Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging

• DOI: 10.1038/nn.3324
• Publication Date: 2013-01-27T18:37:48Z
• Authors: Bryce A Mander; Vikram Rao; Brandon Lu; Jared M Saletin; John R Lindquist; Sonia Ancoli-Israel; William Jagust; Matthew P Walker
• Keywords: Male; 0301 basic medicine; Aging; Adolescent; 1.1 Normal biological development and functioning; Image Processing; Memory, Episodic; Polysomnography; Prefrontal Cortex; Neurodegenerative; Neuropsychological Tests; Alzheimer's Disease; Hippocampus; Article; Young Adult; 03 medical and health sciences; Computer-Assisted; 0302 clinical medicine; Clinical Research; Underpinning research; Memory; Acquired Cognitive Impairment; 80 and over; Image Processing, Computer-Assisted; 2.1 Biological and endogenous factors; Psychology; Humans; Aetiology; Aged; Aged, 80 and over; Brain Mapping; Neurology & Neurosurgery; Neurosciences; Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD); Organ Size; Brain Waves; Brain Disorders; Neurological; Dementia; Cognitive Sciences; Female; Atrophy; Sleep Research; Episodic; Sleep

Aging has independently been associated with regional brain atrophy, reduced slow wave activity (SWA) during non-rapid eye movement (NREM) sleep and impaired long-term retention of episodic memories. However, whether the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. We found that age-related medial prefrontal cortex (mPFC) gray-matter atrophy was associated with reduced NREM SWA in older adults, the extent to which statistically mediated the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex functional connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represents a contributing factor to age-related cognitive decline in later life.