sibly be detected by non-invasive optical scattering [60], Raman spectroscopy or fluorescent tagging techniques. Given the homology between the retinal and cerebral microvasculatures [61], it is not unexpected that changes in the retinal vasculature might also occur in AD. Vascular topography, including the angles at which blood vessels bifurcate and the relationship between the widths of parent to daughter blood vessels at vascular junctions, is optimized in healthy subjects in order to minimize shear stress across a vascular network [62, 63]. Variations from the optimal geometrical topography are known to occur in particular vascular conditions [64, 65] and to be associated with deficiencies in cognitive ability [66]. Similar variations may occur in AD due to the disease’s vascular component and hence are worthy of being explored with retinal photography.

Retinal photography and scanning laser ophthalmoscopy (SLO) have both been used to demonstrate optic disc changes in AD, including optic disc pallor, pathologic disc cupping and thinning of the neuroretinal rim [39, 40]. Some of the retinal morphologies found in AD are also found in the eye disease glaucoma, specifically RNFL thinning, optic disc cupping and visual field loss. The fivefold higher chance of visual field defects and/or optic disc cupping found in AD has been interpreted as a higher occurrence rate of glaucoma in AD [67]. A greater than 10% per year decay in visual field and optic disc cupping was demonstrated in glaucoma patients who were later diagnosed with AD, whereas an average 3% per year decay in visual field was observed in glaucoma patients who did not develop AD, indicating that both diseases are contributing to these ocular effects [68].

Ab plaques as well as retinal microvascular deposition of Ab have been identified in the retinas of AD transgenic mouse models [47]. If retinal Ab plaques occur in human AD, as supported by one recent study [41], they could possibly be detected by non-invasive optical scattering [60], Raman spectroscopy or fluorescent tagging techniques. AD brain tissues exhibit visual and infraredexcited auto-fluorescence (AF) [69]. Retinal AF changes are observed in a number of eye disorders including glaucoma, in which lipofuscin accumulation in parapapillary retinal pigment

epithelial (RPE) cells causes AF changes [70]. Given the similarity of the retinal cell death process reported in glaucoma and AD [71, 72], AF changes are also worthy of being investigated in the AD retina. It is hoped that these techniques could prove useful for non-invasive, early diagnosis of AD using the eye.

9.6Conclusions

AD has a terrible impact on both those directly affected and on society in general. Thus, there is a pressing need for more effective treatments. By the time a person is diagnosed with ‘probable AD’ using current techniques, substantial irreversible neuronal degeneration has already occurred. Therefore, research into better treatments must be paralleled by research into technologies to screen the population for AD, to identify cases before cognitive symptoms arise.

Ocular morphologies reported in AD give hope for a non-invasive, cost-effective screening test for AD. Evidence is accumulating in support of AD-related changes in the eye, but finding a sufficiently sensitive and specific ocular biomarker is proving to be a major challenge. Many reported ocular changes in AD also occur in other disorders such as glaucoma and hypertension. Also, most studies into ocular morphology in AD have been limited by small participant numbers, few study groups and little relevant medical information on participants. Hence, larger studies are required to confirm and investigate further these ocular changes in AD.

There is no doubt that the significant diagnostic error rate in AD is confounding many aspects of AD research. A combination of new brain imaging techniques and CSF biomarkers has the potential to alleviate this problem, leading to more robust results in AD research, including ocular morphology. However, no studies have yet compared ocular morphology in AD to brain Ab loading or CSF protein changes, an approach that has the potential to shed light on connections between ocular changes and AD. In addition, there are also many more ocular parameters left to investigate in AD.

Thus, there remains scope for ocular changes to be utilized for AD screening or diagnosis, providing greater sensitivity and specificity and detection at an earlier stage in the disease process. An ocular screening test for AD would benefit AD sufferers and researchers, providing new insight into the molecular processes and genetic determinants of the disease. An ocular biomarker or biomarkers could turn out to be highly specific for AD or to be a useful component in a multidisciplinary approach aimed at producing an earlier and more accurate diagnosis of Alzheimer’s disease.

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