Cerebral circulation - cognition and behavior最新文献

{"title":"APOE4 leads to Neurovascular dysfunction is an early change of Alzheimer's disease?","authors":"Mun Seong Choi","doi":"10.1016/j.cccb.2024.100236","DOIUrl":"10.1016/j.cccb.2024.100236","url":null,"abstract":"<div><h3>Introduction</h3><p>Vascular contributions to dementia &amp; Alzheimer's disease are increasing recognized. Recent studies have suggested that blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction, including the early clinical stages of AD. Apolipoprotein E4(APOE4), the major AD susceptibility gene, leads to accelerated blood-brain barrier breakdown &amp; degeneration of brain capillary pericyte that maintain blood-brain barrier integrity. Whether APOE4 cerebrovascular effects contribute to cognitive impairment remains, however, largely unknown.</p></div><div><h3>Methods</h3><p>A screening yielded publcations of which relevant articles were selected after an evaluation of their titles &amp; abstracts. And then full text of these articles was obtained &amp; compared about above respective subjects thoroughly.</p></div><div><h3>Results</h3><p>A recent meta-analysis of BBB peameability based on imaging &amp; biochemical cerebrospinal fluid studies indicated that patients with AD have greater increase in BBB peameability compared with neurologically healthy human controls, which has also been confirmed by postmortem brain tissue (for review, see the articles by Zlocovic, &amp; Sergillo et al). Impotantly, postmortem analysis indicated that the BBB breakdown is more pronounced in individuals with AD who carry the APOE4 allele. Astrocyte-derived human apoE2 &amp; apoE3, leads to an age-dependent progressive BBB breakdown by activating a proinflammatory CypA-nuclear factor (NF)- κB-matrix- metalloproteinase-9 pathway (MMP-9) in brain capillary pericytes. The activation of MMP-9 in APOE mice leads to enzymatic degradation of the BBB tight junction &amp; basement membrane proteins resulting in BBB breakdown followed by neuronal uptake of multiple blood-derived neurotoxic proteins (e.g., thrombin, fibrin), perivascular deposition of erythrocyte-derived hemosiderin &amp; microvascular &amp; CBF reductions. The vascular defects in APOE4-expressing mice precede neuronal dysfunction &amp; can initiate neurodegenerative changes. Astrocyte secreated apoE3 &amp; apoE2, but not apoE4, suppress the CypA-NF- κB-MMP-9 pathway in pericytes via the low density lipoprotein receptor related protein1(LRP1). There are apoE isoform-specific effects in the Aβ pathway. ApoE4 expression is assocated with a significant increase in amyloid plaques in brain at earlier ages compared with apoE3 or apoE2. ApoE4 impairs A β clearance from &amp; across the BBB in animal models &amp; patients at risk for developing AD.</p></div><div><h3>Discussion</h3><p>Future studies should explore whether similar early neuroimaging &amp; biochemical markers of BBB disruption are present in humans carrying the apoE4.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100236"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000370/pdfft?md5=4a08032f1c3e02d3d15b2ae784155b5a&pid=1-s2.0-S2666245024000370-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121684","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":"Decipher Cognitive Impairment in Heart Failure by Text Mining","authors":"Malin Overmars,&nbsp;Bram Van Es,&nbsp;Sander Tan,&nbsp;Geert Jan Biessels,&nbsp;Wouter Van Solinge,&nbsp;Saskia Haitjema,&nbsp;Michiel Bots","doi":"10.1016/j.cccb.2024.100237","DOIUrl":"10.1016/j.cccb.2024.100237","url":null,"abstract":"<div><h3>Introduction</h3><p>Heart failure (HF) and cognitive impairment (CI) are prevalent and often co-occurring conditions, affecting a considerable portion of the population. Hemodynamic disturbances are important but do not fully explain CI. Therefore, novel etiological insights are needed to clarify the heart-brain axis. This study focuses on unraveling mechanisms underlying cognitive decline in HF patients. We hypothesized that we could identify symptom commonalities extracted from real- world clinical anamnesis texts of patients with HF and CI using text-mining procedures. This may lead to novel mechanistic clues on cognitive decline in patients with HF and could provide potential leads for future treatment trials.</p></div><div><h3>Methods</h3><p>In this study, we analyzed anamnesis texts of HF and CI patients between 2011 and 2023 using electronic health records (EHRs) from the Utrecht Patient-Oriented Database (UPOD). Patients with HF and CI were identified through text mining of echocardiogram reports and the presence of clinical neurological and geriatric reports from outpatient memory clinics, respectively. To investigate noted symptomatic overlap in HF and CI, we utilized Named Entity Detection and Linking (NER+L) strategies to link noted symptoms in anamnesis texts with three Dutch biomedical ontologies.</p></div><div><h3>Results</h3><p>In total, anamnesis texts of 5597 unique HF and 961 CI patients were extracted and analyzed. Top-3 reported symptoms in HF patients were dyspnea (71.3%), hydrops (47.1%), and dizziness (43.6%) (Figure 2). Top-3 reported symptoms in CI patients were memory impairment (55.5%), cognitive problems (54.2%), and getting lost (21.1%). The noted symptoms that overlapped between HF and CI patients were fear, dizziness, tiredness, uncertain behavior, appetite, headache, and lack of energy. We did not find any noted cognitive symptoms in HF patients' anamnesis texts, nor did we find any noted cardiac symptoms in CI patients.</p></div><div><h3>Discussion</h3><p>Based on real-world evidence, we identified noted overlap in reported symptoms in HF and CI. These symptoms could be potential leads for future treatment trials.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100237"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000382/pdfft?md5=8b94be3b609aebaae7760cc2d064e833&pid=1-s2.0-S2666245024000382-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121685","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":"Investigating TREM2-mediated vasculo-protection during chronic mild hypoxia in vivo","authors":"Mila Redzic,&nbsp;Stefan Szymkowiak,&nbsp;Barry McColl","doi":"10.1016/j.cccb.2024.100321","DOIUrl":"10.1016/j.cccb.2024.100321","url":null,"abstract":"<div><p>Cerebrovascular dysfunction, leading to inadequate brain perfusion and oxygenation, is a major contributor to cognitive decline and dementia. Chronic hypoxia is a putative mechanism of vascular-mediated brain damage, particularly in relation to white matter lesions, as demonstrated by human neuroimaging and histopathology studies. Moreover, increasing evidence suggests that microglia, the primary immune cells of the brain parenchyma, may play a key role in modulating cerebrovascular disease outcomes. Indeed, unpublished work from our lab using a model of chronic cerebral hypoperfusion found greater vascular and white matter abnormalities concomitant with reduced microglial-vascular interactions in mice lacking the microglial immunoreceptor triggering receptor expressed on myeloid cells 2 (TREM2). However, the underlying mechanisms remain incompletely understood. Therefore, this project aims to further investigate whether microglial TREM2 signalling contributes to cerebrovascular resilience, and specifically vasculoprotection, focusing on the context of hypoxia. To address this, we are housing mice at 8%O2 to achieve chronic mild hypoxia (CMH). As corroborated by our studies, CMH induces cerebral microbleeds associated with parenchymal fibrinogen leakage in both grey and white matter regions (Figure 1), and is thus a reductionist approach well-suited for examining microglial mechanisms conferring vasculoprotection. Ongoing studies in young (5-6 months) and aged (15-18 months) cohorts are utilising histology and immunostaining to determine the impact of TREM2 deficiency and ageing on CMH-induced phenotypes, with particular focus on profiling microbleed burden, BBB integrity and interactions between microglia and other cell types within the neurovascular unit. Given that TREM2 is a key regulator of microglial metabolism and lipid processing, future work will utilise flow cytometry and spatial lipidomics to characterise microglia and brain lipid metabolism during CMH, thus providing insight into immunometabolic changes that may underpin microglial vasculoprotection in hypoxia. Findings from these studies will increase our understanding of microglia-vascular interactions, which can ultimately be exploited to promote resilience to cerebrovascular and other hypoxia- related pathologies.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100321"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024001223/pdfft?md5=92fee97ebf571cd01b7292110d4fe01f&pid=1-s2.0-S2666245024001223-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121697","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 correlates of cerebral microbleeds are diminished in individuals with traumatic brain injury","authors":"Audrey Low","doi":"10.1016/j.cccb.2024.100266","DOIUrl":"10.1016/j.cccb.2024.100266","url":null,"abstract":"<div><h3>Introduction</h3><p>Cerebral microbleeds (CMB) are predictive of increased risk of dementia and stroke. Although commonly regarded as vascular markers, CMB can also stem from non-vascular aetiologies like head injuries or traumatic brain injury (TBI), although these are often overlooked. Therefore, this study examines CMB in relation to TBI, and their differential causes (i.e., risk factors) and consequences (i.e., clinical outcomes).</p></div><div><h3>Methods</h3><p>In 605 healthy middle-aged adults (aged 40-59), CMB were rated on 3T susceptibility weighted imaging (SWI) MRI. TBI was assessed using the Brain Injury Screening Questionnaire (BISQ). TBI+ was defined as at least one blow to the head resulting in loss of consciousness (36.0%; n=217). Memory was assessed using the COGNITO battery. Interaction analyses examined TBI*CMB interactions on hypertension, gait, and memory. Dominance analysis examined the relative contribution of TBI and vascular risk factors on predicting gait disturbances and memory. All models adjusted for sex, age, education, and study site.</p></div><div><h3>Results</h3><p>TBI was related to higher CMB count (t=2.06, p=.039), and were more common in males (48.3%) than females (28.0%) (χ2=28.91, p&lt;.001). Number of TBI events related to poorer memory (t=-2.62, p=.009) and gait disturbances (t=3.54, p&lt;.001). Interaction analyses demonstrated that hypertension (t=-2.26, p=.024), memory (t=2.70, p=.007) and gait (t=-2.29, p=.023) were less closely related to CMB in individuals with greater number of TBI events, relative to those with fewer TBIs. Regionally, these interactions were significant for lobar CMB, but not deep subcortical CMB. Within the TBI+ group, dominance analysis demonstrated that number of TBI events outperformed vascular risk factors in predicting gait disturbances (Contribution to R2: TBI=52.9%, vascular risk=32.6%) and memory (TBI=28.7%, vascular risk=1.2%).</p></div><div><h3>Discussion</h3><p>CMB appeared to differ aetiologically and clinically in those with and without TBI. In individuals with TBI, TBI itself was the dominant driver of clinical deficits. While vascular CMB may appear more detrimental than traumatic CMB at baseline, longitudinal analysis is required to determine how traumatic CMB differ in clinical trajectory and downstream pathologies. This study highlights the importance of differentiating between CMB of vascular origins vs. TBI in both research and clinically to aid prognosis and treatment decisions.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100266"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000679/pdfft?md5=fe3145425763f4d5fd9391fdc2fe7778&pid=1-s2.0-S2666245024000679-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121923","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":"Prevalence of Amyloid Cerebral Deposits and Cognitive Outcome After Stroke: The IDEA3 Study","authors":"Olivier Godefroy ,&nbsp;Mélanie Barbay ,&nbsp;Jeanne Martin ,&nbsp;Trevor Shields ,&nbsp;Chantal Lamy ,&nbsp;Audrey Courselle-Arnoux ,&nbsp;Sandrine Canaple ,&nbsp;Claire Leclercq ,&nbsp;Martine Roussel ,&nbsp;Marc-Etienne Meyer ,&nbsp;Etienne Marchal ,&nbsp;Frank A. Wollenweber","doi":"10.1016/j.cccb.2024.100279","DOIUrl":"10.1016/j.cccb.2024.100279","url":null,"abstract":"<div><h3>Introduction</h3><p>The contribution of associated Alzheimer disease to poststroke cognitive impairment has been suggested on clinical grounds. However, the few published studies using amyloid PET have provided a widely ranging prevalence and a questionable relationship with cognitive status.</p><p>The main objective of the study was to determine the prevalence of amyloid PET positivity among poststroke patients with at least one impaired cognitive score. The secondary objectives were to determine the association between clinical, cognitive, and imaging characteristics at baseline with amyloid status.</p></div><div><h3>Methods</h3><p>The IDEA3 cohort included 91 stroke patients (cerebral infarct: 89%; hemorrhage: 11%). They were assessed at 808 ± 589 days poststroke with a cognitive battery, MRI, and florbetapir PET. Clinical, cognitive, and imaging characteristics at baseline were compared according to amyloid status.</p></div><div><h3>Results</h3><p>Amyloid PET was positive for 14 patients, corresponding to a prevalence of 15.4% (95%CI: 7.97-22.8). Amyloid-positive patients were older (p = 0.0001), did not differ according to the cause of stroke, except for a tendency towards a higher frequency of cerebral amyloid angiopathy in the hemorrhagic subgroup (p = 0.06). Their cognitive performance was lower on both the cognitive screening test (p = 0.023) and battery (p = 0.02), without a specific profile.</p></div><div><h3>Discussion</h3><p>This study supports the mild prevalence of amyloid burden and shows that it contributes to poststroke cognitive impairment.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100279"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000801/pdfft?md5=ae56a9886e08a168bd278fe74214d0bb&pid=1-s2.0-S2666245024000801-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121924","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":"Prevalence of incidental DWI-positive lesions in patients with CADASIL: Restuls from the VASCAMY Study","authors":"Annemieketer Telgte ,&nbsp;Anna Dewenter ,&nbsp;Benno Gesierich ,&nbsp;Nadja Gruber ,&nbsp;Anna Kopczak ,&nbsp;Marco Duering","doi":"10.1016/j.cccb.2024.100297","DOIUrl":"10.1016/j.cccb.2024.100297","url":null,"abstract":"<div><h3>Introduction</h3><p>Due to increasing availability of MRI scans, incidental diffusion-weighted imaging (DWI)-positive lesions are increasingly recognized on brain MRI in individuals with vascular disease. Cerebral small vessel disease (SVD) is a putative cause of these lesions. We investigated the prevalence of incidental DWI-positive lesions in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a genetic form of SVD, which frequently manifests as subcortical infarcts at a younger age and serves as a pure disease model for sporadic SVD. Furthermore, in these patients, we assessed risk factors of incidental DWI-positive lesions, including common vascular risk factors and MRI markers of SVD.</p></div><div><h3>Methods</h3><p>64 patients with CADASIL and without acute (&lt; 6 months) ischemic stroke were included from the VASCAMY study. Mean age was 51.9 years (SD 10.5) and 63% was female. Patients underwent 3T MRI at baseline, and 43 patients underwent a second MRI at 18 or 36 months. Incidental DWI- positive lesions were assessed by one expert rater on pre-processed trace images derived from diffusion MRI. At follow-up, difference imaging of the trace images was applied to allow systematic identification of new lesions. Rating was done according to STRIVE-2 criteria.</p></div><div><h3>Results</h3><p>At baseline, incidental DWI-positive lesions were prevalent in 13/64 (20%) patients. In total, 27/107 (25%) scans were DWI-positive, with 19/64 (30%) patients having an incidental DWI- positive lesion at any time point. Most lesions were located subcortically and were either tubular in shape, following the orientation of a perforating arteriole, or ovoid with a small cavitation. A few incidental DWI-positive lesions corresponded to recent microinfarcts. At baseline, incidental DWI- positive lesions were significantly associated with greater white matter hyperintensity volume, and presence and increased volume of lacunes (all p&lt;.05).</p></div><div><h3>Discussion</h3><p>Cross-sectionally, incidental DWI-positive lesions were detected in a fifth of patients with CADASIL. Incidental DWI-positive lesions were mostly subcortical and significantly associated with MRI markers of SVD. Our findings, obtained in patients with pure SVD, i.e., without age-related co- morbidities, provide supporting evidence that subcortical incidental DWI-positive lesions are common in CADASIL and may be a feature of SVD.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100297"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000989/pdfft?md5=0f153f2c6c51c21950cfbf64072d2d9e&pid=1-s2.0-S2666245024000989-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122042","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":"Biomarkers of inflammation and brain damage seven years post-stroke","authors":"Guri Hagberg ,&nbsp;Hege Ihle-Hansen ,&nbsp;Ingebjørg Seljeflot ,&nbsp;Vibeke Bratseth","doi":"10.1016/j.cccb.2024.100282","DOIUrl":"10.1016/j.cccb.2024.100282","url":null,"abstract":"<div><h3>Introduction</h3><p>Biomarkers of inflammation and brain damage are associated with neurodegeneration and dementia but are scarcely investigated post-stroke. We hypothesized that biomarkers of brain tissue damage and inflammation are associated with i) cognition and imaging markers of brain pathology seven years post-stroke and ii) long-term cognitive deterioration post-stroke.</p></div><div><h3>Methods</h3><p>All patients with a first-ever stroke or TIA admitted to the stroke unit, Bærum Hospital, Norway, during 2007/2008 were invited to participate in the CAST (Cognition After Stroke) study and invited to a follow-up after one and seven years with cognitive assessments and diagnoses of dementia, mild cognitive impairment (MCI) or normal. After seven years, we measured serum glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), Interleukin (IL) 8, 12, 18, and high sensitive C-reactive protein (hsCRP) and brain MRI for assessment of Fazekas and global cortical and medial temporal lobe atrophy (MTA).</p></div><div><h3>Results</h3><p>Of 227 subjects recruited, 116 completed the seven-year follow-up, 113 with blood biomarkers, and were included in this study. Of these, 77 had complete MRI examinations. Mean age at baseline was 67.9 (SD 11.0) years, 87 (77 %) suffered an ischemic stroke, and 52 (46%) were women. The mean age after seven years was 75.4 (SD 11.1). At one- and seven-years follow-up, 62 (55%) and 45 (40%) had normal cognition, 37 (33%) and 42 (37 %) MCI, while 14 (12 %) and 26 (23%) had dementia, respectively. Cognitively, 35 patients progressed during follow-up. In unadjusted logistic regression, only hsCRP was associated with post-stroke dementia (odds ratio 1.08, 95% confidence interval 1.02 to 1.14, p=0.01). Adjusting for age did not change the result (OR 1.09, 95% confidence interval 1.06-1.19, p&lt;0.001). In univariate ordinal regression, only NSE was associated MTA, but not after age adjustment. None of the biomarkers was associated with deterioration of cognition from one to seven years post-stroke.</p></div><div><h3>Discussion</h3><p>In this exploratory study, only elevated levels of hsCRP were associated with dementia seven years post-stroke, indicating a role of neuroinflammation in the development of cognitive impairment in long-term follow-up. [Clinicaltrials.gov (NCT00506818)]</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100282"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000837/pdfft?md5=4bf75f468115860506790ca6e93a83ca&pid=1-s2.0-S2666245024000837-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122209","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":"Identification of novel cerebral small vessel disease biomarkers in blood using proteomics","authors":"Claudia Satizabal ,&nbsp;Tiffany Kautz ,&nbsp;Mohsen Sharifi Tabar ,&nbsp;Rebecca Bernal ,&nbsp;Julia Mathews ,&nbsp;Muralidharan Sargurupremraj ,&nbsp;Vinu Philip ,&nbsp;Habil Zare ,&nbsp;Haritha Vardhini Katragadda ,&nbsp;Qiong Yang ,&nbsp;Charles DeCarli ,&nbsp;Pauline Maillard ,&nbsp;Mohamad Habes ,&nbsp;Sudha Seshadri","doi":"10.1016/j.cccb.2024.100302","DOIUrl":"10.1016/j.cccb.2024.100302","url":null,"abstract":"<div><h3>Introduction</h3><p>Identifying novel cerebral small vessel disease (cSVD) biomarkers in blood is critical to advance therapeutic and preventive strategies for Vascular Contributions to Cognitive Impairment and Dementia (VCID). This exploratory analysis aimed to identify novel blood-based markers of cSVD using proteomics in a Hispanic sample. This is critical, as most biomarker discovery has focused on non-Hispanic Whites, despite increased cardiometabolic risk and cognitive impairment among minoritized populations.</p></div><div><h3>Methods</h3><p>We included 107 dementia-free Mexican American participants from the MarkVICD-1 San Antonio site (73% women, mean age 70 ±7 years, Table 1). Participants provided fasting blood samples and underwent a comprehensive clinical and neuroimaging evaluation. Serum aliquots were shipped to Olink for proteomic profiling with the Explore 3072 panel. Normalized protein levels were related to cSVD markers, including White Matter Hyperintensities (WMH), Peak-with of Skeletonized Mean Diffusivity (PSMD), and Free Water (FW), using linear regression models adjusting for age, age2, sex, and total intracranial volume. P-values were corrected using False Discovery Rate (FDR) to account for multiple testing.</p></div><div><h3>Results</h3><p>We identified 36, and 128 proteins significantly associated with PSDM, and FW, respectively (Figure 1). The strongest associations were seen for elevated neurogranin with higher PSMD (Beta ±SE, 0.20 ±0.04, FDR=0.005) and FW (0.23 ±0.04, FDR=0.002), and Cartilage Intermediate Layer Protein (CILP) with higher PSMD (0.07 ±0.014, FDR=0.005). Neurogranin is a marker of synaptic dysfunction and CSF levels have shown potential as a predictor of cognitive decline. CILP may antagonize TGFB1 and IGF1 and has been related to mortality in patients with heart failure.</p></div><div><h3>Discussion</h3><p>Our results uncovered multiple novel blood-based cSVD biomarkers for risk stratification in VCID studies, including neurogranin and CILP. Further studies are needed to confirm these findings in larger samples.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100302"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266624502400103X/pdfft?md5=5493fbd4d4972657512ebca96d41c069&pid=1-s2.0-S266624502400103X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122309","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":"Pulse pressure and APOE ε4 dose interact to affect cerebral blood flow in older adults without dementia","authors":"Lauren Edwards ,&nbsp;Kelsey R. Thomas ,&nbsp;Alexandra J. Weigand ,&nbsp;Emily C. Edmonds ,&nbsp;Alexandra L. Clark ,&nbsp;Einat K. Brenner ,&nbsp;Sarah J. Banks ,&nbsp;Paul E. Gilbert ,&nbsp;Daniel A. Nation ,&nbsp;Lisa Delano-Wood ,&nbsp;Mark W. Bondi ,&nbsp;Katherine J. Bangen ,&nbsp;Alzheimer's Disease Neuroimaging Initiative","doi":"10.1016/j.cccb.2024.100206","DOIUrl":"https://doi.org/10.1016/j.cccb.2024.100206","url":null,"abstract":"<div><p>This study assessed whether the effect of vascular risk on cerebral blood flow (CBF) varies by gene dose of apolipoprotein (APOE) ε4 alleles. 144 older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative underwent arterial spin labeling and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure (BP) assessment. Vascular risk was assessed using pulse pressure (systolic BP – diastolic BP). CBF was examined in six AD-vulnerable regions: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regressions tested the interaction between APOE ε4 dose and pulse pressure on CBF in each region, adjusting for age, sex, cognitive classification, antihypertensive medication use, FDG-PET, reference CBF region, and AD biomarker positivity. There was a significant interaction between pulse pressure and APOE ɛ4 dose on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex, such that higher pulse pressure was associated with lower CBF only among ε4 homozygous participants. These findings demonstrate that the association between pulse pressure and regional CBF differs by APOE ε4 dose, suggesting that targeting modifiable vascular risk factors may be particularly important for those genetically at risk for AD.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100206"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000072/pdfft?md5=87d61e191aec7335c7caaff1513f0432&pid=1-s2.0-S2666245024000072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674308","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":"Low serum HDL-cholesterol is associated with increased risk of the subcortical small vessel type of dementia","authors":"Elin Axelsson Andrén ,&nbsp;Dewa Safi ,&nbsp;Anders Wallin ,&nbsp;Johan Svensson","doi":"10.1016/j.cccb.2024.100229","DOIUrl":"https://doi.org/10.1016/j.cccb.2024.100229","url":null,"abstract":"<div><h3>Background</h3><p>There are conflicting results whether serum lipid pattern is related to the amount of white matter hyperintensities (WMHs) on magnetic resonance imaging. Little is known of the associations between lipid concentrations and the subsequent risk of the subcortical small vessel type of dementia (SSVD), in which WMHs are a prominent manifestation. Here, we determined whether lipid levels are associated with the risk of SSVD, Alzheimer's disease (AD), or mixed dementia (combined AD and SSVD).</p></div><div><h3>Methods</h3><p>This was a longitudinal, prospective study of 329 patients with subjective or objective mild cognitive impairment at baseline. The statistical analyses included Cox proportional hazards regression with adjustments for age, gender, education, body mass index, current smoking, hypertension, diabetes mellitus, and <em>APOE</em> ε4 genotype.</p></div><div><h3>Results</h3><p>During the follow-up (mean 4.1 years), 80 patients converted to dementia [SSVD, <em>n</em> = 15 (5 %); AD, <em>n</em> = 39 (12 %); and mixed dementia, <em>n</em> = 26 (8 %)]. Serum high-density lipoprotein cholesterol (HDL, per SD increase) was inversely associated with the risk of SSVD, whereas triglycerides (TG), low-density lipoprotein cholesterol (LDL)/HDL ratio, and TG/HDL ratio were positively associated with SSVD risk. Furthermore, the lowest HDL tertile was associated with a sevenfold, and the highest tertile of TG/HDL ratio with a threefold, increase in SSVD risk. There were no associations with the risk of AD or mixed dementia after adjustment for covariates.</p></div><div><h3>Conclusion</h3><p>In a memory clinic population, low HDL and high TG/HDL ratio were independent risk factors of SSVD, but not of AD or mixed dementia.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100229"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000308/pdfft?md5=9e09925c27dcfc8bbf12e57fcbec1b40&pid=1-s2.0-S2666245024000308-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141324756","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}