Sleep is evolutionarily preserved in all species, and impaired sleep is a common trait of the diseased brain. Sleep quality declines with age and disruption of normal sleep architecture is a frequent antecedent to the onset of dementia in neurodegenerative diseases. The glycymphatic system, which frees the brain of protein waste products, is primarily active during sleep. However, the glycymphatic system degrades with age, suggesting a causal relationship between sleep disturbances and symptomatic progression in neurodegenerative dementias. The links between sleep, aging, glycymphatic clearance and protein aggregation have shed new light on the pathogenesis of a wide range of neurodegenerative diseases, for which glycymphatic failure may be a therapeutically admirable final common pathway.