Aging constitutes a series of physical, physiological and cognitive changes, affecting independence in the activities of daily living. During this stage, neurodegenerative diseases and cognitive impairment are common. Cognitive Reserve allows to face neuropathological changes and maintain cognitive function in the presence of brain damage. However, there are cases where a high cognitive reserve fails to attenuate and delay the effects of neuropathology, allowing the progression of cognitive damage to advanced stages. The objective of this systematic review is to identify evidence where high cognitive reserve does not limit the effects of cognitive impairment. Results indicate that the protective effect of cognitive reserve occurs only in the presence of minimal cognitive impairment, but not at later stages.