Temporal Order of Alzheimer’s Disease-Related Cognitive Marker Changes in BLSA and WRAP Longitudinal Studies

Article type: Research Article

Authors: Bilgel, Murat^{a; *} | Koscik, Rebecca L.^b | An, Yang^a | Prince, Jerry L.^c | Resnick, Susan M.^a | Johnson, Sterling C.^{b; d; e; f} | Jedynak, Bruno M.^g

Affiliations: [a] Laboratory of Behavioral Neuroscience, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA | [b] Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, USA, Madison, WI, USA | [c] Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA | [d] Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA | [e] Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [f] Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA | [g] Department of Mathematics and Statistics, Portland State University, Portland, OR, USA

Correspondence: [*] Correspondence to: Murat Bilgel, PhD, National Institute on Aging, Laboratory of Behavioral Neuroscience, 251 Bayview Blvd, Suite 100, Rm 04B329, Baltimore, MD 21224, USA; Tel.: +1 410 558 8151; Fax: +1 410 558 8674; E-mail: [email protected].

Abstract: Investigation of the temporal trajectories of currently used neuropsychological tests is critical to identifying earliest changing measures on the path to dementia due to Alzheimer’s disease (AD). We used the Progression Score (PS) method to characterize the temporal trajectories of measures of verbal memory, executive function, attention, processing speed, language, and mental status using data spanning normal cognition, mild cognitive impairment, and AD from 1,661 participants with a total of 7,839 visits (age at last visit 77.6 SD 9.2) in the Baltimore Longitudinal Study of Aging (BLSA) and 1510 participants with a total of 3,473 visits (age at last visit 59.5 SD 7.4) in the Wisconsin Registry for Alzheimer’s Prevention (WRAP). This method aligns individuals in time based on the similarity of their longitudinal measurements to reveal temporal trajectories. As a validation of our methodology, we explored the associations between the individualized cognitive progression scores (Cog-PS) computed by our method and clinical diagnosis. Digit span tests were the first to show declines in both data sets, and were detected mainly among cognitively normal individuals. These were followed by tests of verbal memory, which were in turn followed by Trail Making Tests, Boston Naming Test, and Mini-Mental State Examination. Differences in Cog-PS across the clinical diagnosis and APOE ɛ4 groups were statistically significant, highlighting the potential use of Cog-PS as individualized indicators of disease progression. Identifying cognitive measures that are changing in preclinical AD can lead to the development of novel cognitive tests that are finely tuned to detecting earliest changes.

Keywords: Alzheimer’s disease, cognition, longitudinal studies, neuropsychological tests, preclinical

DOI: 10.3233/JAD-170448

Journal: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1335-1347, 2017