Table_1_Novel Diagnostic Tools for Identifying Cognitive Impairment in Dogs: Behavior, Biomarkers, and Pathology.DOCX

Canine cognitive dysfunction syndrome (CCDS) is a progressive neurodegenerative disorder in senior dogs that is mainly associated with decreased ability to learn and respond to stimuli. It is commonly under-diagnosed because behavioral changes are often attributed to the natural process of aging. In the present study, we used for the first time a comprehensive approach enabling early diagnosis of canine patients with mild cognitive disorders (MiCI). We included CAnine DEmentia Scale (CADES) questionnaires, biochemical parameters, and biomarkers in blood serum, and correlated them with post-mortem histopathological changes. The CADES questionnaires enabled us to identify MiCI dogs developing changes mainly in domains corresponding to social interaction and spatial orientation, which seems to be crucial for delineating early cognitive disorders. Biochemical analyses in these dogs showed slightly elevated liver enzyme parameters (AST and ALT) and significantly decreased sodium and chloride levels in blood serum. Furthermore, we describe for the first time a significant increase of neurofilament light chain (NFL) in blood serum of MiCI dogs, compared to normal aging seniors and young controls, but no changes in TAU protein and amyloid-β (Aβ42) peptide levels. In canine brains with cognitive impairment, amyloid plaques of mainly diffuse and dense types were detected. Furthermore, activated microglia with amoeboid body and dystrophic processes occurred, in some cases with spheroidal and bulbous swellings. On the other hand, no TAU pathology or neurofibrillary tangles were detected. These results suggest that a combination of CADES questionnaire mainly with CNS injury biomarker (NFL) and with biochemical parameters (ALT, AST, Na, and Cl) in blood serum may predict CCDS in senior dogs.

犬类认知功能障碍综合征（Canine cognitive dysfunction syndrome, CCDS）是一种发生于老年犬的进行性神经退行性疾病，主要表现为学习与对刺激作出反应的能力下降。由于其行为变化常被归因于正常衰老过程，该病症常存在诊断不足的情况。本研究首次采用综合策略实现对轻度认知障碍（mild cognitive disorders, MiCI）患犬的早期诊断，纳入犬类痴呆量表（CAnine DEmentia Scale, CADES）问卷、生化指标及血清生物标志物，并将其与死后组织病理学改变进行相关性分析。通过CADES问卷，我们可识别出主要在社交互动与空间定向领域出现认知变化的MiCI患犬，这一发现对早期认知障碍的甄别至关重要。对这些患犬的生化分析显示，其肝酶指标（天冬氨酸氨基转移酶AST、丙氨酸氨基转移酶ALT）轻度升高，而血清钠与氯水平显著降低。此外，本研究首次发现，与正常衰老的老年犬及年轻对照组相比，MiCI患犬血清中的神经丝轻链（neurofilament light chain, NFL）水平显著升高，但Tau蛋白与β淀粉样蛋白（Aβ42）肽段水平无明显变化。在出现认知障碍的犬类大脑中，可检测到主要为弥漫型和致密型的淀粉样斑块。同时可见呈阿米巴样形态且伴随营养不良性突起的活化小胶质细胞，部分细胞还出现球形及膨大隆起。但未检测到Tau蛋白病理变化或神经原纤维缠结。上述结果表明，将CADES问卷与血清中枢神经系统损伤生物标志物（NFL）及生化指标（ALT、AST、钠、氯）相结合，可用于预测老年犬的CCDS发病风险。