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Altered coupling of cerebral blood flow and functional connectivity strength in visual and higher order cognitive cortices in primary open angle glaucoma.

ABSTRACT: Primary open-angle glaucoma (POAG) has been suggested to be a neurodegenerative disease associated with altered cerebral vascular hemodynamics and widespread disruption of neuronal activity within the visual, working memory, attention and executive networks. We hypothesized that disturbed neurovascular coupling in visual and higher order cognitive cortices exists in POAG patients and correlates with glaucoma stage and visual field defects. Through multimodal magnetic resonance imaging, we evaluated the cerebral blood flow (CBF)-functional connectivity strength (FCS) correlations of the whole gray matter and CBF/FCS ratio per voxel for all subjects. Compared with normal controls, POAG patients showed reduced global CBF-FCS coupling and altered CBF/FCS ratios, predominantly in regions in the visual cortex, salience network, default mode network, and dorsal attentional network. The CBF/FCS ratio was negatively correlated with glaucoma stage, and positively correlated with visual field defects in the lingual gyrus in POAG patients. Moreover, early brain changes were detected in early POAG. These findings indicate neurovascular coupling dysfunction might exist in the visual and higher order cognitive cortices in POAG patients and its clinical relevance. The results may contribute to the monitoring of POAG progression and provide insight into the pathophysiology of the neurodegenerative process in POAG.

SUBMITTER: Wang Q

PROVIDER: S-EPMC7983497 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTestosterone may be a possible modifiable risk factor for open-angle glaucoma (OAG) and intraocular pressure (IOP), but evidence has been scarce and conflicting. In this study we evaluated the association of testosterone and its genetic predisposition with incident (i) OAG, IOP, retinal nerve fiber layer (RNFL), and ganglion cell-inner plexiform layer (GCL +).MethodsParticipants aged 45-100 years were derived from the prospective, population-based Rotterdam Study. Ophthalmic examinations and serum testosterone measurements (including bioavailable and free testosterone) were performed from 1991 onwards. Follow-up took place every 4-5 years. A total of 187 out of 7898 participants were diagnosed with incident (i) OAG during follow-up. Genotyping was performed in 165 glaucoma cases and 6708 controls. We calculated sex-specific weighted genetic risk scores (GRS) for total and bioavailable testosterone. Associations with iOAG were analyzed using multivariable logistic regression. Associations with IOP, RNFL, and GCL + were analyzed with multivariable linear regression. Analyses were stratified on sex and adjusted for at least age, body mass index, and follow-up duration.ResultsIn men, testosterone was not associated with iOAG. However, the GRS for higher total testosterone was associated with an increased iOAG risk (odds ratio [OR] with 95% confidence interval [95% CI]: 2.48 [1.18; 5.22], per unit). In women, higher values of bioavailable testosterone (2.05 [1.00; 4.18] per nmol/L) and free testosterone (1.79 [1.00; 3.20] per ng/dL) were significantly associated with increased risk of iOAG. Moreover, the GRS for higher bioavailable testosterone was associated with an increased iOAG risk (2.48 [1.09; 5.65], per unit). Higher bioavailable and free testosterone were adversely associated with IOP (0.58 [0.05; 1.10] per nmol/L and 0.47 [0.04; 0.90] per ng/dL). Higher total testosterone was inversely associated with peripapillary RNFL and GCL + (Beta [95% CI]: - 3.54 [- 7.02; - 0.06] per nmol/L and - 2.18 [- 4.11; - 0.25] per nmol/L, respectively).ConclusionsIn women, higher testosterone levels increased the risk of iOAG. Both IOP-dependent and IOP-independent mechanisms may underlie this association. Managing testosterone levels may be particularly relevant for the prevention of neurodegeneration in the eye. Future research should confirm these findings.

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Altered coupling of cerebral blood flow and functional connectivity strength in visual and higher order cognitive cortices in primary open angle glaucoma.

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