Abstract P425: Central Aortic Stiffening in Late-life and Odds of Dementia: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Priya Palta ◽  
Jingkai Wei ◽  
Aozhou Wu ◽  
Michelle Meyer ◽  
A Richey Sharrett ◽  
...  
Keyword(s):  
Aortic Stiffness ◽  
Late Life ◽  
Cognitive Status ◽  
Cognitive Testing ◽  
Multivariable Logistic Regression Model ◽  
Microvascular Damage ◽  
Atherosclerosis Risk In Communities ◽  
Expert Review ◽  
Adjusted Association ◽  
Aortic Stiffening

Introduction: Stiffening of the aorta is associated with greater pulse pressure and transmission of pulsatile energy into the cerebral circulation, which can increase susceptibility to microvascular damage in the brain. We tested the hypothesis that higher aortic stiffness measured in late-life is associated with a greater prevalence odds of dementia measured ~5 years later. Methods: Dementia-free ARIC-NCS participants (n=4753; mean age: 75 years; 42% male; 21% black) with measures of aortic stiffness at the visit 5 (2011-2013) examination were included. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV) using the VP-1000 Plus device (Omron Co., Japan) and modeled as continuous (per standard deviation (SD)), categorical into distribution-based quartiles, and as elevated vs. non-elevated cfPWV according to the upper 25 th percentile (13.34 m/s). Cognitive status (normal/mild cognitive impairment (MCI)/dementia) was ascertained at the visit 5 and 6 (2016-2017) examinations with expert review by an adjudication committee of in-person cognitive testing. A multivariable logistic regression model estimated the adjusted association of cfPWV with 5-year odds of dementia. Results: Among dementia-free participants, a 1 SD higher cfPWV was associated with a greater odds of dementia (Odds Ratio (OR): 1.19 (95% Confidence Interval (CI): 1.03, 1.39). Elevated cfPWV (upper 25 th percentile) was also associated with a greater odds of dementia (OR: 1.54, 95% CI: 1.08, 2.19) in this sample. This association was stronger among participants who were cognitively normal at visit 5 (n=3758, Table): the multivariable-adjusted OR of dementia = 2.16 (95% CI: 1.35, 3.47) for elevated vs. non-elevated cfPWV. The risk of dementia among those with baseline MCI (n=955) was not associated with cfPWV levels. Results were robust to adjustment for vascular risk factors. Conclusions: Among older adults, especially when MCI is not present, greater central aortic stiffness is associated with dementia risk.

Abstract P014: Aortic Stiffness and Late-life Depression: the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)

Circulation ◽  
2019 ◽  
Vol 139 (Suppl_1) ◽  
Author(s):  
Jingkai Wei ◽  
Priya Palta ◽  
Kenneth R Butler ◽  
Mariana Lazo ◽  
Benjamin D Capistrant ◽  
...  
Keyword(s):  
Aortic Stiffness ◽  
Late Life ◽  
Late Life Depression ◽  
Atherosclerosis Risk In Communities ◽  
Atherosclerosis Risk

scholarly journals Associations between arterial stiffening and brain structure, perfusion, and cognition in the Whitehall II Imaging Sub-study: A retrospective cohort study

PLoS Medicine ◽  
2020 ◽  
Vol 17 (12) ◽  
pp. e1003467
Author(s):  
Sana Suri ◽  
Scott T. Chiesa ◽  
Enikő Zsoldos ◽  
Clare E. Mackay ◽  
Nicola Filippini ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Structure ◽  
Cerebral Perfusion ◽  
Aortic Stiffness ◽  
Verbal Learning ◽  
Late Life ◽  
Semantic Fluency ◽  
Arterial Stiffening ◽  
Aortic Stiffening

Background Aortic stiffness is closely linked with cardiovascular diseases (CVDs), but recent studies suggest that it is also a risk factor for cognitive decline and dementia. However, the brain changes underlying this risk are unclear. We examined whether aortic stiffening during a 4-year follow-up in mid-to-late life was associated with brain structure and cognition in the Whitehall II Imaging Sub-study. Methods and findings The Whitehall II Imaging cohort is a randomly selected subset of the ongoing Whitehall II Study, for which participants have received clinical follow-ups for 30 years, across 12 phases. Aortic pulse wave velocity (PWV) was measured in 2007–2009 (Phase 9) and at a 4-year follow-up in 2012–2013 (Phase 11). Between 2012 and 2016 (Imaging Phase), participants received a multimodal 3T brain magnetic resonance imaging (MRI) scan and cognitive tests. Participants were selected if they had no clinical diagnosis of dementia and no gross brain structural abnormalities. Voxel-based analyses were used to assess grey matter (GM) volume, white matter (WM) microstructure (fractional anisotropy (FA) and diffusivity), white matter lesions (WMLs), and cerebral blood flow (CBF). Cognitive outcomes were performance on verbal memory, semantic fluency, working memory, and executive function tests. Of 542 participants, 444 (81.9%) were men. The mean (SD) age was 63.9 (5.2) years at the baseline Phase 9 examination, 68.0 (5.2) at Phase 11, and 69.8 (5.2) at the Imaging Phase. Voxel-based analysis revealed that faster rates of aortic stiffening in mid-to-late life were associated with poor WM microstructure, viz. lower FA, higher mean, and radial diffusivity (RD) in 23.9%, 11.8%, and 22.2% of WM tracts, respectively, including the corpus callosum, corona radiata, superior longitudinal fasciculus, and corticospinal tracts. Similar voxel-wise associations were also observed with follow-up aortic stiffness. Moreover, lower mean global FA was associated with faster rates of aortic stiffening (B = −5.65, 95% CI −9.75, −1.54, Bonferroni-corrected p < 0.0125) and higher follow-up aortic stiffness (B = −1.12, 95% CI −1.95, −0.29, Bonferroni-corrected p < 0.0125). In a subset of 112 participants who received arterial spin labelling scans, faster aortic stiffening was also related to lower cerebral perfusion in 18.4% of GM, with associations surviving Bonferroni corrections in the frontal (B = −10.85, 95% CI −17.91, −3.79, p < 0.0125) and parietal lobes (B = −12.75, 95% CI −21.58, −3.91, p < 0.0125). No associations with GM volume or WMLs were observed. Further, higher baseline aortic stiffness was associated with poor semantic fluency (B = −0.47, 95% CI −0.76 to −0.18, Bonferroni-corrected p < 0.007) and verbal learning outcomes (B = −0.36, 95% CI −0.60 to −0.12, Bonferroni-corrected p < 0.007). As with all observational studies, it was not possible to infer causal associations. The generalisability of the findings may be limited by the gender imbalance, high educational attainment, survival bias, and lack of ethnic and socioeconomic diversity in this cohort. Conclusions Our findings indicate that faster rates of aortic stiffening in mid-to-late life were associated with poor brain WM microstructural integrity and reduced cerebral perfusion, likely due to increased transmission of pulsatile energy to the delicate cerebral microvasculature. Strategies to prevent arterial stiffening prior to this point may be required to offer cognitive benefit in older age. Trial registration ClinicalTrials.gov NCT03335696

scholarly journals Accelerated aortic stiffness is associated with brain structure, perfusion and cognition in the Whitehall II Imaging Sub-study

2020 ◽  
Author(s):  
Sana Suri ◽  
Scott T. Chiesa ◽  
Enikő Zsoldos ◽  
Clare E. Mackay ◽  
Nicola Filippini ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Perfusion ◽  
Aortic Stiffness ◽  
Grey Matter ◽  
White Matter Lesions ◽  
Late Life ◽  
Grey Matter Volume ◽  
Semantic Fluency ◽  
Matter Volume ◽  
Aortic Stiffening

AbstractBackgroundAortic stiffness is closely linked with cardiovascular diseases, but recent studies suggest that it is also a risk factor for cognitive decline and dementia. However, the brain changes underlying this risk are unclear. We examined whether aortic stiffening in the transition from mid to late-life affects brain structure and cognition.Methods and FindingsAortic pulse wave velocity was measured in 2007-09 (Phase 9) and at a 4-year follow-up in 2012-13 (Phase 11) in the Whitehall II Imaging Sub-study cohort. Between 2012-2016 (Imaging Phase), participants received a multi-modal 3T brain magnetic resonance imaging (MRI) scans and cognitive tests. Participants were selected if they had no clinical diagnosis of dementia and no gross brain structural abnormalities. Voxel-based analyses were used to assess grey matter volume, white matter microstructure (fractional anisotropy and diffusivity), cerebral blood flow, and white matter lesions. Cognitive outcomes were performance on verbal memory, semantic fluency, working memory and executive function tests. Of 544 participants, 445 (81.8%) were men. The mean (SD) age was 63.9 (5.2) years at the baseline Phase 9 examination, 67.9 (5.3) years at Phase 11 and 69.8 (5.2) years at the Imaging Phase. Voxel-based analysis revealed that accelerated aortic stiffening in mid-to-late life was associated with poor white matter integrity, viz. lower fractional anisotropy in 4.2% of white matter and higher radial diffusivity in 6.7% of white matter, including the corpus callosum, corona radiata, superior longitudinal fasciculus and corticospinal tracts. Accelerated aortic stiffening was also related to lower cerebral perfusion in 1.1% of grey matter including the parietal, frontal, and occipital cortices. No associations with grey matter volume or white matter lesions were observed. Further, higher baseline aortic stiffness was associated with poor semantic fluency (B=-0.48, 95%CI −0.77 to −0.19, p<0.005) and verbal learning outcomes (B=-0.36, 95%CI - 0.60 to −0.13, p<0.005).ConclusionsFaster aortic stiffening in mid-to-late life is associated with poor brain white matter microstructural integrity and reduced cerebral perfusion, likely due to increased transmission of pulsatile energy to the delicate cerebral microvasculature. Strategies to prevent arterial stiffening prior to this point may be required to offer cognitive benefit in older age.

scholarly journals Frequency of But Not Capacity for Participation in Everyday Activities Is Associated With Cognitive Impairment in Late Life

2021 ◽  
pp. 073346482098428
Author(s):  
Chao-Yi Wu ◽  
Juleen Rodakowski ◽  
Lauren Terhorst ◽  
Mary Amanda Dew ◽  
Meryl Butters ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Late Life ◽  
Cognitive Status ◽  
Computerized Adaptive Test ◽  
Time Points ◽  
Everyday Activities ◽  
Neuropsychological Status ◽  
Activity Frequency ◽  
Test Version ◽  
Life Function

We examined features of everyday activities (capacity and frequency) between older adults with and without cognitive impairment over 12 months. Participants aged ≥60 years and at risk for depression were included (n = 260); 26% ( n = 69) had an acquired cognitive impairment at baseline. Cognitive impairment was defined as one standard deviation below norms on the Repeatable Battery for the Assessment of Neuropsychological Status. Features of everyday activities were measured by a computerized adaptive test version of Late-Life Function and Disability Instrument (LLFDI) at six time points (baseline, 6 weeks, 3, 6, 9, 12 months). There were significant between-group differences in activity frequency ( p = .04), but not activity capacity ( p = .05). The group difference in activity frequency exceeded minimal detectable changes (MDC90 = 3.7) and reached moderate clinical meaningfulness (∆ at six time points = 3.7–4.7). Generalized linear mixed models revealed no Group × Time interactions on activity capacity and frequency ( p = .65 and p = .98). Practitioners may assess changes in activity frequency to monitor cognitive status of clients even when there is no loss of activity capacity.

scholarly journals Rapid ascending aorta stiffening in bicuspid aortic valve on serial cardiovascular magnetic resonance evaluation: comparison with connective tissue disorders

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Alejandro Perez-Casares ◽  
Audrey Dionne ◽  
Kimberlee Gauvreau ◽  
Ashwin Prakash
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Aortic Valve ◽  
Connective Tissue ◽  
Bicuspid Aortic Valve ◽  
Aortic Stiffness ◽  
Comparison Group ◽  
Aortic Distensibility ◽  
Connective Tissue Disorders ◽  
Aortic Stiffening

Abstract Background Aortic stiffness has been shown to be abnormal in patients with bicuspid aortic valve (BAV), and is considered a component of the aortopathy associated with this condition. Progressive aortic stiffening associated with aging has been previously described in normal adults. However, it is not known if aging related aortic stiffening occurs at the same rate in BAV patients. We determined the longitudinal rate of decline in segmental distensibility in BAV patients using serial cardiovascular magnetic resonance (CMR) studies, and compared to previously published results from a group of patients with connective tissue disorders (CTD). Methods A retrospective review of CMR and clinical data on children and adults with BAV (n = 49, 73% male; 23 ± 11 years) with at least two CMRs (total 98 examinations) over a median follow-up of 4.1 years (range 1–9 years) was performed to measure aortic distensibility at the ascending (AAo) and descending aorta (DAo). Longitudinal changes in aortic stiffness were assessed using linear mixed-effects modeling. The comparison group of CTD patients had a similar age and gender profile (n = 50, 64% male; 20.6 ± 12 years). Results Compared to CTD patients, BAV patients had a more distensible AAo early in life but showed a steeper decline in distensibility on serial examinations [mean 10-year decline in AAo distensibility (× 10−3 mmHg−1) 2.4 in BAV vs 1.3 in CTD, p = 0.005]. In contrast, the DAo was more distensible in BAV patients throughout the age spectrum, and DAo distensibility declined with aging at a rate similar to CTD patients [mean 10 year decline in DAo distensibility (× 10−3 mmHg−1) 0.3 in BAV vs 0.4 in CTD, p = 0.58]. Conclusions On serial CMR measurements, AAo distensibility declined at significantly steeper rate in BAV patients compared to a comparison group with CTDs, while DAo distensibility declined at similar rates in both groups. These findings offer new mechanistic insights into the differing pathogenesis of the aortopathy seen in BAV and CTD patients.

scholarly journals Vascular lesions and functional limitations among older adults: does depression make a difference?

2014 ◽  
Vol 26 (9) ◽  
pp. 1501-1509 ◽  
Author(s):  
Celia F. Hybels ◽  
Carl F. Pieper ◽  
Lawrence R. Landerman ◽  
Martha E. Payne ◽  
David C. Steffens
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
White Matter ◽  
Functional Impairment ◽  
Functional Limitations ◽  
Late Life ◽  
Cognitive Status ◽  
Cerebral White Matter ◽  
Late Life Depression ◽  
Increased Risk

ABSTRACTBackground:The association between disability and depression is complex, with disability well established as a correlate and consequence of late life depression. Studies in community samples report that greater volumes of cerebral white matter hyperintensities (WMHs) seen on brain imaging are linked with functional impairment. These vascular changes are also associated with late life depression, but it is not known if depression is a modifier in the relationship between cerebrovascular changes and functional impairment.Methods:The study sample was 237 older adults diagnosed with major depression and 140 never depressed comparison adults, with both groups assessed at study enrollment. The dependent variable was the number of limitations in basic activities of daily living (ADL), instrumental ADLs, and mobility tasks. The independent variable was the total volume of cerebral white matter lesions or hyperintensities assessed though magnetic resonance imaging.Results:In analyses controlling for age, sex, race, high blood pressure, and cognitive status, a greater volume of WMH was positively associated with the total number of functional limitations as well as the number of mobility limitations among those older adults with late life depression but not among those never depressed, suggesting the association between WMH volume and functional status differs in the presence of late life depression.Conclusions:These findings suggest older patients with both depression and vascular risk factors may be at an increased risk for functional decline, and may benefit from management of both cerebrovascular risk factors and depression.

scholarly journals Midlife Plasma Aβ and Late-Life Risk of Cognitive Impairment: The Atherosclerosis Risk in Communities Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 251-252
Author(s):  
Kevin Sullivan ◽  
Chad Blackshear ◽  
A Richey Sharrett ◽  
Rebecca Gottesman ◽  
David Knopman ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Standard Deviation ◽  
Sex Education ◽  
Lower Risk ◽  
Late Life ◽  
Cognitive Status ◽  
Cognitive Outcomes ◽  
Effective Population ◽  
Standard Deviation Increase ◽  
Cerebral Amyloidosis

Abstract Plasma-based biomarkers of amyloid beta (Aβ), a neuropathological hallmark of Alzheimer’s disease, show promise in predicting cognitive impairment and mapping onto cerebral amyloidosis, but little is known about how midlife plasma Aβ associates with late-life cognitive outcomes. Midlife plasma variants Aβ42 and Aβ40 were measured using a fluorimetric bead-based immunoassay in a subsample of visit 3 ARIC participants (1993-95; n=2585, mean age=59.4±5.2, 57% female, 23% African American). We investigated the relationship between midlife plasma Aβ and late-life mild cognitive impairment (MCI; n=923) and dementia (n=628) diagnosed from 2011-19. Multinomial logistic regressions estimated relative risk ratios (RRR) of MCI, dementia, and death vs normal cognitive status as a function of:(1) Aβ42:Aβ40 ratio, (2) Aβ42 and Aβ40 included as separate terms, and (3) Protected Aβ group (participants with Aβ42≥46 pg/ml and Aβ40 &lt;233 pg/ml). Adjusters included age, sex, education, site-race, and APOE4. Every doubling of midlife plasma Aβ42:Aβ40 up to a threshold of 0.20 was associated with 41% lower risk of developing MCI/dementia in comparison to cognitively normal (RRR=0.59 [95% CI:0.42, 0.82]), with no association for ratio values ≥0.20. Every standard deviation increase in plasma Aβ42 was associated with 17% lower risk of dementia (RRR=0.83 [0.70, 0.99]), whereas every standard deviation increase in plasma Aβ40 was associated with 16% higher risk of MCI (RRR=1.16 [1.02, 1.31]). The protected midlife plasma Aβ group had 86% lower risk of late-life dementia vs all others (RRR=0.14 [0.04, 0.47]). Early measurement of plasma Aβ may prove an accessible and effective population screener for future cognitive impairment.

Abstract P231: Inhibition of Mir-762 Prevents and Reverses Ang II Induced Aortic Stiffening

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Kim Ramil C Montaniel ◽  
Jing Wu ◽  
Matthew R Bersi ◽  
Liang Xiao ◽  
Hana A Itani ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Aortic Stiffness ◽  
Fold Increase ◽  
Organ Damage ◽  
Locked Nucleic Acid ◽  
Ang Ii ◽  
New Approach ◽  
Acid Inhibitor ◽  
Aortic Stiffening

We and others have shown that hypertension (HTN) is linked with striking fibrosis in the aortic adventitia. This leads to aortic stiffening, leading to organ damage. Through a screen of microRNAs (miRNAs) in the aorta, we found that miR-762 is the most upregulated miRNA in Ang II hypertensive mice. qRT-PCR confirmed that miR-762 is upregulated 6.35±1.22 (p=0.03) fold in Ang II-infused mice compared to controls. To study the role of miR-762 in HTN, we administered a locked nucleic acid inhibitor of miR-762. MiR-762 inhibition normalized stress-strain relationships and aortic systolic energy storage (ASE) (Table). Moreover, miR-762 inhibition in the last 2 weeks of Ang II infusion reversed aortic stiffness in mice treated with 4 wk of Ang II (ASE, 4 wk Ang II [51±5.18 kPa] vs 4wk Ang II + LNA-762 (last 2 wk) [20±1.76 kPa], p<0.0001). Further studies showed that miR-762 inhibition reduced mRNA for several collagens and fibronectin and upregulated collagenases MMP1a, 8 and 13 (Table). Lastly, we found that miR-762 inhibition during Ang II infusion led to a 9.11±1.92 (p=0.007) fold increase in Sprouty1 mRNA, suggesting that miR-762 targets Sprouty1 mRNA. Sprouty1 inhibits the activation of p38-MAPK which is critical in the process of aortic stiffening. Hence, miR-762 modulates aortic stiffening and fibrosis through a Sprouty1-p38-MAPK mechanism. Thus, miR-762 has a major role in modulating aortic stiffening and its inhibition dramatically inhibits pathological fibrosis, enhances matrix degradation, prevents and reverses aortic stiffness. miR-762 inhibition might represent a new approach to prevent aortic stiffening and its consequent end-organ damage.

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