Cerebral circulation - cognition and behavior最新文献

{"title":"White matter hyperintensity burden mediates impact of vascular risk factors on cognitive impairment in SOL-INCA","authors":"Charles DeCarli ,&nbsp;Pauline Maillard ,&nbsp;Ariana Stickel ,&nbsp;Wassim Tarraf ,&nbsp;Kevin Gonzalez ,&nbsp;Alejandra Morlett-Paredes ,&nbsp;Donglin Zeng ,&nbsp;Jianwen Cai ,&nbsp;Carmen Isasi ,&nbsp;Robert Kaplan ,&nbsp;Richard Lipton ,&nbsp;Martha Daviglus ,&nbsp;Fernando Testai ,&nbsp;Melissa Lamar ,&nbsp;Linda Gallo ,&nbsp;Gregory Talavera ,&nbsp;Alberto Ramos ,&nbsp;Vladimir Ivanovic ,&nbsp;Stephan Seiler ,&nbsp;Hector Gonzalez","doi":"10.1016/j.cccb.2024.100287","DOIUrl":"10.1016/j.cccb.2024.100287","url":null,"abstract":"<div><h3>Introduction</h3><p>HCHS/SOL is a representative study of Hispanic/Latinos living in the US. SOL-INCA examines cognition amongst those of HCHS/SOL over age 50 and SOL-INCA-MRI obtains quantitative MRI measures on a subgroup of these individuals. Prior research in SOL-INCA found that vascular risk factors summarized by the Framingham Cardiovascular Risk Score (Fram CVD) is associated with Mild Cognitive Impairment (MCI)1. We hypothesize that the extent of white matter hyperintensities (WMH) will partially mediate this impact of Fram CVD on MCI prevalence in this cohort.</p></div><div><h3>Methods</h3><p>SOL-INCA-MRI consists of 2366 individuals of Hispanic/Latino Heritage from 4 centers across the US. Demographics of the cohort are summarized in the Table. High resolution MRI were acquired and WMH burden measured by previously reported methods2. WMH volumes were natural log transformed and corrected for scanner type using NeuroCombat. General linear models were used to test the associated between diagnosis (normal, questionable impairment and MCI) and Fram CVD and WMH adjusting for age, gender, education, heritage, and center. Casual mediation analysis was also performed to assess the extent to which WMH mediated the association between Fram CVD and diagnosis.</p></div><div><h3>Results</h3><p>Subjects were 64.6 + 6.8 years of age at MRI, 68.5% were female, 16% had questionable impairment and 13% had MCI. Mean Fram CVD risk was 11.4 + 0.9%. Mean log WMH was -0.13 +1.55. Diagnosis was significantly associated with Fram CVD (beta= 780, p &lt;0.0001) and WMH (beta =34, p &lt;0.0001). Fram CVD was also strongly associated with WMH (beta = 2.6, p &lt;0.0001). Causal mediation analysis found that WMH significantly mediated the association of Fram CVD to Diagnosis (p &lt; 0.0001) by a proportion of 10%.</p></div><div><h3>Discussion</h3><p>These results indicate that at least part of the impact of Fram CVD of MCI prevalence is mediated by the impact of Fram CVD on white matter injury suggesting that microvascular disease is a strong predictor of cognitive impairment amongst Hispanic/Latinos in the US.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100287"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000886/pdfft?md5=572c45c82e93e8f309fee489865feb39&pid=1-s2.0-S2666245024000886-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validity, Feasibility and Effectiveness of a Voice-recognition Based Digital Cognitive Screener for Dementia and Mild Cognitive Impairment in Community-dwelling Older Chinese Adults: A Large-scale Implementation Study","authors":"Xuhao Zhao ,&nbsp;Haoxuan Wen ,&nbsp;Guohai Xu ,&nbsp;Ting Pang ,&nbsp;Yaping Zhang ,&nbsp;Xindi He ,&nbsp;Ruofei Hu ,&nbsp;Ming Yan ,&nbsp;Christopher Chen ,&nbsp;Xin Xu","doi":"10.1016/j.cccb.2024.100234","DOIUrl":"10.1016/j.cccb.2024.100234","url":null,"abstract":"<div><h3>Introduction</h3><p>To investigate the psychometric properties, administration efficiency and implementational feasibility of a previously piloted voice recognition- based digital cognitive screener for dementia detection in a large-scale community of elderly participants.</p></div><div><h3>Methods</h3><p>Eligible participants completed the demographic, lifestyle investigations and the DCS. Domain-specific and global cognition was assessed by a comprehensive neuropsychological test battery. Diagnosis of mild cognitive impairment(MCI) and dementia was made based on the clinical dementia rating. Completion rate and administration time for the DCS were recorded. Correlation between the DCS and domain-specific and global cognitive performance were assessed. Receiver operating characteristic (ROC) analyses examined the discriminate validity of the DCS in detecting MCI and dementia. A cost-consequences analysis was conducted to compare the screening efficacy of DCS with two traditionally administered cognitive assessment tools, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), was conducted.</p></div><div><h3>Results</h3><p>Among a total of 11,186 participants, the completion rate of the DCS was 97·5% with a conduction time of 5·6–6·1 minutes, regardless of gender, age and education stratifications. DCS total score was significantly associated with domain-specific and global cognitive z-scores. Area under the curves (AUCs) of the DCS were 0·95 (0·92, 0·99) and 0·83 (0·79, 0·88) for dementia and MCI detection, respectively. There was no significant difference on the AUCs among different age- and education-stratified subgroups. Comparing with the MoCA and MMSE, DCS resulted in time savings of 35·4%–36·0% and 30·7%–31·2% for identifying dementia cases, as well as 22·6%–22·8% and 16·2%–16·4% for identifying MCI cases.</p></div><div><h3>Discussion</h3><p>Our findings demonstrated that the DCS was an effective and efficient tool for case-finding of dementia and MCI in a Chinese community. The large-scale implementation of the DCS among older Chinese adults could be a practical cognitive screening strategy to improve the management of healthcare resources.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100234"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000357/pdfft?md5=8e249273e82160bfad9952c03321a1fc&pid=1-s2.0-S2666245024000357-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Nutrition and Cognition in a Multi-Ethnic Cohort from Singapore","authors":"Xiangyuan Huang,&nbsp;Zher Min Tan,&nbsp;Chuen Seng Tan,&nbsp;Yi Lin Ng,&nbsp;Rob van Dam,&nbsp;Saima Hilal","doi":"10.1016/j.cccb.2024.100320","DOIUrl":"10.1016/j.cccb.2024.100320","url":null,"abstract":"<div><h3>Introduction</h3><p>Nutrition, a modifiable risk factor, presents a low-cost prevention strategy to reduce the burden of cognitive impairment and dementia. However, studies examining the effects of dietary patterns on cognition are lacking in multi-ethnic Asian populations. We investigate the association between diet quality, measured with the Alternative Healthy Eating Index (AHEI)-2010, and cognitive impairment in middle-and old-aged adults of different ethnicities (Chinese, Malay, Indian) in Singapore.</p></div><div><h3>Methods</h3><p>This cross-sectional study (n=3138) was based on data from the Singapore Multi-Ethnic Cohort. Dietary intake collected with a validated semi-quantitative Food Frequency Questionnaire were converted into AHEI-2010 scores, where trans-fat and sodium consumption were not considered and a score range of 0-90 was allowed. Higher AHEI-2010 score indicates better compliance to recommended dietary pattern. Cognition, assessed with the Mini-Mental State Examination (MMSE), was analysed as a continuous or binary outcome (cognitively impaired is defined using education-based cut-offs of &lt;23, 25 or 27 for participants with no education, primary school education and secondary school education and above). Multivariable linear and logistic regression models were used to examine associations between AHEI-2010 and cognition, adjusting for covariates.</p></div><div><h3>Results</h3><p>Participants have a mean age of 56.6 (SD = 9.3) years, and 41.6% were male. Participants have a mean AHEI-2010 score of 52.4 (SD = 9.8) and 988 (31.5%) participants had cognitive impairment. Ethnic Chinese (mean = 51.3, SD = 9.6) and Indians (mean = 51.3, SD = 9.7) had higher AHEI-2010 score than Malays (mean = 47.6, SD = 9.9). Higher AHEI-2010 scores were significantly associated with higher MMSE score (p trend &lt; 0.001) and lower odds of cognitive impairment (p trend = 0.01). Compared with lowest quartile, participants from highest quartile had 0.44 (95%CI 0.22, 0.67) higher MMSE score and 31% less cognitive impairment odds (OR = 0.69, 95%CI 0.54, 0.88) after adjusting for all the covariates. However, no significant associations were observed for individual dietary components of the AHEI-2010 with MMSE or cognitive impairment.</p></div><div><h3>Discussion</h3><p>Healthier dietary patterns were associated with better cognitive function in middle- aged and older Singaporeans. These findings could inform better support to promote healthier dietary patterns in Asian populations.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100320"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024001211/pdfft?md5=1766d7f5759fd56631041f893b5b1f08&pid=1-s2.0-S2666245024001211-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What have clinical trials taught us about brain health?","authors":"Keon-Joo Lee ,&nbsp;Hee-Joon Bae","doi":"10.1016/j.cccb.2023.100199","DOIUrl":"https://doi.org/10.1016/j.cccb.2023.100199","url":null,"abstract":"<div><p>The Global Burden of Disease Study projects an almost tripling of dementia cases worldwide in the next 30 years making it important to recognize and understand modifiable risks and preventatives for cognitive impairment. Recent studies suggest that prevention or treatment of cardiovascular risks may be an important strategy to prevent or slow the progression of cognitive impairment. In 2017, the American Heart Association and American Stroke Association introduced metrics for \"optimal brain health\". These metrics defined brain health in terms of ideal health behaviors and factors.</p><p>Since then and leading up to 2017, a number of clinical trials have been conducted to investigate the potential of modification of cardiovascular risks on prevention of dementia or cognitive impairment and thus, enhancement of brain health. This discussion is a review of findings from clinical trials focusing on interventions, including antihypertensive agents, glycemic control and lipid-lowering therapies, multidomain approaches, and antithrombotic medications. Notably, the results highlight the promise of intensive blood pressure lowering strategies and multidomain approaches, as evidenced by the FINGER trial. The review also discusses the potential of treatment or prevention of cerebral small vessel disease (cSVD) and the application of Mendelian randomization as a strategy to preserve brain structure and function.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100199"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245023000430/pdfft?md5=7e9a31e771e7773c7751532b76de912f&pid=1-s2.0-S2666245023000430-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139090205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-stroke delirium is associated with cognitive and psychiatric symptoms over time","authors":"Elise Gjestad ,&nbsp;Vilde Nerdal ,&nbsp;Ingvild Saltvedt ,&nbsp;Stian Lydersen ,&nbsp;Elisabeth Kliem ,&nbsp;Truls Ryum ,&nbsp;Ramune Grambaite","doi":"10.1016/j.cccb.2024.100329","DOIUrl":"10.1016/j.cccb.2024.100329","url":null,"abstract":"<div><h3>Introduction</h3><p>Delirium, an acute and fluctuating disturbance of attention, cognition, and consciousness, may occur in the acute phase of stroke. Research on long-term outcomes of stroke patients experiencing delirium is limited. Our previous findings suggested that patients experiencing acute delirium had increased cognitive and psychiatric symptoms in the chronic phase. In the current study, this was further examined in a larger sample, including measures of global cognition, as well as psychiatric symptoms.</p></div><div><h3>Methods</h3><p>As part of the Nor-COAST study, 373 stroke patients were screened for delirium using the Confusion Assessment</p></div><div><h3>Methods</h3><p>Patients were included in the study if they had available data from any of the follow-ups at three, 18 or 36 months, totaling 334 (44.6% women, mean (SD) age: 72.1 (12.5) years, 17 (5.1%) diagnosed with delirium). Global cognition was measured using the Montreal Cognitive Assessment (MoCA). Psychiatric symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) and the Neuropsychiatric Inventory-Questionnaire (NPI-Q). Subscales of NPI-Q were used to measure specific psychiatric symptoms. Mixed-model linear regression was applied with MoCA, HADS, and NPI-Q, one at a time, as dependent variables. The independent variables were delirium, time as a categorical covariate, and their interaction. Mixed- model binary logistic regression was used to analyze differences in specific psychiatric symptoms.</p></div><div><h3>Results</h3><p>At three months, delirium was only significantly associated with a higher NPI-Q score (mean (SD) 2.9 (3.6) vs 1.4 (2.2)). At 18 and 36 months respectively, delirium was associated with a lower MoCA score (mean (SD) 19.7 (6.6) vs 24.3 (5.0), and 20.6 (7.6) vs 24.6 (4.8)), higher HADS anxiety symptoms (5.0 (4.3) vs 3.3 (3.3), and 5.9 (4.1) vs 3.4 (3.6)), higher HADS depression symptoms (7.2 (4.7) vs 3.4 (3.3), and 6.6 (5.1) vs 3.7 (3.7)), and higher NPI-Q score (2.4 (4.4) vs 1.7 (2.3), 2.6 (4.5) vs 1.0 (1.9)). Delirium significantly predicted the psychiatric symptoms hallucinations and agitation.</p></div><div><h3>Discussion</h3><p>Patients with delirium in the acute phase of stroke may be particularly vulnerable to developing cognitive and psychiatric symptoms in the chronic phase.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100329"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024001302/pdfft?md5=dc5de57774f0ed9654b0a7a1fd0162be&pid=1-s2.0-S2666245024001302-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Haemosiderin Deposits Sign on Susceptibility-Weighted Imaging in Recent Small Subcortical Infarcts","authors":"Yu-Yuan Xu,&nbsp;Francesca Chappell,&nbsp;Carmen Reyes,&nbsp;Joanna Wardlaw","doi":"10.1016/j.cccb.2024.100254","DOIUrl":"10.1016/j.cccb.2024.100254","url":null,"abstract":"<div><h3>Introduction</h3><p>The long-term evolution of recent small subcortical infarcts (SSIs) remains insufficiently characterized. Previous studies have indicated haemosiderin deposits (HD) in SSIs during their subacute and chronic stages. Our study aims to provide a comprehensive description of the morphology and evolution of HD in SSI and explore associated factors.</p></div><div><h3>Methods</h3><p>We enrolled 140 patients with SSI from the Mild Stroke Study 3 (MSS3). Using susceptibility-weighted imaging (SWI), we categorized HD in SSI into five types: none, spots, smudge, rim, and lines/dots around the infarct. The evolution types were classified as single type or mixed type. Over a one-year follow-up period, we examined the evolution of per-infarct associations with HD type and identified influencing factors.</p></div><div><h3>Results</h3><p>Out of the 119 enrolled SSI patients (mean age: 64.3±11.4 years, 80 men [67.2%]), we analyzed 141 small subcortical infarcts, excluding 5 due to motion artifacts or lack of MR scanning at the six-month and one-year follow-ups. During the one-year follow-up, we observed HD in 101 infarcts, with the percentage of HD increasing from 55.0% at baseline to 100% at the one-year follow-up. The predominant initial HD type was smudge, and the main evolution types were retaining smudge of the single type (32.8%) and smudge with rim in the mixed type (23.3%). Logistic regression analysis revealed that infarct volume (OR=1.55, 95% CI 1.13-2.14; P=0.007) and location (basilar ganglia: OR=5.13, 95% CI 1.26-20.83; P=0.022; centrum semiovale: OR=4.125, 95% CI 1.07-15.86, P=0.039) were independent predictors of HD on SWI.</p></div><div><h3>Discussion</h3><p>The presence of HD in SSI detected through SWI may be associated with the volume and location of infarct the infarct. The classification of HD and its evolution hold clinical significance in differentiating an infarct from a primary hemorrhage during the subacute and chronic periods.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100254"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000552/pdfft?md5=6e703d0b43d8d87bbdb1467da3f82ec2&pid=1-s2.0-S2666245024000552-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MINocyclinE to Reduce inflammation and blood brain barrier leakage in small Vessel diseAse - results of the MINERVA randomised controlled trial","authors":"Robin Brown ,&nbsp;Daniel Tozer ,&nbsp;Laurence Loubiere ,&nbsp;Eric Harshfield ,&nbsp;Young Hong ,&nbsp;Tim Fryer ,&nbsp;Guy Williams ,&nbsp;Martin Graves ,&nbsp;Franklin Aigbirhio ,&nbsp;John O'Brien ,&nbsp;Hugh Markus","doi":"10.1016/j.cccb.2024.100316","DOIUrl":"10.1016/j.cccb.2024.100316","url":null,"abstract":"<div><h3>Introduction</h3><p>Cerebral small vessel disease (SVD) is a major cause of cognitive impairment and stroke. Neuroinflammation and blood-brain barrier (BBB) leakage may play a role in pathogenesis, but no definitive causal link has been established. In a rodent SVD model, minocycline treatment reduced brain lesions, neuroinflammation and BBB permeability. We tested whether these processes can be altered in SVD.</p></div><div><h3>Methods</h3><p>MINERVA was a phase II, double-blind, randomised controlled trial in moderate-to-severe symptomatic SVD. Participants with lacunar stroke and confluent white matter hyperintensities underwent simultaneous dynamic contrast-enhanced MRI to measure BBB permeability and 11C- PK11195 positron emission tomography (PET) to quantify microglial signal (figure 1). They were randomised to either minocycline 100mg bd or placebo for three months, after which PET-MRI was repeated. The co-primary outcomes were volumes of ‘hotspots’ of increased BBB permeability and 11C-PK11195 binding in the normal appearing white matter above the 95th percentile of healthy control reference values. A sample size of 44 allowed detection of a 20% reduction in these metrics (power = 80%, α=0.05).</p></div><div><h3>Results</h3><p>44 patients were recruited from September 2019 - June 2022 at 23.1±24.7 months after lacunar stroke. Mean age was 69.9±10.8 years and 28/44 (63.6%) were male. 86.4% had a history of hypertension, 75.0% of hypercholesterolaemia and 18.2% were diabetic. Participants had mean white matter lesion volume of 31.3±26.0cc and median 2 (IQR 1–3) lacunes. The BBB permeability ‘hotspot’ tissue was 4.08±3.69% in the treatment group at baseline and 6.19±5.09% at follow-up; ‘hotspot’ tissue was 8.49±8.45% in the placebo group at baseline and 13.04±9.24% at follow-up (relative risk of treatment 0.97, 95% CI 0.91–1.03). The 11C-PK11195 ‘hotspot’ tissue was 10.71±4.04% in the treatment group at baseline and 9.97±5.50% at follow-up; ‘hotspot’ tissue was 10.11±4.67% in the placebo group at baseline and 7.79±5.67% at follow-up (RR 1.01, 95% CI 0.98–1.04; figure 2).</p></div><div><h3>Discussion</h3><p>Minocycline does not alter BBB permeability or microglial activity (measured using DCE-MRI and 11C-PK11195 respectively) in SVD patients. Secondary outcomes include changes in a panel of serum inflammatory biomarkers, and one-year progression of MRI white matter damage and cognitive performance.</p><p>International Clinical Trials Registry Platform reference: ISRCTN15483452 (<span><span>http://isrctn.com/ISRCTN15483452</span><svg><path></path></svg></span>)</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100316"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266624502400117X/pdfft?md5=63259ecdaa83c0925afb68dd52ca6951&pid=1-s2.0-S266624502400117X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Serum Proteomic Biomarker Profile and Brain Aging in the Swedish Good Aging in Skåne Study (GÅS)","authors":"Katarina Ellström ,&nbsp;Tomas Månsson ,&nbsp;Kasim Abul-Kasim ,&nbsp;Arkadiusz Siennicki-Lantz ,&nbsp;Sölve Elmståhl","doi":"10.1016/j.cccb.2024.100280","DOIUrl":"10.1016/j.cccb.2024.100280","url":null,"abstract":"<div><h3>Introduction</h3><p>Magnetic resonance imaging of the brain reveals age-related pathologies like white matter hyperintensities (WMH), cerebral microbleeds (CMB), lacunar infarcts (LAC) and grey- and white matter atrophy. The term cerebral small vessel disease (CSVD) has been used to collectively describe these changes, believed to emanate from small vessel endothelial dysfunction, although pathophysiological mechanisms are still largely unknown. We hypothesized that an explorative investigation of the plasma biomarker profile in affected subjects might shed some light on underlying mechanisms involved in CSVD and brain atrophy.</p></div><div><h3>Methods</h3><p>In a cross-sectional design, we investigated 401 subjects aged 70-86 from the randomized population study Good Aging in Skåne Study (GÅS) with brain MRI and OLINK immune- assay proteomics of 257 serum proteins previously associated with cardiovascular disease (CVD II and CVD III) and inflammation. The Benjamini-Yekutieli correction was used for keeping the false discovery rate (FDR) at 5%.</p></div><div><h3>Results</h3><p>We could see no significant difference in protein expression in the individual markers of CSVD (WMH, CMB or LAC). We observed a significant association between CSVD severity score (including white and grey matter atrophies, WMH, CMB and LAC) and the elevation of 11 serum proteins (CTSL1, PGF, NTpBNP, TNFr2, GDF15, TNFr1, IL4RA, ADM, CXCL9, TFF3, BNP). Furthermore, 11 proteins were significantly associated with Cortical Atrophy (CDH5, IL4RA, TNFr1, PGF, TF, TNFr2, CD93, CTSL1, LTBR, TNFRSF11A, TNFRSF10A). Five of the proteins were significant in both models. We found an association between moderate/severe medial temporal lobe atrophy (MTA) according to Scheltens scale and overexpression of PI3. Atrophy of presumed non-vascular origin was significantly associated with a greater abundance of IL4RA. All models were corrected for FDR and entered into a multivariable model with age and sex as covariates.</p></div><div><h3>Discussion</h3><p>In a general population cohort of older adults, proteomic analysis of serum identified several proteins associated with MRI-markers of CSVD and brain atrophy. Many of the identified protein biomarkers have previously been associated with hypertension, metabolic disease, or chronic kidney failure. This emphasizes the importance of systemic vascular health on cerebral pathological changes.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100280"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000813/pdfft?md5=b2919ccb3481f63dec01eec6cfd5ee5c&pid=1-s2.0-S2666245024000813-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Cardiac Output and Cerebral Blood Flow in Older Adults from a General Population of GÅS - Good Aging in Scania Study","authors":"Arkadiusz Siennicki-lantz,&nbsp;Sölve Elmståhl","doi":"10.1016/j.cccb.2024.100314","DOIUrl":"10.1016/j.cccb.2024.100314","url":null,"abstract":"<div><h3>Introduction</h3><p>In healthy adults, 15-20% of cardiac output is distributed to the brain. During aging, absolute cerebral blood flow (CBF) values show significant decline across most parts of the brain, approximately 0.38 ∼ 0.45% per year. CBF decline is suggested to be associated with reduction in neuronal activity and degeneration in microvasculature. However, there was no significant association between global CBF and several vascular risk factors. We examined therefore if Cardiac output, a hemodynamic measure of left ventricular pump capacity, is associated with regional CBF during aging.</p></div><div><h3>Methods</h3><p>A population based randomised cohort of older adults (n=341), aged 73-87 years (mean 77.4; SD 3.8), took part in a Swedish GÅS study. The regional CBF was examined with arterial spin labelling MRI. The CBF-maps were directly obtained from the MRI-system without any additional processing and regions (ROIs) were positioned upon anatomical preferences. Hemodynamic measures were obtained with Finometer within 6 months from MRI examination, and Cardiac Output was calculated through waveforms recorded from the middle finger and brachial level. Pulsatility Index was calculated (PSV-EDV/MeanV) in both Common Carotid Arteries using ultrasound. Aortic stiffness has been estimated by carotid-femoral pulse wave velocity (cfPWV) (table 1).</p></div><div><h3>Results</h3><p>Age was associated with Pulsatility indexes (Right r=0.21; left r=0.19), cfPWV (r=0.16), and cardiac output (r= −0.16), but not with mean blood pressure, heart rate or regional CBF.</p><p>Cardiac Output was associated with regional CBF in a majority of areas in left and right hemisphere. A linear regression unstandardized coefficients (B) are presented in Table 2 , adjusted for: age, gender, heart rate, mean blood pressure, pulsatility index of corresponding carotid, and cfPWV. Strongest associations were observed in posterior and cerebellar areas, as well as border zone /watershed areas. Gender was a significant confounder in several ROIs, indicating stronger association in females.</p></div><div><h3>Discussion</h3><p>The variability of regional CBF increases in elderly population and cardiac output is decreasing with age. In older adults, Cardiac Output is strongly associated with regional CBF, especially in posterior and watershed brain areas, independently of central or peripheral arterial stiffness. Sex-related difference observed in younger elderly is still present in aging.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100314"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024001156/pdfft?md5=ac6b46172ca90d30acaf37a5d4f402c8&pid=1-s2.0-S2666245024001156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peak width of skeletonized mean diffusivity as a biomarker of small vessel disease in predementia Alzheimer's disease","authors":"Jonas Jarholm ,&nbsp;Sandra Tecelão ,&nbsp;Lene Pålhaugen ,&nbsp;Atle Bjørnerud ,&nbsp;Bjørn Eivind Kirsebom ,&nbsp;Tormod Fladby ,&nbsp;Per Selnes","doi":"10.1016/j.cccb.2024.100303","DOIUrl":"10.1016/j.cccb.2024.100303","url":null,"abstract":"<div><h3>Introduction</h3><p>Alzheimer's disease (AD) and cerebral small vessel disease (SVD) frequently coexist, and increasing evidence suggest that microvascular changes may be related to AD pathology. SVD is however heterogeneously expressed on magnetic resonance imaging (MRI), and several novel methods can determine different aspects of vascular pathology. These methods need to be explored properly in clinical AD cohorts to better understand the link between AD and SVD, and could possibly be included in the staging and diagnostics of AD.</p></div><div><h3>Methods</h3><p>588 subjects were included from the Norwegian Dementia Disease initiation (DDI) cohort, longitudinal data was available for 285 subjects. Subjects underwent clinical examination including lumbar puncture, and were classified according to the A/T/N-system into the following groups: A-/T-/N- (N=208), A-/T+/N± (N=11), A+/T-/N- (N=75)and A+/T+/N±(N=157) according to positive (+) or negative (-) values of cerebrospinal fluid (CSF) amyloid-β42/40-ratio (A), phosphorylated-tau (T) and total-tau (N)). We used Peak width of skeletonized mean diffusivity (PSMD), a novel MRI Diffusion Tensor Imaging (DTI) method for determination of global SVD-burden based on an automated algorithm (5). We used a mixed linear regression model to determine baseline and longitudinal differences in PSMD across A/T/N-classified subjects in a predementia cohort, adjusted for subject and scanner as a random effect.</p></div><div><h3>Results</h3><p>Compared to A-/T-/N- at baseline, we found significantly larger SVD burden in A+/T-/N- compared to A-/T-/N- (p&lt;0.05). Longitudinally, we found a significantly greater increase in SVD burden measured by PSMD in A+/T+/N± compared to A-/T-/N- (p&lt;0.001).</p></div><div><h3>Discussion</h3><p>Our findings indicate that PSMD reflects AD-related SVD. Notably, SVD burden increased markedly in in A+/T+/N± subjects, compared to biomarker-negative subjects. These microvascular alterations may be subsequent events following the formation of amyloid and neurofibrillary tangle pathology. Our findings thereby contribute to the growing body of evidence linking AD pathology and SVD. Further exploration of this connection via CSF candidate biomarkers reflecting vascular pathology is warranted for a deeper understanding of these intertwined pathologies.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100303"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024001041/pdfft?md5=d3d4e67285fedc575467951c3da11434&pid=1-s2.0-S2666245024001041-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}