Use of Cognitive Testing, Questionnaires, and Plasma Biomarkers to Quantify Cognitive Impairment in an Aging Pet Dog Population

Article type: Research Article

Authors: Fefer, Gilad^{a; 1} | Panek, Wojciech K.^{a; 1} | Khan, Michael Z.^a | Singer, Matthew^d | Westermeyer, Hans D.^a | Mowat, Freya M.^{a; c} | Murdoch, David M.^b | Case, Beth^a | Olby, Natasha J.^{a; 1} | Gruen, Margaret E.^{a; 1; *}

Affiliations: [a] Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA | [b] Department of Medicine, Duke University Medical Center, Durham, NC, USA | [c] Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, WI, USA | [d] Department of Statistics, College of Sciences, North Carolina State University, Raleigh, NC, USA

Correspondence: [*] Correspondence to: Margaret E. Gruen, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27607, USA. Tel.: +1 919 513 6500; E-mail: megruen@ncsu.edu.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Aging dogs may suffer from canine cognitive dysfunction syndrome (CCDS), a condition in which cognitive decline is associated with amyloid pathology and cortical atrophy. Presumptive diagnosis is made through physical examination, exclusion of systemic/metabolic conditions, and completion of screening questionnaires by owners. Objective:This study aimed to determine whether cognitive function could be quantified in aging pet dogs, and to correlate cognitive testing with validated questionnaires and plasma neurofilament light chain (pNfL) concentration. Methods:Thirty-nine dogs from fifteen breeds were recruited (9.3 to 15.3 years). Owners completed the Canine Dementia Scale (CADES) and Canine Cognitive Dysfunction Rating scale (CCDR). Executive control and social cues were tested, and pNfL was measured with single molecule array assay. Comparisons were made between cognitive testing scores, CADES, CCDR scores, and pNfL. Results:CADES scoring classified five dogs as severe CCDS, six as moderate, ten as mild, and eighteen as normal. CCDR identified seven dogs at risk of CCDS and thirty-two as normal. Cognitive testing was possible in the majority of dogs, although severely affected dogs were unable to learn tasks. CADES score correlated with sustained attention duration (r = –0.47, p = 0.002), inhibitory control (r = –0.51, p = 0.002), detour (r = –0.43, p = 0.001), and pNfL (r = 0.41, p = 0.025). Concentration of pNfL correlated with inhibitory control (r = –0.7, p≤0.001). The CCDR scale correlated with performance on inhibitory control (r = –0.46, p = 0.005). Conclusion:Our findings suggest that a multi-dimensional approach using a combination of questionnaires, specific cognitive tests, and pNfL concentration can be used to quantify cognitive decline in aging pet dogs.

Keywords: Blood biomarkers, canine cognitive dysfunction syndrome, CCDS, cognitive testing, dementia, neurofilament light chain, NfL

DOI: 10.3233/JAD-215562

Journal: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1367-1378, 2022