scholarly journals PM2.5 associated with gray matter atrophy reflecting increased Alzheimers risk in older women

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011149
Author(s):  
Diana Younan ◽  
Xinhui Wang ◽  
Ramon Casanova ◽  
Ryan Barnard ◽  
Sarah A. Gaussoin ◽  
...  

Objective:To examine whether late-life exposure to PM2.5 (particulate matter with aerodynamic diameters <2.5-µm) contributes to progressive brain atrophy predictive of Alzheimer’s disease (AD) using a community-dwelling cohort of women (aged 70-89) with up to two brain MRI scans (MRI-1: 2005-6; MRI-2: 2010-11).Methods:AD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the AD Neuroimaging Initiative, was used to capture high-dimensional gray matter atrophy in brain areas vulnerable to AD (e.g., amygdala, hippocampus, parahippocampal gyrus, thalamus, inferior temporal lobe areas and midbrain). Based on participants’ addresses and air monitoring data, we implemented a spatiotemporal model to estimate 3-year average exposure to PM2.5 preceding MRI-1. General linear models were used to examine the association between PM2.5 and AD-PS scores (baseline and 5-year standardized change), accounting for potential confounders and white matter lesion volumes.Results:For 1365 women aged 77.9±3.7 years in 2005-6, there was no association between PM2.5 and baseline AD-PS score in cross-sectional analyses (β=-0.004; 95% CI: -0.019, 0.011). Longitudinally, each interquartile range increase of PM2.5 (2.82-µg/m3) was associated with increased AD-PS scores during the follow-up, equivalent to a 24% (hazard ratio=1.24; 95% CI: 1.14, 1.34) increase in AD risk over 5-years (n=712; aged 77.4±3.5 years). This association remained after adjustment for socio-demographics, intracranial volume, lifestyle, clinical characteristics, and white matter lesions, and was present with levels below US regulatory standards (<12-µg/m3).Conclusions:Late-life exposure to PM2.5 is associated with increased neuroanatomical risk of AD, which may not be explained by available indicators of cerebrovascular damage.

2019 ◽  
Vol 48 (Supplement_3) ◽  
pp. iii1-iii16
Author(s):  
Robert Briggs ◽  
Anne Buckley ◽  
Silvin Knight ◽  
Jim Meaney ◽  
Sean Kennelly ◽  
...  

Abstract Background Cerebral white matter hyperintensity (WMH) burden is a key biological risk factor underpinning late life depression (LLD) and cerebral hypoperfusion has been identified as an important cause of WMH. The aim of this study therefore is to clarify if orthostatic hypotension (OH) and lower systemic blood pressure (BP), both of which cause reduced cerebral blood flow, modify the relationship between depression and cerebral white matter disease in a cohort of community-dwelling older people aged ≥70 years. Methods This study uses data from wave 3 of TILDA. Participants were included if they were aged ≥70 years and had undergone assessment for depressive symptoms, brain MRI and cardiovascular measures. Depressive symptoms were measured using the 8-item Centre for Epidemiological Studies Depression Scale. Scheltens Score was used by a trained radiologist to calculate overall WMH burden. Orthostatic BP was measured by active stand. OH was defined as a drop in Systolic BP≥20 mmHg or drop in diastolic BP≥10 mmHg at 30, 60 or 90 seconds post standing. Results Participants with depressive symptoms (8%, 16/202) had a significantly higher burden of WMH measured by Scheltens Score (14.6 (95% CI:11.0–18.2) vs. 11.0 (95% CI:10.1–11.8); p=0.0211). Two-way interaction models demonstrated that the association between depressive symptoms and WMH burden is significant only in those with co-existing OH. Similarly, the two-way interaction between depressive symptoms and systolic BP shows that this association remains statistically significant only in those with both depressive symptoms and lower BP, i.e. <130 mm Hg. Conclusion This study demonstrates that depressive symptoms are associated with cerebral WMH in a cohort of community-dwelling people aged ≥70 years but this relationship is modified by co-existing OH or lower BP. Identifying the processes that lead to WMH accumulation and progression in depression is crucial in order to inform strategies aimed at preventing and ameliorating LLD.


Neurology ◽  
2018 ◽  
Vol 91 (21) ◽  
pp. e1961-e1970 ◽  
Author(s):  
Justin B. Echouffo-Tcheugui ◽  
Sarah C. Conner ◽  
Jayandra J. Himali ◽  
Pauline Maillard ◽  
Charles S. DeCarli ◽  
...  

ObjectiveTo assess the association of early morning serum cortisol with cognitive performance and brain structural integrity in community-dwelling young and middle-aged adults without dementia.MethodsWe evaluated dementia-free Framingham Heart Study (generation 3) participants (mean age 48.5 years, 46.8% men) who underwent cognitive testing for memory, abstract reasoning, visual perception, attention, and executive function (n = 2,231) and brain MRI (n = 2018) to assess total white matter, lobar gray matter, and white matter hyperintensity volumes and fractional anisotropy (FA) measures. We used linear and logistic regression to assess the relations of cortisol (categorized in tertiles, with the middle tertile as referent) to measures of cognition, MRI volumes, presence of covert brain infarcts and cerebral microbleeds, and voxel-based microstructural white matter integrity and gray matter density, adjusting for age, sex, APOE, and vascular risk factors.ResultsHigher cortisol (highest tertile vs middle tertile) was associated with worse memory and visual perception, as well as lower total cerebral brain and occipital and frontal lobar gray matter volumes. Higher cortisol was associated with multiple areas of microstructural changes (decreased regional FA), especially in the splenium of corpus callosum and the posterior corona radiata. The association of cortisol with total cerebral brain volume varied by sex (p for interaction = 0.048); higher cortisol was inversely associated with cerebral brain volume in women (p = 0.001) but not in men (p = 0.717). There was no effect modification by the APOE4 genotype of the relations of cortisol and cognition or imaging traits.ConclusionHigher serum cortisol was associated with lower brain volumes and impaired memory in asymptomatic younger to middle-aged adults, with the association being evident particularly in women.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jagoda Jacków-Nowicka ◽  
Przemysław Podgórski ◽  
Joanna Bladowska ◽  
Dorota Szcześniak ◽  
Joanna Rymaszewska ◽  
...  

Introduction: The aim of the study was to evaluate the impact of multiple risk factors (age, diabetes, hypertension, hyperlipidemia, BMI, smoking, alcohol) on the gray and white matter volumes as well as on the burden of white matter hyperintensities (WMH).Material and Methods: The study group consisted of 554 subjects (age range: 50–69 yrs, F/M: 367/187) recruited from the larger cohort of the Polish fraction of the Prospective Urban Rural Epidemiological (PURE) study. The participants answered questionnaires about their lifestyle, underwent physical and psychological examination (MoCA test), laboratory blood tests followed by brain MRI. Volumetric measurements of the total gray matter (GMvol), total white matter (WMvol) and WHM (WMHvol) normalized to the total intracranial volume were performed using the Computational Anatomy Toolbox 12 (CAT12) and Statistical Parametric Maps 12 (SPM12) based on 3D T1-weighted sequence. The influence of risk factors was assessed using multiple regression analysis before and after correction for multiple comparisons.Results: Older age was associated with lower GMvol and WMvol, and higher WMHvol (p &lt; 0.001). Smaller GMvol volume was associated with higher WMHvol (p &lt; 0.001). Higher WMHvol was associated with hypertension (p = 0.01) and less significantly with hyperlipidemia (only before correction p = 0.03). Diabetes, abnormal BMI, smoking and alcohol intake did not have any significant impact on GMvol, WMvol or WMHvol (p &gt; 0.05). MoCA score was not influenced by any of the factors.Conclusions: Gray matter loss is strongly associated with the accumulation of WMH which seems to be potentially preventable by maintaining normal blood pressure and cholesterol levels.


2014 ◽  
Vol 29 (S3) ◽  
pp. 546-547
Author(s):  
F. Cyprien ◽  
P. Courtet ◽  
P. Poulain ◽  
J. Maller ◽  
C. Meslin ◽  
...  

BackgroundRecent research on late-life depression (LLD) pathophysiology suggests the implication of abnormalities in cerebral white matter [1] and particularly in interhemispheric transfer [2]. Corpus callosum (CC) is the main brain interhemispheric commissure [3]. Hence, we investigated the association between baseline CC measures and risk of LDD.MethodsWe studied 467 non-demented individuals without LLD at baseline from a cohort of community-dwelling people aged 80 years or younger (the ESPRIT study). LLD was assessed at year 2, 4, 7 and 10 of the study follow-up. At baseline, T1-weighted magnetic resonance images were manually traced to measure the mid-sagittal areas of the anterior, mid and posterior CC. Multivariate Cox proportional hazards models stratified by sex were used to predict LLD incidence over 10 years.ResultsA significant interaction between gender and CC size was found (P = 0.02). LLD incidence in elderly women, but not in men, was significantly associated with smaller anterior (HR 1.37 [1.05–1.79] P = 0.017), mid (HR 1.43 [1.09–1.86] P = 0.008), posterior (HR1.39 [1.12–1.74] P = 0.002) and total (HR 1.53 [1.16–2.00] P = 0.002) CC areas at baseline in Cox models adjusted for age, education, global cognitive impairment, ischemic pathologies, left-handedness, white matter lesion, intracranial volume and past depression.LimitationsThe main limitation was the retrospective assessment of major depression.ConclusionsSmaller CC size is a predictive factor of incident LLD over 10 years in elderly women. Our finding suggests a possible role of CC and reduced interhemispheric connectivity in LLD pathophysiology. Extensive explorations are needed to clarify the mechanisms leading to CC morphometric changes in mood disorders.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Benjamin S Aribisala ◽  
Maria C Valdes Hernandez ◽  
Natalie A Royle ◽  
Susana Maniega ◽  
Mark Bastin ◽  
...  

Background: White matter lesions (WML) are associated with hypertension. Blood pressure (BP) is transmitted to the brain via the carotid arteries, and autoregulation helps protect the brain. We investigated if BP via carotid waveform parameters were associated with WML. Methods: We obtained BP measurements from a cohort of community dwelling subjects at mean ages 70±1 and 73±1 years; brain MRI and carotid artery ultrasound at mean age 73±1 years. We calculated mean values of BP (systolic, diastolic, mean, variability and pulsatility), measured WML by volume, and Fazekas scale. We calculated internal carotid artery (ICA) mean blood flow velocity, pulsatility index (PI), and resistivity index (RI). We tested associations between BP and ICA flow parameters and WML using multiple linear regression, corrected for intracranial volume (ICV), age, gender, BMI, previous MI, diabetes, hypertension, smoking, hypercholesterolaemia, PVD and stroke. Results: Amongst 694 subjects, diastolic and mean BP decreased and hence BP pulsatility increased significantly between ages 70 and 73 years. Lower diastolic BP and higher BP pulsatility were associated with higher ICA PI (standardized β, age 70= -0.24, age 73= -0.19, both p<0.001; age 70 β=0.18, p<0.001, age 73 β=0.10, p=0.008 respectively). WML volume was weakly associated with BP at age 70 (diastolic β=0.08, systolic β=0.08, mean β=0.09, all p<0.05) but not with BP variability or pulsatility. Similar but weaker associations were seen at age 73. After adjusting for BP, larger WML volume was associated with higher ICA PI (β=0.10, p=0.012), but not any other measures. All associations were the same for WML Fazekas scores. Conclusions: The relatively weak association between BP and WML may be mediated via ICA pulsatility which is largely driven by falling diastolic BP. This questions the nature of the apparent link between BP and WML.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
YANPENG LIU ◽  
YIWEI XIA ◽  
XIAOXIAO WANG ◽  
YI WANG ◽  
LUMENG YANG ◽  
...  

Background and purpose: White matter hyperintensities (WMH) are common in elderly individuals and contribute to age-related cognitive dysfunction. Converging evidence indicates that WMH affect white matter (WM) microstructural integrity in WMH and their penumbra. We aimed to investigate whether this effect extends to the distal WM tracts, and to examine the association between distal WM microstructural integrity and cognitive dysfunction in community-dwelling elderly people. Methods: Brain MRI data including FLAIR and DTI sequences of 174 participants (74 ± 5 years) of the Shanghai Aging Study (SAS) were collected and analyzed. For each participant, WMH lesions were segmented automatically. Eighteen major WM tracts were reconstructed using automated quantitative tractography, and the mean diffusivity (MD) of distal WM tracts (excluding an area of 12 mm around the WMH) was calculated. Multivariable linear regression was performed. Results: A high burden of tract-specific WMH was related to a high MD of distal WM tracts in the forceps major (FMA), anterior thalamic radiations (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a high MD of distal tracts was linked to worse attention and executive function in the forceps minor (FMI), right CCG, left inferior longitudinal fasciculus (ILF), SLFP, SLFT and UNC. Conclusions: The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions farther than the penumbra and eventually might affect attention and executive function.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013215
Author(s):  
Tiing Yee Siow ◽  
Cheng Hong Toh ◽  
Jung-Lung Hsu ◽  
Geng-Hao Liu ◽  
Shwu-Hua Lee ◽  
...  

Background and Objectives:The glymphatic system, which is robustly enabled during some stages of sleep, is a fluid-transport pathway that clears cerebral waste products. Most contemporary knowledge regarding glymphatic system is inferred from rodent experiments and human research is limited. The objective of the research is to explore the associations between human glymphatic function, sleep, neuropsychological performances, and cerebral gray matter volumes.Methods:This cross-sectional study included individuals 60 years or older who had participated in the Integrating Systemic Data of Geriatric Medicine to Explore the Solution for Health Aging study between September 2019 and October 2020. Community-dwelling older adults were enrolled at 2 different sites. Participants with dementia, major depressive disorders, and other major organ system abnormalities were excluded. Sleep profile was accessed using questionnaires and polysomnography. Administered neuropsychological test batteries included Everyday Cognition (ECog) and the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery (CERAD-NB). Gray matter volumes were estimated based on magnetic resonance imaging (MRI). Diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS) index was used as the MRI marker of glymphatic function.Results:A total of 84 participants (mean [SD] age, 73.3 [7.1] years, 47 [56.0%] women) were analyzed. Multivariate linear regression model determined that age (unstandardized β, -0.0025 [SE, 0.0001]; P = 0.02), N2 sleep duration (unstandardized β, 0.0002 [SE, 0.0001]; P = 0.04), and the apnea-hypopnea index (unstandardized β, -0.0011 [SE, 0.0005]; P = 0.03) were independently associated with DTI-ALPS. Higher DTI-ALPS was associated with better ECog language scores (unstandardized β, -0.59 [SE, 0.28]; P = 0.04) and better CERAD-NB word-list-learning delayed recall subtest scores (unstandardized β, 6.17 [SE, 2.31]; P = 0.009) after co-varying for age and education. Higher DTI-ALPS was also associated with higher gray matter volume (unstandardized β, 107.00 [SE, 43.65]; P = 0.02) after controlling for age, gender, and total intracranial volume.Discussion:Significant associations were identified between glymphatic function and sleep stressing the importance of sleep for brain health. This study also revealed associations between DTI-ALPS, neuropsychological performances, and cerebral gray matter volumes suggesting the potential of DTI-ALPS as a biomarker for cognitive disorders.


2007 ◽  
Vol 19 (4) ◽  
pp. 757-766 ◽  
Author(s):  
Qiong Yang ◽  
Xuebing Huang ◽  
Nan Hong ◽  
Xin Yu

Objective: To evaluate the location and the degree of white matter damage in late-life depression using diffusion tensor imaging (DTI).Methods: Thirty-one patients with late-life depression and 15 healthy volunteers matched for age, gender and years of education received conventional MRI (magnetic resonance imaging) and MR-diffusion tensor scanning. The fractional anisotropy (FA) values of white matter were measured respectively in frontal and temporal regions and the corpus callosum.Results: FA values were significantly decreased in the frontal (superior and middle frontal gyrus), and temporal (right parahippocampal gyrus) regions of elderly patients with depression compared with healthy controls.Conclusion: Microstructural changes in the frontal (superior and middle frontal gyrus) and temporal (right parahippocampal gyrus) areas are associated with late-life depression.


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