A δ Homolog for Dementia Case Finding with Replication in the Alzheimer’s Disease Neuroimaging Initiative

Article type: Research Article

Authors: Royall, Donald R.^{a; b; c; d; *} | Palmer, Raymond F.^c | the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Psychiatry, The University of Texas Health Science Center, San Antonio, TX, USA | [b] Department of Medicine, The University of Texas Health Science Center, San Antonio, TX, USA | [c] Department of Family and Community Medicine, The University of Texas Health Science Center, San Antonio, TX, USA | [d] South Texas Veterans’ Health System Audie L. Murphy Division GRECC, San Antonio, TX, USA

Correspondence: [*] Correspondence to: Donald R. Royall, MD, Department of Psychiatry, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX78229-3900, USA.Tel.: +1 210 567 1255; Fax: +1 210 567 1269; E-mail: [email protected].

Note: [1] Some data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). ADNI had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. However, ADNI investigators contributed to the design and implementation of ADNI and/or provided data. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: Dementia can be empirically described by the latent dementia phenotype “δ” and its various composite “homologs”. We have explored δ’s blood-based protein biomarkers in the Texas Alzheimer’s Research and Care Consortium (TARCC) study. However, it would be convenient to replicate those associations in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). To this end, we have engineered a δ homolog from observed cognitive performance measures common to both projects. Our findings were replicated in randomly selected 50% splits of TARCC data (Group 1, N = 1,747; Group 2, N = 1,755), and then independently in ADNI (N = 1,737). The new δ homolog, i.e., “dT2A” (d-TARCC to ADNI), fit the data of both studies well, and was strongly correlated with dementia severity, as rated by the Clinical Dementia Rating Scale “sum of boxes” (TARCC: r = 0.99, p < 0.001; ADNI: r = 0.96, p < 0.001). dT2A achieved an area under the receiver operating characteristic curve of 0.981 (0.976–0.985) for the discrimination of Alzheimer’s disease from normal controls in TARCC, and 0.988 (0.983–0.993) in ADNI. dT2A is the 12th δ homolog published to date, and opens the door to independent replications across these and similar studies.

Keywords: Aging, Alzheimer Disease Neuroimaging Initiative, cognition, dementia, g , intelligence, TARCC

DOI: 10.3233/JAD-171053

Journal: Journal of Alzheimer's Disease, vol. 67, no. 1, pp. 67-79, 2019