Sleep inefficiency is associated with altered hippocampal functional connectivity during encoding in postmenopausal women

Abstract

AbstractBackgroundIn a recent systematic review, the Alzheimer’s Association concluded that it is yet unclear whether sleep disturbance may be a modifiable risk factor for cognitive decline and dementia. This conclusion underscored the gap in understanding of which specific aspects of sleep (e.g., amount or quality) are associated with that risk and whether the sleep problems are a cause or precursor of dementia. To address that gap, we examined objective (actigraphy) measures of sleep in relation to hippocampal functional connectivity during a memory task. We focused on community‐dwelling postmenopausal women, a population with frequent poor sleep and a heightened lifetime risk of Alzheimer’s disease. We hypothesized that lower sleep efficiency but not sleep quantity would be associated with alterations in connectivity between the hippocampus and prefrontal cortex.MethodA total of 109 women (mean age=59.11 years; mean MOCA= 26.36; 78.0% white) from the MsBrain study completed 72‐hour sleep actigraphy assessments (Phillips Actiwatch‐A2) and blood‐oxygen‐level‐dependent (BOLD) fMRI assessments of verbal encoding and recognition. A generalized psychophysiological interaction (gPPI) analysis estimated task‐based hippocampal functional connectivity using SPM12 and Conn. The design matrix included principal time series of the seed region (left or right hippocampus), task conditions (novel words, familiar words), interaction variables (seed times series × task condition), and motion parameters. Sleep efficiency (% of time in bed spent sleeping) and total sleep time (hours slept) were regressed on patterns of brain connectivity in a region of interest confined to the hippocampus and prefrontal cortex, controlling for age, education and body mass index.ResultSleep inefficiency but not sleep quantity was associated with lower hippocampal‐prefrontal connectivity during encoding (corrected p < .05). During encoding, sleep inefficiency was associated with lower connectivity between the /right hippocampus and left/right middle frontal gyrus and dorsal anterior cingulate cortex (ACC). No effects were evident for recognition.ConclusionThe well‐established association between poor sleep and memory dysfunction in aging may be driven by poor sleep efficiency, which in turn may influence memory performance through decreased hippocampal‐prefrontal connectivity during encoding. Findings indicate a need for sleep interventions that help older adults to sleep better rather than longer.