Olfactory deficit: a potential functional marker across the Alzheimer's disease continuum

Dongming Liu; Jiaming Lu; Liangpeng Wei; Mei Yao; Huiquan Yang; Pin Lv; Haoyao Wang; Yajing Zhu; Zhengyang Zhu; Xin Zhang; Jiu Chen; Qing X Yang; Bing Zhang

doi:10.3389/fnins.2024.1309482

Olfactory deficit: a potential functional marker across the Alzheimer's disease continuum

Front Neurosci. 2024 Feb 16:18:1309482. doi: 10.3389/fnins.2024.1309482. eCollection 2024.

Authors

Dongming Liu^#^{1

2

3}, Jiaming Lu^#^{1

2

3}, Liangpeng Wei^{1

2

3}, Mei Yao^{1

2

3}, Huiquan Yang^{1

2

3}, Pin Lv^{1

2

3}, Haoyao Wang^{1

2

3}, Yajing Zhu¹, Zhengyang Zhu¹, Xin Zhang^{1

2

3}, Jiu Chen^{1

2

3}, Qing X Yang⁴, Bing Zhang^{1

2

3

5

6

7

8}

Affiliations

¹ Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
² Institute of Medical Imaging and Artificial Intelligence, Nanjing University, Nanjing, China.
³ Medical Imaging Center, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
⁴ Department of Radiology, Center for NMR Research, Penn State University College of Medicine, Hershey, PA, United States.
⁵ State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
⁶ Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China.
⁷ Institute of Brain Science, Nanjing University, Nanjing, China.
⁸ Jiangsu Provincial Medical Key Discipline (Laboratory), Nanjing, China.

^# Contributed equally.

Abstract

Alzheimer's disease (AD) is a prevalent form of dementia that affects an estimated 32 million individuals globally. Identifying early indicators is vital for screening at-risk populations and implementing timely interventions. At present, there is an urgent need for early and sensitive biomarkers to screen individuals at risk of AD. Among all sensory biomarkers, olfaction is currently one of the most promising indicators for AD. Olfactory dysfunction signifies a decline in the ability to detect, identify, or remember odors. Within the spectrum of AD, impairment in olfactory identification precedes detectable cognitive impairments, including mild cognitive impairment (MCI) and even the stage of subjective cognitive decline (SCD), by several years. Olfactory impairment is closely linked to the clinical symptoms and neuropathological biomarkers of AD, accompanied by significant structural and functional abnormalities in the brain. Olfactory behavior examination can subjectively evaluate the abilities of olfactory identification, threshold, and discrimination. Olfactory functional magnetic resonance imaging (fMRI) can provide a relatively objective assessment of olfactory capabilities, with the potential to become a promising tool for exploring the neural mechanisms of olfactory damage in AD. Here, we provide a timely review of recent literature on the characteristics, neuropathology, and examination of olfactory dysfunction in the AD continuum. We focus on the early changes in olfactory indicators detected by behavioral and fMRI assessments and discuss the potential of these techniques in MCI and preclinical AD. Despite the challenges and limitations of existing research, olfactory dysfunction has demonstrated its value in assessing neurodegenerative diseases and may serve as an early indicator of AD in the future.

Keywords: Alzheimer’s disease; early assessment; olfaction; olfactory behavior; olfactory fMRI.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Science and Technology Innovation 2030 – Major program of “Brain Science and Brain-Like Research” (2022ZD0211800); the Jiangsu Funding Program for Excellent Postdoctoral Talent (2023ZB184); the China Postdoctoral Science Foundation (2023 M741648); the National Natural Science Foundation of China (82271965, 81971596, 82001793); the Fundamental Research Funds for the Central Universities, Nanjing University (2020–021414380462); the Key Scientific Research Project of Jiangsu Health Committee (K2019025); Industry and Information Technology Department of Nanjing (SE179-2021); Educational Research Project of Nanjing Medical University (2019ZC036); Key Project supported by Medical Science and technology development Foundation, Nanjing Department of Health (ZKX21031), and fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2021-LCYJ-PY-36, 2022-LCYJ-MS-25). Project of Modern Hospital Management and Development Institute, Nanjing University and Aid project of Nanjing Drum Tower Hospital Health, Education & Research Foundation (NDYG2021005). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.