Recent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep ...physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible PVS volumes, a putative marker of perivascular dysfunction, are associated with compensatory differences in real-world human sleep behavior.
We analyzed data from 152 cerebrovascular disease patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). PVS volumes were measured using 3T-MRI. Self-reported total sleep time, time in bed, and daytime dysfunction were extracted from the Pittsburgh Sleep Quality Index.
Individuals with greater PVS volumes reported longer time in bed (+0.85 h per log10 proportion of intracranial volume (ICV) occupied by PVS, SE = 0.30, p = 0.006) and longer total sleep times (+0.70 h per log10 proportion of ICV occupied by PVS volume, SE = 0.33, p = 0.04), independent of vascular risk factors, sleep apnea, nocturnal sleep disturbance, depression, and global cognitive status. Further analyses suggested that the positive association between PVS volumes and total sleep time was mediated by greater time in bed. Moreover, despite having on average greater total sleep times, individuals with greater basal ganglia PVS volumes were more likely to report daytime dysfunction (OR 5.63 per log10 proportion of ICV occupied by PVS, 95% CI: 1.38–22.26, p = 0.018).
Individuals with greater PVS volumes spend more time in bed, resulting in greater total sleep time, which may represent a behavioral compensatory response to perivascular space dysfunction.
•Normal perivascular spaces (PVS) play an important role in sleep function.•Perivascular abnormalities may be an important determinant of sleep behavior.•Interventions targeting PVS biology may modify sleep need and daytime dysfunction.
Gender differences in instrumental activities of daily living (IADLs) in mild cognitive impairment (MCI) and Alzheimer's disease may be explained by gender differences in IADL involvement.
We ...introduce a novel theoretical construct, termed functional reserve, and empirically examine gender differences in IADL experience as a proxy of this reserve.
We cross-sectionally examined men (n = 502) and women (n = 340) with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Demographic factors, depressive symptoms, neuropsychological scores, and IADL experience were included as independent variables and total Functional Activities Questionnaire (FAQ) scores as the dependent variable. Regression analyses were performed on the full cohort and stratified by gender to identify differential predictive relationships for men and women.
Gender was associated with total FAQ (p < 0.05) until adjusting for IADL experience. Furthermore, the combination of cognitive measures accounted for the most variance in functional dependence (12% explained, p < 0.001), although IADL experience was the most important single variable (4.8% explained, p < 0.001). Stratification by gender revealed that IADL experience accounted for 6.6% of the variance in FAQ score in men (p < 0.001) but only 2.4% in women (p = 0.001); however, the interaction between gender and experience was not statistically significant.
A small effect of men showing greater functional dependence in MCI may be explained by lower IADL experience. Additionally, IADL experience was associated with superior functioning in all analyses, potentially through increased functional reserve. This concept of functional reserve may have implications for identifying individuals at risk for IADL dependence, preventing or delaying decline, and potentially treating functional impairment.
Given the limited research comparing men and women in terms of instrumental activities of daily living (IADLs), this research examined sex differences cross-sectionally and longitudinally with data ...from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Furthermore, the influence of IADL experience was included as a proxy measure of functional reserve. All participants had mild cognitive impairment (MCI) at baseline. Linear regression, mixed-effects modeling, and chi-square analyses were conducted. Female sex was associated with superior IADL functioning at baseline, although no sex difference was found in the rate of decline. However, once IADL experience was included in regression analysis, this baseline sex difference was no longer significant. Furthermore, IADL experience was associated with superior functioning at baseline and a slower decline longitudinally. Moreover, experience within specific IADLs was associated with independence in other, unrelated activities. This research supports the notion that performing IADLs may have a protective influence on functioning with neurodegeneration.
PURPOSEMagnetic resonance imaging (MRI) scanner-specific geometric distortions may contribute to scanner induced variability and decrease volumetric measurement precision for multi-site studies. The ...purpose of this study was to determine whether geometric distortion correction increases the precision of brain volumetric measurements in a multi-site multi-scanner study. METHODSGeometric distortion variation was quantified over a one-year period at 10 sites using the distortion fields estimated from monthly 3D T1-weighted MRI geometrical phantom scans. The variability of volume and distance measurements were quantified using synthetic volumes and a standard quantitative MRI (qMRI) phantom. The effects of geometric distortion corrections on MRI derived volumetric measurements of the human brain were assessed in two subjects scanned on each of the 10 MRI scanners and in 150 subjects with cerebrovascaular disease (CVD) acquired across imaging sites. RESULTSGeometric distortions were found to vary substantially between different MRI scanners but were relatively stable on each scanner over a one-year interval. Geometric distortions varied spatially, increasing in severity with distance from the magnet isocenter. In measurements made with the qMRI phantom, the geometric distortion correction decreased the standard deviation of volumetric assessments by 35% and distance measurements by 42%. The average coefficient of variance decreased by 16% in gray matter and white matter volume estimates in the two subjects scanned on the 10 MRI scanners. CONCLUSIONGeometric distortion correction using an up-to-date correction field is recommended to increase precision in volumetric measurements made from MRI images.
Hypertension is an important risk factor for Alzheimer's disease (AD) and cerebral small vessel disease. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are ...common anti-hypertensive treatments, but have differential effects on cortical amyloid.
The objective of this study was to evaluate associations between anti-hypertensive treatment, brain volume, and cognition, using a propensity-weighted analysis to account for confounding by indication.
We identified a cohort of normal elderly adults and individuals with mild cognitive impairment (MCI) or AD (N = 886; mean age = 75.0) from the Alzheimer's Disease Neuroimaging Initiative. Primary outcomes were brain parenchymal fraction, total hippocampal volume, and white matter hyperintensity (WMH) volume. Secondary outcomes were standardized scores on neuropsychological tests. Propensity-weighted adjusted multivariate linear regression was used to estimate associations between anti-hypertensive treatment class and MRI volumes and cognition.
Individuals treated with ARBs showed larger hippocampal volumes (R2 = 0.83, p = 0.05) and brain parenchymal fraction (R2 = 0.83, p = 0.01) than those treated with ACEIs. When stratified by diagnosis, this effect remained only in normal elderly adults and MCI patients, and a significant association between ARBs and lower WMH volume (R2 = 0.83, p = 0.03) emerged for AD patients only. ARBs were also associated with significantly better performance on tests of episodic and verbal memory, language, and executive function (all p < 0.05).
Findings are consistent with evidence for a neuroprotective effect of treatment with ARBs for brain structure and cognition. This study has potential implications for the treatment of hypertension, particularly in elderly adults at risk of cognitive decline and AD.
Background Cerebral small vessel disease is associated with higher ratios of soluble-epoxide hydrolase derived linoleic acid diols (12,13-dihydroxyoctadecenoic acid DiHOME and 9,10-DiHOME) to their ...parent epoxides (12(13)-epoxyoctadecenoic acid EpOME and 9(10)-EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra-high-performance liquid chromatography-mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13-DiHOME/12(13)-EpOME ratio (β=0.251,
=0.023). The 12,13-DiHOME/12(13)-EpOME ratio was associated with more lacunes (β=0.266,
=0.028) but not with large vessel stroke volumes. Ratios of 12,13-DiHOME/12(13)-EpOME and 9,10-DiHOME/9(10)-EpOME were associated with greater volumes of white matter hyperintensities (β=0.364,
<0.001; β=0.362,
<0.001) and white matter MRI-visible perivascular spaces (β=0.302,
=0.011; β=0.314,
=0.006). In small vessel stroke, the 12,13-DiHOME/12(13)-EpOME ratio was associated with higher white matter free water diffusion (β=0.439,
=0.016), which was specific to the temporal lobe in exploratory regional analyses. The 9,10-DiHOME/9(10)-EpOME ratio was associated with temporal lobe atrophy (β=-0.277,
=0.031). Conclusions Linoleic acid markers of cytochrome P450/soluble-epoxide hydrolase activity were associated with small versus large vessel stroke, with small vessel disease markers consistent with blood brain barrier and neurovascular-glial disruption, and temporal lobe atrophy. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration.
