244 Physical fitness attenuates the deleterious association of sleep apnea with gray matter volume in the Wisconsin Sleep Cohort Study

Abstract

Introduction Recent evidence has illustrated that gray matter (GM) atrophy, a diagnostic hallmark of Alzheimer’s disease (AD), may be influenced by psychosocial risk modifiers such as physical exercise and sleep. Cardiorespiratory fitness, a measure of oxygen delivery and utilization during exercise, is positively associated with both sleep quality and gray matter volume in brain areas associated with age-related cognitive decline, such as the hippocampus. In contrast, sleep apnea has been linked to global and regional gray matter atrophy, which is thought to be driven in-part by the incomplete modulation of cardiovascular and respiratory control during sleep. This study examines whether cardiorespiratory fitness modifies the deleterious relationship between sleep apnea and GM volume in a sample of non-demented older participants from the Wisconsin Sleep Cohort (WSC). Methods Using data from a subset of WSC participants (n=129, 51% female, mean [range] age at baseline=68 [49-85] years), cardiorespiratory fitness was estimated using a Non-Exercise CardioRespiratory Fitness Measure (NECRFM; based on age, sex, BMI, self-reported physical activity, and resting heart rate). Sleep apnea severity was measured by overnight polysomnography and characterized by the base 10 logarithm of the apnea-hypopnea index, log10(AHI+1). We assembled cross-sectional linear models of MRI-measured total GM volume using NECRFM and log10(AHI+1) as predictors while controlling for age, sex, BMI, education, and hypertension. Regional volumetric changes in the hippocampus and amygdala were assessed using analogous linear models, adjusting both outcome volumetrics for total intracranial volume. Results While the interaction between fitness and apnea severity was not significant (p=0.50), results stratified at the median NECRFM illustrated that among the less fit individuals, higher log10(AHI+1) was associated with a significant reduction in total GM volume (B(SE)=-0.06 (0.02); p=0.007); this relationship was not significant among those who were more fit (B(SE)=-0.03 (0.02); p=0.11). There were no significant effects in the hippocampus or amygdala. Conclusion These results indicate that cardiovascular fitness may attenuate the effect of severe sleep apnea on GM volume in older adults, supporting the protective role of cardiovascular fitness in aging brain health. Support (if any) This work was supported by United States National Institutes of Health grants R01AG058680, R01HL62252, 1R01AG036838, 1UL1RR025011, and R01AG062167.

Cardiorespiratory Fitness as a Moderator of Sleep-Related Associations with Hippocampal Volume and Cognition

“…Using data from 74 older adults in the Wisconsin Registry of Alzheimer’s Prevention, an interaction was reported between self-reported sleep quality—measured by the Medical Outcomes Study Sleep Scale—and aerobic fitness on CSF levels of total tau (t-tau), phosphorylated tau (p-tau), and the p-tau/β-amyloid 42 ratio, in which poor sleep was associated with greater neurodegeneration among older individuals with lower but not higher cardiorespiratory fitness [ 21 ]. The other study, which was conducted using data from the Wisconsin Sleep Cohort (and currently only published in abstract form), demonstrated an adverse relationship between sleep apnea severity and total gray matter volume among less-fit (but not more-fit) cognitively normal older individuals [ 8 ]. Although our study was different in both measurement and design, our results demonstrating the modifying effects of HRR M on hippocampal volume in disturbed sleepers are congruent with the findings from this report.…”

“…Similar to previous studies of this nature [ 8 , 48 , 49 ], our index of cardiorespiratory fitness ( ) was dichotomized using a median split (≥14 beats per minute; bpm) and analyzed as a binary variable (high fitness = 0, low fitness = 1).…”

“…Converging lines of evidence indicate that sleep plays a pivotal role in neurocognitive aging [ 2 , 3 ]. Studies have shown that poor sleep quality is linked with cognitive deficits [ 4 , 5 ] and that both self-reported poor sleep quality and abnormal sleep duration, as well as objective indices of sleep fragmentation, are associated with cortical and subcortical brain atrophy [ 6 , 7 , 8 ].…”