Retinal thickness as a potential biomarker in patients with amyloid‐proven early‐ and late‐onset Alzheimer's disease

Haan, Jurre den; Kreeke, Jacoba A. van de; Konijnenberg, Elles; Kate, Mara ten; Braber, Anouk den; Barkhof, Frederik; Berckel, Bart N. van; Teunissen, Charlotte E.; Scheltens, Philip; Visser, Pieter Jelle; Verbraak, Frank D.; Bouwman, Femke H.

doi:10.1016/j.dadm.2019.05.002

Cited by 28 publications

(21 citation statements)

References 51 publications

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“…However, den Haan et al (2018) found no retinal thinning in amyloid + AD patients. Further studies found that retinal thickness cannot discriminate between healthy individuals and preclinical AD individuals ( den Haan et al, 2019a , b ). In a recent study involving 930 participants (414 cognitively healthy people, 192 with probable amnestic MCI, and 324 probable AD patients), the results showed that there were no significant differences in retinal thickness in different layers ( Sánchez et al, 2020 ).…”

Section: Discussionmentioning

confidence: 96%

Decreased Retinal Vascular Density in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI): An Optical Coherence Tomography Angiography (OCTA) Study

Zhao

Tao

et al. 2021

Front. Aging Neurosci.

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BackgroundTo explore the retinal vascular density changes in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) patients using optical coherence tomography angiography (OCTA).MethodsWe recruit 62 AD patients, 47 MCI patients, and 49 cognitively healthy controls (HC) in this study. All participants in the study received a comprehensive ophthalmological and neurological evaluation, including global cognitive screening, as well as the Mini-Mental State Examination (MMSE), and completed the following eye examinations: visual acuity (VA), intraocular pressure (IOP), examination with slit-lamp, fundus photography (Version 1.5.0.0, NIDEK CO, LTD) and Optical coherence tomography imaging (software ReVue version 2017.1.0.155, Optovue Inc., Fremont, CA, United States). The visual rating scales for atrophy and white matter lesion in MRI was evaluated for all the patients with AD and MCI.ResultsIn the AD patient group, the superficial vascular density in the superior, inferior and whole retina was 44.64 ± 3.34, 44.65 ± 3.55, and 44.66 ± 3.36, respectively. These values were 44.24 ± 3.15, 43.72 ± 3.16, and 44 ± 3.07, respectively, in the MCI patient group. After multivariate analysis of the generalized linear model, adjustments for the confounding factors of sex, age, hypertension, diabetes and the quality index of OCTA image, the superficial vascular density in the AD and MCI patient groups was significantly lower than that in the HC group (P < 0.05): 46.94 ± 2.04, 46.67 ± 2.26, and 46.82 ± 2.08, respectively. No difference in the area of the FAZ among the three groups was observed (AD group: 0.34 ± 0.11 mm2; MCI group: 0.36 ± 0.12 mm2; control group: 0.33 ± 0.12 mm2, p > 0.05). The ganglion cell complex (GCC) thickness, inner parafovea thickness, and peripapillary retinal nerve fiber layer (p-RNFL) thickness were associated with the superficial vascular density. We found no significant correlation between the global cognition (MMSE scores) or between the Fazekas score and retinal OCT angiogram flow density.ConclusionThe superficial vascular density in the AD and MCI patient groups was significantly lower than that in the HC group. Our findings suggest the retinal microvascular dysfunction occurred in MCI and AD.

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Section: Discussionmentioning

confidence: 96%

Decreased Retinal Vascular Density in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI): An Optical Coherence Tomography Angiography (OCTA) Study

Zhao

Tao

et al. 2021

Front. Aging Neurosci.

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“…This study suggested that RNFL, IPL and GCL changes might be useful for AD diagnosis, however Bruch's membrane opening-minimum rim width (BMO-MRW) remained unchanged. Thus, advancements in ocular imaging have provided evidence of inner retinal thinning and loss of the retinal nerve fiber layer (RNFL) in AD and its preclinical and prodromal stages, although some studies have also suggested a non-significant relationship between the effects of AD and changes in retinal imaging by OCT (den Haan et al, 2019;Haan et al, 2019a;Sanchez et al, 2020;Sanchez et al, 2018). An initial meta-analysis concluded that there was a significant RNFL thinning in early stages of AD (Knoll et al, 2016).…”

Section: Retinal Structural Changes In Ad Patientsmentioning

confidence: 99%

Retinal changes in Alzheimer's disease— integrated prospects of imaging, functional and molecular advances

Gupta

Chitranshi

Haan

et al. 2021

Progress in Retinal and Eye Research

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Alzheimer's Disease (AD) is a devastating neurodegenerative disorder of the brain, clinically characterised by cognitive deficits that gradually worsen over time. There is, at present, no established cure, or disease-modifying treatments for AD. As life expectancy increases globally, the number of individuals suffering from the disease is projected to increase substantially. Cumulative evidence indicates that AD neuropathological process is initiated several years, if not decades, before clinical signs are evident in patients, and diagnosis made. While several imaging, cognitive, CSF and blood-based biomarkers have been proposed for the early detection of AD; their sensitivity and specificity in the symptomatic stages is highly variable and it is difficult to justify their use in even earlier, pre-clinical stages of the disease. Research has identified potentially measurable functional, structural, metabolic and vascular changes in the retina during early stages of AD. Retina offers a distinctively accessible insight into brain pathology and current and developing ophthalmic technologies have provided us with the possibility of detecting and characterising subtle, disease-related changes. Recent human and animal model studies have further provided mechanistic insights into the biochemical pathways that are altered in the retina in disease, including amyloid and tau deposition. This information coupled with advances in molecular imaging has allowed attempts to monitor biochemical changes and protein aggregation pathology in the retina in AD. This review summarises the existing knowledge that informs our understanding of the impact of AD on the retina and highlights some of the gaps that need to be addressed. Future research will integrate molecular imaging innovation with functional and structural changes to enhance our knowledge of the AD pathophysiological mechanisms and establish the utility of monitoring retinal changes as a potential biomarker for AD.

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“…Their findings suggested that cerebral cortical changes were reflected in the retina. However, absence of retinal thinning in amyloid proven AD patients was reported in their studies [27,28]. Further studies are needed to evaluate the correlation between RNFL and AD.…”

Section: Discussionmentioning

confidence: 89%

Correlations between retinal nerve fiber layer thickness and cognitive progression in Parkinson's disease: A longitudinal study

Zhang

Cao

et al. 2021

Parkinsonism & Related Disorders

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Background: Retinal abnormalities measured by optical coherence tomography (OCT) have been detected in both Parkinson's disease (PD) and Alzheimer's disease (AD). Cognitive impairment is not only found in AD, but 75-90% of PD patients will also develop dementia in the late stage of disease. We assessed whether baseline retinal nerve fiber layer (RNFL) thickness predicted worsening of cognitive status over time and the correlation between RNFL thickness and the detailed impaired cognitive domains in PD. Methods: RNFL thickness was measured using high-definition OCT in 78 non-dementia PD patients. Clinical and cognitive assessments were performed at baseline and at 3.61 ± 0.65 years follow-up. Linear mixed-effects models were used to examine associations between RNFL thickness and the changes in cognitive test scores, after adjusting for age, sex, disease duration and education. Results: Analysis of outcomes according to baseline RNFL tertiles showed worse performance in global cognitive tests, delayed memory, and executive functions in patients with a thin RNFL. During follow-up, greater cognitive deterioration was found in thin RNFL tertile patients. Lower baseline average RNFL thickness was associated with greater annualized decline in Mini-Mental State Examination and Montreal Cognitive Assessment. Conclusion:The correlation between RNFL thickness and cognitive dysfunction suggests that OCT may be useful for predicting cognitive dysfunction in PD patients.

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Retinal thickness as a potential biomarker in patients with amyloid‐proven early‐ and late‐onset Alzheimer's disease

Cited by 28 publications

References 51 publications

Decreased Retinal Vascular Density in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI): An Optical Coherence Tomography Angiography (OCTA) Study

Decreased Retinal Vascular Density in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI): An Optical Coherence Tomography Angiography (OCTA) Study

Retinal changes in Alzheimer's disease— integrated prospects of imaging, functional and molecular advances

Correlations between retinal nerve fiber layer thickness and cognitive progression in Parkinson's disease: A longitudinal study

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