The light/dark (LD) cycle is the main external synchronizer of the central circadian pacemaker (via melanopsin and visual photoreceptors) and a direct retinohypothalamic tract. There is evidence for an NDD-driven loss of melanopsin-expressing intrinsically photoreceptive retinal ganglion cells (ipRGCs). The reduction in the ability of light to reset the circadian clock could provide an explanation for the reduction in rhythm amplitude under LD conditions, as well as the increase in cycle-to-cycle variability. The master clock in the SCN serves to synchronize central and peripheral oscillators to optimize the function of the organism relative to the 24-hour periodicities in the environment. There are a number of cell populations within the SCN as defined by gene expression and anatomical analysis. Some of these cell populations are vulnerable to AD-driven degeneration, and the data are at least consistent with the possibility that damage to the SCN itself underlies circadian disruption in NDD, at least in later stages of disease. SCN circuits send projections throughout the CNS and endocrine system, providing multiple pathways by which the SCN can convey temporal information to the brain and body. There is evidence that NDD can alter the amplitude and regularity of SCN-driven outputs such as rhythms in melatonin and cortisol. The weakening of the rhythms in these three key outputs would be expected to reduce the synchrony of molecular clocks found throughout the body, leading to a state of internal desynchronization. ZT, zeitgeber time.