Cardiorespiratory Fitness Attenuates the Deleterious Effects of Sleep Apnea on Cerebral Structure and Perfusion in the Wisconsin Sleep Cohort Study.

BACKGROUND: Emerging evidence suggests that age-related changes in cerebral health may be sensitive to vascular risk modifiers, such as physical activity and sleep. OBJECTIVE: We examine whether cardiorespiratory fitness modifies the association of obstructive sleep apnea (OSA) severity with MRI-assessed measures of cerebral structure and perfusion. METHODS: Using data from a cross-sectional sample of participants (n = 129, 51% female, age range 49.6-85.3 years) in the Wisconsin Sleep Cohort study, we estimated linear models of MRI-assessed total and regional gray matter (GM) and white matter (WM) volumes, WM hyperintensity (WMH:ICV ratio), total lesion volume, and arterial spin labeling (ASL) cerebral blood flow (CBF), using an estimated measure of cardiorespiratory fitness (CRF) and OSA severity as predictors. Participants' sleep was assessed using overnight in-laboratory polysomnography, and OSA severity was measured using the apnea-hypopnea index (AHI), or the mean number of recorded apnea and hypopnea events per hour of sleep. The mean±SD time difference between PSG data collection and MRI data collection was 1.7±1.5 years (range: [0, 4.9 years]). RESULTS: OSA severity was associated with reduced total GM volume (ß=-0.064; SE = 0.023; p = 0.007), greater total WM lesion volume (interaction p = 0.023), and greater WMHs (interaction p = 0.017) in less-fit subjects. Perfusion models revealed significant differences in the association of AHI and regional CBF between fitness groups (interaction ps < 0.05). CONCLUSION: This work provides new evidence for the protective role of cardiorespiratory fitness against the deleterious effects of OSA on brain aging in late-middle age to older adults.

Age-related differences in white matter microstructure measured by advanced diffusion MRI in healthy older adults at risk for Alzheimer's disease.

Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric-fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO-is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer's disease (AD). Age was significantly associated with all but one diffusion parameters and regions of interest. NDI and MD in the cingulate region adjacent to the cingulate cortex showed a significant association with a composite measure of Executive Function and was proven to partially mediate the relationship between aging and Executive Function decline. These results suggest that both DTI and NODDI parameters are sensitive to age-related differences in white matter regions vulnerable to aging, particularly among older adults at risk for AD.

Impact of sex and APOE ε4 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults: A longitudinal study.

Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer's disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40-89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13-8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (ß=-1.43), hippocampus (-1.25), superior frontal gyrus (-1.70), middle frontal gyrus (-1.99), posterior cingulate (-2.46), and precuneus (-2.14), with all P-values < 0.01. Compared with male-ɛ4 carriers, female-ɛ4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-ɛ4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-ɛ4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.

Cardiorespiratory Fitness Associates with Cerebral Vessel Pulsatility in a Cohort Enriched with Risk for Alzheimer's Disease.

BACKGROUND: There is increasing evidence that vascular disease risk factors contribute to evolution of the dementia syndrome of Alzheimer's disease (AD). One important measure of cerebrovascular health is pulsatility index (PI) which is thought to represent distal vascular resistance, and has previously been reported to be elevated in AD clinical syndrome. Physical inactivity has emerged as an independent risk factor for cardiovascular disease. OBJECTIVE: This study aims to examine the relationship between a measure of habitual physical activity, cardiorespiratory fitness (CRF), and PI in the large cerebral vessels. METHODS: Ninety-two cognitively-healthy adults (age = 65.34±5.95, 72% female) enrolled in the Wisconsin Registry for Alzheimer's Prevention participated in this study. Participants underwent 4D flow brain MRI to measure PI in the internal carotid artery (ICA), basilar artery, middle cerebral artery (MCA), and superior sagittal sinus. Participants also completed a self-report physical activity questionnaire. CRF was calculated using a previously-validated equation that incorporates sex, age, body-mass index, resting heart rate, and self-reported physical activity. A series of linear regression models adjusted for age, sex, APOE4 status, and 10-year atherosclerotic cardiovascular disease risk were used to analyze the relationship between CRF and PI. RESULTS: Inverse associations were found between CRF and mean PI in the inferior ICA (p = .001), superior ICA (p = .035), and basilar artery (p = .040). No other cerebral vessels revealed significant associations between CRF and PI (p≥.228). CONCLUSIONS: Higher CRF was associated with lower PI in several large cerebral vessels. Since increased pulsatility has been associated with poor brain health and reported in persons with AD, this suggests that aerobic fitness might provide protection against cerebrovascular changes related to the progression of AD clinical syndrome.

Evolution of Magnetic Resonance Imaging as Predictors and Correlates of Functional Outcome after Spinal Cord Contusion Injury in the Rat.

Clinical methods for determining the severity of traumatic spinal cord injury (SCI) and long-term functional outcome in the acute setting are limited in their prognostic accuracy because of the heterogeneity of injury and dynamic injury progression. The aim of this study was to evaluate the time course and sensitivity of advanced magnetic resonance imaging (MRI) methods to neurological function after SCI in a rat contusion model. Rats received a graded contusion injury at T10 using a weight-drop apparatus. MRI consisted of morphological measures from T2-weighted imaging, quantitative T2 imaging, and diffusion-weighted imaging (DWI) at 1, 30, and 90 days post-injury (dpi). The derived metrics were compared with neurological function assessed using weekly Basso, Beattie, and Bresnahan (BBB) locomotor scoring and return of reflexive micturition function. At the acute time point (1 dpi), diffusion metrics sensitive to axonal injury at the injury epicenter had the strongest correlation with time-matched BBB scores and best predicted 90-dpi BBB scores. At 30 dpi, axonal water fraction derived from DWI and T2 values were both correlated with time-matched locomotor scores. At the chronic time point (90 dpi), cross-sectional area was most closely correlated to BBB. Overall, the results demonstrate differential sensitivity of MRI metrics at different time points after injury, but the metrics follow the expected pathology of acute axonal injury followed by continued degeneration and finally a terminal level of atrophy. Specificity of DWI in the acute setting may make it impactful as a prognostic tool while T2 imaging provided the most information about injury severity in chronic injury.

Longitudinal In Vivo Diffusion Magnetic Resonance Imaging Remote from the Lesion Site in Rat Spinal Cord Injury.

Diffusion tensor imaging (DTI) has demonstrated success as a biomarker of spinal cord injury (SCI) severity as shown from numerous pre-clinical studies. However, artifacts from stabilization hardware at the lesion have precluded its use for longitudinal assessments. Previous research has documented ex vivo diffusion changes in the spinal cord both caudal and cranial to the injury epicenter. The aim of this study was to use a rat contusion model of SCI to evaluate the utility of in vivo cervical DTI after a thoracic injury. Forty Sprague-Dawley rats underwent a thoracic contusion (T8) of mild, moderate, severe, or sham severity. Magnetic resonance imaging (MRI) of the cervical cord was performed at 2, 30, and 90 days post-injury, and locomotor performance was assessed weekly using the Basso, Bresnahan, and Beattie (BBB) scoring scale. The relationships between BBB scores and MRI were assessed using region of interest analysis and voxel-wise linear regression of DTI, and free water elimination (FWE) modeling to reduce partial volume effects. At 90 days, axial diffusivity (ADFWE), mean diffusivity (MDFWE), and free water fraction (FWFFWE) using the FWE model were found to be significantly correlated with BBB score. FWE was found to be more predictive of injury severity than conventional DTI, specifically at later time-points. This study validated the use of FWE technique in spinal cord and demonstrated its sensitivity to injury remotely.