0074 The Relationship of Sleep Disorder History with Gray Matter BOLD-CSF Coupling Among Persons at Risk for and with Alzheimer’s Disease
Year: 2025
Type: conference-abstract
Abstract: Introduction The glymphatic system has been proposed to remove metabolic waste from the brain through CSF movement and its exchange with interstitial fluid. It has been hypothesized to mediate the impact of sleep deficiency on Alzheimer’s disease [AD] pathogenesis. gBOLD-CSF is the coupling of slow (i.e., < 0.1 Hz) gray matter blood-oxygen-level-dependent-signals and slow cerebrospinal fluid flow, and a proposed proxy measure of glymphatic transport. However, its association with sleep disorder history in persons along the AD spectrum remains unknown. Methods This study included twenty-seven participants who completed medical interview and MRI at the Yale’s Alzheimer’s Disease Research Center (3 AD, 1 mild cognitive impairment, and 23 cognitively normal). Sleep disorder history was based on reporting active management for a diagnosis of insomnia or apnea. gBOLD-CSF coupling was quantified based on resting-state fMRI (repetition time=1000ms), using a previously published approach. Briefly, timeseries of gBOLD were extracted by aligning the fMRI and Harvard-Oxford atlas to each participant’s native space. CSF-signal timeseries were extracted from the bottom slice with a manually drawn CSF mask. For each participant, cross-correlation function between gBOLD and CSF timeseries was calculated. The negative peak correlation coefficient occurring within a 2-6 second time lag was used to quantify maximum gBOLD-CSF coupling. T-tests were used to compare gBOLD-CSF coupling by sleep disorder history. Results Mean age was 65.4 (SD=8.6), 59.3% were women, 44% carried ≥1 ApoE4 allele (1 missing), and mean educational attainment was 17 (SD=2.6) years. Mean gBOLD-CSF coupling in individuals who had insomnia was -0.16, which was weaker than that of individuals without insomnia (absolute difference=0.12, [95%CI=-0.15,0.40];p=0.19). Mean gBOLD-CSF coupling in individuals with apnea was -0.16, which was weaker than that among people without apnea (0.13, [-0.07,0.33];p=0.09). Conclusion Among individuals at risk of/with AD, there was a trend for reduced gBOLD-CSF coupling associated with insomnia and apnea. These findings provide preliminary evidence that glymphatic-related fluid transport among persons with a sleep disorder may be disrupted. This finding supports the hypothesis that glymphatic transport is associated with sleep. Future work should validate these findings in larger samples. Support (if any) Gawon Cho was supported by the Alzheimer’s Association’s Research Fellowship to improve Diversity (AARF-24-1306796).
Source: SLEEP
Authors: Gawon Cho, Xiao Liu, Adam Mecca, Brienne Miner
Institutions: Yale University, Pennsylvania State University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Funder: Alzheimer's Association
OpenAlex ID: W4410482031