Scp In Ad Individuals
We showed that AD participants have a sparser VD of the SCP compared with control participants. Our findings support most of the previous OCTA studies in AD participants , which is in keeping with studies on larger retinal vessels using fundus photographs . It should be noted that three other studies did not observe any differences in the VD of the SCP in AD participants . Furthermore, a study in presymptomatic AD found A+ participants had higher VD on OCTA than A participants, after accounting for age . OCTA quantification metrics may potentially be affected by several confounders. First, OCTA signal strength quality can affect the VD, where the VD decreased linearly with signal strength . In our study, the scan qualities were extremely high between controls and AD/MCI and we adjusted the OCTA signal strength quality. Second, although studies have excluded participants with uncontrolled hypertension, the BP levels can affect the VD . In the current study, we statistically adjusted the BP levels to remove the BP bias. Last, the physiological variability of FAZ can affect the VD . This is mainly dependent on how much FAZ one includes in the analytical regions. In eyes with a larger FAZ, the FAZ would occupy a larger portion of the analytical area, resulting in a lower VD. In the current study, we mitigated the potential measurement bias by manually delineating the FAZ region and masking it from the calculation.
A Need For Early Detection
Experts and providers say that early detection of a patient’s risk for neurodegenerative diseases could support advance planningand potentially help researchers develop treatments.
Early detection “is sort of the holy grail,” Ron Petersen, director of Mayo Clinic‘s Alzheimer’s Disease Research Center and the Mayo Clinic Study of Aging, told Brown.
That’s because patients typically already have experienced a significant amount of neurodegeneration by the time they start showing symptoms, Brown notes. And at that point, current treatments usually aren’t very effective.
If providers are able to detect brain changes that could signal the onset of neurodegenerative diseases, the hope is they could slow the disease’s progression, Petersen said. “he sooner we intervene, the better we will be” at staving off cognitive impairment, he told Brown.
An Intriguing Journey: From Compound To Camera
As always, inventions are born out of need. While developing compounds to treat early Alzheimers, More and Vince were faced with an urgent need for a much faster way to test the efficacy of potential drug candidates. They began using a specialized hyperspectral imaging microscope to monitor the development of amyloid plaques, the tell-tale sign of Alzheimers, in brain cells and to see a potential compounds impact when they came up with a new hypothesis.
The eye is an extension of the brain, said Vince. If we can see these plaques develop in the brain, maybe we can also see it in the eye.
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Diagnosis Of Alzheimers Disease
There is no single test to diagnose Alzheimers disease. The diagnosis is made only after a complete medical history, a thorough medical exam and ancillary testing.
Your doctor will use a multifaceted approach to make the diagnosis of AD and to insure that there are no other medical diseases which can mimic the symptoms of AD.
Additional testing may include:
- Blood tests while there is no diagnostic blood test for Alzheimers, but testing may rule out other diseases
- Brain imaging may help support the diagnosis of AD and rule out other causes such as bleeding, tumors or stroke
- CT computerized tomography
- PET scan positron emission tomography
Presently, the diagnosis of AD is not made easily. The diagnosis requires individualized evaluation and use of expensive ancillary testing and scanning.
There is no screening test of those at risk for developing Alzheimers disease. Identifying individuals at risk for developing the disease will allow early institution of treatment and future planning.
The OCTA retina scan may indeed become an inexpensive, yet specific, method for screening and making the diagnosis of Alzheimers disease.
Other New Retinal Imaging Technologies Related To Ad
Several new retinal imaging technologies are also being explored which might provide additional value in this field.
Retinal hyperspectral imaging obtains a series of hyperspectral reflectance images, combing both spectral and spatial information, by scanning the retina with a continuous range of wavelengths of light.S119 More et al showed that amyloid- exerts a characteristic influence on the reflectance of light as assessed by retinal hyperspectral imaging and that the magnitude of this effect varies in proportion with the amount of amyloid- in the retina of AD mouse.S120,S121 This finding was further validated in recent in vivo human clinical studies by showing optical density spectral profiles are different between AD and controls,S122 and cases who are amyloid- positive and negative on PET can be discriminated from the reflectance of hyperspectral retinal images with a machine learningbased model for the classification.S123,S124 Hyperspectral imaging technology is also being investigated to identify brain cancerS125 as well as to estimate cerebral metabolism and haemodynamics from brain tissues.S126
Given that the retina is an easily accessible window and connected to the CNS, it is believed that further advance in retinal imaging as well as multimodal, composite biomarkers for AD will be continuously developed.
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Diagnostic Performance Of Octa To Detect Cognitive Impairment
We found that the OCTA parameters were superior to MTA scores for distinguishing between normal and AD/MCI participants. This is in favor of the potential clinical utility of the OCTA as a screening tool for cognitive impairment. Incorporating both components of the retinal microvasculature and retinal ganglion cell axons may further improve the screening performance of OCTA for cognitive impairment. We had previously shown that the structural component of the retina can be extracted from OCTA system with good reliability . Nevertheless, there are many important considerations when determining whether some form of screening for cognitive impairment in older adults is worthwhile these include the technical challenge of motion artifacts in OCTA scans.
Dcp In Ad Individuals
Four OCTA studies have investigated DCP VD in AD individuals, but there is generally a lack of agreement between studies . Two studies showed a significant reduction in VD in AD individuals whereas the others did not observe any differences. Obtaining accurate OCTA metrics from the DCP layer is particularly challenging as it is affected by the physiologic variability of FAZ and projection artifacts . First, previous OCTA studies did not account for the FAZ in the deeper plexus. This is crucial because the FAZ in the deep plexus is considerably larger than superficial plexus . Second, while Zabel et al. removed the projection artifacts in the DCP , the rest did not . In the current study, we quantified the VD of the DCP without the influence of FAZ and projection artifacts, which hopefully reduced measurement bias. We found a sparser VD of the DCP in AD participants but not in MCI individuals, which suggests the possibility of using the VD of the DCP to discriminate between AD and MCI individuals.
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Retinal Arteriolar And Venular Changes
There is also substantial evidence indicating a vascular disease component in AD pathophysiology. Clinical and epidemiological studies show that vascular diseases and their risk factors commonly accompanies AD. Vascular risk factors are associated with higher cerebral burden. Comorbidity of cerebrovascular disease and amyloid- is associated with cognitive decline and neurodegeneration. In particular, microvascular or small vessel disease is now thought to be a major contributor to dementia and cognitive decline.S49-S52 For example, an autopsy-based neuropathological study showed that a large majority of patients diagnosed with AD without clinical evidence of mixed dementia had microvascular pathology including lacunes, cerebral microbleeds and multiple microinfarcts indicative of small vessel disease.
Why The Retina Is A Good Biomarker For The Brain
The retina is part of the central nervous system, and some of its cells connect directly to the brain.
Many of the processes that happen in the brain also occur in retinal ganglion cells, another layer of cells that make up the retina. This includes some of the abnormal processes common in Alzheimers disease, such as the abnormal deposition of amyloid beta protein and cell loss.
Retinal imaging has many advantages over other imaging technologies. Its fast, with each scan taking only a few seconds, non-invasive, painless and relatively cheap.
Its also already widely available. In Aotearoa, every hospital eye department has an optical coherence tomography device for imaging the retina, and these devices are increasingly available in primary care clinics and retail optometrists.
Retinal imaging also lends itself to being interpreted by artificial intelligence applications. This means assessment of Alzheimers disease risk from the retina could be quick, easy and widely available.
For these reasons, researchers are beginning to investigate how early the retina starts to thin in Alzheimers disease. The disease has an insidious onset, with a gradual decline in cognitive processes such as memory, but the underlying pathology tends to be fairly far along by the time people notice the symptoms and seek medical treatment.
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The Retina A Window To Ad
As an extension of the CNS, the retina and optic nerve share many features in terms of embryological origin, anatomy, response to injury, immunology and physiological characteristics, with the brain . The retina and optic nerve originate from the diencephalon during embryonic development, and therefore are considered as an extension of the CNS. Photoreceptor cells of the retina capture light and initiate neuronal signals that eventually reach the RGCs. The optic nerve composed of the axons of RGCs passes the visual information to the higher visual processing centers in the brain. RGCs show the typical patterns of CNS neurons and comprise a cell body, dendrites and an axon. Similar to all fiber tracts of CNS, the optic nerve is myelinated as they leave the eyes. Insult to the optic nerve leads to degeneration of the axons, myelin damage and inducing a neurotoxic condition, which are also observed in other CNS axons . After injury, similar limited regeneration environment exists in the retina, optic nerve and other CNS compartments. The eye and the brain normally maintain strict interactions with immune system, and both are immune-privileged organs. Furthermore, ocular inner BRB resembles the BBB strongly with respect to structures, characteristics and mechanisms .
Retinal Vessel Oxygen Saturation Changes
The retina is one of the most metabolically active tissues in the human body. Retinal vessel oxygen saturation can now also be measured non-invasively, based on estimation of haemoglobin oxygen saturation in retinal vessels by taking two simultaneous retinal photographs with 570 and 600nm light.S87 Studies have reported that retinal oxygen saturation in arterioles and venules is significantly higher in both AD dementia and MCI eyes compared with controls.S88, S89 Einarsdottir et al showed that retinal arterioles have 94.2%±5.4% oxygen saturation in moderate AD compared with 90.5%±3.1% in healthy subjects . Retinal venules were 51.9%±6.0% saturated in moderate AD compared with 49.7%±7.0% in healthy subjects .S88 Olafsdottir et al further showed that arteriolar and venular oxygen saturation was increased in patients with MCI compared with healthy individuals .S89 These studies demonstrate a decreased metabolic activity in the retina and this exploratory finding may provide new insight into the pathophysiology of AD related to hypometabolism.
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Retinal Thinning And Cognitive Decline In Middle Age
The people we studied are all part of the unique Dunedin Study, which tracked the development of a thousand babies born in tepoti Dunedin between April 1972 and March 1973.
Theyve been assessed repeatedly every few years since, on a wide range of topics including mental health, risk-taking behaviours, respiratory and cardiovascular function, social support and dental health, among others.
Theyve also repeatedly undergone cognitive tests since they were children, each time using similar formats and standardised tests. This means we can compare their cognitive performance in middle age with their own results from childhood.
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Most cognitive tests used in Alzheimers studies are blunt tools designed to detect large drops in cognition. But the detailed cognitive data we have allow us to detect even small cognitive changes.
Using statistical techniques, we used each persons cognitive scores in childhood to predict what wed expect their cognitive score to be at age 45, and measured how far away they were from what wed predicted.
A number of study members scores were substantially lower than what wed expect, indicating they were experiencing cognitive decline, even in middle age.
Can Your Eyes Help Detect Alzheimers
According to a study published in Ophthalmology Retina conducted by the Duke Eye Center, a new, non-invasive imaging technology can detect indicators of Alzheimers disease in a matter of seconds.
The researchers discovered that in Alzheimers patients, the tiny blood vessels in the retina change in appearance.
They also demonstrated that they can tell the difference between those with Alzheimers disease and those with mild cognitive impairment.
This study is the largest to date, and it adds to the current literature as scientists try to identify a rapid, noninvasive and low-cost way to diagnose Alzheimers disease in its early stages.
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Foveal Avascular Zone Area
Previous OCTA studies have quantified the FAZ area within the SCP region automatically using the OCTA software and reported conflicting results . Some reported a significant enlargement of the FAZ in individuals with AD compared to controls , whereas others reported no difference in the FAZ area . In the current study, we did not find any differences in either of the plexuses between groups. Overall, the FAZ area has numerous limitations to serve as a biomarker of cognitive impairment given its physiologic variability, effect of axial length on OCT scan dimensions, and segmentation/measurement limitations .
Confocal Scanning Laser Ophthalmoscopy
Confocal scanning laser ophthalmoscopy is an imaging technique and allows for reconstructing three-dimensional structures with advantages of increasing resolution and contrast. Morphological changes in the ONH measured by cSLO, including a significant reduction in the RNFL, neuroretinal rim, and increased vertical cup-to-disk, were found in AD patients in comparison to healthy subjects . In contrast to this finding, a recent study using cSLO did not document significant difference in the ONH between AD patients and healthy controls . However, AD patients could be differentiated from glaucoma patients, implying the potential utility of cSLO as a new biomarker to recognize specific neurodegenerative diseases . Using a lipid curcumin fluorochome and a modified point cSLO, a recent study reported the increased burden of retinal amyloid deposits in live AD patients, which might lead to a practical approach for large-scale AD screening and monitoring .
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Advances In Imaging Of Retinal Neural Structure And Microvasculature Based On Oct And Octa
Previous studies based on fundus photography have demonstrated that the quantitative retinal vascular parameters including fractal dimension , central retinal artery equivalent, and central retinal vein equivalent, as well as the qualitative retinopathy, are associated with dementia . Nevertheless, findings from other studies are inconsistent, especially in the early stage of AD . This discrepancy may be because that the relatively large blood vessels detected by the fundus camera were not sufficient to reflect the subtle pathology in the early stage of the disease.
As a milestone in the development of retinal imaging technology, the OCTA can detect the movement of red blood cells in the vascular lumen via changes in OCT signal measured by multiple scans in the same cross section. Combined with continuous en-face blood cell movement information, complete three-dimensional imaging of retinal and choroid vessels can be achieved. This is a novel imaging technique that can noninvasively and rapidly depict the microvasculature in different retinal layers with high resolution . In addition to the retinal vessel density , FD , which represents the retinal capillary complexity, can be obtained from OCTA to detect subtle microvascular changes in the early stage of retinopathies and neurodegenerative diseases . In the following, we summarize relevant studies of OCT/OCTA in AD, MCI and preclinical AD patients .
Why Is The Retina A Window To The Brain
The retina originates from the neural tube as a part of the central nervous system during embryonic development . The RNFL is mainly composed of axons, while the ganglion cell- inner plexiform layer mainly contains cell bodies and dendrites. In terms of the brain parenchyma, the white matter of the brain is mainly composed of axons, while the gray matter is mainly composed of cell bodies and dendrites of neurons. Research has demonstrated that thinning of the GC-IPL is significantly associated with the gray matter volume obtained from MRI scans, suggesting that the retinal ganglion cells are potential markers of cerebral neurodegeneration .
In terms of the retinal microvasculature around macula, the inner layer of retina is supplied by the ophthalmic artery through the central retinal artery. The ophthalmic artery originates from the internal carotid artery, similar to the intracranial artery. The external retina is supplied by choroid vessels. The blood supply of the optic disc is derived from the posterior ciliary artery circulation, with the retinal circulation supplying the surface nerve fiber layer . The retinal arterioles and venules, with diameters from 100m to 300m, have similar anatomical features and physiological properties with cerebral small vessels, which provides a unique and accessible window to study the subclinical microvascular pathology of the brain .
Fig. 1
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Changes In Rnfl And Gcc In Ad Mci And Preclinical Ad
Similarly, pRNFL, GC-IPL or GCC thinning has also been found in MCI patients . Others even discovered thickening and thinning of regions adjacent to each other in MCI patients, indicating that the two layers undergo dynamic changes during progression from MCI to AD . Interestingly, the mean thickness of GC-IPL and GCC in MCI patients is significantly reduced compared with that in controls, while changes in the pRNFL thickness are not significant . The above findings suggest that the ganglion cells around macula, reflected by the thickness of GC-IPL or GCC, are sensitive in detecting neural structural changes in the initial stage of MCI.