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

Abstract Atrophyof the medial temporal lobeof the brainis 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 lobevolume is most associated with common polymorphisms in the GRIN2Bgene that encodes for the 2B subunit (NR2B) of the NMDA receptor. Because sleep disruption induces a selective loss of NR2B from hippocampal synaptic membranesin rodents, and because of several other reports on medial temporal lobesensitivity 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 actigraphyin 138 aged individuals showed that individual differences in sleep-wake rhythm fragmentation accounted for more (19%) of the variance in medial temporal lobe atrophythan 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.