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Background: Lower cerebral blood flow (CBF) and excessive brain atrophy are linked to Alzheimer’s disease (AD). It is still undetermined whether reduced CBF precedes or follows brain tissue loss. Objective: We compared total CBF (tCBF), global cerebral perfusion (GCP), and volumes of AD-prone regions between cognitively normal (CN) and early amnestic mild cognitive impairment (aMCI) and tested their associations with cognitive performance to assess their predictive value for differentiation between CN and early aMCI. Methods: A total of 74 participants (mean age 69.9±6.2 years, 47 females) were classified into two groups: 50 CN and 24 aMCI, of whom 88% were early aMCI. tCBF, GCP, and global and regional brain volumetry were measured using phase-contrast and T1-weighted MRI. Neuropsychological tests tapping global cognition and four cognitive domains (memory, executive function, language, and visuospatial) were administered. Comparisons and associations were investigated using analyses of covariance (ANCOVA) and linear regression analyses, respectively. Results: Women had significantly higher GCP than men. Both, tCBF and GCP were significantly reduced in aMCI compared with CN, while differences in volumes of cerebral gray matter, white matter, and AD-prone regions were not significant. tCBF and GCP were significantly associated with global cognition (standardized beta (stβ) = 0.324 and stβ= 0.326) and with memory scores (stβ≥0.297 and stβ≥0.264) across all participants. Associations of tCBF and GCP with memory scores were also significant in CN (stβ= 0.327 and stβ= 0.284) and in aMCI (stβ= 0.627 and stβ= 0.485). Conclusion: Reduced tCBF and GCP are sensitive biomarkers of early aMCI that likely precede brain tissue loss.

Neurofluids is a term introduced to define all fluids in the brain and spine such as blood, cerebrospinal fluid, and interstitial fluid. Neuroscientists in the past millennium have steadily identified the several different fluid environments in the brain and spine that interact in a synchronized harmonious manner to assure a healthy microenvironment required for optimal neuroglial function. Neuroanatomists and biochemists have provided an incredible wealth of evidence revealing the anatomy of perivascular spaces, meninges and glia and their role in drainage of neuronal waste products. Human studies have been limited due to the restricted availability of noninvasive imaging modalities that can provide a high spatiotemporal depiction of the brain neurofluids. Therefore, animal studies have been key in advancing our knowledge of the temporal and spatial dynamics of fluids, for example, by injecting tracers with different molecular weights. Such studies have sparked interest to identify possible disruptions to neurofluids dynamics in human diseases such as small vessel disease, cerebral amyloid angiopathy, and dementia. However, key differences between rodent and human physiology should be considered when extrapolating these findings to understand the human brain. An increasing armamentarium of noninvasive MRI techniques is being built to identify markers of altered drainage pathways. During the three-day workshop organized by the International Society of Magnetic Resonance in Medicine that was held in Rome in September 2022, several of these concepts were discussed by a distinguished international faculty to lay the basis of what is known and where we still lack evidence. We envision that in the next decade, MRI will allow imaging of the physiology of neurofluid dynamics and drainage pathways in the human brain to identify true pathological processes underlying disease and to discover new avenues for early diagnoses and treatments including drug delivery. Evidence level: 1 Technical Efficacy: Stage 3.

Background The perfusion-related diffusion coefficient obtained from triexponential diffusion analysis is closely correlated with regional cerebral blood flow (rCBF), as assessed by arterial spin labeling (ASL) methods. However, this provides only a semiquantitative measure of rCBF, thereby making absolute rCBF quantification challenging. Purpose To obtain rCBF in a noninvasive manner using a novel diffusion imaging method with phase contrast (DPC), in which the total CBF from phase-contrast (PC) MRI was utilized to convert perfusion-related diffusion coefficients to rCBF values. Study type Prospective. Subjects Eleven healthy volunteers (nine men and two women; mean age, 23.9 years) participated in this study. Field strength/sequence A 3.0 T, single-shot diffusion echo-planar imaging with multiple b-values (0-3000 s/mm2 ), PC-MRI, pulsed continuous ASL, and 3D T1 -weighted fast field echo. Assessment rCBF and its correlations in the gray matter (GM) and white matter (WM) were compared between DPC and ASL methods. rCBF in the GM and WM and the GM/WM ratio were compared with the literature values obtained using [15 O]-water positron emission tomography (15 O-H2 O PET). Statistical tests Spearman's correlation coefficient and Wilcoxon signed-rank test were used. Significance was set at P Results A significant positive correlation between DPC and ASL in terms of rCBF was observed in GM (R = 0.9), whereas the correlation between the two methods was poor in WM (R = 0.09). The rCBF in GM and WM and the GM/WM ratio obtained using DPC were consistent with the literature values assessed using 15 O-H2 O PET. The rCBF value obtained using DPC was significantly higher in the GM and WM than that using ASL. Data conclusion DPC enabled noninvasive quantification of rCBF. Evidence level 2 TECHNICAL EFFICACY: Stage 1.

Episodic memory is widely recognized as a critically important aspect of cognition that is often impacted by cognitive and brain aging. Prior work has shown that episodic memory is related to the presence of teeth-like folds on the dentate gyrus, called dentation. We hypothesized that episodic memory performance relates to overall hippocampal structure (i.e., dentation and volume) in an oldest-old cohort. We used data from the McKnight Brain Aging Registry, which consisted of cognitively healthy 85+-year-old adults. We conducted a canonical correlation analysis on 111 participants between a set of episodic memory tests and a set of characterizations of hippocampal structure. The analysis yielded a strong canonical correlation between episodic memory and hippocampal structure (r = 0.491, p = HighlightsWe characterized hippocampal dentation in a healthy oldest-old sample.Hippocampal structure is related to episodic memory in healthy oldest-old adults.Memory functioning is related to both hippocampal volume and dentation.

Objective Fatigue is among the most common complaints in community-dwelling older adults, yet its etiology is poorly understood. Based on models implicating frontostriatal pathways in fatigue pathogenesis, we hypothesized that smaller basal ganglia volume would be associated with higher levels of subjective fatigue and reduced set-shifting in middle-aged and older adults without dementia or other neurologic conditions. Methods Forty-eight non-demented middle-aged and older adults ( Mage = 68.1, SD = 9.4; MMMSE = 27.3, SD = 1.9) completed the Fatigue Symptom Inventory, set-shifting measures, and structural MRI as part of a clinical evaluation for subjective cognitive complaints. Associations were examined cross-sectionally. Results Linear regression analyses showed that smaller normalized basal ganglia volumes were associated with more severe fatigue (β = −.29, P = .041) and poorer Trail Making Test B-A (TMT B-A) performance (β = .30, P = .033) controlling for depression, sleep quality, vascular risk factors, and global cognitive status. Putamen emerged as a key structure linked with both fatigue ( r = −.43, P = .003) and TMT B-A (β = .35, P = .021). The link between total basal ganglia volume and reduced TMT B-A was particularly strong in clinically fatigued patients. Conclusion This study is among the first to show that reduced basal ganglia volume is an important neurostructural correlate of subjective fatigue in physically able middle-aged and older adults without neurological conditions. Findings suggest that fatigue and rapid set-shifting deficits may share common neural underpinnings involving the basal ganglia, and provide a framework for studying the neuropathogenesis and treatment of subjective fatigue.

High dimensional neuroimaging datasets and machine learning have been used to estimate and predict domain-specific cognition, but comparisons with simpler models composed of easy-to-measure variables are limited. Regularization methods in particular may help identify regions-of-interest related to domain-specific cognition. Using data from the Northern Manhattan Study, a cohort study of mostly Hispanic older adults, we compared three models estimating domain-specific cognitive performance: sociodemographics and APOE ε4 allele status (basic model), the basic model and MRI markers, and a model with only MRI markers. We used several machine learning methods to fit our regression models: elastic net, support vector regression, random forest, and principal components regression. Model performance was assessed with the RMSE, MAE, and R(2) statistics using 5-fold cross-validation. To assess whether prediction models with imaging biomarkers were more predictive than prediction models built with randomly generated biomarkers, we repeated our prediction analyses using 1000 datasets with random biomarkers and compared the distribution of the RMSE and R(2) in models using these random biomarkers to the RMSE and R(2) from observed models. Basic models explained ~30–41% of the variance in domain-specific cognition. Addition of MRI markers did not improve estimation. However, elastic net models with only MRI markers performed significantly better than random MRI markers (one-sided P

Background How cerebrovascular disease and neurodegeneration affect each other to impact cognition is not yet known. We aimed to test whether Alzheimer’s disease-signature (AD) cortical thickness mediates the association between cholinergic white matter lesion load and change in domain-specific cognition. Methods Clinically stroke-free participants from the Northern Manhattan Study with both regional white matter hyperintensity volume (WMHV) and gray matter measurements were included (N = 894). Tract-specific WMHVs were quantified through FSL using the Johns Hopkins University white matter tract atlas. We used Freesurfer 5.1 to estimate regional cortical thickness. We fit structural equation models, including multiple indicator latent change score models, to examine associations between white matter hyperintensity volume (WMHV) in cholinergic tracts, AD-signature region cortical thickness (CT), and domain-specific cognition. Results Our sample (N = 894) had a mean (SD) age = 70 (9) years, years of education = 10 (5), 63% women, and 67% Hispanics/Latinos. Greater cholinergic WMHV was significantly related to worse processing speed at baseline (standardized β = −0.17, SE = 0.05, p = .001) and over time (standardized β = −0.28, SE = 0.09, p = .003), with a significant indirect effect of AD-signature region CT (baseline: standardized β = −0.02, SE = 0.01, p = .023; change: standardized β = −0.03, SE = 0.02, p = .040). Conclusions Cholinergic tract WMHV is associated with worse processing speed, both directly and indirectly through its effect on AD-signature region CT.

Poor sleep quality is a known risk factor for Alzheimer's disease. This longitudinal imaging study aimed to determine the acceleration in the rates of tissue loss in cognitively critical brain regions due to poor sleep in healthy elderly individuals. Cognitively-normal healthy individuals, aged ≥60 years, reported Pittsburgh Sleep Quality Index (PSQI) and underwent baseline and 2-year follow-up magnetic resonance imaging brain scans. The links between self-reported sleep quality, rates of tissue loss in cognitively-critical brain regions, and white matter hyperintensity load were assessed. A total of 48 subjects were classified into normal (n = 23; PSQI score5) and poor sleepers (n = 25; PSQI score ≥5). The two groups were not significantly different in terms of age, gender, years of education, ethnicity, handedness, body mass index, and cognitive performance. Compared to normal sleepers, poor sleepers exhibited much faster rates of volume loss, over threefold in the right hippocampus and fivefold in the right posterior cingulate over 2 years. In contrast, there were no significant differences in the rates of volume loss in the cerebral and cerebellar grey and white matter between the two groups. Rates of volume loss in the right posterior cingulate were negatively associated with global PSQI scores. Poor sleep significantly accelerates volume loss in the right hippocampus and the right posterior cingulate cortex. These findings demonstrate that self-reported sleep quality explains inter-individual differences in the rates of volume loss in cognitively-critical brain regions in healthy older adults and provide a strong impetus to offer sleep interventions to cognitively normal older adults who are poor sleepers.

We aim to determine the sleep correlates of age-related brain loss in a sample of middle-aged to older males with obstructive sleep apnea (OSA). We recruited consecutive treatment naïve male patients with moderate to severe OSA from January to November of 2019. We excluded participants if they had dementia, stroke or heart disease. We collected demographic variables and vascular risk factors. We also obtained the insomnia severity index, the Epworth sleepiness scale and the Pittsburgh sleep quality index. We also obtained computerized neurocognitive testing with the go-no-go response inhibition test, Stroop interference test, catch game test, staged information processing speed test, verbal memory test and non-verbal memory test. We derived age and education adjusted domain-specific Z-scores for global cognition, memory, attention, processing speed and executive function. We used brain MRI T1-weighted images to derive total hippocampal and gray matter volumes. Partial correlations evaluated associations between variables from sleep questionnaires (e.g., insomnia severity index score), and polysomnographic variables (the apnea-hypopnea index, average oxygen levels during sleep) with cognitive domains and brain volumes. We examined 16 participants with an age range of 40–76 years, 73% Hispanic/Latino. The mean apnea-hypopnea index was 48.9 ± 25.5 and average oxygen saturation during sleep was 91.4% ± 6.9%. Hypertension was seen in 66% and diabetes mellitus in 27%. We found that the insomnia severity index score and average oxygen levels during sleep had the strongest correlations with brain volumes and cognition. These preliminary findings may aid in developing future strategies to improve age-related brain loss in patients with OSA.

Recent studies demonstrated reduced hippocampal volumes in elderly healthy individuals who are cognitively normal but poor sleepers. The association between sleep quality and the pattern of volume loss across hippocampal subfields (HSs) is not well known. Thus, it is the focus of the present study. Sleep quality was self-assessed using the Pittsburgh Sleep Quality Index (PSQI). The HS volumes were measured using sub-millimetre in-plane resolution T2-weighted magnetic resonance imaging data. A total of 67 cognitively normal elderly individuals aged 60-83 years were classified into 30 normal sleepers with a PSQI

Background Adiposity may increase risk for dementia and Alzheimer's disease (AD), but mechanisms are unclear. Objective To examine associations between measures of adiposity with AD-signature region cortical thickness and hippocampal volume. Methods We used data from the Northern Manhattan Study, a clinically stroke-free cohort of mostly Hispanic participants. Exposures of interest included body mass index (BMI), waist-hip-ratio (WHR), waist circumference (WC), and adiponectin concentration, measured at study entry. AD-signature region cortical thickness and hippocampal volume were obtained using Freesurfer. We estimated associations using multivariable linear regression, adjusting for sociodemographics and health behaviors. We re-examined estimates after adjustment for APOEɛ4 allele status or carotid intima-media thickness (cIMT), among those cognitively unimpaired, and after weighting for the inverse probability of selection into the MRI sub-study. We also repeated analyses for cortical thickness in non-AD signature regions. Results The sample (N = 947, 63% women, 66% Hispanic/Latino, 26% obese) had a mean (SD) age = 63 (8) years. Greater BMI and WC (both z-scored) were associated with thinner AD-signature region cortex (also z-scored) (BMI: β [95% CI] = -0.09 [-0.18, -0.01], WC: β [95% CI] = -0.11 [-0.20, -0.02]). We did not find evidence that adiposity was related to hippocampal volume. Results were consistent after adjustment for APOEɛ4 allele status or cIMT, after weighting for selection, among those cognitively unimpaired, and for non-AD signature region cortical thickness. Conclusion Greater BMI and WC were related to cortical thinning within and outside the AD-signature region, suggesting a global effect not specific to AD.

ObjectiveTo examine associations between measures of obesity in middle to early-old age with later-life MRI markers of brain aging.MethodsWe analyzed data from the Northern Manhattan MRI Sub-Study (n = 1,289). Our exposures of interest were body mass index (BMI), waist circumference (WC), waist-to-hip ratio, and plasma adiponectin levels. Our outcomes of interest were total cerebral volume (TCV), cortical thickness, white matter hyperintensity volume (WMHV), and subclinical brain infarcts (SBI). Using multivariable linear and logistic regression models adjusted for sociodemographics, health behaviors, and vascular risk factors, we estimated β coefficients (or odds ratios) and 95% confidence intervals (CIs) and tested interactions with age, sex, and race/ethnicity.ResultsOn average at baseline, participants were aged 64 years and had 10 years of education; 60% were women and 66% were Caribbean Hispanic. The mean (SD) time lag between baseline and MRI was 6 (3) years. Greater BMI and WC were significantly associated with thinner cortices (BMI β [95% CI] −0.089 [−0.153, −0.025], WC β [95% CI] −0.103 [−0.169, −0.037]) in fully adjusted models. Similarly, compared to those with BMI ConclusionsAdiposity in early-old age is related to reduced global gray matter later in life in this diverse sample. Future studies are warranted to elucidate causal relationships and explore region-specific associations.

We aim to determine the sleep correlates of age-related brain loss in a sample of middle-aged to older males with obstructive sleep apnea. We evaluated consecutive treatment naïve male patients with OSA (AHI≥15 events/hr) without dementia, stroke or heart disease, from January to November of 2019. We collected demographic variables, vascular risk factors, and sleep questionnaires. We also obtained computerized neurocognitive testing with the Go-No-Go Response Inhibition Test, Stroop Interference Test, Catch Game Test, Staged Information Processing Speed Test, Verbal Memory Test and Non-Verbal Memory Test. We derived age and education adjusted domain-specific Z-scores for global cognition, memory, attention, processing speed and executive function. We used brain MRI T1-weighted images to derive total hippocampal and gray matter volumes. Partial correlations evaluated associations between the ISI, AHI, and oxygen level during sleep, with cognitive domains and brain volumes. Sixteen participants, age 40-76 years, 73% Hispanic/Latino, with mean AHI=48.9±25.5 and mean oxygen saturation of 91.4±6.9% during sleep. Hypertension was seen in 66% and diabetes in 27%. We observed that ISI and oxygen level during sleep had strong correlations with brain volumes and cognition. These preliminary findings may aid in developing future strategies to improve age-related brain loss in OSA.

Mechanical compliance of a compartment is defined by the change in its volume with respect to a change in the inside pressure. The compliance of the spinal canal regulates the intracranial pressure (ICP) under postural changes. Understanding how gravity affects ICP is beneficial for poorly understood cerebrospinal fluid (CSF)-related disorders. The aim of this study was to evaluate postural effects on cranial hemo- and hydrodynamics. This was a prospective study, which included 10 healthy volunteers (three males, seven females, mean ± standard deviation age: 29 ± 7 years). Cine gradient-echo phase-contrast sequence acquired at 0.5 T, "GE double-doughnut" scanner was used. Spinal contribution to overall craniospinal compliance (CSC), craniospinal CSF stroke volume (SV), magnetic resonance (MR)-derived ICP (MR-ICP), and total cerebral blood flow (TCBF) were measured in supine and upright postures using automated blood and CSF flows quantification. Statistical tests performed were two-sided Student's t-test, Cohen's d, and Pearson correlation coefficient. MR-ICP and the craniospinal CSF SV were significantly correlated with the spinal contribution to the overall CSC (r = 0.83, p < 0.05) and (r = 0.62, p < 0.05), respectively. Cranial contribution to CSC increased from 44.5% ± 16% in supine to 74.9% ± 8.4% in upright posture. The average MR-ICP dropped from 9.9 ± 3.4 mmHg in supine to -3.5 ± 1.5 mmHg. The CSF SV was over 2.5 times higher in the supine position (0.55 ± 0.14 ml) than in the upright position (0.21 ± 0.13 ml). In contrast, TCBF was slightly higher in the supine posture (822 ± 152 ml/min) than in the upright posture (761 ± 139 ml/min), although not statistically significant (p = 0.16). The spinal-canal compliance contribution to CSC is larger than the cranial contribution in the supine posture and smaller in the upright posture. Thereby, the spinal canal plays a role in modulating ICP upon postural changes. The lower pressure craniospinal CSF system was more affected by postural changes than the higher-pressure cerebral vascular system. Craniospinal hydrodynamics is affected by gravity and is likely to be altered by its absence in space. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Background and Purpose— Few studies have examined the separate contributions of systolic blood pressure and diastolic blood pressures (DBP) on subclinical cerebrovascular disease, especially using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines. Furthermore, associations with region-specific white matter hyperintensity volume (WMHV) are underexplored. Methods— Using data from the NOMAS (Northern Manhattan Study), a prospective cohort study of stroke risk and cognitive aging, we examined associations between systolic blood pressure and DBP, defined by the 2017 American College of Cardiology/American Heart Association guidelines, with regional WMHV. We used a linear mixed model approach to account for the correlated nature of regional brain measures. Results— The analytic sample (N=1205; mean age 64±8 years) consisted of 61% women and 66% Hispanics/Latinos. DBP levels were significantly related to WMHV differentially across regions ( P for interactiont tests showed that estimates for periventricular WMHV were significantly different from estimates for temporal WMHV (Holms stepdown–adjusted P Conclusions— Lower DBP levels, defined by the 2017 American College of Cardiology/American Heart Association guidelines, were related to lower white matter lesion load, especially in the periventricular regions relative to the temporal region.

ObjectiveWe examined whether greater depressive symptoms were associated with domain-specific cognitive performance, change in cognition, and MRI markers of brain atrophy and subclinical cerebrovascular disease in a diverse sample of older adults from the Northern Manhattan Study.MethodsData were analyzed from the Northern Manhattan Study, a prospective cohort study of mostly Caribbean Hispanic, stroke-free, older adults. A total of 1,111 participants had baseline measures of depressive symptoms, measured as the Center of Epidemiological Studies–Depression Scale, MRI markers, and cognitive function. A Center of Epidemiological Studies–Depression score ≥16 was considered indicative of greater depressive symptoms. Multivariable linear and logistic regression models were used to examine the associations of interest.ResultsAt baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographic, vascular risk factor, behavioral, and antidepressive medication variables (β [95% confidence interval] = −0.21 [−0.33 to −0.10],p= 0.0003). Greater depressive symptoms were also associated with smaller cerebral parenchymal fraction (β [95% confidence interval] = −0.56 [−1.05 to −0.07],p= 0.02) and increased odds of subclinical brain infarcts (odds ratio [95% confidence interval] = 1.55 [1.00–2.42],p= 0.05), after adjustment for sociodemographic, behavioral, and vascular risk factor variables. Greater depressive symptoms were not significantly associated with white matter hyperintensity volume, hippocampal volume, or change in cognition over an average of 5 years. Results were unchanged when stabilized inverse probability weights were applied to address selective attrition during the study period.ConclusionsIn this sample of mostly Caribbean Hispanic, stroke-free, older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts.

Objectives: To test the hypothesis that brain arterial diameters are associated with cognitive performance, particularly in arteries supplying domain-specific territories. Methods: Stroke-free participants in the Northern Manhattan Study were invited to have a brain MRI from 2003–2008. The luminal diameters of 13 intracranial arterial segments were obtained using time-of-flight magnetic resonance angiogram (MRA), and then averaged and normalized into a global score and region-specific arterial diameters. Z-Scores for executive function, semantic memory, episodic memory and processing speed were obtained at MRI and during follow-up. Adjusted generalized additive models were used to assess for associations. Results: Among the 1034 participants with neurocognitive testing and brain MRI, there were non-linear relationships between left anterior (ACA) and middle cerebral artery (MCA) diameter and semantic memory Z-scores (χ2=10.00; DF=3; p=.019), and left posterior cerebral artery (PCA) and posterior communicating artery (Pcomm) mean diameter and episodic memory Z-scores (χ2=9.88; DF=3; p=.020). Among the 745 participants who returned for 2nd neuropsychological testing, on average 5.0±0.4 years after their MRI, semantic memory change was associated non-linearly with the left PCA/Pcomm mean diameter (χ2=13.09; DF=3; p=.004) and with the right MCA/ACA mean diameter (χ2=8.43; DF=3; p=.03). In both cross-sectional and longitudinal analyses, participants with the larger brain arterial diameters had more consistently lower Z-scores and greater decline than the rest of the participants. Conclusions: Brain arterial diameters may have downstream effects in brain function presenting as poorer cognition. Identifying the mechanisms and the directionality of such interactions may increase the understanding of the vascular contribution to cognitive impairment and dementia. (JINS, 2018, 24, 335–346)

Background/Objectives We previously showed that global brain white matter hyperintensity volume (WMHV) was associated with accelerated long-term functional decline. The objective of the current study was to determine whether WMHV in particular brain regions is more predictive of functional decline. Design Prospective population-based study. Setting Northern Manhattan magnetic resonance imaging (MRI) study. Participants Individuals free of stroke at baseline (N = 1,195; mean age 71 ± 9; n = 460 (39%) male). Measurements Participants had brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences. Volumetric WMHV distribution across 14 brain regions (brainstem; cerebellum; bilateral frontal, occipital, temporal, and parietal lobes; and bilateral anterior and posterior periventricular white matter (PVWM)) was determined using a combination of bimodal image intensity distribution and atlas-based methods. Participants had annual functional assessments using the Barthel Index (BI) (range 0–100) over a mean of 7.3 years and were followed for stroke, myocardial infarction (MI), and mortality. Because there were multiple collinear variables, least absolute shrinkage and selection operator (LASSO) regression–selected regional WMHV variables most associated with outcomes and adjusted generalized estimating equations models were used to estimate associations with baseline BI and change over time. Results Using LASSO regularization, only right anterior PVWM was found to meet criteria for selection, and each standard deviation greater WMHV was associated with accelerated functional decline of 0.95 additional BI points per year (95% confidence interval (CI) = −1.20 to −0.70) in an unadjusted model, −0.92 points per year (95% CI = −1.18 to −0.67) with baseline covariate adjustment, and −0.87 points per year (95% CI = −1.12 to −0.62) after adjusting for incident stroke and MI. Conclusion In this large population-based study with long-term repeated measures of function, periventricular WMHV was particularly associated with accelerated functional decline.

PURPOSE: To determine whether MRI volumetric and image texture analysis correlates with treatment-induced biologic changes in desmoid fibromatosis (DF) earlier than conventional response criteria. MATERIALS AND METHODS: This retrospective study included 27 patients with histologically proven extra-abdominal DF who were managed with active surveillance or systemic therapy (from 2004 to 2016). MRI volumetric and image texture parameters were derived from manual tumor segmentations, and tumor signal intensity was normalized to muscle. Results were compared with objective response rates based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, World Health Organization (WHO) lesion response, volumetrics, and MRI-modified Choi criteria. Correlation coefficients (r) between image texture features and maximum tumor diameters were obtained by using a meta-analysis approach. RESULTS: The 27 included patients (mean age, 39 years; 74% women) were followed for an average of 4 years, comprising 207 distinct time-point assessments. The mean baseline tumor maximum diameter was 7.9 cm (range, 3.4–15.2 cm). Partial response (PR) rates as best response were 37%, 44%, 70%, and 81% by RECIST, WHO, volumetrics, and MRI-modified Choi criteria, respectively. Among the 10 tumors showing RECIST PR, a preceding MRI-modified Choi PR was observed in 70% (seven of 10), on average 1.3 years earlier. Multiple image texture parameters showed associations with objective measurements of tumor diameter including mean tumor-to-muscle signal ratio (r = 0.51; P = .004), median tumor-to-muscle signal ratio (r = 0.52; P = .003), energy (r = 0.48; P < .001), run entropy (r = 0.32, P = .04), and gray-level nonuniformity (r = 0.54; P ≤ .001). CONCLUSION: Volumetric signal and image texture assessment allows more comprehensive analysis of DF biologic change and may permit early prediction of DF behavior and therapeutic response. Keywords: MR Imaging, Soft Tissues/Skin, Neoplasms-Primary © RSNA, 2021

Objective:To assess the effect of weightlessness and the respective roles of CSF and vascular fluid on changes in white matter hyperintensity (WMH) burden in astronauts.Methods:We analyzed prespaceflight and postspaceflight brain MRI scans from 17 astronauts, 10 who flew a long-duration mission on the International Space Station (ISS) and 7 who flew a short-duration mission on the Space Shuttle. Automated analysis methods were used to determine preflight to postflight changes in periventricular and deep WMH, CSF, and brain tissue volumes in fluid-attenuated inversion recovery and high-resolution 3-dimensional T1-weighted imaging. Differences between cohorts and associations between individual measures were assessed. The short-term reversibility of the identified preflight to postflight changes was tested in a subcohort of 5 long-duration astronauts who had a second postflight MRI scan 1 month after the first postflight scan.Results:Significant preflight to postflight changes were measured only in the long-duration cohort and included only the periventricular WMH and ventricular CSF volumes. Changes in deep WMH and brain tissue volumes were not significant in either cohort. The increase in periventricular WMH volume was significantly associated with an increase in ventricular CSF volume (ρ = 0.63, p = 0.008). A partial reversal of these increases was observed in the long-duration subcohort with a 1-month follow-up scan.Conclusions:Long-duration exposure to microgravity is associated with an increase in periventricular WMH in astronauts. This increase was linked to an increase in ventricular CSF volume documented in ISS astronauts. There was no associated change in or abnormal levels of WMH volumes in deep white matter as reported in U-2 high-altitude pilots.

Purpose To quantify the acute effect of the head-down tilt (HDT) posture on intracranial hemodynamics and hydrodynamics. Materials and Methods We evaluated the intracranial physiological parameters, blood flow-related parameters, and brain morphology in the HDT (–6° and –12°) and the horizontal supine (HS) positions. Seven and 15 healthy subjects were scanned for each position using 3.0 T magnetic resonance imaging system. The peak-to-peak intracranial volume change, the peak-to-peak cerebrospinal fluid (CSF) pressure gradient (PGp-p), and the intracranial compliance index were calculated from the blood and CSF flow determined using a cine phase-contrast technique. The brain volumetry was conducted using SPM12. The measurements were compared using the Wilcoxon signed-rank test or a paired t-test. Results No measurements changed in the –6° HDT. The PGp-p and venous outflow of the internal jugular veins (IJVs) in the –12° HDT were significantly increased compared to the HS (P < 0.001 and P = 0.025, respectively). The cross-sectional areas of the IJVs were significantly larger (P < 0.001), and the maximum, minimum, and mean blood flow velocity of the IJVs were significantly decreased (P = 0.003, < 0.001, and = 0.001, respectively) in the –12° HDT. The mean blood flow velocities of the internal carotid arteries were decreased (P = 0.023). Neither position affected the brain volume. Conclusion Pressure gradient and venous outflow were increased in accordance with the elevation of the intracranial pressure as an acute effect of the HDT. However, the CSF was not constantly shifted from the spinal canal to the cranium. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017.

Background There is growing evidence that proactive semantic interference (PSI) and failure to recover from PSI may represent early features of Alzheimer's disease (AD). Objective This study investigated the association between PSI, recovery from PSI, and reduced MRI volumes in AD signature regions among cognitively impaired and unimpaired older adults. Methods Performance on the LASSI-L (a novel test of PSI and recovery from PSI) and regional brain volumetric measures were compared between 38 cognitively normal (CN) elders and 29 older participants with amnestic mild cognitive impairment (MCI). The relationship between MRI measures and performance on the LASSI-L as well as traditional memory and non-memory cognitive measures was also evaluated in both diagnostic groups. Results Relative to traditional neuropsychological measures, MCI patients' failure to recover from PSI was associated with reduced volumes in the hippocampus (rs = 0.48), precuneus (rs = 0.50); rostral middle frontal lobules (rs = 0.54); inferior temporal lobules (rs = 0.49), superior parietal lobules (rs = 0.47), temporal pole (rs = 0.44), and increased dilatation of the inferior lateral ventricle (rs = -0.49). For CN elders, only increased inferior lateral ventricular size was associated with vulnerability to PSI (rs = -0.49), the failure to recover from PSI (rs = -0.57), and delayed recall on the Hopkins Verbal Learning Test-Revised (rs = -0.48). Discussion LASSI-L indices eliciting failure to recover from PSI were more highly associated with more MRI regional biomarkers of AD than other traditional cognitive measures. These results as well as recent amyloid imaging studies with otherwise cognitively normal subjects, suggest that recovery from PSI may be a sensitive marker of preclinical AD and deserves further investigation.

Background: Basilar artery (BA) dolichoectasia is defined as dilatation, tortuosity, and/or elongation of the basilar artery. Hospital-based studies have demonstrated an association between BA dilatation and risk of death and stroke. We hypothesized that BA tortuosity and elongation increase risk of death and stroke independent of BA dilatation. Methods: We included stroke-free participants in the Northern Manhattan Study, a population-based prospective cohort study, with an available time of flight MRA. BA tortuosity was defined as BA localization lateral to margin of the clivus, and BA elongation as BA tip distal to margin of the sella. BA diameters were obtained with semi-automated in-house software. Primary outcomes were any death and ischemic stroke. Cox proportional hazards models were used to obtain hazards ratios [HR] and 95% confidence intervals [CI] after adjusting for demographics and vascular risks. Results: Participants (N=1032, mean age 70.7 years, 39.5% men, 65.7% Hispanic) were followed on average for 10.4 ± 3.1 years after their MRA. Among these, 97 (9.4%) had BA tortuosity, 294 (28.5%) had BA elongation, and 98 (9.5%) had both tortuosity and elongation. Participants with BA tortuosity were more likely men, and participants with BA elongation were older, more likely women, non-Hispanic white and were more likely hypertensive. There was no association between BA tortuosity (HR 0.89; 95% CI 0.73 – 1.09, P=0.27), BA elongation (HR 1.12; 0.96 – 1.31, P=0.14), or BA dilatation (HR 1.03; 95% CI 0.84 – 1.27, P=0.76) and risk of death. There was an interaction between BA tortuosity and elongation (P for interaction=0.02); BA elongation was associated with an increased risk of death only among those with BA tortuosity (HR 2.06; 1.29 – 3.29; P=0.002). Adjusting for BA dilatation attenuated the association (HR 1.66; 0.99 – 2.81, P=0.05). We found no association between BA tortuosity (HR 0.92; 95% CI 0.77 – 1.10) or elongation (HR 1.07; 95% CI 0.92 – 1.23), or their combination, and ischemic stroke. Conclusion: Stroke-free individuals with both basilar elongation and tortuosity may have a higher risk of death, but not stroke. Further studies of vasculopathy seen in dolichoectasia and its relationship to systemic vascular disease and mortality are warranted.

STUDY OBJECTIVES: This study aims to evaluate the extent to which sleep quality impacts amnestic mild cognitive impairment (aMCI)-related brain regions in a cognitively normal cohort of individuals. METHODS: Seventy-four participants were rigorously evaluated using a battery of cognitive tests and a detailed clinical assessment to verify normal cognitive status. We then screened for sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and depressive symptoms using the Geriatric Depression Scale (GDS). Five subjects were excluded due to mild depression. Overall 38 individuals with mean age 70.7 ± 7 were classified as poor sleepers and 31 with mean age of 69.6 ± 6 years as normal sleepers. Structural MRI and Freesurfer brain parcellation were used to measure aMCI-related brain regions. RESULTS: Relative to normal sleepers, poor sleepers exhibited significant reductions in cortical and subcortical volumes bilaterally in the hippocampi, as well as in the superior parietal lobules and left amygdala. The effects were strongest in the left superior parietal lobule (p < .015), followed by the hippocampi. Diffuse patterns of cortical thinning were observed in the frontal lobes, but significant effects were concentrated in the right mesial frontal cortex. Lower sleep duration was most correlated with cortical volume and thickness reductions among all subjects. CONCLUSIONS: Atrophy related to poor sleep quality impacted a number of regions implicated in aMCI and Alzheimer’s disease (AD). As such, interventions targeted towards improving sleep quality amongst the elderly may prove an effective tool for modulating the course of aMCI and AD.

Background The distribution of cranio-spinal compliance (CSC) in the brain and spinal cord is a fundamental question, as it would determine the overall role of the compartments in modulating ICP in healthy and diseased states. Invasive methods for measurement of CSC using infusion-based techniques provide overall CSC estimate, but not the individual sub-compartmental contribution. Additionally, the outcome of the infusion-based method depends on the infusion site and dynamics. This article presents a method to determine compliance distribution between the cranium and spinal canal non-invasively using data obtained from patients. We hypothesize that this CSC distribution is indicative of the ICP. Methods We propose a lumped-parameter model representing the hydro and hemodynamics of the cranio-spinal system. The input and output to the model are phase-contrast MRI derived volumetric transcranial blood flow measured in vivo, and CSF flow at the spinal cervical level, respectively. The novelty of the method lies in the model mathematics that predicts CSC distribution (that obeys the physical laws) from the system dc gain of the discrete-domain transfer function. 104 healthy individuals (48 males, 56 females, age 25.4 ± 14.9 years, range 3–60 years) without any history of neurological diseases, were used in the study. Non-invasive MR assisted estimate of ICP was calculated and compared with the cranial compliance to prove our hypothesis. Results A significant negative correlation was found between model-predicted cranial contribution to CSC and MR-ICP. The spinal canal provided majority of the compliance in all the age groups up to 40 years. However, no single sub-compartment provided majority of the compliance in 41–60 years age group. The cranial contribution to CSC and MR-ICP were significantly correlated with age, with gender not affecting the compliance distribution. Spinal contribution to CSC significantly positively correlated with CSF stroke volume. Conclusions This paper describes MRI-based non-invasive way to determine the cranio-spinal compliance distribution in the brain and spinal canal sub-compartments. The proposed mathematics makes the model always stable and within the physiological range. The model-derived cranial compliance was strongly negatively correlated to non-invasive MR-ICP data from 104 patients, indicating that compliance distribution plays a major role in modulating ICP.

BACKGROUND AND PURPOSE: Automated methods for quantitation of tissue and CSF volumes by MR imaging are available for the cranial but not the spinal compartment. We developed an iterative method for delineation of the spinal CSF spaces for automated measurements of CSF and cord volumes and applied it to study craniospinal CSF redistribution following lumbar withdrawal in patients with idiopathic intracranial hypertension. MATERIALS AND METHODS: MR imaging data were obtained from 2 healthy subjects and 8 patients with idiopathic intracranial hypertension who were scanned before, immediately after, and 2 weeks after diagnostic lumbar puncture. Imaging included T1-weighted and T2-weighted sequences of the brain and T2-weighted scans of the spine. Repeat scans in 4 subjects were used to assess measurement reproducibility. Whole CNS CSF volumes measured prior to and following lumbar puncture were compared with the withdrawn amounts of CSF. RESULTS: CSF and cord volume measurements were highly reproducible with mean variabilities of −0.7% ± 1.4% and −0.7% ± 1.0%, respectively. Mean spinal CSF volume was 77.5 ± 8.4 mL. The imaging-based pre- to post-CSF volume differences were consistently smaller and strongly correlated with the amounts removed (R = 0.86, P = .006), primarily from the lumbosacral region. These differences are explained by net CSF formation of 0.41 ± 0.18 mL/min between withdrawal and imaging. CONCLUSIONS: Automated measurements of the craniospinal CSF redistribution following lumbar withdrawal in idiopathic intracranial hypertension reveal that the drop in intracranial pressure following lumbar puncture is primarily related to the increase in spinal compliance and not cranial compliance due to the reduced spinal CSF volume and the nearly unchanged cranial CSF volume.

Introduction We aim to determine the effect of positive airway pressure (PAP) on total cerebral blood flow in a sample of middle-aged to older male patients with obstructive sleep apnea (OSA). Methods We evaluated consecutive treatment-naïve male OSA patients with Apnea hypopnea Index (AHI)≥15, from January to November of 2019. We obtained demographic variables, vascular risk factors, the Epworth sleepiness scale (ESS) and the Pittsburgh sleep quality index (PSQI). Brain magnetic resonance imaging (MRI) consisted of high resolution anatomical imaging and velocity encoded phase contrast MRI to measure volumetric blood flow rate to the brain, or the total cerebral blood flow (tCBF), by summation of the flow rate through the two internal carotid and vertebral arteries. Positive airway pressure at various pressures was provided during the MRI, while subjects were awake, starting at 0 cm H20, then 5 cmH20, 10, 15, and 20 cmH20. Each setting was applied for six minutes. Two subjects did not tolerate pressure setting of 20 cmH2O. Results We had a total of 11 participants’ age 40-73 years, 70% Hispanic/Latino background. The average ESS was 8.2±6.0, PSQI=5.7±4.9, and AHI=48.9±25.5. Five of the subjects had hypertension and a quarter had diabetes. In all subjects total CBF monotonically decreased with increasing PAP. The initial decreases in total CBF (PAP from 0 to 5 and 5 to 10) where significantly larger than the decrease in the higher pressure range. In two subjects the total decrease in tCBF was nearly 50%. The average tCBF was 682.3 mL/min at 0 cmH20 and 506.3 ml/min at 20 cmH20. Conclusion Incremental increases in PAP lead to substantial decrease in tCBF during wake. Substantial decrease in tCBF is possibly explained by decreasing end tidal CO2 pressure. The specific physiologic cause and the neurologic impact of prolonged decreased tCBF during CPAP therapy needs to be further investigated. Support Scientific Advisory Committee, Pilot grant, Miller School of Medicine; R21AG056952; R21HL140437; Jazz-Pharmaceutical.

Introduction We aim to determine the cognitive domains associated with obstructive sleep apnea (OSA) age-related brain atrophy in a sample of middle-aged to older males. Methods We evaluated consecutive treatment naïve male OSA patients (AHI≥15) without dementia, stroke or heart disease (infarction, heart failure), from March to November of 2019. We obtained demographic variables, vascular risk factors, the Epworth sleepiness scale (ESS) and the Pittsburgh sleep quality index (PSQI). We also obtained computerized neurocognitive testing with the Go-NoGo Response Inhibition Test, Stroop Interference Test, Catch Game Test, Staged Information Processing Speed Test, Verbal Memory Test and Non-Verbal Memory Test. We derived domain-specific Z-scores age and education adjusted for global cognition, memory, attention, processing speed and executive function. Pearson correlation was used to evaluate bivariate associations between the sleep exposures and neurocognitive outcomes. Linear regression was used to evaluate associations between AHI and neurocognitive domains, adjusting for the ESS. Results A total of 15 participants 40 to 76 years of age, 73% of Hispanic/Latino background, completed neurocognitive testing. The average ESS was 8.2±6.0, PSQI=5.7±4.9, and AHI=48.9±25.5. Hypertension was seen in 66% and diabetes in 27%. The AHI was correlated with global cognition (r= -0.66; p=0.008), memory (r= -0.73; p=0.002) and attention (r= -0.67; p =0.007), but not executive function or processing speed. In addition, the AHI correlated with verbal memory (r= -0.76; p=0.001), but not with non-verbal memory. In adjusted models, the AHI was associated with global cognition (β= -0.60; p=0.05) and decreased memory (β= -0.85; p=0.006). However, the association with attention was explained by the ESS. The PSQI was not correlate with the cognitive domains. Conclusion In this pilot-study, the AHI was associated with decreased global cognition, and verbal memory accounting for sleepiness. Findings suggest the left-hippocampus as a region vulnerable to early age-related brain loss in OSA. Support Scientific Advisory Committee, Pilot grant, Miller School of Medicine; R21AG056952; R21HL140437.

Background The American Heart Association Life's Simple 7 metric defines ideal cardiovascular health (CVH) on 7 factors: smoking, diet, physical activity, body mass index, blood sugar, blood pressure, and cholesterol. This metric has been used to define optimal brain health, but data relative to subclinical imaging biomarkers of brain aging are lacking. This study examines the association between Life's Simple 7 with white matter hyperintensity volume, silent brain infarcts, and cerebral volume. Methods and Results A subsample of stroke‐free participants from the population‐based Northern Manhattan Study underwent brain magnetic resonance imaging an average of 7 years after baseline. Linear and logistic regression models were constructed to estimate associations between the number of ideal CVH metrics achieved with imaging biomarkers of brain aging, adjusting for sociodemographics. Among 1031 participants (mean age at magnetic resonance imaging=72±8, 40% men, 19% black, 16% white, and 65% Hispanic), no one had ideal status in all 7 factors, 1% had ideal status in 6 factors, 18% in 4 to 5 factors, 30% in 3 factors, 33% in 2 factors, and 18% in 0 to 1 factors. The number of ideal CVH factors achieved was inversely associated with white matter hyperintensity volume (beta per factor=−0.047; P =0.04) and silent brain infarct (odds ratio per factor=0.84; 95% confidence interval=0.72–0.97) and positively associated with cerebral volume (beta per factor=0.300; P =0.002). Conclusions An increasing ideal CVH score was associated with less white matter hyperintensity volume and silent brain infarcts and greater cerebral volumes, supporting the Life's Simple 7 metric as a useful measure to quantify optimal brain health. Monitoring and promoting achievement of Life's Simple 7 ideal CVH factors may improve subclinical and clinical brain health outcomes.

Most of the astronauts onboard the International Space Station (ISS) develop visual impairment and ocular structural changes that are not fully reversible upon return to earth. Current understanding assumes that the so-called visual impairments/intracranial pressure (VIIP) syndrome is caused by cephalad vascular fluid shift. This study assesses the roles of cerebrospinal fluid (CSF) and intracranial pressure (ICP) in VIIP.Seventeen astronauts, 9 who flew a short-duration mission on the space shuttle (14.1 days [SD 1.6]) and 7 who flew a long-duration mission on the ISS (188 days [SD 22]) underwent MRI of the brain and orbits to assess the pre-to-post spaceflight changes in four categories: VIIP severity measures: globe flattening and nerve protrusion; orbital and ventricular CSF volumes; cortical gray and white matter volumes; and MR-derived ICP (MRICP).Significant pre-to-post-flight increase in globe flattening and optic nerve protrusion occurred only in the long-duration cohort (0.031 [SD 0.019] vs -0.001 [SD 0.006], and 0.025 [SD 0.013] vs 0.001 [SD 0.006]; p0.00002 respectively). The increased globe deformations were associated with significant increases in orbital and ventricular CSF volumes, but not with increased tissue vascular fluid content. Additionally, a moderate increase in MRICP of 6 mmHg was observed in only two ISS astronauts with large ocular structure changes.These findings are evidence for the primary role of CSF and a lesser role for intracranial cephalad fluid-shift in the formation of VIIP. VIIP is caused by a prolonged increase in orbital CSF spaces that compress the globes' posterior pole, even without a large increase in ICP.

Objective: Examine the association of adiponectin and metabolic syndrome components with measures of global and lobar cortical thickness. Background: Metabolic syndrome has been associated with structural brain changes, but the relationship of adiponectin and cortical thickness is understudied. Methods: The Northern Manhattan Study MRI Sub-Study is a mostly Hispanic, stroke-free, prospective cohort study of older adults. Cortical thickness (mm) was obtained from T1-weighted brain MRIs using the publically-available Freesurfer software. Regional cortical thickness metrics were averaged to obtain mean lobar cortical thickness. Adiponectin (μg/mL) was measured at baseline (1993-2001). Metabolic syndrome components were measured at MRI Sub-Study baseline (2003-2008). We estimated the cross-sectional associations of adiponectin (per 1 SD) and metabolic syndrome components with global and lobar cortical thickness (per 1 SD) using multivariable linear regression models adjusted for sociodemographic factors, APOE ε4 allele presence, and health-related behaviors. All hypothesis testing was two-sided with an alpha level of 5%. Results: Freesurfer data were available in 947 participants (mean±SD age=70±9 years, 63% women, 66% Hispanics, 16% black, and 15% white). Global cortical thickness was normally distributed (mean±SD = 2.3±0.1mm). In fully adjusted models, 1 SD (4.9μg/mL) increase in adiponectin was associated with smaller overall (β [95%CI] = -0.07 [-0.14, -0.0002]) and parietal cortical thickness (β [95%CI] = -0.08 [-0.03, -0.0002]). Greater blood glucose levels significantly associated with smaller occipital cortical thickness (β [95%CI] = -0.003 [-0.006, -0.0007]). Greater waist circumference was significantly associated with smaller frontal cortical thickness (β [95%CI] = -0.02 [-0.04, -0.0007]). Neither blood pressure (systolic and diastolic) nor cholesterol (total, HDL-C, and LDL-C) were associated with global or regional cortical thickness. Conclusions: There was heterogeneity in the cross-sectional associations between adiponectin, metabolic syndrome components, and regional cortical thickness. Further studies are needed to explore the temporal relationship between risk factors and cortical thinning.