Visual impairment and retinal and brain neurodegeneration: A population‐based study

Garzone, Davide; Finger, Robert P.; Mauschitz, Matthias M.; Koch, Alexandra; Reuter, Martin; Breteler, Monique M.B.; Aziz, N. Ahmad

doi:10.1002/hbm.26237

Cited by 9 publications

(14 citation statements)

References 62 publications

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“…A pathophysiological relationship appears to exist between regions involved in sensory processing and diabetic peripheral neuropathy severity, 22 neuropathic pain 4 and worsening visual impairment in diabetic retinopathy. 23 Previous studies reported structural alterations in the central nervous system in T1D 24 and T2D. 25 26 This was demonstrated in a large cohort of deeply phenotyped participants with diabetes, where mild cognitive impairment prevalence was comparable to age-adjusted rates of the general population despite accelerated incipient cognitive decline.…”

Section: Discussionmentioning

confidence: 91%

Brain alterations in regions associated with end‐organ diabetic microvascular disease in diabetes mellitus: A UK Biobank study

Burgess,

de Bezenac,

Keller

et al. 2024

Diabetes Metabolism Res

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BackgroundDiabetes mellitus (DM) is associated with structural grey matter alterations in the brain, including changes in the somatosensory and pain processing regions seen in association with diabetic peripheral neuropathy. In this case‐controlled biobank study, we aimed to ascertain differences in grey and white matter anatomy in people with DM compared with non‐diabetic controls (NDC).MethodsThis study utilises the UK Biobank prospective, population‐based, multicentre study of UK residents. Participants with diabetes and age/gender‐matched controls without diabetes were selected in a three‐to‐one ratio. We excluded people with underlying neurological/neurodegenerative disease. Whole brain, cortical, and subcortical volumes (188 regions) were compared between participants with diabetes against NDC corrected for age, sex, and intracranial volume using univariate regression models, with adjustment for multiple comparisons. Diffusion tensor imaging analysis of fractional anisotropy (FA) was performed along the length of 50 white matter tracts.ResultsWe included 2404 eligible participants who underwent brain magnetic resonance imaging (NDC, n = 1803 and DM, n = 601). Participants with DM had a mean (±standard deviation) diagnostic duration of 18 ± 11 years, with adequate glycaemic control (HbA1C 52 ± 13 mmol/mol), low prevalence of microvascular complications (diabetic retinopathy prevalence, 5.8%), comparable cognitive function to controls but greater self‐reported pain. Univariate volumetric analyses revealed significant reductions in grey matter volume (whole brain, total, and subcortical grey matter), with mean percentage differences ranging from 2.2% to 7% in people with DM relative to NDC (all p < 0.0002). The subcortical (bilateral cerebellar cortex, brainstem, thalamus, central corpus callosum, putamen, and pallidum) and cortical regions linked to sensorimotor (bilateral superior frontal, middle frontal, precentral, and postcentral gyri) and visual functions (bilateral middle and superior occipital gyri), all had lower grey matter volumes in people with DM relative to NDC. People with DM had significantly reduced FA along the length of the thalamocortical radiations, thalamostriatal projections, and commissural fibres of the corpus callosum (all; p < 0·001).InterpretationThis analysis suggests that anatomic differences in brain regions are present in a cohort with adequately controlled glycaemia without prevalent microvascular disease when compared with volunteers without diabetes. We hypothesise that these differences may predate overt end‐organ damage and complications such as diabetic neuropathy and retinopathy. Central nervous system alterations/neuroplasticity may occur early in the natural history of microvascular complications; therefore, brain imaging should be considered in future mechanistic and interventional studies of DM.

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Section: Discussionmentioning

confidence: 91%

Brain alterations in regions associated with end‐organ diabetic microvascular disease in diabetes mellitus: A UK Biobank study

Burgess,

de Bezenac,

Keller

et al. 2024

Diabetes Metabolism Res

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“…However, visual acuity was not associated with any brain MRI measures, in contrast to another study. (38) Myopia was associated with decreased risk of dementia in observational models. Although this is consistent with some prior work,(54) we believe this is likely due to residual confounding, as the Myopia-GRS was not associated with all-cause dementia, AD, or VaD.…”

Section: Discussionmentioning

confidence: 98%

“…Our findings are strengthened by evaluating multiple ADRD-related outcomes including neuroimaging makers. Few prior studies have examined associations between vision and ADRD-related neurodegeneration (38,39,52). In our study, cataracts were associated with increased brain atrophy, including total grey matter and occipital volumes.…”

Section: Discussionmentioning

confidence: 99%

“…We also included the volume of one visual region, lateral occipitalcortex, under the hypothesis that visual impairment may cause atrophy in visual tracts and brain regions. (38,39) MRI was obtained from the first imaging visit (n=36,855), which was acquired using identical scanners (Siemens Skyra 3T scanner with a standard 32-channel head coil) and the same protocol across sites. (40) Volumetric, cortical thickness, and surface area measures were obtained using FreeSurfer.…”

Section: Methodsmentioning

confidence: 99%

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Relationships of visual impairment and eye conditions with imaging markers, cognition, and diagnoses of dementia: a bi-directional Mendelian randomization study

Ferguson,

Thoma,

Buto

et al. 2024

Preprint

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ObjectiveTo evaluate the causal relationships between visual acuity, eye conditions (focusing on cataracts and myopia), and Alzheimer disease (AD) and related dementias.DesignCohort and two sample bi-directional mendelian randomization (MR) study.SettingUK Biobank participants and summary statistics from previously published genome-wide association studies on cataract, myopia, and AD.ParticipantsUK Biobank participants (n=304,953) aged 55-70 without dementia at baseline, underwent genotyping, reported on eye conditions, and a subset completed visual acuity exams (n=113,756) or brain imaging (n=36,855)Main outcome measuresAll-cause dementia, AD, and vascular dementia (VaD) identified from electronic medical records.ResultsThe sample averaged 62.1 years (SD=4.1) of age at baseline, 4.7% had cataracts, and 3.9% had worse than 20/40 vision. History of cataracts (HR=1.18, 95% CI: 1.07 to 1.29) and 20/40 vision (HR=1.35, 95% CI: 1.06 to 1.70) were associated with higher hazard of all-cause dementia. In MR analyses to estimate causal effects, cataracts increased risk of VaD inverse-variance weighted (OR=1.92, 95% CI: 1.26-2.92) borderline increased all-cause dementia (OR =1.21, 95% CI: 0.98 to 1.50) but not AD (OR=1.01, 95% CI: 0.97-1.06). There was no significant association between observed or genetic risk for myopia and dementia. In MR for reverse causality using genetic risk for AD, AD was not significantly associated with cataracts (inverse-variance weighted OR=0.99, 95% CI: 0.96 to 1.01). Genetic risk for cataracts were associated with smaller total brain (β= −597.4 mm3, 95% CI: −1077.9 to −117.0) and grey matter volumes (β= −375.2 mm3, 95% CI: −680.1 to −70.2), but not other brain regions or cognition.ConclusionsOur findings suggest cataracts increase risk of dementia and may reduce brain volume. This lends further support to the hypothesis that cataract extraction may reduce risk for dementia.

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“…This is because dopaminergic cells—RGC and amacrine cells (ACs)—reside in these layers and are principal cells involved in PD. 10 …”

Section: Introductionmentioning

confidence: 99%

Retinal Vessel Density and Retinal Nerve Fiber Layer Thickness: A Prospective Study of One-Year Follow-Up of Patients with Parkinson’s Disease

Tu,

Yang,

Zeng

et al. 2023

IJGM

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Objective This study aims to compare the superficial vascular density from the macular region and the retinal nerve fiber layer (RNFL) thickness from the optic disc region between Parkinson’s disease (PD) patients and controls. Methods We enrolled 56 idiopathic PD patients, totaling 86 eyes (PD group), and 45 sex- and age-matched healthy individuals, amounting to 90 eyes (control group). All subjects underwent examination using Zeiss wide-field vascular optical coherence tomography (OCT) (Cirrus HD-OCT 5000 Carl Zeiss, Germany), with a scanning range of 3 mm × 3 mm. We divided the images into two concentric circles with diameters of 1 mm and 3 mm at the macular fovea’s center. Patients with PD were evaluated during their “off” phase using the Unified Parkinson’s Disease Rating Scale III (UPDRS-III) and the Hoehn-Yahr scale (H-Y scale) to assess disease severity. Results The PD group exhibited significantly lower RNFL thickness (106.13±12.36 μm) compared to the control group (115.95±11.37 μm, P < 0.05). Similarly, the superficial retinal vessel length density was significantly lower in the PD group (20.7 [19.62, 22.17] mm −1 ) than in the control group (21.79±1.16 mm −1 , P < 0.05). Correlation analysis revealed a negative correlation between RNFL thickness and UPDRS III score (r s =−0.036, P=0.037), and RNFL thickness tended to decrease with increasing severity of movement disorders. However, during the 6 and 12-month follow-up of some PD patients, we observed no progressive thinning of the RNFL or decreased superficial vascular density. Conclusion PD patients show retinal structural damage characterized by RNFL thinning and reduced retinal vessel length density. However, RNFL thickness did not correlate with vascular density nor did it decrease with the disease’s progression.

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Visual impairment and retinal and brain neurodegeneration: A population‐based study

Cited by 9 publications

References 62 publications

Brain alterations in regions associated with end‐organ diabetic microvascular disease in diabetes mellitus: A UK Biobank study

Brain alterations in regions associated with end‐organ diabetic microvascular disease in diabetes mellitus: A UK Biobank study

Relationships of visual impairment and eye conditions with imaging markers, cognition, and diagnoses of dementia: a bi-directional Mendelian randomization study

Retinal Vessel Density and Retinal Nerve Fiber Layer Thickness: A Prospective Study of One-Year Follow-Up of Patients with Parkinson’s Disease

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