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ORIGINAL RESEARCH article

Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 16 - 2024 | doi: 10.3389/fnagi.2024.1513302
This article is part of the Research Topic Early Dementia Detection: Memory, Cortical Function, and Biomarkers in the Classification of High-Risk Pre-Dementia Individuals in the Healthy Aging People View all 4 articles

Retinal biomarkers for the risk of Alzheimer's disease and frontotemporal dementia

Provisionally accepted
Ruihan Wang Ruihan Wang 1Jiajie Cai Jiajie Cai 2Yuzhu Gao Yuzhu Gao 3Yingying Tang Yingying Tang 1Hui Gao Hui Gao 1Linyuan Qin Linyuan Qin 1Hanlin Cai Hanlin Cai 1Feng Yang Feng Yang 1Yimeng Ren Yimeng Ren 1Caimei Luo Caimei Luo 1Shiyu Feng Shiyu Feng 1Hongbo Yin Hongbo Yin 3Ming Zhang Ming Zhang 3Chunyan Luo Chunyan Luo 4Qiyong Gong Qiyong Gong 4Xiong Xiao Xiong Xiao 2Qin Chen Qin Chen 1*
  • 1 Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
  • 2 Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University, Chengdu, Sichuan Province, China
  • 3 Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China
  • 4 Department of Radiology, West China Hospital, Sichuan University, Chengdu, China

The final, formatted version of the article will be published soon.

    Purpose: Differentiating between Alzheimer’s disease (AD) and Frontotemporal dementia (FTD) can be challenging due to overlapping cognitive and behavioral manifestations. Evidence on noninvasive and early-stage biomarkers is still limited. Our aim was to identify retinal biomarkers for the risk of AD and FTD in non-demented populations and explore underlying brain structural mechanisms. Methods: We involved a total of 30573 UK Biobank participants without dementia, ocular disorders, and diabetes who underwent baseline retinal optical coherence tomography (OCT) imaging. Cox proportional hazard models estimated the associations of macular OCT parameters with the risk of AD and FTD respectively. Mediation analysis explored the underlying mechanisms affected by brain structures. Results: The mean age at recruitment was 55.27, and 46.10% of the participants were male. During a mean follow-up of 9.15 ± 2.59 years, 148 AD and 8 FTD patients were identified. Reduced thickness of ganglion cell-inner plexiform layer (GC-IPL) at baseline was associated with increased risk of AD (HR, 1.033; 95% CI, 1.001–1.066; P=0.044), while thinner retinal pigment epithelial at inner superior subfield at baseline was associated with elevated risk of FTD (HR, 1.409; 95% CI, 1.060–1.871; P=0.018). Structurally abnormal visual pathways related cortical and subcortical gray matter volume, as well as white matter integrity mediated the association between GC-IPL thickness and AD risk. Conclusion: Our findings provided preliminary empirical support for a relationship between prodromal changes in retinal layers and higher risk for AD or FTD, suggesting macular OCT may serve as a non-invasive sensitive high-risk biomarkers years before onset of dementia.

    Keywords: Alzheimer's disease, Frontotemporal Dementia, Retina, biomarkers, Optical Coherence Tomography

    Received: 18 Oct 2024; Accepted: 26 Dec 2024.

    Copyright: © 2024 Wang, Cai, Gao, Tang, Gao, Qin, Cai, Yang, Ren, Luo, Feng, Yin, Zhang, Luo, Gong, Xiao and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Qin Chen, Department of Neurology, West China Hospital, Sichuan University, Chengdu, China

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