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Neurobiol Learn Mem. 2018 Jun 1. pii: S1074-7427(18)30128-X. doi: 10.1016/j.nlm.2018.05.017. [Epub ahead of print]

Medial temporal lobe atrophy relates more strongly to sleep-wake rhythm fragmentation than to age or any other known risk.

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Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Departments of Integrative Neurophysiology and Psychiatry, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University and Medical Center, Amsterdam, The Netherlands. Electronic address:
Donders Centre for Cognition and Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Department of Neurology, St Lucas Andreas Hospital, Amsterdam, The Netherlands.
Department of Neurology and Alzheimer Center, VU, University Medical Center, The Netherlands.
Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy.
Department of Clinical Neuropsychology, Vrije Universiteit, Amsterdam, The Netherlands.


Atrophy of the medial temporal lobe of the brain is key to memory function and memory complaints in old age. While age and some morbidities are major risk factors for medial temporal lobe atrophy, individual differences remain, and mechanisms are insufficiently known. The largest combined neuroimaging and whole genome study to date indicates that medial temporal lobe volume is most associated with common polymorphisms in the GRIN2B gene that encodes for the 2B subunit (NR2B) of the NMDA receptor. Because sleep disruption induces a selective loss of NR2B from hippocampal synaptic membranes in rodents, and because of several other reports on medial temporal lobe sensitivity to sleep disruption, we hypothesized a contribution of the typical age-related increase in sleep-wake rhythm fragmentation to medial temporal lobe atrophy. Magnetic resonance imaging and actigraphy in 138 aged individuals showed that individual differences in sleep-wake rhythm fragmentation accounted for more (19%) of the variance in medial temporal lobe atrophy than age did (15%), or any of a list of health and brain structural indicators. The findings suggest a role of sleep-wake rhythm fragmentation in age-related medial temporal lobe atrophy, that might in part be prevented or reversible.


Aging; Circadian rhythm; Medial temporal lobe atrophy; Neurodegeneration; Physical activity; Rhythm fragmentation; Sleep

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