":1785537082907,"version":"3.56.0"},"reference-count":89,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T00:00:00Z","timestamp":1574380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Julia and Vann Buren Parr"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dementia severity can be quantitatively described by the latent dementia phenotype \u2018\u03b4\u2019 and its various composite \u2018homologues\u2019. We have explored \u03b4\u2019s blood-based protein biomarkers in the Texas Alzheimer\u2019s Research and Care Consortium. However, it would be convenient to replicate them in the Alzheimer\u2019s Disease Neuroimaging Initiative. To that end, we have engineered a \u03b4 homologue from the observed cognitive performance measures common to both projects [i.e. \u2018d:Texas Alzheimer\u2019s Research and Care Consortium to Alzheimer\u2019s Disease Neuroimaging Initiative\u2019 (dT2A)]. In this analysis, we confirm 13\/22 serum proteins as partial mediators of age\u2019s effect on dementia severity as measured by dT2A in the Texas Alzheimer\u2019s Research and Care Consortium and then replicate 4\/13 in the Alzheimer\u2019s Disease Neuroimaging Initiative\u2019s plasma data. The replicated mediators of age-specific effects on dementia severity are adiponectin, follicle-stimulating hormone, pancreatic polypeptide and resistin. In their aggregate, the 13 confirmed age-specific mediators suggest that \u2018cognitive frailty\u2019 pays a role in dementia severity as measured by \u03b4. We provide both discriminant and concordant support for that hypothesis. Weight, calculated low-density lipoprotein and body mass index are partial mediators of age\u2019s effect in the Texas Alzheimer\u2019s Research and Care Consortium. Biomarkers related to other disease processes (e.g. cerebrospinal fluid Alzheimer\u2019s disease-specific biomarkers in the Alzheimer\u2019s Disease Neuroimaging Initiative) are not. It now appears that dementia severity is the sum of multiple independent processes impacting \u03b4. Each may have a unique set of mediating biomarkers. Age\u2019s unique effect appears to be at least partially mediated through proteins related to frailty. Age-specific mediation effects can be replicated across cohorts and biofluids. These proteins may offer targets for the remediation of age-specific cognitive decline (aka \u2018senility\u2019), help distinguish it from other determinants of dementia severity and\/or provide clues to the biology of Aging Proper.<\/jats:p>","DOI":"10.1093\/braincomms\/fcz036","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T13:10:28Z","timestamp":1574428228000},"source":"Crossref","is-referenced-by-count":16,"title":["Blood-based protein mediators of senility with replications across biofluids and cohorts"],"prefix":"10.1093","volume":"2","author":[{"given":"Donald R","family":"Royall","sequence":"first","affiliation":[{"name":"Department of Psychiatry, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA"},{"name":"Department of Medicine, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA"},{"name":"Department of Family and Community Medicine, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA"},{"name":"The Glenn Biggs Institute for Alzheimer\u2019s & Neurodegenerative Diseases, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond F","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Family and Community Medicine, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,22]]},"reference":[{"key":"2020081108573713900_fcz036-B1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mad.2019.01.004","article-title":"Resistin: a reappraisal","volume":"178","author":"Acquarone","year":"2019","journal-title":"Mech Ageing 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