Brain Magnetic Resonance Imaging Markers Research Articles

Lung function in relation to brain aging and cognitive transitions in older adults: A population-based cohort study.

We investigated the association of peak expiratory flow (PEF) with dementia; cognitive impairment, no dementia (CIND); and transition from CIND to dementia, and possible underlying neuropathological mechanisms. A population-based cohort of adults aged 60+ was followed over 15 years to detect dementia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria), CIND (assessed through a cognitive battery), and progression from CIND to dementia, in relation to baseline PEF observations. A subsample (n=462) had 6-year follow-up data on brain magnetic resonance imaging markers of neurodegeneration and small vessel disease. In fully adjusted models, poor PEF performance (< 10th vs. ≥ 80th percentile) was associated with increased hazards for dementia (hazard ratio [HR]=1.89; 95% confidence interval [CI]=1.23-2.92) and CIND (HR=1.55; 95% CI=1.01-2.38) and CIND progression to dementia, although not statistically significantly (HR=2.44; 95% CI=0.78-6.88). People with poor PEF also experienced the fastest ventricular enlargement (β coefficient=0.67mL/year; 95% CI=0.13-1.21) and had the highest likelihood of developing lacunes (odds ratio=5.05; 95%CI=1.01-25.23). Poor lung function contributes to cognitive deterioration possibly through accelerated brain atrophy and microvascular damage. Poor lung function increased the risk of dementia and mild cognitive impairment (MCI). Poor lung function accelerated the progression from MCI to dementia. Poor lung function was linked to brain microvascular damage and global brain atrophy.

Prediction of dementia risk from multimodal repeated measures: The added value of brain MRI biomarkers.

The utility of brain magnetic resonance imaging (MRI) for predicting dementia is debated. We evaluated the added value of repeated brain MRI, including atrophy and cerebral small vessel disease markers, for dementia prediction. We conducted a landmark competing risk analysis in 1716 participants of the French population-based Three-City Study to predict the 5-year risk of dementia using repeated measures of 41 predictors till year 4 of follow-up. Brain MRI markers improved significantly the individual prediction of dementia after accounting for demographics, health measures, and repeated measures of cognition and functional dependency (area under the ROC curve [95% CI] improved from 0.80 [0.79 to 0.82] to 0.83 [0.81 to 0.84]). Nonetheless, accounting for the change over time through repeated MRIs had little impact on predictive abilities. These results highlight the importance of multimodal analysis to evaluate the added predictive abilities of repeated brain MRI for dementia and offer new insights into the predictive performances of various MRI markers. We evaluated whether repeated brain volumes and cSVD markers improve dementia prediction.The 5-year prediction of dementia is slightly improved when considering brain MRI markers.Measures of hippocampus volume are the main MRI predictors of dementia.Adjusted on cognition, repeated MRI has poor added value over single MRI for dementia prediction.We utilized a longitudinal analysis that considers error-and-missing-prone predictors, and competing death.

Utility of multimodal longitudinal imaging data for dynamic prediction of cardiovascular and renal disease: the CARDIA study.

Medical examinations contain repeatedly measured data from multiple visits, including imaging variables collected from different modalities. However, the utility of such data for the prediction of time-to-event is unknown, and only a fraction of the data is typically used for risk prediction. We hypothesized that multimodal longitudinal imaging data could improve dynamic disease prognosis of cardiovascular and renal disease (CVRD). In a multi-centered cohort of 5,114 CARDIA participants, we included 166 longitudinal imaging variables from five imaging modalities: Echocardiography (Echo), Cardiac and Abdominal Computed Tomography (CT), Dual-Energy x-ray Absorptiometry (DEXA), Brain Magnetic Resonance Imaging (MRI) collected from young adulthood to mid-life over 30 years (1985-2016) to perform dynamic survival analysis of CVRD events using machine learning dynamic survival analysis (Dynamic-DeepHit, LTRCforest, and Extended Cox for Time-varying Covariates). Risk probabilities were continuously updated as new data were collected. Model performance was assessed using integrated AUC and C-index and compared to traditional risk factors. Longitudinal imaging data, even when being irregularly collected with high missing rates, improved CVRD dynamic prediction (0.03 in integrated AUC, up to 0.05 in C-index compared to traditional risk factors; best model's C-index = 0.80-0.83 up to 20 years from baseline) from young adulthood followed up to midlife. Among imaging variables, Echo and CT variables contributed significantly to improved risk estimation. Echo measured in early adulthood predicted midlife CVRD risks almost as well as Echo measured 10-15 years later (0.01 C-index difference). The most recent CT exam provided the most accurate prediction for short-term risk estimation. Brain MRI markers provided additional information from cardiac Echo and CT variables that led to a slightly improved prediction. Longitudinal multimodal imaging data readily collected from follow-up exams can improve CVRD dynamic prediction. Echocardiography measured early can provide a good long-term risk estimation, while CT/calcium scoring variables carry atherosclerotic signatures that benefit more immediate risk assessment starting in middle-age.

Periodontitis and brain magnetic resonance imaging markers of Alzheimer's disease and cognitive aging.

We examined the association of clinical, microbiological, and host response features of periodontitis with MRI markers of atrophy/cerebrovascular disease in the Washington Heights Inwood Columbia Aging Project (WHICAP) Ancillary Study of Oral Health. We analyzed 468 participants with clinical periodontal data, microbial plaque and serum samples, and brain MRIs. We tested the association of periodontitis features with MRI features, after adjusting for multiple risk factors for Alzheimer's disease/Alzheimer's disease-related dementia (AD/ADRD). In fully adjusted models, having more teeth was associated with lower odds for infarcts, lower white matter hyperintensity (WMH) volume, higher entorhinal cortex volume, and higher cortical thickness. Higher extent of periodontitis was associated with lower entorhinal cortex volume and lower cortical thickness. Differential associations emerged between colonization by specific bacteria/serum antibacterial IgG responses and MRI outcomes. In an elderly cohort, clinical, microbiological, and serological features of periodontitis were associated with MRI findings related to ADRD risk. Further investigation of causal associations is warranted.

Quantitative Analysis of Retinal Perfusion in Patients with Frontotemporal Dementia Using Optical Coherence Tomography Angiography.

Optical coherence tomography angiography (OCT-A) provides detailed visualization of the perfusion of the vascular network of the eye. While in other forms of dementia, such as Alzheimer's disease and mild cognitive impairment, reduced retinal perfusion was frequently reported, data of patients with frontotemporal dementia (FTD) are lacking. Retinal and optic nerve head perfusion was evaluated in patients with FTD with OCT-A. Quantitative OCT-A metrics were analyzed and correlated with clinical markers and vascular cerebral lesions in FTD patients. OCT-A was performed in 18 eyes of 18 patients with FTD and 18 eyes of 18 healthy participants using RTVue XR Avanti with AngioVue. In addition, patients underwent a detailed ophthalmological, neurological, and neuropsychological examination, cerebral magnetic resonance imaging (MRI), and lumbar puncture. The flow density in the optic nerve head (ONH) and in the superficial capillary plexus (SCP) of the macula of patients was significantly lower compared to that of healthy controls (p < 0.001). Similarly, the VD in the deep capillary plexus (DCP) of the macula of patients was significantly lower compared to that of healthy controls (p < 0.001). There was no significant correlation between the flow density data, white matter lesions in brain MRI, cognitive deficits, and cerebrospinal fluid markers of dementia. Patients with FTD showed a reduced flow density in the ONH, and in the superficial and deep retinal capillary plexus of the macula, when compared with that of healthy controls. Quantitative analyses of retinal perfusion using OCT-A may therefore help in the diagnosis and monitoring of FTD. Larger and longitudinal studies are necessary to evaluate if OCT-A is a suitable biomarker for patients with FTD.

Heart rate fragmentation and brain MRI markers of small vessel disease in MESA.

Heart rate (HR) fragmentation indices quantify breakdown of HR regulation and are associated with atrial fibrillation and cognitive impairment. Their association with brain magnetic resonance imaging (MRI) markers of small vessel disease is unexplored. In 606 stroke-free participants of the Multi-Ethnic Study of Atherosclerosis (mean age 67), HR fragmentation indices including percentage of inflection points (PIP) were derived from sleep study recordings. We examined PIP in relation to white matter hyperintensity (WMH) volume, total white matter fractional anisotropy (FA), and microbleeds from 3-Tesla brain MRI completed 7 years later. In adjusted analyses, higher PIP was associated with greater WMH volume (14% per standard deviation [SD], 95% confidence interval [CI]: 2, 27%, P=0.02) and lower WM FA (-0.09 SD per SD, 95% CI: -0.16, -0.01, P=0.03). HR fragmentation was associated with small vessel disease. HR fragmentation can be measured automatically from ambulatory electrocardiogram devices and may be useful as a biomarker of vascular brain injury.

Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk.

Cancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD). In the UK Biobank, we investigated associations between cancer history and five structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed-effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution of MRI markers. Cancer history was associated with smaller mean hippocampal volume (b=-19 mm3 , 95% CI=-36, -1) and lower mean cortical thickness in the Alzheimer's disease signature region (b=-0.004 mm, 95% CI=-0.007, -0.000). Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history. Some brain MRI markers associated with ADRD risk were elevated in adults with a history of cancer. The magnitude of the adverse associations varied across quantiles of neuroimaging markers, and the pattern suggests possible harmful associations for individuals already at high ADRD risk. We found no evidence of an inverse association between cancer history and ADRD-related neurodegeneration. Cancer history was associated with smaller mean hippocampal volume and lower mean cortical thickness in the Alzheimer's disease signature region. Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.

Optical coherence tomography versus other biomarkers: Associations with physical and cognitive disability in multiple sclerosis

Background: Optical coherence tomography (OCT) is a biomarker of neuroaxonal loss in multiple sclerosis (MS). Objective: The objective was to assess the relative role of OCT, next to magnetic resonance imaging (MRI) and serum markers of disability in MS. Methods: A total of 100 patients and 52 controls underwent OCT to determine peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layers (GCIPL). Serum neurofilament light chain (sNfL), total lesion volume (TLV), and brain parenchymal fraction (BPF) were also assessed. The associations of OCT with disability were examined in linear regression models with correction for age, vision, and education. Results: In patients, pRNFL was associated with the Symbol Digit Modalities Test (SDMT; p = 0.030). In the multivariate analysis including sNfL and MRI measures, pRNFL (β = 0.19, p = 0.044) and TLV (β = −0.24, p = 0.023) were the only markers associated with the SDMT. pRNFL (p < 0.001) and GCIPL (p < 0.001) showed associations with the Expanded Disability Status Scale (EDSS). In the multivariate analysis, GCIPL showed the strongest association with the EDSS (β = −0.32, p < 0.001) followed by sNfL (β = 0.18, p = 0.024). Conclusion: The associations of OCT measures with cognitive and physical disability were independent of serum and brain MRI markers of neuroaxonal loss. OCT can be an important tool for stratification in MS, while longitudinal studies using combinations of biomarkers are warranted.

Associations between dietary patterns and structural neuroimaging markers of relevance for dementia

AbstractBackgroundDiet is a lifestyle factors that could influence the risk of developing dementia. However, the impact of diet on the brain is not fully understood. Investigating associations between dietary patterns and neuroimaging markers of relevance for dementia could potentially increase this understanding.MethodThis study includes cross‐sectional data from the population‐based Gothenburg H70 Birth Cohort Studies, Sweden, including 610 dementia‐free 70‐year‐olds (born 1944, examined 2014‐16) with dietary and magnetic resonance imaging (MRI) data (54% women). Three dietary patterns were derived with principal component analysis, a western‐like pattern (e.g., refined cereal products, sweets, savory bakery/fast food), a Mediterranean‐like pattern (e.g., vegetables, fruits, whole grain cereal products) and a low‐fiber and high‐alcohol pattern (e.g., red meat/processed red meat, eggs, alcoholic beverages). Brain MRI markers were of overall neurodegeneration (i.e., mean cortical thickness), Alzheimer’s disease (AD) neurodegeneration (based on cortical thickness of AD‐signature areas), and vascular brain pathology including early abnormalities in the white matter microstructure (derived from diffusion tensor imaging) and small vessel disease (presence of white matter hyperintensities, lacunes, cerebral microbleeds, and/or perivascular spaces). In data analysis, linear and ordinal regression models were adjusted for sex, energy intake, educational level, physical activity level, smoking and body mass index.ResultResults from this study showed a positive association between higher adherence to the Mediterranean‐like dietary pattern and higher white matter microstructural integrity (B 0.077; 95% CI 0.002 – 0.153). Moreover, a higher adherence to the low‐fibre and high‐alcohol dietary pattern was negatively associated with total mean cortical thickness (B ‐0.011; 95% CI ‐0.019 – ‐0.003) and an AD signature of cortical thickness (mean entorhinal, inferior temporal, middle temporal, and fusiform thickness) (B ‐0.013; 95% CI ‐0.024 – ‐0.001) in the fully adjusted models. No associations were found between the dietary patterns and the small vessel disease markers. Nor were there any associations between the western‐like dietary pattern and the MRI markers.ConclusionThis study suggests that there may be an association between certain dietary patterns and dementia‐related alterations. These findings could be of importance for dementia prevention strategies and for future intervention studies investigating the effect of dietary patterns in relation to dementia.

Association of inflammatory proteins with cognitive aging, brain MRI markers, and incident dementia

AbstractBackgroundInflammatory cytokines and chemokines related to the innate and adaptive immune system have been linked to neuroinflammation in Alzheimer’s Disease (AD) dementia. We hypothesized that individual blood‐based inflammatory biomarkers would associate with cognitive function, brain magnetic resonance imaging (MRI) volumes, and risk for dementia in Framingham Heart Study (FHS) participants.MethodProtein biomarkers related to immune cells or associated with inflammatory responses including CD14, CD163, CD5L, CD56, CD40L, CXCL16, SDF1, DPP4, SGP130, sRAGE, and MPO were measured at FHS Offspring exam 7. We identified FHS Offspring participants who underwent neuropsychological (NP) testing (n = 2394) or brain MRI (n = 2135) within five years of the examination; and who were followed up 10 years after age 60 for incident all‐cause dementia (n = 1650). We used linear mixed effect models accounting for family relationships to investigate the associations between the protein biomarkers and NP test performance and brain MRI volumes and Cox proportional hazards models to examine the association with incident dementia. A false discovery rate (FDR) within each outcome set was computed to adjust for multiple testing and FDR ≤ 0.1 indicated significance.ResultParticipants from the NP and MRI samples were on average 61 years old and 54% female. Participants from the incident dementia sample (mean age 68 years) included 126 incident dementia cases within 10 years. In addition to CD14 which has an established association, we observed significant associations between higher CD40L and MPO with poorer NP performance from the executive function domain. Higher CD5L levels were significantly associated with smaller total brain volumes (TCBV), whereas higher sRAGE was associated with larger TCBV. Associations persisted after further adjusting for APOE ϵ4 carrier status and cardiovascular risk factors. None of the protein biomarkers included were significantly associated with risk of incident dementia, with trend towards an association for CD5L.ConclusionSince the proinflammatory factors CD5L, CD40L, sRAGE and MPO are associated with immune cells and are involved in vascular pathology, our study suggests the immune‐vascular axis is associated with cognitive and brain aging. If confirmed in other samples, our findings may provide informative biomarkers of abnormal brain aging.

Twenty-four-hour ambulatory blood pressure variability and association with ischemic stroke subtypes in the subacute stage.

Blood pressure (BP) variability (BPV) increases the risk of cerebral disease in both hemorrhagic and ischemic strokes. However, whether BPV is associated with different types of ischemic stroke remains unclear. In this study, we explored the relationship between BPV and ischemic stroke subtypes. We enrolled consecutive patients aged 47-95 years with ischemic stroke in the subacute stage. We categorized them into four groups based on their artery atherosclerosis severity, brain magnetic resonance imaging markers, and disease history: large-artery atherosclerosis, branch atheromatous disease, small-vessel disease, and cardioembolic stroke. Twenty-four-hour ambulatory blood pressure monitoring was performed, and the mean systolic blood pressure/diastolic blood pressure, standard deviation, and coefficient of variation were calculated. A multiple logistic regression model and random forest were used to test the relationship between BP and BPV in the different types of ischemic stroke. A total of 286 patients, including 150 men (73.0 ± 12.3 years) and 136 women (77.8 ± 9.6 years) were included in the study. Of these, 86 (30.1%) patients had large-artery atherosclerosis, 76 (26.6%) had branch atheromatous disease, 82 (28.7%) had small-vessel disease, and 42 (14.7%) had cardioembolic stroke. There were statistically significant differences in BPV between subtypes of ischemic stroke in 24-h ambulatory blood pressure monitoring. The random forest model showed that BP and BPV were important features associated with ischemic stroke. Multinomial logistic regression analysis demonstrated that systolic blood pressure levels; systolic blood pressure variability at 24 h, daytime and nighttime; and nighttime diastolic blood pressure were independent risk factors for large-artery atherosclerosis after adjustment for confounders. When compared to branch atheromatous disease and small-vessel disease, nighttime diastolic blood pressure and standard deviation of diastolic blood pressure were significantly associated with patients in the cardioembolic stroke group. However, a similar statistical difference was not seen in patients with large-artery atherosclerosis. The results of this study indicate a discrepancy in blood pressure variability among different ischemic stroke subtypes during the subacute stage. Higher systolic blood pressure and systolic blood pressure variability during the 24 h, daytime, and nighttime, and nighttime diastolic blood pressure were independent predictors for large-artery atherosclerosis stroke. Increased nighttime diastolic BPV was an independent risk factor for cardioembolic stroke.

Higher Dietary Inflammatory Index scores are associated with brain MRI markers of brain aging: Results from the Framingham Heart Study Offspring cohort.

We investigated cross-sectional associations between the Dietary Inflammatory Index (DII) and measures of brain volume and cerebral small vessel disease among participants of the Framingham Heart Study Offspring cohort. A total of 1897 participants (mean ± standard deviation, age 62±9) completed Food Frequency Questionnaires and brain magnetic resonance imaging (MRI). Higher (pro-inflammatory) DII scores, averaged across a maximum of three time points, were associated with smaller total brain volume (beta ± standard error: -0.16 ± 0.03; P < .0001) after adjustment for demographic, clinical, and lifestyle covariates. In addition, higher DII scores were associated with smaller total gray matter volume (-0.08 ± 0.03; P = .003) and larger lateral ventricular volume (0.04 ± 0.02; P = .03). No associations were observed with other brain MRI measures. Our findings showed associations between higher DII scores and global brain MRI measures. As we are one of the first groups to report on the associations between higher DII scores and brain volume, replication is needed to confirm our findings.

The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy.

ABSTRACTBackgroundThe second consensus criteria for the diagnosis of multiple system atrophy (MSA) are widely recognized as the reference standard for clinical research, but lack sensitivity to diagnose the disease at early stages.ObjectiveTo develop novel Movement Disorder Society (MDS) criteria for MSA diagnosis using an evidence‐based and consensus‐based methodology.MethodsWe identified shortcomings of the second consensus criteria for MSA diagnosis and conducted a systematic literature review to answer predefined questions on clinical presentation and diagnostic tools relevant for MSA diagnosis. The criteria were developed and later optimized using two Delphi rounds within the MSA Criteria Revision Task Force, a survey for MDS membership, and a virtual Consensus Conference.ResultsThe criteria for neuropathologically established MSA remain unchanged. For a clinical MSA diagnosis a new category of clinically established MSA is introduced, aiming for maximum specificity with acceptable sensitivity. A category of clinically probable MSA is defined to enhance sensitivity while maintaining specificity. A research category of possible prodromal MSA is designed to capture patients in the earliest stages when symptoms and signs are present, but do not meet the threshold for clinically established or clinically probable MSA. Brain magnetic resonance imaging markers suggestive of MSA are required for the diagnosis of clinically established MSA. The number of research biomarkers that support all clinical diagnostic categories will likely grow.ConclusionsThis set of MDS MSA diagnostic criteria aims at improving the diagnostic accuracy, particularly in early disease stages. It requires validation in a prospective clinical and a clinicopathological study. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Abstract P007: Liver Biomarkers And Brain Health: The Atherosclerosis Risk In Communities (aric) Study

Introduction: Animal studies and emerging population data link liver function and integrity to brain health, although mostly based on cross-sectional estimates. We reported that low liver transaminases are associated with risk of dementia, but prospective studies on liver biomarkers and altered brain morphology are lacking. Methods: We studied 1,596 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort examined in 1996-98 (mean age: 62 years, 59% female, 27% Black) free of chronic liver disease, cirrhosis, and stroke, and with alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio ≤2. Brain magnetic resonance imaging (MRI) scans were performed in 2011-13, at the time of re-examination. Serum transaminases (ALT, AST) and gamma-glutamyl transferase (GGT) at baseline were analyzed as sex-specific quintiles, with the first quintile further subdivided into a &lt;10 th and 10 th -20 th percentiles to allow for nonlinear associations at low biomarker levels. Brain MRI markers were measured with 3 Tesla MRI. Multinomial logistic and linear regressions were used, adjusted for demographics and APOE-ε4. Results: Monotonic associations were observed between higher GGT levels and smaller cortical volume and temporal lobe volume meta regions of interest (Figure) . The lowest GGT levels were associated with smaller volumes of white matter hyperintensities. In contrast, associations of transaminases with brain morphological measures were inconclusive. Conclusions: GGT levels measured in late mid-life are associated vascular sequelae on brain MRI among older adults. As a potent regulator of antioxidant capacity and a predictor of atherosclerosis, GGT may point to vascular pathways that influence brain health. The lack of association between low transaminases and brain MRI findings suggests non-vascular pathways for their association with incident dementia. A deeper understanding of the links between hepatic metabolic dysregulation and brain health is warranted.

The relationship between cognitive and social leisure activities across the lifespan and neural markers for brain health: A systematic literature review

AbstractBackgroundCognitive and social leisure activities (CA/SA) as well as social network size (SNS) have been associated with performance on cognitive tasks and lower dementia risk. However, the neural mechanisms behind these associations remain unclear. Therefore, this systematic literature review aims at summarizing the available evidence on these associations across the adult lifespan.MethodMEDLINE, PsychINFO, CINAHL and the Cochrane Library of Controlled Trials were searched for potential publications until January 2021. Eligible studies included those with cognitively normal individuals older than 18 years, and assessed the direct association between CA/SA or SNS and brain structure. CA/SA were defined as those cognitively and/or socially stimulating activities being performed for the sake of pleasure. Eligible outcome measures included magnetic resonance imaging (MRI) of macro (grey/white matter volumes) and micro (diffusion tensor imaging) structure, or computerized tomography (CT). Both observational and (quasi)experimental designs were included. Study‐quality was assessed using the NIH tool for study quality appraisal and the Newcastle‐Ottawa Scale. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. A full protocol is available in PROSPERO (CRD42020193278).Result6115 unique abstracts were identified and screened by two independent raters. Sixty‐six full‐text articles were retained for further appraisal, of which thirty‐five (0.6%) were included for qualitative analysis. Of those, 20 cross‐sectional, 4 cohort and 3 experimental studies investigated the association between CA/SA and brain structure. Eight cross‐sectional studies investigated the relationship between social network size and brain structure. All studies included in this review used structural MRI (3 used DTI) as outcome measure. In the majority of studies, CA/SA and SNS showed associations with structural brain MRI markers. Detailed results of this ongoing review and possible meta‐analysis will be presented.ConclusionCA and SA are associated with structural MRI markers.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Prediabetes and diabetes accelerate cognitive decline and predict microvascular lesions: A population-based cohort study

IntroductionThe impact of prediabetes and diabetes on cognitive decline and the potential underlying mechanisms remain unclear. We investigated whether prediabetes and diabetes accelerate cognitive decline and brain aging, and the initial pathological changes linked to microvascular processes. MethodsNine-year longitudinal data from the Swedish National Study on Aging and Care-Kungsholmen (n = 2746, age ≥60 years) and the magnetic resonance imaging subsample (n = 455) were used. Cognitive function was assessed with Mini-Mental State Examination. Brain magnetic resonance imaging markers included total brain tissue, white matter, gray matter, white matter hyperintensities, and hippocampal volumes. ResultsCompared with diabetes-free status, prediabetes and diabetes were independently associated with accelerated cognitive decline. Prediabetes was cross-sectionally associated with smaller total brain tissue volume (P < .01), particularly smaller white matter volume. Diabetes was associated with larger white matter hyperintensities volume. Longitudinally, diabetes was associated with faster white matter hyperintensities accumulation. No associations between prediabetes or diabetes and hippocampal volume were found. DiscussionDiabetes and prediabetes accelerate cognitive decline and might predict microvascular lesions among dementia-free older adults.

Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease: The Atherosclerosis Risk in Communities Study.

It is currently unclear whether midlife systemic inflammation promotes the development of white matter (WM) abnormalities and small vessel disease in the elderly. We examined the association of midlife systemic inflammation with late-life WM hyperintensity volume, deep and periventricular WM microstructural integrity (fractional anisotropy and mean diffusivity [MD]), cerebral infarcts, and microbleeds in a biracial prospective cohort study. Linear and logistic regression examined the relation between midlife high-sensitivity C-reactive protein (CRP)-a nonspecific marker of inflammation-and brain magnetic resonance imaging markers assessed 21 years later in the Atherosclerosis Risk in Communities Study. We included 1485 participants (baseline age, 56[5]; 28% black). After adjusting for demographic factors and cardiovascular disease, each SD increase in midlife CRP was associated with lower fractional anisotropy (-0.09 SD; 95% confidence interval, -0.15 to -0.02) and greater MD (0.08 SD; 95% confidence interval, 0.03-0.15) in deep WM and lower fractional anisotropy (-0.07 SD; 95% confidence interval, -0.13 to 0.00) in periventricular WM. We found stronger associations between CRP and periventricular WM microstructural integrity among black participants (P interaction=0.011). Although an association between higher CRP levels and greater WM hyperintensity volume was found only among APOE ε4-positive participants in our primary analysis (0.14 SD; 95% confidence interval, 0.01-0.26; P interaction=0.028), this relationship extended to the entire sample after accounting for differential attrition. Midlife CRP was not associated with the presence of cerebral infarcts or microbleeds in late life. Our findings support the hypothesis that midlife systemic inflammation may promote the development of chronic microangiopathic structural WM abnormalities in the elderly.

P 1 Effect of ocrelizumab on magnetic resonance imaging markers of neurodegeneration in patients with relapsing multiple sclerosis – analysis of the phase III, double-blind, double-dummy, interferon beta-1a- controlled OPERA I and OPERA II studies

Background Ocrelizumab (OCR) is a humanised monoclonal antibody that selectively targets CD20+B cells. The pathogenesis of multiple sclerosis (MS), including neurodegeneration, is thought to be influenced by B cells. Volumetric magnetic resonance imaging (MRI) measurements can be used to assess neurodegeneration. Objective To evaluate the effect of OCR vs interferon beta-1a (IFN β -1a) on brain MRI markers of neurodegeneration in patients with relapsing MS enrolled in two identical Phase III, randomised, double-blind, double-dummy trials (OPERA I and OPERA II). Methods In OPERA I and OPERA II, patients were randomised (1:1) to receive OCR 600 mg via intravenous infusion every 24 weeks or subcutaneous IFN β -1a 44 μ g three-times weekly over 96 weeks. MRI endpoints thought to be related to neurodegeneration included the change in whole brain volume, change in cortical grey matter volume and change in cerebral white matter volume. Results Compared with IFN β -1a, OCR reduced the rate of whole brain volume loss from baseline to Week 96 by 23.5% ( p p = 0.0001), and from Week 24 to Week 96 by 22.8% ( p = 0.0042) and 14.9% ( p = 0.0900) in OPERA I and OPERA II, respectively. OCR-treated patients showed a smaller mean percentage of cortical grey matter volume loss compared with IFN β -1a from baseline to Week 96, with a mean difference of 0.273% ( p = 0.0005) in OPERA I and 0.516% ( p β -1a from baseline to Week 96, with a mean difference of 0.261% ( p = 0.0024); in OPERA II, there was no difference ( p = 0.2748) in cerebral white matter volume loss in patients treated with OCR compared with IFN β -1a from baseline to Week 96. Conclusion The rate of neurodegeneration as measured by whole brain, cortical grey and cerebral white matter volume loss on MRI was reduced by OCR compared with IFN β -1a in patients with relapsing MS over 96 weeks. This study is sponsored by F. Hoffmann-La Roche Ltd.

Retinal Microvascular Calibers Are Associated With Enlarged Perivascular Spaces in the Brain.

Perivascular enlargement in the brain is a putative imaging marker for microvascular brain damage, but this link has not yet been confirmed using direct in vivo visualization of small vessels. We investigated the relation between microvascular calibers on retinal imaging and enlarged perivascular spaces (ePVSs) on brain magnetic resonance imaging. We included 704 participants from the Rotterdam study. Retinal arteriolar and venular calibers were measured semiautomatically on fundus photographs. ePVSs were counted in the centrum semiovale, basal ganglia, hippocampus, and mesencephalon, using a standardized rating method. We determined the association between retinal microvascular calibers and ePVSs with negative binomial regression models, adjusting for age, sex, the other vascular caliber, structural brain magnetic resonance imaging markers, and cardiovascular risk factors. Both narrower arteriolar and wider venular calibers were associated with more ePVSs in the centrum semiovale and hippocampal region. Rate ratios (95% confidence interval) for arterioles in the centrum semiovale and hippocampus were 1.07 (1.01-1.14) and 1.13 (1.04-1.22), respectively, and for venules 1.08 (1.01-1.16) and 1.09 (1.00-1.18), respectively. These associations were independent from other brain magnetic resonance imaging markers and cardiovascular risk factors. Retinal microvascular calibers are related to ePVSs, confirming the putative link between microvascular damage and ePVSs.