Language dysfunction correlates with cognitive impairments in older adults without dementia mediated by amyloid pathology

Chunchen Xiang; Weiping Ai; Yumei Zhang; Alzheimer's Disease Neuroimaging Initiative

doi:10.3389/fneur.2023.1051382

Language dysfunction correlates with cognitive impairments in older adults without dementia mediated by amyloid pathology

Front Neurol. 2023 May 17:14:1051382. doi: 10.3389/fneur.2023.1051382. eCollection 2023.

Authors

Chunchen Xiang¹, Weiping Ai², Yumei Zhang^{3

4

5}; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² Department of Neurology, Zhangjiakou First Hospital, Zhangjiakou, China.
³ Department of Rehabilitation Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁴ Center of Stroke, Beijing Institute for Brain Disorders, Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
⁵ China National Clinical Research Center for Neurological Diseases, Beijing, China.

Abstract

Background: Previous studies have explored the application of non-invasive biomarkers of language dysfunction for the early detection of Alzheimer's disease (AD). However, language dysfunction over time may be quite heterogeneous within different diagnostic groups.

Method: Patient demographics and clinical data were retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database for the participants without dementia who had measures of cerebrospinal fluid (CSF) biomarkers and language dysfunction. We analyzed the effect of longitudinal neuropathological and clinical correlates in the pathological process of semantic fluency and confrontation naming. The mediation effects of AD biomarkers were also explored by the mediation analysis.

Result: There were 272 subjects without dementia included in this analysis. Higher rates of decline in semantic fluency and confrontation naming were associated with a higher risk of progression to MCI or AD, and a greater decline in cognitive abilities. Moreover, the rate of change in semantic fluency was significantly associated with Aβ deposition, while confrontation naming was significantly associated with both amyloidosis and tau burden. Mediation analyses revealed that both confrontation naming and semantic fluency were partially mediated by the Aβ aggregation.

Conclusion: In conclusion, the changes in language dysfunction may partly stem from the Aβ deposition, while confrontation naming can also partly originate from the increase in tau burden. Therefore, this study sheds light on how language dysfunction is partly constitutive of mild cognitive impairment and dementia and therefore is an important clinical predictor.

Keywords: Alzheimer's disease; amyloid; confrontation naming; neurodegeneration; semantic fluency; tau.

Grants and funding

This study was supported by the National Key Technology Research and Development Program of China (2020YFC2004105) and the National Natural Science Foundation of China (NSFC: 81972144 and 81972148). The sponsors had no role in the study design; the collection, analysis, or interpretation of data; the writing of the report; or the decision to submit the article for publication. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The guarantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.