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INTRODUCTION: Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi‐site study, using a predefined hypothesis. METHODS: We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes. RESULTS: CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function. DISCUSSION: The predefined hypothesis on the association between CVR and a global cognitive score was validated in three independent analysis sites, providing support for CVR as a biomarker in VCID. Highlights: This study measured a novel functional index of small arteries referred to as cerebrovascular reactivity (CVR).CVR was positively associated with global cognition in older adults.This finding was observed in three independent cohorts at three sites.Our statistical analysis plan was predefined before beginning data collection. [ABSTRACT FROM AUTHOR]

Introduction: Oxygen extraction fraction (OEF) reflects the balance between oxygen delivery and consumption. We longitudinally measured OEF in older adults to examine the relationship with markers of Alzheimer's disease (AD) and vascular pathology. Methods: One hundred thirty‐seven participants were studied at two time‐points at an interval of 2.16 years. OEF was measured using T2‐relaxation‐under‐spin‐tagging (TRUST) magnetic resonance imaging (MRI). The association between OEF and vascular risks, white matter hyperintensities (WMH), cerebrospinal fluid (CSF) measures of amyloid beta (Aβ), total tau (t‐tau), and phosphorylated tau 181 (p‐tau181) was examined. Results: OEF increased from baseline to follow‐up. The increase in OEF was more prominent in individuals with high vascular risks compared to those with low vascular risks, and was associated with progression of vascular risks and the growth in WMH volume. OEF change was not related to CSF markers of AD pathology or their progression. Discussion: Longitudinal OEF change in older adults is primarily related to vascular pathology. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence suggests that enlarged perivascular spaces (ePVS) on magnetic resonance images (MRIs) are associated with cognitive dysfunction in aging. However, the etiology of ePVS remains unknown. Here we tested the possibility that cerebrovascular dysfunction, as assessed by an MRI measure of cerebrovascular reactivity (CVR), may contribute to ePVS development. Method: 79 cognitively normal, older adults (46 women, age range 60‐84) were recruited to undergo baseline MRI scanning and follow‐up scanning approximately 2.5 years later. Of the 79 participants scanned at baseline, 50 returned for follow‐up. Participants were scanned on a 3T Siemens Prisma scanner with a 64‐channel head coil. All scanning methods were identical across time points and included collection of T1‐weighted, T2‐weighted FLAIR, and quantitative susceptibility mapping (QSM) images. Cerebrovascular dysfunction was assessed using CVR, a measure of the ability of cerebrovasculature to dilate in response to vasoactive stimuli. Participants underwent blocked administration of breathing either room air or hypercapnic gas, while blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) was performed. CVR values were computed for baseline scans in specific regions by dividing change in BOLD signal by change in end‐tidal CO2. Baseline and follow‐up ePVS counts were performed by a single rater who was blinded to participant demographics. ePVS were individually and manually counted using STRIVE criteria in a representative, axial slice of the basal ganglia (BGePVS) and centrum semiovale (CSePVS). Result: BGePVS and CSePVS significantly increased during the follow‐up period. Mixed effects models indicated that baseline basal ganglia CVR values significantly predicted increased BGePVS counts after controlling for age, sex, education, and time point (p = <0.001). Furthermore, this effect was present bilaterally: Baseline CVR in the left hemisphere predicted increased BGePVS in the left hemisphere (p = <0.001) and baseline CVR in the right hemisphere predicted increased BGePVS in the right hemisphere (p = <0.001). Conversely, there was no longitudinal relationship between baseline CVR and increased CSePVS (p = 0.449). Conclusion: These results demonstrate that low baseline CVR is a risk factor for later development of ePVS. Localization of these findings to the basal ganglia suggests that it is particularly vulnerable to cerebrovascular dysfunction. [ABSTRACT FROM AUTHOR]

Background: Vascular cognitive decline is a prominent cause of late‐life cognitive impairment. Compared to Alzheimer's disease(AD), there is a paucity of biomarkers for its diagnosis, stratification, and treatment monitoring. Cerebrovascular‐Reactivity(CVR) MRI measures small‐vessel dilation to vasoactive‐stimuli(e.g. CO2), and has been shown to be associated with cognitive impairment. However, previous CVR studies were based on Blood‐Oxygenation‐Level‐Dependent (BOLD) MRI signal, which reflects a complex interplay of many physiological parameters and thus presents interpretation challenges. We measured CVR using quantitative CBF‐imaging in older participants, and tested for associations with diagnosis (Healthy Control [HC] vs. mild‐cognitive‐impairment [MCI] vs. dementia) cognitive and physical function, amyloid and tau burden, and vascular risk. Methods: A cross‐sectional study enrolled 67 participants aged 69±6.5 years (22 HC, 37 MCI, 8 dementia). MoCA (Montreal‐Cognitive‐Assessment) and composite cognition (a z‐score average of 4‐domains: verbal‐memory, executive‐function, language, processing‐speed) assessed overall cognition. Gait(sec,4‐meter‐walk) and chair‐stands (sec,5‐chair‐stands) assessed physical‐function. Clinical Dementia Rating(CDR)7 indexed disease‐severity. Phase‐contrast flow MRI(3T) was performed while participants breathed room‐air for 1‐minute, followed by 'CO2‐enriched‐air'(5%CO2, 21%O2, 74%N2) for 2‐minutes. Blood‐flux at Superior‐Sagittal‐Sinus(SSS)(Figure‐1) was quantified for both states. Breathing rate and End‐tidal(Et)‐CO2 were recorded via capnography. CBF‐based CVR was then obtained by: CBF‐CVR = [HypercapniaSSSflux(ml/min)‐RoomairSSSflux(ml/min)]/RoomairSSSflux(ml/min) HypercapniaEtCo2(mmHg)‐RoomairEtCo2(mmHg) FLAIR‐MRI‐images were assigned Fazekas‐scores by a neuroradiologist. AD‐Biomarkers Aβ40, Aβ42, tau, and p‐tau181(pg/ml), were measured in cerebrospinal fluid (CSF) and vascular‐biomarkers HbA1c (mg/dL), homocysteine (umol/l), HDL(mg/dL), and LDL (mg/dL) in blood. Vascular‐Risk‐Score (VRS) is a composite score based on the presence of hypertension, hypercholesterolemia, diabetes, smoking or obesity (body mass index>30 kg/m2). Results: Table‐1 summarizes participant‐demographics. CBF‐CVR (%/mmHg) differentiated diagnostic‐categories, and was lower in impaired vs. HC (p=0.027, Figure‐2a). Higher CBF‐CVR predicted better cognitive‐performance [MoCA(p=0.000089) (Figure‐2b), composite‐cognition (p=0.007) and language (p=0.000064)], physical function [faster gait(p=0.001), chair‐stands(p=0.021)], and disease‐severity [global‐CDR (p=0.003), CDR‐sum‐of‐boxes (p=0.001)(Table‐2). These relationships remained after adjusting for AD‐biomarkers. CBF‐CVR remained associated with cognition and physical‐function except chair‐stands, after adjusting for vascular‐markers: WMH‐Fazekas‐score, VRS, and whole‐brain‐CBF(Table‐2). CBF‐CVR was associated with HbA1c(p=0.007) and history of Diabetes (p=0.043), but not other blood biomarkers or VRS. Conclusion: We show that a 3‐minute CBF‐based CVR MRI can differentiate diagnostic‐categories, and predict cognitive and physical function, independent of AD pathology. [ABSTRACT FROM AUTHOR]