**3. Visual abnormalities in Alzheimer's disease and in patients with dementia**

A variety of visual abnormalities have been reported in patients with AD ranging from visuoconstructional and visuo-perceptual dysfunctions, object agnosia, prosopagnosia to visual hallucinations as well as simultanagnosia [5, 18, 19]. Patients with posterior cortical atrophy (PCA), which is associated with degeneration of the posterior cortex, also report particular difficulties with visual tasks often presenting with visual agnosia, visual neglect and visual hallucinations [20, 21]. However, compared to memory loss, visual deficits have received little attention and are thus poorly understood. Patients in the spectrum of, and leading to, clinical AD show marked reductions in the number of RGC [22], narrowing of venous blood column diameter and reduced venous blood flow rates [23], as well as optic nerve abnormalities such as loss of axonal densities [24], RGCs [25] and increased receptor expression for advances glycation end products [26]. Abnormalities are also observed in regions of AD brains that synapse with the optic nerve and/or are associated with the visual processing pathway (**Figure 2**). Some examples include the loss of myelin, diminished nucleolar volume in the LGN, as well as accumulation of lipofuscin (autofluorescent pigment granules) [27]. AD brains also show the presence of NFT in the SC [28] (which receives ~10% of the RGC axons), as well as the presence of Aβ/neuritic plaques in regions of the brain that are implicated in visual attention and the control of eye movement. Aβ deposition has also been reported in the lens of AD patients [29]. Additionally, histopathological evidence from post-mortem brains reveals significant pathological changes in the visual processing regions of the brain including the loss of pyramidal cells and reduced myelin in the outer laminae of the visual cortex [30–33]. A comprehensive list of such neurological changes in areas of the brain associated with vision has been described by Armstrong (2009) indicating the extensive nature of psyco-visual abnormalities in patients with AD and dementia [29].

Not surprisingly, a large number of AD transgenic animal models also develop visual deficits and have therefore been used to investigate retinal pathologies. These include, but are not limited to, the Tg2576 [34], APPswe/PS1M146L and APPswe/PSΔE9 [35], 5xFAD [36, 37], and P301S [38] mice. A wide range of retinal changes have been documented in these animals, including an age-dependent increase in APP/Aβ immunoreactivity in the neuroretina and associated vasculature, the accumulation of Aβ plaques/ hyperphosphorylated tau in the nerve fibre layer (NFL) and RGC, thinning of the RGC, as well as glial cell-derived neuro-inflam‐ matory responses within the retina [4]. Of importance, a number of these changes are common to well-established animal models of retinal degeneration that are widely used to study AMD [39, 40].
