scholarly journals Plasma Metabolites Associated with Brain MRI Measures of Neurodegeneration in Older Adults in the Atherosclerosis Risk in Communities–Neurocognitive Study (ARIC-NCS)

2019 ◽  
Vol 20 (7) ◽  
pp. 1744
Author(s):  
Danni Li ◽  
Jeffrey Misialek ◽  
Clifford Jack ◽  
Michelle Mielke ◽  
David Knopman ◽  
...  

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm3] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm3 [5.5, 18.6], 11.8 cm3 [5.0, 18.6], and 7.3 cm3 [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

Author(s):  
Danni Li ◽  
Jeffrey R. Misialek ◽  
Clifford R. Jack ◽  
Michelle M. Mielke ◽  
David Knopman ◽  
...  

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm3] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm3 [5.5, 18.6], 11.8 cm3 [5.0, 18.6], and 7.3 cm3 [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.


Author(s):  
Hediyeh Baradaran ◽  
Alen Delic ◽  
J. Scott McNally ◽  
Matthew Alexander ◽  
Jennifer J. Majersik ◽  
...  

<b><i>Introduction:</i></b> We evaluated the association between carotid compliance, a measure of arterial stiffness, to parahippocampal volume (PHV) and hippocampal volume (HV) over 20 years later in the Atherosclerosis Risk in the Community study. <b><i>Methods:</i></b> We included participants with common carotid compliance measurements at visit 1 (1987–1989) and volumetric brain MRI at visit 5 (2011–2013). The primary outcomes are pooled bilateral PHV and HV. We performed linear regression models adjusting for age, sex, vascular risk factors, and total brain volume. <b><i>Results:</i></b> Of the 614 participants, higher compliance was correlated with higher PHV (<i>R</i> = 0.218[0.144–0.291], <i>p</i> &#x3c; 0.001) and HV (<i>R</i> = 0.181 [0.105–0.255, <i>p</i> &#x3c; 0.001]). The association was linear and significant after adjusting for confounders. At follow-up MRI, 30 patients with dementia had lower PHV and HV than patients without dementia (<i>p</i> &#x3c; 0.001 and <i>p</i> &#x3c; 0.001, respectively). <b><i>Conclusion:</i></b> Carotid compliance is associated with higher PHV and HV when measured 20 years later, further supporting the link between arterial stiffness and cognitive decline.


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Hamdi S Adam ◽  
Kamakshi Lakshminarayan ◽  
Wendy Wang ◽  
Faye L Norby ◽  
Thomas Mosley ◽  
...  

Background: Periodontal disease (PD) is associated positively with neurocognitive outcomes. Few studies have investigated the relationship between PD and indicators of brain aging and vascular changes. Hypothesis: PD is associated with greater cerebral small vessel disease, lower total and regional brain volumes and elevated β-amyloid (Aβ) deposition. Methods: We included 6,793 participants who received full-mouth periodontal examinations and tooth counts at Visit 4 (1996-1998) of the Atherosclerosis Risk in Communities Study. We used a modified 3-level version of the Periodontal Profile Class to categorize PD based on severity and extent of gingival inflammation and tissue loss. Among participants who attended Visit 5 (2011-2013), n=1,306 received a brain MRI and n=248 received a PET scan. Total brain volume, Alzheimer’s disease signature volume, and presence of microhemorrhages and cerebral infarctions were ascertained via 3T MRI; Aβ deposition was assessed from PET. We regressed brain volumes on baseline PD status using weighted multivariable linear regression. Presence of cerebrovascular microhemorrhages, infarctions, or elevated Aβ (standardized uptake value ratio>1.2) were regressed on PD category using logistic models. We examined the interaction between Apolipoprotein E ε4 ( APOE ) allele possession and PD categories on the Aβ outcome. Results: Prevalence of baseline periodontal disease was 73% (959/1306) and 87% (206/248) among the MRI and PET subgroups, respectively. PD was not associated with volumetric brain measures nor microhemorrhages. PD was inversely associated with the odds of subcortical and lacunar infarctions. PD and Aβ were not associated in main effect or interaction analyses, although there was a notably stronger association among carriers of APOE . Conclusion: PD was not associated with altered brain structure, cerebral microhemorrhages or elevated Aβ deposition. Counter to the hypothesis, PD and complete tooth loss were inversely associated with cerebral infarctions.


Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 783-788 ◽  
Author(s):  
Jeremy P. Berman ◽  
Faye L. Norby ◽  
Thomas Mosley ◽  
Elsayed Z. Soliman ◽  
Rebecca F. Gottesman ◽  
...  

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.


2022 ◽  
Vol 15 ◽  
Author(s):  
Eilidh MacNicol ◽  
Paul Wright ◽  
Eugene Kim ◽  
Irene Brusini ◽  
Oscar Esteban ◽  
...  

Age-specific resources in human MRI mitigate processing biases that arise from structural changes across the lifespan. There are fewer age-specific resources for preclinical imaging, and they only represent developmental periods rather than adulthood. Since rats recapitulate many facets of human aging, it was hypothesized that brain volume and each tissue's relative contribution to total brain volume would change with age in the adult rat. Data from a longitudinal study of rats at 3, 5, 11, and 17 months old were used to test this hypothesis. Tissue volume was estimated from high resolution structural images using a priori information from tissue probability maps. However, existing tissue probability maps generated inaccurate gray matter probabilities in subcortical structures, particularly the thalamus. To address this issue, gray matter, white matter, and CSF tissue probability maps were generated by combining anatomical and signal intensity information. The effects of age on volumetric estimations were then assessed with mixed-effects models. Results showed that herein estimation of gray matter volumes better matched histological evidence, as compared to existing resources. All tissue volumes increased with age, and the tissue proportions relative to total brain volume varied across adulthood. Consequently, a set of rat brain templates and tissue probability maps from across the adult lifespan is released to expand the preclinical MRI community's fundamental resources.


2019 ◽  
Author(s):  
SR Cox ◽  
SJ Ritchie ◽  
C Fawns-Ritchie ◽  
EM Tucker-Drob ◽  
IJ Deary

AbstractThe associations between indices of brain structure and measured intelligence are not clear. In part, this is because the evidence to date comes from mostly small and heterogenous studies. Here, we report brain structure-intelligence associations on a large sample from the UK Biobank study. The overall N = 29,004, with N = 18,363 participants providing both brain MRI and cognitive data, and a minimum N = 7318 providing the MRI data alongside a complete four-test battery. Participants’ age range was 44-81 years (M = 63.13, SD = 7.48). A general factor of intelligence (g) was extracted from four varied cognitive tests, accounting for one third of the variance in the cognitive test scores. The association between (age-and sex-corrected) total brain volume and a latent factor of general intelligence is r = 0.275, 95% C.I. = [0.252, 0.299]. A model that incorporated multiple global measures of grey and white matter macro-and microstructure accounted for more than double the g variance in older participants compared to those in middle-age (13.4% and 5.9%, respectively). There were no sex differences in the magnitude of associations between g and total brain volume or other global aspects of brain structure. The largest brain regional correlates of g were volumes of the insula, frontal, anterior/superior and medial temporal, posterior and paracingulate, lateral occipital cortices, thalamic volume, and the white matter microstructure of thalamic and association fibres, and of the forceps minor.


2019 ◽  
Author(s):  
Curtis W Dewey ◽  
Mark Rishniw ◽  
Philippa J Johnson ◽  
Emma S Davies ◽  
Joseph J Sackman ◽  
...  

The objective of this study was to compare specific brain MRI anatomic measurements between three groups of geriatric ( > 8yrs) dogs: 1) neurologically impaired dogs with presumptive spontaneous brain microhemorrhages and no clinical evidence of canine cognitive dysfunction 2) dogs with canine cognitive dysfunction 3) dogs without clinical evidence of cognitive impairment or abnormalities on neurologic examination (control dogs). MR images from 46 geriatric dogs were reviewed and measurements were obtained of interthalamic adhesion height (thickness) and mid-sagittal interthalamic adhesion area for all dogs, in addition to total brain volume. Interthalamic adhesion measurements, either absolute or normalized to total brain volume were compared between groups. Signalment (age, breed, sex), body weight, presence and number of SBMs, as well as other abnormal MRI findings were recorded for all dogs. All interthalamic adhesion measurement parameters were significantly (p<0.05) different between control dogs and affected dogs. Both dogs with cognitive dysfunction (12/13; 92 %) and dogs with isolated brain microhemorrhages had more microhemorrhages than control dogs (3/19; 16%). Affected dogs without cognitive dysfunction had more microhemorrhages than dogs with cognitive dysfunction. In addition to signs of cognitive impairment for the CCD group, main clinical complaints for SBM and CCD dogs were referable to central vestibular dysfunction, recent-onset seizure activity, or both. Geriatric dogs with spontaneous brain microhemorrhages without cognitive dysfunction have similar MRI abnormalities as dogs with cognitive dysfunction but may represent a distinct diseasecategory.


2019 ◽  
Author(s):  
Curtis W Dewey ◽  
Mark Rishniw ◽  
Philippa J Johnson ◽  
Emma S Davies ◽  
Joseph J Sackman ◽  
...  

The objective of this study was to compare specific brain MRI anatomic measurements between three groups of geriatric ( > 8yrs) dogs: 1) neurologically impaired dogs with presumptive spontaneous brain microhemorrhages and no clinical evidence of canine cognitive dysfunction 2) dogs with canine cognitive dysfunction 3) dogs without clinical evidence of cognitive impairment or abnormalities on neurologic examination (control dogs). MR images from 46 geriatric dogs were reviewed and measurements were obtained of interthalamic adhesion height (thickness) and mid-sagittal interthalamic adhesion area for all dogs, in addition to total brain volume. Interthalamic adhesion measurements, either absolute or normalized to total brain volume were compared between groups. Signalment (age, breed, sex), body weight, presence and number of SBMs, as well as other abnormal MRI findings were recorded for all dogs. All interthalamic adhesion measurement parameters were significantly (p<0.05) different between control dogs and affected dogs. Both dogs with cognitive dysfunction (12/13; 92 %) and dogs with isolated brain microhemorrhages had more microhemorrhages than control dogs (3/19; 16%). Affected dogs without cognitive dysfunction had more microhemorrhages than dogs with cognitive dysfunction. In addition to signs of cognitive impairment for the CCD group, main clinical complaints for SBM and CCD dogs were referable to central vestibular dysfunction, recent-onset seizure activity, or both. Geriatric dogs with spontaneous brain microhemorrhages without cognitive dysfunction have similar MRI abnormalities as dogs with cognitive dysfunction but may represent a distinct diseasecategory.


Neurology ◽  
2017 ◽  
Vol 88 (5) ◽  
pp. 449-455 ◽  
Author(s):  
Michelle Luciano ◽  
Janie Corley ◽  
Simon R. Cox ◽  
Maria C. Valdés Hernández ◽  
Leone C.A. Craig ◽  
...  

Objective:To assess the association between Mediterranean-type diet (MeDi) and change in brain MRI volumetric measures and mean cortical thickness across a 3-year period in older age (73–76 years).Methods:We focused on 2 longitudinal brain volumes (total and gray matter; n = 401 and 398, respectively) plus a longitudinal measurement of cortical thickness (n = 323), for which the previous cross-sectional evidence of an association with the MeDi was strongest. Adherence to the MeDi was calculated from data gathered from a food frequency questionnaire at age 70, 3 years prior to the baseline imaging data collection.Results:In regression models adjusting for relevant demographic and physical health indicators, we found that lower adherence to the MeDi was associated with greater 3-year reduction in total brain volume (explaining 0.5% of variance, p < 0.05). This effect was half the size of the largest covariate effect (i.e., age). Cross-sectional associations between MeDi and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume.Conclusions:Lower adherence to the MeDi in an older Scottish cohort is predictive of total brain atrophy over a 3-year interval. Fish and meat consumption does not drive this change, suggesting that other components of the MeDi or, possibly, all of its components in combination are responsible for the association.


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