Cerebral circulation - cognition and behavior最新文献

{"title":"What will it take to achieve brain health globally?","authors":"Philip B. Gorelick ,&nbsp;Atticus H. Hainsworth ,&nbsp;Anders Wallin","doi":"10.1016/j.cccb.2024.100209","DOIUrl":"10.1016/j.cccb.2024.100209","url":null,"abstract":"<div><p>Brain health initiatives and programs are gaining traction worldwide. Some are clinically based, others research based, and some are a combination of clinical and research action plans. Achievement of global brain health is a challenging endeavor with prerequisites including but not limited to multidisciplinary and multisectoral approaches, strengthening of neurologic policies at local and regional levels, global advocacy, leadership and collaboration amongst stakeholders, development of technical and guidance documents, and strengthening and interpretation of the relevant evidence. Over 1 billion persons worldwide are impacted by neurologic disorders, and brain health initiatives are needed to curb the human suffering and cost of these disorders. We provide a brief review of select brain health initiatives and programs and offer possible steps to achieve brain health globally.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100209"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000102/pdfft?md5=dc0f13b3eaf7edb4c05cf761efe22c4b&pid=1-s2.0-S2666245024000102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139633170","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":"Fluid biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: A systematic review and meta-analysis","authors":"Gurpreet Kaur Hansra ,&nbsp;Tharusha Jayasena ,&nbsp;Satoshi Hosoki ,&nbsp;Anne Poljak ,&nbsp;Ben Chun Pan Lam ,&nbsp;Ruslan Rust ,&nbsp;Abhay Sagare ,&nbsp;Berislav Zlokovic ,&nbsp;Anbupalam Thalamuthu ,&nbsp;Perminder S. Sachdev","doi":"10.1016/j.cccb.2024.100216","DOIUrl":"10.1016/j.cccb.2024.100216","url":null,"abstract":"<div><h3>Background</h3><p>The disruption of the neurovascular unit (NVU), which maintains the integrity of the blood brain barrier (BBB), has been identified as a critical mechanism in the development of cerebrovascular and neurodegenerative disorders. However, the understanding of the pathophysiological mechanisms linking NVU dysfunction to the disorders is incomplete, and reliable blood biomarkers to measure NVU dysfunction are yet to be established. This systematic review and meta-analysis aimed to identify biomarkers associated with BBB dysfunction in large vessel disease, small vessel disease (SVD) and vascular cognitive disorders (VCD).</p></div><div><h3>Methods</h3><p>A literature search was conducted in PubMed, EMBASE, Scopus and PsychINFO to identify blood biomarkers related to dysfunction of the NVU in disorders with vascular pathologies published until 20 November 2023. Studies that assayed one or more specific markers in human serum or plasma were included. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Effects were pooled and methodological heterogeneity examined using the random effects model.</p></div><div><h3>Results</h3><p>A total of 112 studies were included in this review. Where study numbers allowed, biomarkers were analysed using random effect meta-analysis for VCD (1 biomarker; 5 studies) and cerebrovascular disorders, including stroke and SVD (9 biomarkers; 29 studies) while all remaining biomarkers (<em>n</em> = 17 biomarkers; 78 studies) were examined through qualitative analysis. Results of the meta-analysis revealed that cerebrospinal fluid/serum albumin quotient (Q-Alb) reliably differentiates VCD patients from healthy controls (MD = 2.77; 95 % CI = 1.97–3.57; <em>p</em> &lt; 0.0001) while commonly measured biomarkers of endothelial dysfunction (VEGF, VCAM-1, ICAM-1, vWF and E-selectin) and neuronal injury (NfL) were significantly elevated in vascular pathologies. A qualitative assessment of non-meta-analysed biomarkers revealed NSE, NfL, vWF, ICAM-1, VCAM-1, lipocalin-2, MMP-2 and MMP-9 levels to be upregulated in VCD, although these findings were not consistently replicated.</p></div><div><h3>Conclusions</h3><p>This review identifies several promising biomarkers of NVU dysfunction which require further validation. A panel of biomarkers representing multiple pathophysiological pathways may offer greater discriminative power in distinguishing possible disease mechanisms of VCD.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100216"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000175/pdfft?md5=2fc4c46f54237bc876668e0051ea5020&pid=1-s2.0-S2666245024000175-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139967097","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}

{"title":"DEveloping BBB-ASL as non-Invasive Early biomarker of Alzheimer's Disease (DEBBIE-AD): Study design","authors":"Beatriz Padrela ,&nbsp;Amnah Mahroo ,&nbsp;Mervin Tee ,&nbsp;Markus Sneve ,&nbsp;Paulien Moyaert ,&nbsp;Oliver Geier ,&nbsp;Joost Kuijer ,&nbsp;Soetkin Beun ,&nbsp;Wibeke Nordhøy ,&nbsp;Yufei David Zhu ,&nbsp;Mareike Buck ,&nbsp;Daniel Hoinkiss ,&nbsp;Simon Konstandin ,&nbsp;Jörn Huber ,&nbsp;Julia Wiersinga ,&nbsp;Roos Rikken ,&nbsp;Diederick de Leeuw ,&nbsp;Håkon Grydeland ,&nbsp;Lynette Tippett ,&nbsp;Erin Cawston ,&nbsp;Henk J.M.M. Mutsaerts","doi":"10.1016/j.cccb.2024.100308","DOIUrl":"10.1016/j.cccb.2024.100308","url":null,"abstract":"<div><h3>Introduction</h3><p>Arterial spin labeling (ASL) MRI, a non-invasive technique for imaging perfusion, now allows studying BBB permeability. The DEveloping BBB-ASL as a non-Invasive Early biomarker of Alzheimer's Disease (DEBBIE-AD) multi-cohort study integrates this modified BBB-ASL technique in several healthy and diseased populations (Table 1) to study methodological and clinical research questions (Table 2) on the ability of BBB-ASL as an early AD biomarker.</p></div><div><h3>Methods</h3><p>DEBBIE-AD will enroll various cohorts with subjective cognitive decline, mild cognitive impairment, and AD dementia, as well as age-matched healthy controls, at seven sites (Table 1). Our newly developed BBB-ASL sequence — implemented with the vendor-independent MRI framework gammaSTAR — will be added to multiple MRI protocols. The BBB-ASL sequence combines time-encoded multi-post labeling delay pseudo-continuous ASL with a multi-echo 3D GRASE readout, allowing estimating CBF, ATT, and the BBB time of exchange (Tex). Data analyses will be conducted using ExploreASL. Beyond MRI standard sequences, including T1w, T2w, FLAIR, DWI, the DEBBIE clinical outcomes include amyloid-PET and blood and CSF fluid biomarkers (Table 1).</p></div><div><h3>Expected Results</h3><p>Preliminary testing of the BBB-ASL has been conducted on 3T systems (different Siemens Heathineers scanners) in different cohorts at multiple sites. Data processing with ExploreASL includes FSL-FABBER4 for quantification, allowing harmonized image processing. An example of the mean and standard deviation Tex maps of two DEBBIE cohorts is shown in Figure 1 to illustrate the similarities of the Tex patterns from two cohorts of similar-aged healthy adults from different sites.</p></div><div><h3>Discussion</h3><p>The DEBBIE-AD study aims to provide evidence on the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD-related pathologies. The presented sequence may provide novel and unique insights into the staging of BBB permeability changes in groups at greater risk of developing AD, which may, in turn, provide new targets for treatment.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100308"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024001090/pdfft?md5=9642149bfb9a366c72c7f5f36b7c4edb&pid=1-s2.0-S2666245024001090-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121920","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":"Clinical value of plasma brain-derived tau and p-tau217 in acute ischemic stroke","authors":"Julia K. Gundersen ,&nbsp;Fernando Gonzalez-Ortiz ,&nbsp;Thomas Karikari ,&nbsp;Bjørn-Eivind Kirsebom ,&nbsp;Katrin Mertes ,&nbsp;Henrik Zetterberg ,&nbsp;Hlin Kvartsberg ,&nbsp;Ole Morten Rønning ,&nbsp;Berglind Gísladóttir ,&nbsp;Kaj Blennow ,&nbsp;Tormod Fladby","doi":"10.1016/j.cccb.2024.100291","DOIUrl":"10.1016/j.cccb.2024.100291","url":null,"abstract":"<div><h3>Introduction</h3><p>Diagnosis of acute ischemic stroke (AIS) as based on clinical examination and neuroimaging has limitations in determining subgroup aetiology and subsequent long-term motor and cognitive impairment. Identification of high-risk patients enables personalised prophylaxis and rehabilitation strategies. This study explores the clinical value of plasma brain-derived tau (BD-tau) and phosphorylated-tau217 (p-tau217), primarily associated with neurodegeneration, in identifying patients at risk of sequela after AIS.</p></div><div><h3>Methods</h3><p>We analysed a cohort of 193 patients admitted to the stroke unit at Akershus University Hospital in Oslo, Norway. Each patient received a diagnosis of AIS (n=102), transient ischemic attack (TIA, n=63) or stroke mimic (n=31). Patient characteristics were collected from hospital records. Biomarkers were quantified using Simoa HDX in venous blood sampled obtained the day after admission. Inpatient short-term outcomes, including stroke diameter on magnetic resonance imaging (MRI, n=134) and mini mental state examination (MMSE, n=153), were assessed prior to discharge. Non-parametric statistics, including Kruskal-Wallis and Kendall´s tau-b correlation tests were applied. Backwards stepwise linear regression analysis was used to determine the association between stroke diameter or MMSE and the biomarkers. A full model was fitted with explanatory variables as listen in table 1.</p></div><div><h3>Results</h3><p>BD-tau was significantly increased in AIS patients as compared to mimics (p=.004), whereas p- tau217 did not differentiate between the diagnostic groups. MRIs were available for 66 (64.7%) of AIS patients, of whom n=36 were diagnosed with cortical and n=30 with subcortical stroke. Cortical stroke diameter showed a strong correlation with BD-tau (fig. 1, &lt;.001) and p-tau217 (=.003). In regression analysis, only BD-tau was found to be significantly associated with stroke diameter (table 1). Subcortical strokes were mot associated with any of the biomarkers. Furthermore, MMSE score correlated with BD-tau (fig. 2, &lt;.001) and p-tau217 (&lt;.001). In regression analysis, age was the strongest predictor of MMSE score, followed by p-tau217.</p></div><div><h3>Discussion</h3><p>Our findings suggest that blood-based BD-tau and p-tau217 have clinical potential in determining AIS subgroup aetiology and provide insights into cognitive impairment in AIS patients. These findings may have implications for rehabilitation and secondary prophylaxis after stroke.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100291"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000928/pdfft?md5=5bddfa9033ea3d027124dce3a85b8f25&pid=1-s2.0-S2666245024000928-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122119","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}