Associations between Performance on an Abbreviated CogState Battery, Other Measures of Cognitive Function, and Biomarkers in People at Risk for Alzheimer’s Disease

Article type: Research Article

Authors: Racine, Annie M.^{c; d; e} | Clark, Lindsay R.^{a; b; c} | Berman, Sara E.^c | Koscik, Rebecca L.^b | Mueller, Kimberly D.^b | Norton, Derek^o | Nicholas, Christopher R.^{a; c} | Blennow, Kaj^{h; i} | Zetterberg, Henrik^{h; i; j} | Jedynak, Bruno^k | Bilgel, Murat^{m; n} | Carlsson, Cynthia M.^{a; b; c} | Christian, Bradley T.^{g; l} | Asthana, Sanjay^{a; c} | Johnson, Sterling C.^{a; b; c; e; g; *}

Affiliations: [a] Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA | [b] Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [c] Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [d] Institute on Aging, University of Wisconsin-Madison, Madison, WI, USA | [e] Neuroscience & Public Policy Program, University of Wisconsin-Madison, Madison, WI, USA | [f] Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [g] Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA | [h] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [i] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [j] Institute of Neurology, University College London, London, UK | [k] Department of Mathematics and Statistics, Portland State University, Portland, OR, USA | [l] Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA | [m] Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA | [n] Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Baltimore, MD, USA | [o] Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA

Correspondence: [*] Correspondence to: Sterling C. Johnson, PhD, William S. Middleton Memorial VA Hospital, 2500 Overlook Terrace(11G), GRECC, Madison, WI, 53705, USA. Tel.: +1 608 256 1901 x 11946; Fax: +1 608 280 7165; E mail: [email protected].

Abstract: It is not known whether computerized cognitive assessments, like the CogState battery, are sensitive to preclinical cognitive changes or pathology in people at risk for Alzheimer’s disease(AD). In 469 late middle-aged participants from the Wisconsin Registry for Alzheimer’s Prevention(mean age 63.8±7 years at testing; 67% female; 39% APOE4+), we examined relationships between a CogState abbreviated battery(CAB) of seven tests and demographic characteristics, traditional paper-based neuropsychological tests as well as a composite cognitive impairment index, cognitive impairment status(determined by consensus review), and biomarkers for amyloid and tau(CSF phosphorylated-tau/Aβ42 and global PET-PiB burden) and neural injury(CSF neurofilament light protein). CSF and PET-PiB were collected in n = 71 and n = 91 participants, respectively, approximately four years prior to CAB testing. For comparison, we examined three traditional tests of delayed memory in parallel. Similar to studies in older samples, the CAB was less influenced by demographic factors than traditional tests. CAB tests were generally correlated with most paper-based cognitive tests examined and mapped onto the same cognitive domains. Greater composite cognitive impairment index was associated with worse performance on all CAB tests. Cognitively impaired participants performed significantly worse compared to normal controls on all but one CAB test. Poorer One Card Learning test performance was associated with higher levels of CSF phosphorylated-tau/Aβ42. These results support the use of the CogState battery as measures of early cognitive impairment in studies of people at risk for AD.

Keywords: Amyloid, biomarkers, cerebrospinal fluid, cognitive impairment, CogState, computerized cognitive testing, neural injury, preclinical Alzheimer’s disease

DOI: 10.3233/JAD-160528

Journal: Journal of Alzheimer's Disease, vol. 54, no. 4, pp. 1395-1408, 2016