The association of sleep-disordered breathing and white matter hyperintensities in heart failure patients.

Heart failure patients often manifest white matter hyperintensites on brain magnetic resonance imaging (MRI). White matter hyperintnsities have also been linked with cognitive problems in patients with heart failure. Sleep disordered breathing may contribute to structural brain changes in heart failure. The purpose of this study was to test the extent to which the apnea hypopnea index is associated with global and regional white matter hyperintensities, and is a moderating factor in the relationship between age and white matter hyperintensites. A total of 28 HF patients [mean age (SD) = 67.89 (5.8)] underwent T1-weighted and T2FLAIR MRI and a home sleep monitoring study. The apnea hypopnea index cut off of 10 was used to compare between higher and lower risks of sleep disordered breathing. Regression analysis was used to test the association between apnea hypopnea index and both global and regional white matter hyperintensities. The interaction term was entered to identify the moderation effect. Apnea hypopnea index was associated with higher regional white matter hyperintensities but not global white matter hyperintensities. There was a significant interaction between the apnea hypopnea index and age, such that older participants with the apnea hypopnea index ≥10 showed greater regional white matter hyperintensities than those with the apnea hypopnea index <10. The results of this preliminary study indicate that a higher apnea hypopnea index is associated with more white matter hyperintensities. The age-related white matter hyperintensities appear to be exacerbated by apnea hypopnea index in our individuals with heart failure. Future studies are needed to further investigate the underlying mechanisms.

Multimodal brain imaging investigation of self-reported sleep quality and daytime sleepiness in older adults with heart failure.

PURPOSE OF THE STUDY: Individuals with heart failure (HF) have a high frequency of sleep problems. Patients with HF present with structural brain changes different from normal aging including reductions in brain volume, increases in white matter hyperintensity (WMH) and reduced cerebral blood flow. These structural changes in the brain may explain the pathophysiology of sleep and daytime problems. The objective of this study was to determine whether multimodal imaging data are related to self-reported sleep problems and daytime sleepiness in older adults with HF. METHODS: Participants in this study underwent magnetic resonance imaging scans on the General Electric 3.0 T Discovery MR750 to acquire WMH, cerebral blood flow and brain volume. Data on 37 stable HF patients (mean age = 68; SD = 5.75) were included. RESULTS: In this sample, WMH was associated with daytime sleepiness (p = 0.025). However, gray and white matter volume and cerebral blood flow were not associated with daytime sleepiness, sleep quality or insomnia. CONCLUSION: Although further studies are needed to determine the relationship between WMH and sleep and daytime problems, the findings preliminarily support that increases in WMH from ischemic changes could explain increases in daytime sleepiness among people with HF.

Sleep-disordered breathing, brain volume, and cognition in older individuals with heart failure.

BACKGROUND AND PURPOSE: Sleep-disordered breathing is common in individuals with heart failure and may contribute to changes in the brain and decreased cognition. However, limited research has explored how the apnea-hypopnea index contributes to brain structure and cognition in this population. The aims of this study were to explore how the apnea-hypopnea index is associated with brain volume and cognition in heart failure patients. METHODS: Data of 28 heart failure patients (mean age = 67.93; SD = 5.78) were analyzed for this cross-sectional observational study. We evaluated the apnea-hypopnea index using a portable multichannel sleep-monitoring device. All participants were scanned using 3.0 Tesla magnetic resonance imaging and neuropsychological tests. Brain volume was evaluated using a voxel-based morphometry method with T1-weighted images. We used multiple regressions to analyze how the apnea-hypopnea index is associated with brain volume and cognition. RESULTS: We found an inverse association between apnea-hypopnea index scores and white matter volume (ß = -0.002, p = 0.026), but not in gray matter volume (ß = -0.001, p = 0.237). Higher apnea-hypopnea index was associated with reduced regional gray and white matter volume (p < 0.001, uncorrected). Cognitive scores were not associated with the apnea-hypopnea index (p-values were >0.05). CONCLUSION: Findings from this study provide exploratory evidence that higher apnea-hypopnea index may be associated with greater brain volume reduction in heart failure patients. Future studies are needed to establish the relationship between sleep-disordered breathing, brain volume, and cognition in heart failure samples.

Cerebrospinal Fluid Markers of Alzheimer's Disease Pathology and Microglial Activation are Associated with Altered White Matter Microstructure in Asymptomatic Adults at Risk for Alzheimer's Disease.

BACKGROUND: The immune response in Alzheimer's disease (AD) involves activation of microglia which may remove amyloid-ß (Aß). However, overproduction of inflammatory compounds may exacerbate neural damage in AD. AD pathology accumulates years before diagnosis, yet the extent to which neuroinflammation is involved in the earliest disease stages is unknown. OBJECTIVE: To determine whether neuroinflammation exacerbates neural damage in preclinical AD. METHODS: We utilized cerebrospinal fluid (CSF) and magnetic resonance imaging collected in 192 asymptomatic late-middle-aged adults (mean age = 60.98 years). Neuroinflammatory markers chitinase-3-like protein 1 (YKL-40) and monocyte chemoattractant protein-1 (MCP-1) in CSF were utilized as markers of neuroinflammation. Neural cell damage was assessed using CSF neurofilament light chain protein (NFL), CSF total tau (T-Tau), and neural microstructure assessed with diffusion tensor imaging (DTI). With regard to AD pathology, CSF Aß42 and tau phosphorylated at threonine 181 (P-Tau181) were used as markers of amyloid and tau pathology, respectively. We hypothesized that higher YKL-40 and MCP-1 in the presence of AD pathology would be associated with higher NFL, T-Tau, and altered microstructure on DTI. RESULTS: Neuroinflammation was associated with markers of neural damage. Higher CSF YKL-40 was associated with both higher CSF NFL and T-Tau. Inflammation interacted with AD pathology, such that greater MCP-1 and lower Aß42 was associated with altered microstructure in bilateral frontal and right temporal lobe and that greater MCP-1 and greater P-Tau181 was associated with altered microstructure in precuneus. CONCLUSION: Inflammation may play a role in neural damage in preclinical AD.

White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease.

INTRODUCTION: Little is still known about the effects of risk factors for Alzheimer's disease (AD) on white matter microstructure in cognitively healthy adults. The purpose of this cross-sectional study was to assess the effect of two well-known risk factors for AD, parental family history and APOE4 genotype. METHODS: This study included 343 participants from the Wisconsin Registry for Alzheimer's Prevention, who underwent diffusion tensor imaging (DTI). A region of interest analysis was performed on fractional anisotropy maps, in addition to mean, radial, and axial diffusivity maps, aligned to a common template space using a diffeomorphic, tensor-based registration method. The analysis focused on brain regions known to be affected in AD including the corpus callosum, superior longitudinal fasciculus, fornix, cingulum, and uncinate fasciculus. Analyses assessed the impact of APOE4, parental family history of AD, age, and sex on white matter microstructure in late middle-aged participants (aged 47-76 years). RESULTS: Both APOE4 and parental family history were associated with microstructural white matter differences. Participants with parental family history of AD had higher FA in the genu of the corpus callosum and the superior longitudinal fasciculus. We observed an interaction between family history and APOE4, where participants who were family history positive but APOE4 negative had lower axial diffusivity in the uncinate fasciculus, and participants who were both family history positive and APOE4 positive had higher axial diffusivity in this region. We also observed an interaction between APOE4 and age, whereby older participants (=65 years of age) who were APOE4 carriers, had higher MD in the superior longitudinal fasciculus and in the portion of the cingulum bundle running adjacent to the cingulate cortex, compared to non-carriers. Older participants who were APOE4 carriers also showed higher radial diffusivity in the genu compared to non-carriers. Across all participants, age had an effect on FA, MD, and axial and radial diffusivities. Sex differences were observed in FA and radial diffusivity. CONCLUSION: APOE4 genotype, parental family history of AD, age, and sex are all associated with microstructural white matter differences in late middle-aged adults. In participants at risk for AD, alterations in diffusion characteristics-both expected and unexpected-may represent cellular changes occurring at the earliest disease stages, but further work is needed. Higher mean, radial, and axial diffusivities were observed in participants who are more likely to be experiencing later stage preclinical pathology, including participants who were both older and carried APOE4, or who were positive for both APOE4 and parental family history of AD.