In addition to the above reported changes, irregularities in efferent ocular pathways in conjunction with retinal abnormalities were also associated with altered pupillary light response (PLR) in patients. These alterations include increased latency of pupillary constriction to light, decreased constriction amplitude, faster redilation after light offset, decreased maximum constriction velocity and acceleration (Chougule et al., 2019), and altered pupil dilation response during cognitive tasks (Granholm et al., 2017; Kremen et al., 2019). Therefore, there is growing interest in exploring various aspects of pupillary responses, using specialized pupillometry tools, in pre-clinical and clinically diagnosed AD patients. Further to being governed by both the sympathetic and parasympathetic systems, PLR is also regulated by retinal rods, cones, and mRGCs (Hattar et al., 2003). In line with this, altered PLR in AD patients was associated with retinal mRGC loss (La Morgia et al., 2016), highlighting the consequences of retinal AD pathology for various ocular and visual dysfunctions. Moreover, these intrinsically photosensitive RGCs are also reported to regulate light photoentrainment of circadian rhythms, supported by their tightly regulated communication with photoreceptors and their projections to the central circadian clock in the hypothalamic suprachiasmatic nucleus (SCN) (Lu et al., 1999; Berson et al., 2002; Gooley et al., 2003; Markwell et al., 2010; Chen et al., 2011). Therefore, retinal mRGC loss is suggested to play a key role in the sleep-wake cycle dysfunctions observed in AD patients (La Morgia et al., 2016, 2017). Sleep abnormalities reported in MCI and AD patients include prolonged sleep latency, reduced total sleep duration and rapid eye movement (REM) sleep, sleep fragmentation, frequent awakenings and lower melatonin levels at night, and daytime somnolence (Petit et al., 2004; Ju et al., 2013; Peter-Derex et al., 2015; Feng et al., 2016; La Morgia et al., 2016, 2017; Weissová et al., 2016; Asanad et al., 2019b). Intriguingly, there are reports of sleep disturbances exacerbating or even preceding cognitive impairments (Ju et al., 2014; Bubu et al., 2017; Brzecka et al., 2018). The essential discovery that Aβ accumulates within or in close proximity to mRGCs, which undergo degeneration and dendrite diameter loss, at least in part, can explain impaired sleep patterns and altered pupil dilation in AD patients (La Morgia et al., 2016). These findings also suggest that certain retinal cells are more susceptible to Aβ-induced neurotoxicity and proposes the first retinal damage-based mechanism for functional disturbances commonly seen in AD patients.