Introduction: Sleep disturbances are increasingly recognized as a risk factor for Alzheimer’s disease. However, no study has assessed the relationships between objective sleep fragmentation (SF) and brain and cognitive integrity across different cognitive stages, from cognitively unimpaired elderly subjects to patients with subjective cognitive decline and/or mild cognitive impairment.Methods: 30 cognitively unimpaired elderly participants and 36 patients with subjective cognitive decline and/or mild cognitive impairment underwent a neuropsychological evaluation, structural MRI, 18F-fluorodeoxyglucose, and 18F-florbetapir-PET scans, and an actigraphy recording over a minimum of six consecutive nights. Multiple regression and mediation analyses were performed between SF parameters, neuroimaging data, and cognitive scores.Results: In cognitively unimpaired elderly participants, SF intensity mediated the association between frontohippocampal hypometabolism and lower executive functioning. Moreover, to a lower extent, increased SF variability was related to thalamic atrophy and ventromedial prefrontal amyloid burden. However, in patients with subjective cognitive decline and/or mild cognitive impairment, SF no longer contributed to the expression of cognitive deficits.Discussion: These findings suggest that SF may directly contribute to lower cognitive performance in cognitively unimpaired elderly subjects. Therefore, treating sleep disturbances before the onset of cognitive deficits may help to cope with brain alterations and maintain cognitive functioning.