Prediction of Preclinical Alzheimer's Disease: Longitudinal Rates of Change in Cognition

Article type: Research Article

Authors: Riley, Kathryn P.^{e; f} | Jicha, Gregory A.^{c; e; f; *} | Davis, Daron^g | Abner, Erin L.^{e; f} | Cooper, Gregory E.^{c; e; f} | Stiles, Nancy^{e; f} | Smith, Charles D.^{c; e; f} | Kryscio, Richard J.^{b; e; f} | Nelson, Peter T.^{d; e; f} | Van Eldik, Linda J.^{a; e; f} | Schmitt, Frederick A.^{c; e; f}

Affiliations: [a] Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY, USA | [b] Department of Biostatistics, University of Kentucky College of Medicine, Lexington, KY, USA | [c] Department of Neurology, University of Kentucky College of Medicine, Lexington, KY, USA | [d] Department of Pathology, University of Kentucky College of Medicine, Lexington, KY, USA | [e] Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, KY, USA | [f] University of Kentucky Alzheimer's Disease Center, University of Kentucky College of Medicine, Lexington, KY, USA | [g] Central Baptist Hospital, Lexington, KY, USA

Correspondence: [*] Correspondence to: Gregory A. Jicha, M.D., Ph.D., Department of Neurology, Sanders-Brown Center on Aging, Room 223, 800 South Limestone Street, University of Kentucky College of Medicine, Lexington, KY 40536. Tel.: 859 257 1412 x255; Fax: 859 257 3819; E-mail: [email protected].

Abstract: Preclinical Alzheimer's disease (pAD) reflects neuropathological findings of AD in cognitively normal subjects. The present study represents an effort to determine if differences could be identified in the longitudinal patterns of cognitive performance in persons classified as pAD compared to those who did not meet criteria for AD at autopsy. We included 121 subjects who were cognitively normal from baseline through their last assessment before death and who underwent autopsy. Participants were classified into two groups: pathologically normal (PN; NIA-Reagan low or no-likelihood of AD, n = 89) and preclinical AD (pAD; NIA-Reagan criteria of intermediate or high-likelihood of AD in the absence of clinical dementia symptoms, n = 32) followed for a mean 7.5 years prior to death. Longitudinal rates and patterns of change in scores on a standard cognitive battery were compared between these two groups. While cognitive results at baseline and last evaluations revealed no clear cross sectional group differences after adjustment for age, ApoE status, education, and gender, statistically significant differences between the pAD and PN groups in slope of decline were seen on a composite score of cognitive function. Further analyses showed three components of this score reached significance: constructional praxis, delayed recall of a word list, and category verbal fluency. Despite being clinically viewed as normal at enrollment and at the final exam, there are significant differences in rates of cognitive decline in participants classified as pAD compared to those without this pathology. Longitudinal changes in slope of decline in specific cognitive test measures can serve as non-invasive methods for the detection of pAD.

Keywords: Alzheimer's disease, cognition, normal, preclinical

DOI: 10.3233/JAD-2011-102133

Journal: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 707-717, 2011