Macular vessel density is associated with cognitive function in preclinical p.R544C NOTCH3 mutation carriers

Chien-Chih Chou; Chiao-Ying Liang; Chen-Yu Lin; I-Jong Wang; Chia-Jen Chang; Jun-Peng Chen; Hsin Tung; Hung-Chieh Chen; Hsian-Min Chen; Yi-Ming Chen; Wei-Ju Lee

doi:10.1097/JCMA.0000000000001262

Macular vessel density is associated with cognitive function in preclinical p.R544C NOTCH3 mutation carriers

J Chin Med Assoc. 2025 Jul 3. doi: 10.1097/JCMA.0000000000001262. Online ahead of print.

Authors

Chien-Chih Chou^{1

2

3

4}, Chiao-Ying Liang², Chen-Yu Lin², I-Jong Wang^{1

5

6}, Chia-Jen Chang², Jun-Peng Chen⁷, Hsin Tung⁸, Hung-Chieh Chen^{3

9}, Hsian-Min Chen¹⁰, Yi-Ming Chen^{3

4

11

12

13

14}, Wei-Ju Lee^{4

8

15

16}

Affiliations

¹ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
² Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
³ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
⁴ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan, ROC.
⁵ Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, ROC.
⁶ Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan, ROC.
⁷ Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
⁸ Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
⁹ Division of Neuroradiology, Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
¹⁰ Center for Quantitative Imaging in Medicine, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
¹¹ Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
¹² Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
¹³ Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine & Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan, ROC.
¹⁴ Precision Medicine Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan, ROC.
¹⁵ Dementia Center, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
¹⁶ Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.

PMID: 40604365
DOI: 10.1097/JCMA.0000000000001262

Abstract

Background: The study aimed to examine the relationship between retinal microcirculation, brain white matter hyperintensities (WMH) seen on MRI, and cognitive decline in asymptomatic carriers of NOTCH3 mutations, a preclinical stage of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Methods: Forty-nine asymptomatic carriers without stroke history or cognitive complaints were studied. Retinal vessel density and WMH volume were measured via optical coherence tomography angiography and MRI, respectively. Cognitive function was assessed using various tests.

Results: In a multivariable regression model which included both, the whole brain WMH volume and parafoveal vessel density of superficial retinal plexus (SRP) as independent variables, parafoveal vessel density of SRP emerged as a significant predictor for MoCA score (β = -0.31; 95% confidence interval -0.1516 to -0.0002, p = 0.044) in this cohort, and consistent findings were observed for CTT-1 and CTT-2 scores.

Conclusion: In asymptomatic NOTCH3 mutation carriers, higher parafoveal vessel density of the SRP may serve as an indicator of cognitive decline, and may also indicate autoregulatory compensatory mechanisms in response to a dysfunctional capillary plexus, potentially signifying early-stage cognitive decline.

Keywords: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; Cognitive decline; Optical coherence tomography angiography; Retinal microcirculation..