Sensitive Measures of Cognition in Mild Cognitive Impairment

Article type: Research Article

Authors: Klooster, Nathaniel^{a; b; *} | Humphries, Stacey^{a; c} | Cardillo, Eileen^{a; c} | Hartung, Franziska^{a; c} | Xie, Long^{d; e} | Das, Sandhitsu^d | Yushkevich, Paul^d | Pilania, Arun^{d; f} | Wang, Jieqiong^a | Wolk, David A.^{a; f} | Chatterjee, Anjan^{a; b; c; f}

Affiliations: [a] Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA | [b] Moss Rehabilitation Research Institute, Elkins Park, PA, USA | [c] Penn Center for Neuroaesthetics, University of Pennsylvania, Philadelphia, PA, USA | [d] Penn Image Computing and Science Laboratory (PICSL), University of Pennsylvania, Philadelphia, PA, USA | [e] Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA | [f] Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA

Correspondence: [*] Correspondence to: Nathaniel B. Klooster, Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA. Tel.: +1 616 994 2039; E-mail: klooster@pennmedicine.upenn.edu.

Abstract: Background:Sensitive measures of cognition are needed in preclinical and prodromal Alzheimer’s disease (AD) to track cognitive change and evaluate potential interventions. Neurofibrillary tangle pathology in AD is first observed in Brodmann Area 35 (BA35), the medial portion of the perirhinal cortex. The importance of the perirhinal cortex for semantic memory may explain early impairments of semantics in preclinical AD. Additionally, our research has tied figurative language impairment to neurodegenerative disease. Objective:We aim to identify tasks that are sensitive to cognitive impairment in individuals with mild cognitive impairment (MCI), and that are sensitive to atrophy in BA35. Methods:Individuals with MCI and cognitively normal participants (CN) were tested on productive and receptive experimental measures of semantic memory and experimental tests of figurative language comprehension (including metaphor and verbal analogy). Performance was related to structural imaging and standard neuropsychological assessment. Results:On the experimental tests of semantics and figurative language, people with MCI performed worse than CN participants. The experimental semantic memory tasks are sensitive and specific; performance on the experimental semantic memory tasks related to medial temporal lobe structural integrity, including BA35, while standard neuropsychological assessments of semantic memory did not, demonstrating the sensitivity of these experimental measures. A visuo-spatial analogy task did not differentiate groups, confirming the specificity of semantic and figurative language tasks. Conclusion:These experimental measures appear sensitive to cognitive change and neurodegeneration early in the AD trajectory and may prove useful in tracking cognitive change in clinical trials aimed at early intervention.

Keywords: Alzheimer’s disease, figurative language, medial temporal lobe, mild cognitive impairment, perirhinal cortex, semantic memory

DOI: 10.3233/JAD-201280

Journal: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 1123-1136, 2021