646Coffee, Brain Volume and Risk of Dementia and Stroke

Abstract Background Coffee is a highly popular beverage worldwide, containing caffeine which is a central nervous system stimulant. The aim was to examine whether habitual coffee consumption is associated with differences in brain volumes or the risk odds of dementia or stroke. Methods Prospective analyses of habitual coffee consumption were conducted in 398,646 participants (age 37-73 years) within the UK Biobank, including 17,702 participants with volumetric MRI information. We examined associations between coffee consumption and brain volume using covariate adjusted linear regression, and with odds of dementia and stroke using logistic regression. All participants were free of dementia and stroke at baseline. We obtained 4,333 incident dementia and 6,181 incident stroke cases. Results There were inverse linear associations between coffee consumption and total brain (β per cup -1·42, p = 1·4x10-8), grey matter (-0·92, p = 5·2x10-10), white matter (-0·50, p = 0·002) and hippocampal volumes (-0·01, p = 0·009), but no evidence to support associations with white matter hyperintensity volume (-0·01, p = 0·72). After full covariate adjustment, consumption of > 6 cups/day of coffee was associated with 53% higher odds of dementia compared to consumption of 1-2 cups/day (OR 1.53, 95% CI 1.28, 1.83), with less evidence for an association with stroke (OR 1.17, 95% CI 1.00, 1.37, p = 0.055). Conclusions High coffee consumption was associated with smaller total brain volumes and increased odds of dementia. Key messages The findings suggest caution at higher levels of coffee consumption, however further studies are required to establish causality, and to explore the clinical relevance of brain volume changes.

Download Full-text

Association of Air Pollution and Physical Activity With Brain Volumes

Neurology ◽

10.1212/wnl.0000000000013031 ◽

2021 ◽

pp. 10.1212/WNL.0000000000013031

Author(s):

Melissa A. Furlong ◽

Gene E. Alexander ◽

Yann C. Klimentidis ◽

David A. Raichlen

Keyword(s):

Physical Activity ◽

Air Pollution ◽

White Matter ◽

Multiple Testing ◽

Vigorous Physical Activity ◽

White Matter Hyperintensity ◽

Brain Volumes ◽

Negatively Associated ◽

Adult Participants ◽

The Uk

Objective:In high pollution areas, physical activity may have a paradoxical effect on brain health by increasing particulate deposition in the lungs. We examined whether physical activity modifies associations of air pollution with brain volumes in an epidemiological framework.Methods:The UK Biobank (UKB) enrolled >500,000 adult participants from 2006-2010. Wrist accelerometers, multimodal MRI with T1 images and T2 FLAIR data, and land use regression, were used to estimate vigorous physical activity (VigPA), structural brain volumes, and air pollution (AP) respectively in subsets of the full sample. We evaluated associations between AP interquartile ranges, VigPA, and brain structure volumes, and assessed interactions between AP and VigPA.Results:8,600 participants were included, with an average age of 55.55 (sd=7.46). After correcting for multiple testing, in overall models VigPA was positively associated with grey matter (GMV) and negatively associated with white matter hyperintensity volumes (WMHV), while NO2, PM2.5absorbance, and PM2.5 were negatively associated with GMV. NO2 and PM2.5absorbance interacted with VigPA on WMHV (FDR-corrected interaction p-values=0.037). Associations between these air pollutants and WMHVs were stronger among participants with high VigPA. Similarly, VigPA was negatively associated with WMHV for those in areas of low NO2 and PM2.5absorbance, but was null among those living in areas of high NO2 and PM2.5absorbance.Conclusions:Physical activity is associated with beneficial brain outcomes, while AP is associated with detrimental brain outcomes. Vigorous physical activity may exacerbate associations of AP with white matter hyperintensity lesions, and AP may attenuate the beneficial associations of physical activity with these lesions.

Download Full-text

Adiposity is related to cerebrovascular and brain volumetry outcomes in the RUN DMC study

Neurology ◽

10.1212/wnl.0000000000008002 ◽

2019 ◽

Vol 93 (9) ◽

pp. e864-e878 ◽

Cited By ~ 4

Author(s):

Ilse A.C. Arnoldussen ◽

Deborah R. Gustafson ◽

Esther M.C. Leijsen ◽

Frank-Erik de Leeuw ◽

Amanda J. Kiliaan

Keyword(s):

White Matter ◽

Brain Imaging ◽

Gray Matter ◽

Diffusion Tensor ◽

Hippocampal Volume ◽

White Matter Hyperintensity ◽

Brain Volumes ◽

Brain Volumetry ◽

Total Brain

ObjectiveAdiposity predictors, body mass index (BMI), waist circumference (WC), and blood leptin and total adiponectin levels were associated with components of cerebral small vessel disease (CSVD) and brain volumetry in 503 adults with CSVD who were ≥50 years of age and enrolled in the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC).MethodsRUN DMC participants were followed up for 9 years (2006–2015). BMI, WC, brain imaging, and dementia diagnoses were evaluated at baseline and follow-up. Adipokines were measured at baseline. Brain imaging outcomes included CSVD components, white matter hyperintensities, lacunes, microbleeds, gray and white matter, hippocampal, total brain, and intracranial volumes.ResultsCross-sectionally among men at baseline, higher BMI, WC, and leptin were associated with lower gray matter and total brain volumes, and higher BMI and WC were associated with lower hippocampal volume. At follow-up 9 years later, higher BMI was cross-sectionally associated with lower gray matter volume, and an obese WC (>102 cm) was protective for ≥1 lacune or ≥1 microbleed in men. In women, increasing BMI and overweight or obesity (BMI ≥25 kg/m2 or WC >88 cm) were associated with ≥1 lacune. Longitudinally, over 9 years, a baseline obese WC was associated with decreasing hippocampal volume, particularly in men, and increasing white matter hyperintensity volume in women and men.ConclusionsAnthropometric and metabolic adiposity predictors were differentially associated with CSVD components and brain volumetry outcomes by sex. Higher adiposity is associated with a vascular-neurodegenerative spectrum among adults at risk for vascular forms of cognitive impairment and dementias.

Download Full-text

White Matter is Increased in the Brains of Adults With Neurofibromatosis 1

10.21203/rs.3.rs-898452/v1 ◽

2021 ◽

Author(s):

Su Wang ◽

Jan M. Friedman ◽

Per Suppa ◽

Ralph Buchert ◽

Victor-Felix Mautner

Keyword(s):

White Matter ◽

Grey Matter ◽

Brain Volume ◽

Neurofibromatosis 1 ◽

Brain Morphology ◽

White Matter Volume ◽

Total Brain Volume ◽

Brain Volumes ◽

Matter Volume ◽

Total Brain

Abstract Background: Neurofibromatosis 1 (NF1) is a rare autosomal dominant disease characterized by increased Schwann cell proliferation in peripheral nerves. Several small studies of brain morphology in children with NF1 have found increased total brain volume, total white matter volume and/or corpus callosum area. Several studies (mostly in children with NF1) also attempted to correlate changes in brain morphology and volume with cognitive or behavioural abnormalities, though findings were inconsistent. We aimed to characterize alterations in brain volumes by three-dimensional (3D) MRI in adults with NF1 in major intracranial sub-regions. We also aimed to assess the effect of age on these volumes and correlated brain white matter and grey matter volumes with neuropsychometric findings in adults with NF1.Methods: We obtained brain volume measurements using 3D magnetic resonance imaging for 351 adults with NF1 and, as a comparison group, 43 adults with neurofibromatosis 2 (NF2) or Schwannomatosis. We assessed a subset of 19 adults with NF1 for clinical severity of NF1 features and neurological problems and conducted psychometric testing for attention deficiencies and intelligence quotient. We compared brain volumes between NF1 patients and controls and correlated volumetric measurements to clinical and psychometric features in the NF1 patients. Results:Total brain volume and total and regional white matter volumes were all significantly increased in adults with NF1. Grey matter volume decreased faster with age in adults with NF1 than in controls. Greater total brain volume and white matter volume were correlated with lower attention deficits and higher intelligence quotients in adults with NF1.Conclusion:Our findings are consistent with the hypothesis that dysregulation of brain myelin production is a cardinal manifestation of NF1 and that these white matter changes may be functionally important in affected adults.

Download Full-text

White Matter Hyperintensity Quantification in Large-Scale Clinical Acute Ischemic Stroke Cohorts – The MRI-GENIE Study

10.1101/552844 ◽

2019 ◽

Cited By ~ 2

Author(s):

Markus D. Schirmer ◽

Adrian V. Dalca ◽

Ramesh Sridharan ◽

Anne-Katrin Giese ◽

Kathleen L. Donahue ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Large Scale ◽

Brain Volume ◽

Expert Knowledge ◽

White Matter Hyperintensity ◽

Total Brain Volume ◽

Brain Extraction ◽

Total Brain

AbstractWhite matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype linked to prediction of diagnosis and prognosis of diseases, such as acute ischemic stroke (AIS). However, current approaches to its quantification on clinical MRI often rely on time intensive manual delineation of the disease on T2 fluid attenuated inverse recovery (FLAIR), which hinders high-throughput analyses such as genetic discovery.In this work, we present a fully automated pipeline for quantification of WMH in clinical large-scale studies of AIS. The pipeline incorporates automated brain extraction, intensity normalization and WMH segmentation using spatial priors. We first propose a brain extraction algorithm based on a fully convolutional deep learning architecture, specifically designed for clinical FLAIR images. We demonstrate that our method for brain extraction outperforms two commonly used and publicly available methods on clinical quality images in a set of 144 subject scans across 12 acquisition centers, based on dice coefficient (median 0.95; inter-quartile range 0.94-0.95) and Pearson correlation of total brain volume (r=0.90). Subsequently, we apply it to the large-scale clinical multi-site MRI-GENIE study (N=2783) and identify a decrease in total brain volume of -2.4cc/year. Additionally, we show that the resulting total brain volumes can successfully be used for quality control of image preprocessing.Finally, we obtain WMH volumes by building on an existing automatic WMH segmentation algorithm that delineates and distinguishes between different cerebrovascular pathologies. The learning method mimics expert knowledge of the spatial distribution of the WMH burden using a convolutional auto-encoder. This enables successful computation of WMH volumes of 2,533 clinical AIS patients. We utilize these results to demonstrate the increase of WMH burden with age (0.950 cc/year) and show that single site estimates can be biased by the number of subjects recruited.

Download Full-text

White Matter is Increased in the Brains of Adults with Neurofibromatosis 1

10.1101/2021.06.13.21258853 ◽

2021 ◽

Author(s):

Su Wang ◽

Jan M Friedman ◽

Per Suppa ◽

Ralph Buchert ◽

Victor-Felix Mautner

Keyword(s):

White Matter ◽

Brain Volume ◽

Psychometric Testing ◽

Neurofibromatosis 1 ◽

Clinical Severity ◽

Grey Matter Volume ◽

Total Brain Volume ◽

Brain Volumes ◽

Matter Volume ◽

Total Brain

Objective: To characterize alterations in brain volumes by three-dimensional (3D) MRI in adults with neurofibromatosis 1 (NF1). Methods: We obtained brain volume measurements using 3D magnetic resonance imaging for 351 adults with NF1 and, as a comparison group, 43 adults with neurofibromatosis 2 (NF2) or Schwannomatosis. We assessed a subset of 19 adults with NF1 for clinical severity of NF1 features and neurological problems and conducted psychometric testing for attention deficiencies and intelligence quotient. We compared brain volumes between NF1 patients and controls and correlated volumetric measurements to clinical and psychometric features in the NF1 patients. Results: Total brain volume and total and regional white matter volumes were all significantly increased in adults with NF1. Grey matter volume decreased faster with age in adults with NF1 than in controls. Greater total brain volume and white matter volume were correlated with lower attention deficits and higher intelligence quotients in adults with NF1. Interpretations: Our findings are consistent with the hypothesis that dysregulation of brain myelin production is a cardinal manifestation of NF1 and that these white matter changes may be functionally important in affected adults.

Download Full-text

Postnatal Decrease in Circulating Insulin-Like Growth Factor-I and Low Brain Volumes in Very Preterm Infants

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-2440 ◽

2011 ◽

Vol 96 (4) ◽

pp. 1129-1135 ◽

Cited By ~ 39

Author(s):

Ingrid Hansen-Pupp ◽

Holger Hövel ◽

Ann Hellström ◽

Lena Hellström-Westas ◽

Chatarina Löfqvist ◽

...

Keyword(s):

White Matter ◽

Magnetic Resonance ◽

Preterm Infants ◽

Brain Volumes ◽

Very Preterm Infants ◽

Very Preterm ◽

Matter Volume ◽

Total Brain ◽

Igf I ◽

Igfbp 3

Abstract Context: IGF-I and IGF binding protein-3 (IGFBP-3) are essential for growth and maturation of the developing brain. Objective: The aim of this study was to evaluate the association between postnatal serum concentrations of IGF-I and IGFBP-3 and brain volumes at term in very preterm infants. Design: Fifty-one infants with a mean (sd) gestational age (GA) of 26.4 (1.9) wk and birth weight (BW) of 888 (288) g were studied, with weekly blood sampling of IGF-I and IGFBP-3 from birth until 35 gestational weeks (GW) and daily calculation of protein and caloric intake. Magnetic resonance images obtained at 40 GW were segmented into total brain, cerebellar, cerebrospinal fluid, gray matter, and unmyelinated white matter volumes. Main Outcome Measures: We evaluated brain growth by measuring brain volumes using magnetic resonance imaging. Results: Mean IGF-I concentrations from birth to 35 GW correlated with total brain volume, unmyelinated white matter volume, gray matter volume, and cerebellar volume [r = 0.55 (P < 0.001); r = 0.55 (P < 0.001); r = 0.44 (P = 0.002); and r = 0.58 (P < 0.001), respectively]. Similar correlations were observed for IGFBP-3 concentrations. Correlations remained after adjustment for GA, mean protein and caloric intakes, gender, severe brain damage, and steroid treatment. Protein and caloric intakes were not related to brain volumes. Infants with BW small for GA had lower mean concentrations of IGF-I (P = 0.006) and smaller brain volumes (P = 0.001–0.013) than infants with BW appropriate for GA. Conclusion: Postnatal IGF-I and IGFBP-3 concentrations are positively associated with brain volumes at 40 GW in very preterm infants. Normalization of the IGF-I axis, directly or indirectly, may support normal brain development in very preterm infants.

Download Full-text

Cognition, structural brain changes and complicated grief. A population-based study

Psychological Medicine ◽

10.1017/s0033291714002499 ◽

2014 ◽

Vol 45 (7) ◽

pp. 1389-1399 ◽

Cited By ~ 20

Author(s):

H. C. Saavedra Pérez ◽

M. A. Ikram ◽

N. Direk ◽

H. G. Prigerson ◽

R. Freak-Poli ◽

...

Keyword(s):

White Matter ◽

Brain Volume ◽

Complicated Grief ◽

Population Based ◽

Word Fluency ◽

Total Brain Volume ◽

Population Based Study ◽

Total Brain ◽

Fluency Task ◽

Structural Brain

BackgroundSeveral psychosocial risk factors for complicated grief have been described. However, the association of complicated grief with cognitive and biological risk factors is unclear. The present study examined whether complicated grief and normal grief are related to cognitive performance or structural brain volumes in a large population-based study.MethodThe present research comprised cross-sectional analyses embedded in the Rotterdam Study. The study included 5501 non-demented persons. Participants were classified as experiencing no grief (n = 4731), normal grief (n = 615) or complicated grief (n = 155) as assessed with the Inventory of Complicated Grief. All persons underwent cognitive testing (Mini-Mental State Examination, Letter–Digit Substitution Test, Stroop Test, Word Fluency Task, word learning test – immediate and delayed recall), and magnetic resonance imaging to measure general brain parameters (white matter, gray matter), and white matter lesions. Total brain volume was defined as the sum of gray matter plus normal white matter and white matter lesion volume. Persons with depressive disorders were excluded and analyses were adjusted for depressive symptoms.ResultsCompared with no-grief participants, participants with complicated grief had lower scores for the Letter–Digit Substitution Test [Z-score −0.16 v. 0.04, 95% confidence interval (CI) −0.36 to −0.04, p = 0.01] and Word Fluency Task (Z-score −0.15 v. 0.03, 95% CI −0.35 to −0.02, p = 0.02) and smaller total volumes of brain matter (933.53 ml v. 952.42 ml, 95% CI −37.6 to −0.10, p = 0.04).ConclusionsParticipants with complicated grief performed poorly in cognitive tests and had a smaller total brain volume. Although the effect sizes were small, these findings suggest that there may be a neurological correlate of complicated grief, but not of normal grief, in the general population.

Download Full-text

Abstract P420: Alcohol Consumption and Longitudinal Changes in Magnetic Resonance Imaging-defined Brain Abnormalities: The Cardiovascular Health Study

Circulation ◽

10.1161/circ.141.suppl_1.p420 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Simona Costanzo ◽

Traci M Bartz ◽

Giovanni de Gaetano ◽

Augusto F Di Castelnuovo ◽

Licia Iacoviello ◽

...

Keyword(s):

White Matter ◽

Alcohol Consumption ◽

Brain Atrophy ◽

Alcohol Intake ◽

Cardiovascular Health ◽

Health Study ◽

Cardiovascular Health Study ◽

Brain Volumes ◽

Total Brain

Introduction: Alcohol intake has been related with a complex group of associations with brain structure in cross-sectional analyses, but to our knowledge, its prospective relationship with structural brain abnormalities detected by MRI has never been reported. Hypothesis: We hypothesized that consumers of 1-<7 drinks/week would have slower progression of leukoaraiosis (white matter abnormalities) but more rapid progression of brain atrophy than longer-term abstainers. Methods: As part of the Cardiovascular Health Study, 1 996 adults aged ≥65 years underwent MRI scanning in 1991-94 and again in 1997-99, having excluded 120 participants with a history of cerebrovascular disease before the initial scan. Alcohol consumption was assessed at each annual visit by self-reported intake of wine, beer and liquor. A 10-point white matter grade (WMG) and ventricular grade (VG) were assessed in a standardized and blinded manner in both scans; hippocampal and total brain volumes were also quantified on the second scan. We estimated the associations of alcohol intake in categories (as reported closest to the date of initial scan), with MRI findings at follow-up with multinomial ordered logistic regression (WMG ≤ 3 ref and ≥ 4; VG ≤ 3 ref , =4 and ≥5) using inverse probability weighting to account for attrition. Results: We observed a U-shaped association with WMG, with significantly lower risk among participants consuming 1-<7 drinks/week (OR 0.38; 95% CI 0.17-0.82, table) than long-term abstainers (P quadtrend = 0.01). For VG, the association was inverse (P trend = 0.06), with significantly less progression among drinkers of 1-<7 drinks/week than long-term abstainers (OR 0.62; 95% CI 0.40-0.97). We identified no significant associations of alcohol intake with quantitative mean hippocampal or total brain volumes at the second scan. Conclusions: Compared with long-term abstention, consumption of 1-<7 drinks/week of alcohol was generally associated with less progression of leukoaraiosis and some measures of brain atrophy in older adults.

Download Full-text

Atrial Fibrillation and Brain Magnetic Resonance Imaging Abnormalities

Stroke ◽

10.1161/strokeaha.118.024143 ◽

2019 ◽

Vol 50 (4) ◽

pp. 783-788 ◽

Cited By ~ 6

Author(s):

Jeremy P. Berman ◽

Faye L. Norby ◽

Thomas Mosley ◽

Elsayed Z. Soliman ◽

Rebecca F. Gottesman ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Brain Volume ◽

Brain Mri ◽

Brain Magnetic Resonance Imaging ◽

White Matter Hyperintensity ◽

Resonance Imaging ◽

Total Brain Volume ◽

Cross Sectional ◽

Total Brain ◽

Sectional Analysis

Background and Purpose— Atrial fibrillation (AF) is associated with dementia independent of clinical stroke. The mechanisms underlying this association remain unclear. In a community-based cohort, the ARIC study (Atherosclerosis Risk in Communities), we evaluated (1) the longitudinal association of incident AF and (2) the cross-sectional association of prevalent AF with brain magnetic resonance imaging (MRI) abnormalities. Methods— The longitudinal analysis included 963 participants (mean age, 73±4.4 years; 62% women; 51% black) without prevalent stroke or AF who underwent a brain MRI in 1993 to 1995 and a second MRI in 2004 to 2006 (mean, 10.6±0.8 years). Outcomes included subclinical cerebral infarctions, sulcal size, ventricular size, and, for the cross-sectional analysis, white matter hyperintensity volume and total brain volume. Results— In the longitudinal analysis, 29 (3.0%) participants developed AF after the first brain MRI. Those who developed AF had higher odds of increase in subclinical cerebral infarctions (odds ratio [OR], 3.08; 95% CI, 1.39–6.83), worsening sulcal grade (OR, 3.56; 95% CI, 1.04–12.2), and worsening ventricular grade (OR, 9.34; 95% CI, 1.24–70.2). In cross-sectional analysis, of 969 participants, 35 (3.6%) had prevalent AF at the time of the 2004 to 2006 MRI scan. Those with AF had greater odds of higher sulcal (OR, 3.9; 95% CI, 1.7–9.1) and ventricular grade (OR, 2.4; 95% CI, 1.0–5.7) after multivariable adjustment and no difference in white matter hyperintensity or total brain volume. Conclusions— AF is independently associated with increase in subclinical cerebral infarction and worsening sulcal and ventricular grade—morphological changes associated with aging and dementia. More research is needed to define the mechanisms underlying AF-related neurodegeneration.

Download Full-text

Arterial stiffness and dementia pathology

Neurology ◽

10.1212/wnl.0000000000005259 ◽

2018 ◽

Vol 90 (14) ◽

pp. e1248-e1256 ◽

Cited By ~ 42

Author(s):

Timothy M. Hughes ◽

Lynne E. Wagenknecht ◽

Suzanne Craft ◽

Akiva Mintz ◽

Gerardo Heiss ◽

...

Keyword(s):

White Matter ◽

Arterial Stiffness ◽

Small Vessel Disease ◽

Brain Mri ◽

Volume Ratio ◽

Cognitive Testing ◽

White Matter Hyperintensity ◽

Cross Sectional ◽

Brain Volumes ◽

Atherosclerosis Risk In Communities

ObjectiveArterial stiffness has been associated with evidence of cerebral small vessel disease (cSVD) and fibrillar β-amyloid (Aβ) deposition in the brain. These complex relationships have not been examined in racially and cognitively diverse cohorts.MethodsThe Atherosclerosis Risk in Communities (ARIC)–Neurocognitive Study collected detailed cognitive testing for adjudication of dementia and mild cognitive impairment (MCI), brain MRI, and arterial stiffness by pulse wave velocity (PWV, carotid-femoral [cfPWV] and heart-carotid [hcPWV]). The ARIC-PET ancillary study added Aβ imaging using florbetapir ([18F]-AV-45) to obtain standardized uptake volume ratios and defined global Aβ-positivity as standardized uptake volume ratio >1.2. One-SD increase in PWV was related to brain volume, MRI-defined cSVD (e.g., cerebral microbleeds and white matter hyperintensity), and cortical Aβ deposition adjusted for age, body mass index, sex, race, and APOE ε4 status. We examined the cross-sectional relationships including interactions by race, APOE ε4 status, and cognition.ResultsAmong the 320 ARIC-PET participants (76 [5] years, 45% black, 27% MCI), greater central stiffness (hcPWV) was associated with greater Aβ deposition (odds ratio [OR] = 1.31, 95% confidence interval [CI] 1.01–1.71). Greater central stiffness (cfPWV) was significantly associated with having lower brain volumes in Alzheimer disease–susceptible regions (in mm3, β = −1.5 [0.7 SD], p = 0.03) and high white matter hyperintensity burden (OR = 1.6, 95% CI 1.2–2.1). Furthermore, cfPWV was associated with a higher odds of concomitant high white matter hyperintensity and Aβ-positive scans (OR = 1.4, 95% CI 1.1–2.1). These associations were strongest among individuals with MCI and did not differ by race or APOE ε4 status.ConclusionsArterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and Aβ deposition.

Download Full-text