Energetic cost of walking and Brain Atrophy in Mid-to-Late Life

Author(s):  
Ryan Dougherty ◽  
Fangyu Liu ◽  
Yang An ◽  
Amal A Wanigatunga ◽  
Qu Tian ◽  
...  

Abstract Background Higher energetic costs for mobility are associated with declining gait speed and slow gait is linked to cognitive decline and Alzheimer’s disease. However, the physiological underpinnings of gait and brain health have not been well explored. We examined the associations of the energetic cost of walking with brain volume in cognitively unimpaired adults from the Baltimore Longitudinal Study of Aging. Methods We used brain MRI data from 850 participants (mean baseline age 66.3±14.5 years), of whom 451 had longitudinal MRI data (2.8±1.0 MRI scans over 4.0±2.0 years). The energetic cost of walking was assessed as the average energy expended (V̇O2) during 2.5 minutes of customary-paced overground walking. Multivariable linear mixed effects models examined the associations between baseline energetic cost of walking and regional brain volumes adjusting for covariates. Results At baseline, higher energetic cost of walking was cross-sectionally associated with lower gray and white matter volumes within the frontal, parietal, and temporal lobes, as well as hippocampal, total brain, and larger ventricular volumes (all FDR p< 0.05). A baseline energetic cost of walking × time interaction demonstrated that participants with higher energetic cost of walking had faster annual decline in hippocampal volume (FDR p= 0.01) and accelerated annual increase in ventricular volumes (FDR p= 0.01). Conclusions The energetic cost of walking is associated with gray and white matter volumes and subsequent hippocampal atrophy and ventricular enlargement. Collectively, these data suggest the energetic cost of walking may be an early marker of neurodegeneration that contributes to the gait brain connection.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Khawlah Alateeq ◽  
Erin Walsh ◽  
Walter Abhayaratna ◽  
Nicolas Cherbuin

Objective: To quantify the association between blood pressure (BP) across its full range and brain volumes and white matter lesions (WMLs) while investigating the effects of age, sex, body mass index (BMI), antihypertensive medication, and other risk factors. Methods: UK Biobank participants ( N =36,260) aged 40 to 70 years were included and stratified by sex and age into four groups (age ≤ 45, 46-55, 56-65 and > 65 years old). Multi-level regression analyses were used to assess the association between mean arterial (MAP), systolic (SBP), and diastolic (DBP) blood pressure, and brain volumes segmented using the FreeSufer software (gray matter [GMV], white matter [WMV], left [L] and right hippocampal volume [RHCV]) and WMLs. We also investigated the interaction effects between body mass index (BMI) and antihypertensive medication and BP in predicting brain volumes and WMLs. Results: Every 10-mmHg higher DBP was associated with lower brain volumes (GMV: -1300– -2800) [SE=34–90]; WMV: -903.44– -1171.7[SE=34.66–53.03]; LHCV: -7.7– -14.26 [SE=0.44–0.57]; RHCV: -6.25– -22.64[SE=0.32–0.95]) across all age groups. A similar pattern was detected in both sexes, although it was weaker, in men. Also, every 10-mmHg higher MAP was associated with larger WMLs across all age groups but peaked > 65 years (0.1 [SE=0.002]). Both lower BMI and anti-hypertensive medication appeared to afford a protective effect. Conclusion: Higher BP is associated with worse cerebral health across the full BP range from middle adulthood and across the life course. Therefore, it is important that prevention efforts be directed at younger adults with focus on achieving optimal BP to decrease future risk of developing dementia.


Author(s):  
Claire E Kelly ◽  
Deanne K Thompson ◽  
Alicia J Spittle ◽  
Jian Chen ◽  
Marc L Seal ◽  
...  

ObjectiveTo explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate–late preterm (MLPT).Study designA cohort of MLPT infants had brain MRI at approximately TEA (38–44 weeks’ postmenstrual age) and had a developmental assessment (Bayley Scales of Infant and Toddler Development and Infant Toddler Social Emotional Assessment) at 2 years’ corrected age. Relationships between cortical grey matter and white matter volumes and 2-year developmental outcomes were explored using voxel-based morphometry. Relationships between diffusion tensor measures of white matter microstructure (fractional anisotropy (FA) and axial (AD), radial (RD) and mean (MD) diffusivities) and 2-year developmental outcomes were explored using tract-based spatial statistics.Results189 MLPT children had data from at least one MRI modality (volumetric or diffusion) and data for at least one developmental domain. Larger cortical grey and white matter volumes in many brain regions, and higher FA and lower AD, RD and MD in several major white matter regions, were associated with better cognitive and language scores. There was little evidence that cortical grey matter and white matter volumes and white matter microstructure were associated with motor and behavioural outcomes.ConclusionsRegional cortical grey matter and white matter volumes and white matter microstructure are associated with cognitive and language development at 2 years of age in MLPT children. Thus, early alterations to brain volumes and microstructure may contribute to some of the developmental deficits described in MLPT children.


Neurology ◽  
2018 ◽  
Vol 90 (14) ◽  
pp. e1248-e1256 ◽  
Author(s):  
Timothy M. Hughes ◽  
Lynne E. Wagenknecht ◽  
Suzanne Craft ◽  
Akiva Mintz ◽  
Gerardo Heiss ◽  
...  

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.


Neurology ◽  
2021 ◽  
Vol 96 (17) ◽  
pp. e2172-e2183 ◽  
Author(s):  
Rashid Ghaznawi ◽  
Mirjam I. Geerlings ◽  
Myriam Jaarsma-Coes ◽  
Jeroen Hendrikse ◽  
Jeroen de Bresser ◽  
...  

ObjectiveTo determine whether white matter hyperintensity (WMH) markers on MRI are associated with long-term risk of mortality and ischemic stroke.MethodsWe included consecutive patients with manifest arterial disease enrolled in the Second Manifestations of Arterial Disease–Magnetic Resonance (SMART-MR) study. We obtained WMH markers (volume, type, and shape) from brain MRI scans performed at baseline using an automated algorithm. During follow-up, occurrence of death and ischemic stroke was recorded. Using Cox regression, we investigated associations of WMH markers with risk of mortality and ischemic stroke, adjusting for demographics, cardiovascular risk factors, and cerebrovascular disease.ResultsWe included 999 patients (59 ± 10 years; 79% male) with a median follow-up of 12.5 years (range 0.2–16.0 years). A greater periventricular or confluent WMH volume was independently associated with a greater risk of vascular death (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13–1.47) for a 1-unit increase in natural log-transformed WMH volume and ischemic stroke (HR 1.53, 95% CI 1.26–1.86). A confluent WMH type was independently associated with a greater risk of vascular (HR 1.89, 95% CI 1.15-3.11) and nonvascular death (HR 1.65, 95% CI 1.01–2.73) and ischemic stroke (HR 2.83, 95% CI 1.36-5.87). A more irregular shape of periventricular or confluent WMH, as expressed by an increase in concavity index, was independently associated with a greater risk of vascular (HR 1.20, 95% CI 1.05–1.38 per SD increase) and nonvascular death (HR 1.21, 95% CI 1.03–1.42) and ischemic stroke (HR 1.28, 95% CI 1.05–1.55).ConclusionsWMH volume, type, and shape are associated with long-term risk of mortality and ischemic stroke in patients with manifest arterial disease.


2011 ◽  
Vol 14 (3) ◽  
pp. 268-276 ◽  
Author(s):  
Rebecca C. Knickmeyer ◽  
Chaeryon Kang ◽  
Sandra Woolson ◽  
J. Keith Smith ◽  
Robert M. Hamer ◽  
...  

Twin studies suggest that global and regional brain volumes are highly heritable. However, estimates of heritability vary across development. Given that all twin studies are open to the potential criticism of non-generalizability due to differences in intrauterine environment between twins and singletons, these age effects may reflect the influence of perinatal environmental factors, which are unique to twins and which may be especially evident early in life. To address this question, we compared brain volumes and the relationship of brain volumes to gestational age in 136 singletons (67 male, 69 female) and 154 twins (75 male, 79 female; 82 DZ, 72 MZ) who had received high resolution MRI scans of the brain in the first month of life. Intracranial volume, total white matter, and ventricle volumes did not differ between twins and singletons. However, cerebrospinal fluid and frontal white matter volume was greater in twins compared to singletons. While gray matter volumes at MRI did not differ between groups, the slope of the relationship between total and cortical gray matter and gestational age at the MRI scan was steeper in MZ twins compared to DZ twins. Post-hoc analyses suggested that gray matter development is delayed in MZ twins in utero and that they experience ‘catch-up’ growth in the first month of life. These differences should be taken into account when interpreting and designing studies in the early postnatal period.


2021 ◽  
Author(s):  
Danielle Newby ◽  
Laura Winchester ◽  
William Sproviero ◽  
Marco Fernandes ◽  
Upamanyu Ghose ◽  
...  

Hypertension is a well-established risk factor for cognitive impairment, brain atrophy, and dementia. However, the relationship of other types of hypertension, such as, isolated hypertension on brain health and its comparison to systolic-diastolic hypertension (where systolic and diastolic measures are high), is still relatively unknown. Due to its increased prevalence, it is important to investigate the impact of isolated hypertension to help understand its potential impact on cognitive decline and future dementia risk. In this study, we compared a variety of global brain measures between participants with isolated hypertension to those with normal blood pressure or systolic-diastolic hypertension using the largest cohort of healthy individuals. Using the UK Biobank cohort, we carried out a cross-sectional study using 29775 participants [mean age 63 years, 53% female] with BP measurements and brain MRI data. We used linear regression models adjusted for multiple confounders to compare a variety of global, sub cortical and white matter brain measures. We compared participants with either isolated systolic or diastolic hypertension with normotensives and then with participants with systolic-diastolic hypertension. The results showed that participants with isolated systolic or diastolic hypertension taking BP medications had smaller grey matter but larger white matter microstructures and macrostructures compared to normotensives. However, isolated hypertensives had larger total grey matter and smaller white matter traits when comparing these regions with participants with systolic-diastolic hypertension.These results provide support to investigate possible preventative strategies that target isolated hypertension as well as systolic-diastolic hypertension to maintain brain health and/or reduce dementia risk earlier in life particularly in white matter regions.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jane Cannon ◽  
Mark Findlay ◽  
Krishna Dani ◽  
Jesse Dawson ◽  
David A Dickie ◽  
...  

Introduction: Atrial fibrillation (AF) and heart failure (HF) are associated with cognitive impairment. We used neuroimaging to describe if this association is explained by cardioembolism or other mechanisms. Methods: We included adults with HF (ejection fraction<45%) and AF but no stroke history. Healthy volunteer controls were matched, 1:2 ratio. Participants were assessed with Repeatable Battery for the Assessment of Neurospychological Status (RBANS), Hospital Anxiety and Depression Score (HADS) and 3-T brain MRI. Scans were graded for:infarct, enlarged perivascular spaces, microbleeds, global and regional (hippocampal) atrophy with consensus scoring by four raters using validated, ordinal assessment scales. Brain volumes were semi-automatically acquired using cluster analysis of T1-weighted and FLAIR voxel intensities and diffeomorphic atlas-based segmentation. CSF, hippocampal and white matter volumes were corrected for intracranial volume. We described univariable differences between groups and then created multivariable models where cardiac status was the dependent variable, RBANS and MRI data were the predictors. Results: Of 50 participants, AF-HF (n=34) had poorer RBANS (MD:16.9, SE:3.44; p<0.001). Differences were independent of education and HADS. Infarcts and ordinal markers of atrophy were significantly different between groups, SVD markers were increased in AF-HF but did not reach significance. Quantitative measures of white matter differed between groups but measures of atrophy did not.(Table) On multivariable models, no imaging feature was independently associated with cardiac status. Discussion: The association between cognitive impairment and cardiac disease may not be solely driven by occult cardioembolism; small vessel disease and other, neuroimaging independent, factors also interact. Differences between ordinal scales and quantitative scores suggest that future studies should use robust volumetric analyses.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Claudia L Satizabal ◽  
Alexa Beiser ◽  
Jayandra J Himali ◽  
Rhoda Au ◽  
Philip A Wolf ◽  
...  

Metabolic and vascular dysregulation are related to stroke, cognitive decline and dementia. Growth factor biomarkers of these processes, such as Insulin-like Growth Factor 1 (IGF1) and Vascular Endothelial Growth Factor (VEGF) have been associated with risk of neurodegeneration and stroke in middle-aged and older Framingham participants. Additionally, hepatocyte growth factor (HGF) and angiopoietin 2 are novel biomarkers of interest as they have been related to cardiovascular events. As abnormal brain changes probably start years before clinical symptoms, we hypothesize that circulating growth factors are related to MRI endophenotypes of brain aging. We included 1,877 individuals aged 46±8 years from the Framingham Study. Blood samples were collected during 2008-2011, and used to measure IGF1, VEGF, HGF, angiopoietin 2 and its receptor tyrosine kinase (TIE2). Participants underwent brain MRI examination (2009-2013) from which brain volumes and white matter hyperintensities were estimated. We related growth factor levels to brain MRI markers adjusting for age, sex, time between blood draw and MRI, and cardiovascular risk factors. Lower IGF1, as well as higher HGF and angiopoietin 2 levels were associated with higher ventricular volumes indicative of brain shrinkage. Higher TIE2 levels were associated with lower total brain and gray matter volumes, while higher angiopoietin 2 levels were associated with lower white matter volumes. Lower IGF1 levels were also associated with reduced hippocampal volumes. Finally, higher TIE2 levels were associated with larger white matter hyperintensities. Our results suggest that growth factors are associated with neurodegenerative and cerebrovascular markers of brain aging in healthy young adults. Whereas IGF1 seems protective, higher levels of HGF, angiopoietin 2 and TIE2 were associated with greater subclinical brain injury. These associations expand our understanding of the earliest stages of brain aging. We will extend our findings by analyzing cognitive outcomes.


Neurology ◽  
2019 ◽  
Vol 93 (9) ◽  
pp. e864-e878 ◽  
Author(s):  
Ilse A.C. Arnoldussen ◽  
Deborah R. Gustafson ◽  
Esther M.C. Leijsen ◽  
Frank-Erik de Leeuw ◽  
Amanda J. Kiliaan

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.


Neurology ◽  
2017 ◽  
Vol 89 (21) ◽  
pp. 2187-2191 ◽  
Author(s):  
Noam Alperin ◽  
Ahmet M. Bagci ◽  
Sang H. Lee

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.


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