Cerebral circulation - cognition and behavior最新文献

{"title":"Angiotensin-converting enzyme 2 (ACE-2) is dysregulated in Alzheimer's disease but not Vascular dementia","authors":"Ozge Guzel,&nbsp;Hannah Mary Tayler,&nbsp;James Scott Miners,&nbsp;Patrick Gavin Kehoe","doi":"10.1016/j.cccb.2024.100298","DOIUrl":"10.1016/j.cccb.2024.100298","url":null,"abstract":"<div><h3>Introduction</h3><p>The brain renin-angiotensin system (RAS) is dysregulated in dementia. We have previously shown that ACE-2, a central regulator of the protective counter-regulatory arm of RAS, is inversely associated with disease pathology in Alzheimer's disease (AD). We have investigated whether ACE-2 is similarly deficient in Vascular dementia (VaD) and mixed dementia (AD-VaD), in addition to AD. We also investigated whether ACE-2 is related to vascular pathology including CAA and SVD and explored whether ACE-2 varies according to gender, hypertension status, and ACE-2 genotype.</p></div><div><h3>Methods</h3><p>We studied brain tissue (frontal cortex) from 147 dementia cases (AD (n=94), VaD (n=20) and AD-VaD (n=33)) and 104 age-matched non-demented controls from the South West Dementia Brain Bank, University of Bristol. Amyloid β (Aβ) and tau pathology and levels, had previously been measured by IHC and ELISA, respectively. ACE-2 protein levels were measured by ELISA, and ACE-2 enzyme activity was measured using a fluorometric sensolyte kit (Anaspec). ACE-1 activity was measured using a fluorogenic assay; Ang-II and Ang-(1-7) were measured by in-house direct ELISA. ACE-2 genotypes (rs2285666 and rs4240157) were obtained by PCR.</p></div><div><h3>Results</h3><p>ACE-2 enzyme activity was significantly reduced in AD and AD-VaD cases (p&lt;0.0001 and p=0.0039, respectively) but not VaD. ACE-2 protein levels were unchanged between dementia groups. ACE-2 activity correlated inversely with parenchymal Aβ (r=-0.223, p=0.0005) and tau load (r=-0.294, p&lt;0.0001) and with insoluble Aβ40 and Aβ42 levels (r=-0.267 and r=-0.289, both p&lt;0.0001). ACE-2 activity correlated inversely with ACE-1 activity (r=−0.227, p=0.0004), and the ratio of ACE-1 to ACE-2 was significantly increased in AD and AD-VaD cases (p&lt;0.0001 and p=0.0029, respectively) but not in VaD. ACE-2 activity was lower in females with AD (p=0.0015). There is no relationship with CAA/SVD. ACE-2 activity was higher in people with late-stage hypertension (p=0.044), and females with hypertension have lower enzyme activity than males (p=0.041). ACE-2 levels and activity werenot associated with ACE-2 genotypes.</p></div><div><h3>Discussion</h3><p>These findings indicate that, despite strong vascular properties, changes in ACE-2 function are AD-related and not altered in VaD. The reduction in ACE-2 in females in AD warrants further investigation. We did not find any association with ACE-2 genotypes.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100298"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000990/pdfft?md5=8b7a017a0f50fecbe251364f6a3fce3a&pid=1-s2.0-S2666245024000990-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122043","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":"Baseline levels of soluble amyloid precursor proteins predict conversion to subcortical small-vessel disease","authors":"Petronella Kettunen ,&nbsp;Francesco Locatelli ,&nbsp;Emir Basic ,&nbsp;Maria Bjerke ,&nbsp;Michael Jonsson ,&nbsp;Johan Svensson ,&nbsp;Anders Wallin","doi":"10.1016/j.cccb.2024.100301","DOIUrl":"10.1016/j.cccb.2024.100301","url":null,"abstract":"<div><h3>Introduction</h3><p>The Gothenburg Mild Cognitive Impairment (MCI) study is a longitudinal mono-center study of patients seeking help for cognitive complaints at the memory clinic in Gothenburg, Sweden. The study includes both pre-clinical diagnoses, e.g. subjective cognitive impairment (SCI) and mild cognitive impairment (MCI), as well as patients with manifest dementia, including Alzheimer's disease (AD), subcortical small-vessel disease (SSVD) and mixed AD/SSVD. The International Working Group (IWG) for New Research Criteria for the Diagnosis of AD has proposed a conceptual framework for guiding diagnosis by biomarker analysis. In short, patients with typical AD and mixed AD/SSVD should display decreased amyloid-β (Aβ) 1-42 together with increased total tau or phosphorylated tau in cerebrospinal fluid (CSF).</p></div><div><h3>Methods</h3><p>In this project, we used the IWG-2 criteria to help the exploration of preclinical CSF biomarkers for SSVD. To this end, we investigated the odds of SCI and MCI patients with and without AD pathology converting to SSVD. Moreover, we investigated how CSF biomarker levels at baseline affected risk of converting to SSVD. The applied cut-offs for AD pathology were Aβ-42 &lt; 530 ng/L, t-tau&gt;350 ng/L and p-tau181&gt;59 ng/L. The study cohort consisted of 29 SCI with AD pathology and 173 SCI without AD pathology, and 98 MCI with AD pathology and 203 MCI without AD pathology. CSF biomarkers Aβ-38, Aβ-40 and Aβ-42, and soluble amyloid precursor protein (sAPP) alpha and beta were analyzed at baseline.</p></div><div><h3>Results</h3><p>While SCI and MCI patients with pathological AD biomarkers were 30 times more likely to convert to AD and 15 times more likely to convert to mixed AD/SSVD, pathological AD biomarkers did not predict conversion to SSVD. Using Cox regression analysis, we found that higher levels of sAPP-α and sAPP-β at baseline were associated with lower risk of converting to SSVD. Moreover, Kaplan- Meier estimations showed that when preclinical subjects were stratified according to baseline levels of sAPP-α or Aβ-40, those with the lower levels of the proteins had increased probability of converting to SSVD. No other biomarkers were associated with conversion to SSVD.</p></div><div><h3>Discussion</h3><p>sAPP-α/-β and Aβ-40 could be used as potential biomarkers to evaluate progression to SSVD.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100301"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024001028/pdfft?md5=82f0f4a80ce5b6c91d1ed94ab6a1b443&pid=1-s2.0-S2666245024001028-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122046","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":"Diabetes and MRI Infarction in the Hispanic Community Health Study, Study of Latinos","authors":"Vincent Chen ,&nbsp;Ariana Stickel ,&nbsp;Wassim Tarraf ,&nbsp;Kevin Gonzalez ,&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;Vladimir Ivanovic ,&nbsp;Stephan Seiler ,&nbsp;Hector Gonzalez ,&nbsp;Charles DeCarli","doi":"10.1016/j.cccb.2024.100289","DOIUrl":"10.1016/j.cccb.2024.100289","url":null,"abstract":"<div><h3>Introduction</h3><p>HCHS/SOL is a representative study of Hispanic/Latinos living in the US. HCHS/SOL participants have a high prevalence of diabetes (1) and diabetic associated cognitive decline (2). Previous studies of predominantly non-Hispanic White populations indicate that silent brain infarcts are associated with incident dementia (3). Given that diabetes is prevalent in HCHS/SOL and associated with cognitive decline, we examined whether diabetes may also lead to infarction on MRI.</p></div><div><h3>Methods</h3><p>SOL-INCA-MRI consists of 2668 individuals of Hispanic/Latino Heritage from 4 centers across the US. Demographics of the cohort are summarized in the Table. The presence or absence of infarction on MRI was determined from review of high resolution T1, T2 and FLAIR imaging as well as gradient echo imaging by a neuroradiologist and a stroke neurologist with a high level of agreement (ICC &gt;0.90). Desperate readings were adjudicated by a neurologist with experience in vascular brain injury. Diabetes based on American Diabetes Association definition of normal, prediabetic and diabetic. This definition used measures serum glucose levels adjusted for fasting time and, if available, post-OGTT glucose levels, A1C percentages, and scanned/transcribed anti- diabetic medication use. General linear model was used to test the associated between the presence or absence of MRI and diabetes adjusting for age, gender, heritage, and center.</p></div><div><h3>Results</h3><p>Subjects were 62.3 + 9.2 years of age at MRI range [35-86], 67% were female and the prevalence of MRI infarction was 7% (Table). Pre-diabetes was present in 45% and diabetes in 22%. Stroke prevalence increased with age ranging from &lt;1% at age 40 to 18% at age 80 (Figure 1). Diabetes or pre-diabetes prevalence also increased with age being 10% at 40 and over 60% at age 80 (Figure 2). Adjusting for age, men were 2 times more likely to be diabetic. In the full model, age, gender, and diabetes were significantly associated with infarction seen on MRI with the likelihood of infarction 1.9 times greater in persons with diabetes.</p></div><div><h3>Discussion</h3><p>These results indicate that the presence of diabetes is strongly associated with infarction on MRI in Hispanic/Latinos in the US. This association may explain, in part, the association between diabetes and cognitive decline.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100289"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000904/pdfft?md5=f537124251def64cd9c846fc95353e0e&pid=1-s2.0-S2666245024000904-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122117","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":"Modes of covariation between vascular risk factors and cognition in cohorts with cultural and geographical variations","authors":"Bonnie Yin Ka Lam ,&nbsp;Vincent Hui ,&nbsp;Huijing Zheng ,&nbsp;Yuan Cai ,&nbsp;Ludovica Griffanti ,&nbsp;Sana Suri ,&nbsp;Klaus P. Ebmeier ,&nbsp;Thomas E. Nichols ,&nbsp;Vincent C.T. Mok ,&nbsp;Heidi Johansen-Berg ,&nbsp;Piergiorgio Salvan","doi":"10.1016/j.cccb.2024.100296","DOIUrl":"10.1016/j.cccb.2024.100296","url":null,"abstract":"<div><h3>Introduction</h3><p>The number of people living with dementia worldwide is growing. Devising and implementing preventive strategies that are globally applicable is of paramount importance. However, previous studies have largely been limited to cohorts that are geographically and culturally homogenous. It is not known whether the associations between demographics, vascular risk factors (VRFs), and cognitive changes are consistent across cohorts with cultural and geographical variations.</p></div><div><h3>Methods</h3><p>Data were analysed retrospectively from 6 community-dwelling cohorts (&gt; 60 years old) with cultural and geographical variations (British = 536; Hong Kong Chinese = 494; Australian = 302; Singaporean Chinese = 108; German = 102; Swedish = 94). Clinical demographics, VRFs, longitudinal cognitive changes, and MRI data (including T1, FLAIR, and diffusion images) were analysed from all 6 cohorts. First, across all cohorts, a grand canonical correlation analysis (n=1636) was used to establish common modes of covariation between demographics and VRFs on one side, and cognitive changes on the other side. Second, separately for each cohort, mediation analysis was used to investigate the mediating role of normalised total grey matter volume, microstructural integrity, white matter hyperintensity, and hippocampal structural network in the association mentioned above. Then the mediation outputs will be used in the meta- analysis to assess the indirect effect estimates and variance of each significant brain mediator.</p></div><div><h3>Results</h3><p>We identified three modes of covariation between dementia risk and cognition across all cohorts (p&lt; 0.01). The strongest mode linked younger age and higher levels of education with better cognition at baseline and follow-up (Figure 1). Meta-analysis showed that, across cohorts, normalised total grey matter volume (Indirect effect = 0.02, Z = 3.13, p &lt; 0.001, I² = 0%) was a significant mediator between demographics, VRFs, and cognitive decline after Bonferroni correction (Figure 2). The hippocampal structural network did not survive Bonferroni correlation while other brain mediators were not significant in the meta-analyses.</p></div><div><h3>Discussion</h3><p>This study investigated the complex relationship between demographics, VRFs, brain health, and cognition. Cohorts with cultural and demographic variations shared a common relationship between age, education, and cognition. However, individual cohort differences are detected in the contribution of different neuroimaging metrics.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100296"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000977/pdfft?md5=886bf63c637d9c622cb4749bb6387460&pid=1-s2.0-S2666245024000977-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122124","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":"Role of neurovascular uncoupling in cognitive decline induced by metabolic disturbances: vascular explorations in a mice model","authors":"Manon Haas ,&nbsp;Maud Pétrault ,&nbsp;Thavarak Ouk ,&nbsp;Patrick Gelé ,&nbsp;Olivier Pétrault ,&nbsp;Michèle Bastide","doi":"10.1016/j.cccb.2024.100247","DOIUrl":"10.1016/j.cccb.2024.100247","url":null,"abstract":"<div><h3>Introduction</h3><p>A link between vascular risk factors caused by metabolic disorders in mid-life and the onset of cognitive impairments has been evidenced. Our team has demonstrated that, in a mice model, a cognitive decline occurred after 6 months of high-fat diet (HFD). The cognitive impairment onset was concomitant to that of metabolic disorders and a dysfunction in cerebrovascular relaxation in regions involved in the altered cognitive tasks. This could be caused by a neurovascular coupling dysfunction, which allows the adjustment of cerebral blood flow to neuronal activity. Glutamate, both an excitative neurotransmitter and potent vasodilator, could be involved. When released, glutamate can activate a neuronal pathway involving nNOS and COX2 and/or an astrocytic pathway involving COX1. Those enzymes then produce vasodilatory agents. Our aim is to investigate potential neurovascular alterations induced by metabolic disorders by focusing on the role of vasoactive enzymes.</p></div><div><h3>Methods</h3><p>Male C57Bl6/J mice are fed with HFD or normal diet for 12 months. Vasomotricity of basilar artery and neurovascular coupling assessments are performed with Halpern's arteriograph and with an ex-vivo brain slice model using pharmacological modulation.</p></div><div><h3>Results</h3><p>Mice fed with HFD demonstrate a significantly decreased myogenic tone of the basilar artery, that is conversely correlated with weight gain. The vasodilatory response to glutamate was decreased in intraparenchymal arterioles of the animals in the HFD group compared to that of the control group. Specific inhibition of the enzymes involved in the glutamatergic pathways may demonstrate a different pattern of involvement of each of these enzymes in the vasodilatory response to glutamate of the HFD-fed mice, pointing to a greater participation of the neuronal pathway enzymes (nNOS and COX2).</p></div><div><h3>Discussion</h3><p>These results indicate that HFD could modify the basal functioning of cerebral arteries as well as their interaction with neurons and astrocytes, indicating a potential neurovascular uncoupling in our model. The reduced vasodilatory effect of glutamate in HFD-mice seems to be related to a decreased activation of COX1 to the profit of the glutamatergic neuronal pathway, notably of COX 2, whose expression is known to be increased in neuroinflammation, a recurrent occurrence in metabolic syndrome models as ours.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100247"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000485/pdfft?md5=fd82b3d2456703a17ede0c3be9855600&pid=1-s2.0-S2666245024000485-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122288","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":"Cerebral microbleeds are associated with slowed processing speed in middle-aged adults with type 1 diabetes","authors":"Iiris Kyläheiko ,&nbsp;Aleksi Tarkkonen ,&nbsp;Juha Martola ,&nbsp;Teemu Paajanen ,&nbsp;Jussi Virkkala ,&nbsp;Per-Henrik Groop ,&nbsp;Lena M. Thorn ,&nbsp;Jukka Putaala ,&nbsp;Daniel Gordin ,&nbsp;Hanna Jokinen ,&nbsp;FinnDiane Study Group","doi":"10.1016/j.cccb.2024.100276","DOIUrl":"10.1016/j.cccb.2024.100276","url":null,"abstract":"<div><h3>Introduction</h3><p>Type 1 diabetes (T1D) is an important risk factor for cerebral small vessel disease (SVD). Cerebral microbleeds (CMB) and white matter hyperintensities (WMH) can already be observed in early midlife in individuals with T1D, even though generally, this pathology is seen decades later in those without diabetes. Whether these changes affect cognitive functions, remains unclear. We investigated the associations of CMB and WMH with processing speed and attention in adults with T1D without major neurological symptoms.</p></div><div><h3>Methods</h3><p>As part of an ongoing FinnDiane sub-study, brain magnetic resonance imaging, and extensive clinical and neuropsychological examinations were done for 142 participants with T1D (age 47.2±7.6 years, diabetes duration 31.6±11.0 years). CMB and WMH were evaluated visually by an experienced neuroradiologist and categorized according to number and severity (CMB: 0 vs 1-2 vs ≥3; WMH: Fazekas score 0 vs ≥1). The assessment of processing speed and attention included the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding and Symbol search subtests, the Stroop test, and the computerized Flexible Attention Test (FAT) Simple Visuomotor Speed, Numbers and Number-Letter subtasks.</p></div><div><h3>Results</h3><p>CMB (≥3) and mild WMH were associated with poorer performance in WAIS-IV Coding and Symbol Search, and Stroop and FAT subtasks (p&lt;0.05) in univariate linear regression analyses. After controlling for age and years of education, the associations of CMB with Coding (stand. β=-0.17, p=0.038), FAT Simple Visuomotor Speed (stand. β=0.16, p=0.048) and Stroop color- incongruent part (stand. β=0.18, p=0.038) remained significant, whereas WMH were no longer related to cognitive performance. When CMB and WMH were entered together in multiple linear regression models adjusted for age and education, CMB had independent negative contributions to Coding (stand. β=-0.17, p=0.045). The effect sizes of the significant associations were small (Cohen's f2=0.04) (Fig. 1).</p></div><div><h3>Discussion</h3><p>CMB were related to a subtle decline in processing speed and attention in middle-aged adults with T1D. The associations were only partly explained by age. Effect sizes on a group level were small indicating minor clinical significance. However, our results provide insight into the development of SVD-related cognitive changes already in midlife and suggest an increased risk of cognitive decline in individuals with T1D.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100276"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000771/pdfft?md5=2d6f7ad47617253ace745cdd6a6e439f&pid=1-s2.0-S2666245024000771-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122303","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":"Baseline predictors and clinical outcomes of incident infarcts in the year after a mild stroke","authors":"Una Clancy ,&nbsp;Carmen Arteaga ,&nbsp;Daniela Jaime Garcia ,&nbsp;Will Hewins ,&nbsp;Rachel Locherty ,&nbsp;Maria Valdes-Hernandez ,&nbsp;Stewart Wiseman ,&nbsp;Michael Stringer ,&nbsp;Michael J Thrippleton ,&nbsp;Agniete Kampaite ,&nbsp;Olivia KL Hamilton ,&nbsp;Francesca M Chappell ,&nbsp;Angela CC Jochems ,&nbsp;Salvatore Rudilosso ,&nbsp;Xiaodi Liu ,&nbsp;Yajun Cheng ,&nbsp;Junfang Zhang ,&nbsp;Rosalind Brown ,&nbsp;Mark E Bastin ,&nbsp;Susana Munoz Maniega ,&nbsp;Joanna M Wardlaw","doi":"10.1016/j.cccb.2024.100331","DOIUrl":"10.1016/j.cccb.2024.100331","url":null,"abstract":"<div><h3>Introduction</h3><p>Factors associated with incident infarcts after stroke are unclear. We aimed to determine whether subsequent incident infarcts continue to develop one year post-stroke and how incident infarcts relate to baseline imaging features, vascular risks, and cognitive outcomes.</p></div><div><h3>Methods</h3><p>We recruited patients with non-disabling stroke. After diagnostic MRI, we repeated MRI at 3-6 monthly intervals for 12 months, visually assessing incident infarcts on DWI or FLAIR. We used logistic regression to determine associations with incident infarcts, including baseline vascular risks, SVD score, and index stroke subtype. We quantified 7-level ordinal cognitive outcome status at one year, using MoCA/telephone MoCA and modified Rankin Scale.[1,2] We used ordinal regression to determine whether cognitive outcomes associated with incident infarcts and baseline age, mRS, MoCA, and WMH volume.</p></div><div><h3>Results</h3><p>We recruited 229 participants, mean age 65.9 (SD 11.1) years; 77/229 (33.6%) female; 130/229 (56.8%) index lacunar stroke. From baseline to one-year MRI, we detected 117 incident infarcts in n=57/229 participants at 80 visits. Most were small subcortical infarcts: 86/117 (73.5%) infarcts in n=38/57 (66%). N=39 participants had incident infarcts at one visit; n=14 at two visits; n=3 at three visits, and n=1 at four visits. Nineteen participants had multiple incident infarcts at a single visit. Baseline summary SVD score was the strongest predictor of incident infarcts (aOR 1.74, 95%CI 1.29-2.41, Figure 1). At one year, 10/218 (4.6%) participants met criteria for single-domain and 62/218 (28.4%) for multi-domain neurocognitive disorder; 15/218 (6.8%) for mild dementia; 2/218 (0.9%) for moderate dementia; none severe; 3/229 (1.3%) had died. Participants’ odds of impaired one-year cognition increased for every one-unit increment in baseline mRS (aOR=2.03 [1.30-3.10]) and decreased for every one-unit increment in baseline MoCA (aOR=0.78 [0.71-0.85]). For participants with incident small subcortical infarcts, the odds of impaired cognition were 23% higher than for incident cortical infarcts, though not statistically significant (aOR 1.23 [0.55-2.1])(Figure 2).</p></div><div><h3>Discussion</h3><p>In a mild stroke population, incident infarcts, mostly small subcortical, occur in one quarter and associate with worse baseline SVD. Minor neurocognitive disorder occurs in one third and associates with baseline mRS, MoCA, and trends towards incident small subcortical rather than cortical infarcts.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100331"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024001326/pdfft?md5=86852cb873b4b5a5cb8aed7352dec199&pid=1-s2.0-S2666245024001326-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122306","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":"Subjective cognitive complaints are related to depressive symptoms but not objective impairment in covert cerebral small vessel disease","authors":"Anne Arola ,&nbsp;Hanna M. Laakso ,&nbsp;Heidi Heinonen ,&nbsp;Johanna Pitkänen ,&nbsp;Matti Ahlström ,&nbsp;Juha Lempiäinen ,&nbsp;Teemu Paajanen ,&nbsp;Jussi Virkkala ,&nbsp;Juha Koikkalainen ,&nbsp;Jyrki Lötjönen ,&nbsp;Antti Korvenoja ,&nbsp;Susanna Melkas ,&nbsp;Hanna Jokinen","doi":"10.1016/j.cccb.2024.100332","DOIUrl":"10.1016/j.cccb.2024.100332","url":null,"abstract":"<div><h3>Introduction</h3><p>Subjective cognitive complaints are common in patients with cerebral small vessel disease (SVD), yet their correspondence to informant evaluations, objective cognitive functions and severity of brain changes are poorly understood. We studied the associations of subjective and informant reports of cognitive difficulties (executive functions and memory) with findings from a comprehensive neuropsychological assessment and brain MRI (white matter hyperintensities, WMH volume) as well as depressive symptoms and functional abilities (instrumental activities of daily living, IADL).</p></div><div><h3>Methods</h3><p>In the Helsinki SVD Study, 152 older adults with varying degrees of WMH but without stroke or dementia were classified as having normal cognition or mild cognitive impairment (MCI) based on Jak/Bondi neuropsychological criteria. The objective cognitive measures also included continuous domain scores for memory and executive functions. Cognitive complaints were evaluated with the subjective- and informant-versions of Prospective and Retrospective Memory Questionnaire (PRMQ) and Dysexecutive Questionnaire (DEX), functional abilities with the Amsterdam IADL Questionnaire and depressive symptoms with the Geriatric Depression Scale (GDS-15).</p></div><div><h3>Results</h3><p>Subjective cognitive complaints correlated significantly with informant reports (r=0.40-0.50, p&lt;0.001). After controlling for age, gender and years of education, subjective and informant DEX and PRMQ were not related to MCI or cognitive domain scores (all p-values&gt;0.05). Instead, subjective DEX (OR 1.10, CI 95% 1.05-1.16, p&lt;0.001) and subjective PRMQ (OR 1.06, CI 95% 1.01-1.11, p=0.014) were significantly associated with GDS-15. Informant DEX (standardised β=0.26, p=0.002, f2=0.08) and informant PRMQ (standardised β=0.24, p=0.007, f2=0.06) were significantly related to WMH volume. They were also associated with IADL score (informant DEX, standardised β=-0.33, p=0.001, f2=0.30; informant PRMQ, standardised β=-0.24, p=0.011, f2=0.19).</p></div><div><h3>Discussion</h3><p>Neither subjective nor informant-reported cognitive complaints were associated with objective cognitive performance in terms of MCI categorisation or more sensitive domain scores of executive functioning or memory. Informant-evaluations were related to functional impairment in IADL and more severe WMH, whereas subjective complaints only associated with depressive symptoms. These findings suggest that awareness of cognitive impairment may be limited in early-stage SVD and highlight the value of informant assessments in the identification of patients with functional impairment.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100332"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024001338/pdfft?md5=8c8b4ccf9ef1d7ab5bc68040c4f5dcf2&pid=1-s2.0-S2666245024001338-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122307","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":"A multicenter, single-arm, phase II clinical trial of adrenomedullin in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy","authors":"Kazuo Washida ,&nbsp;Satoshi Saito ,&nbsp;Tomotaka Tanaka ,&nbsp;Yuriko Nakaoku ,&nbsp;Hiroyuki Ishiyama ,&nbsp;Soichiro Abe ,&nbsp;Takehito Kuroda ,&nbsp;Shinsaku Nakazawa ,&nbsp;Chikage Kakuta ,&nbsp;Katsuhiro Omae ,&nbsp;Kenta Tanaka ,&nbsp;Manabu Minami ,&nbsp;Yoshiaki Morita ,&nbsp;Tetsuya Fukuda ,&nbsp;Akihiro Shindo ,&nbsp;Takakuni Maki ,&nbsp;Kazuo Kitamura ,&nbsp;Hidekazu Tomimoto ,&nbsp;Toshihiko Aso ,&nbsp;Masafumi Ihara","doi":"10.1016/j.cccb.2024.100211","DOIUrl":"https://doi.org/10.1016/j.cccb.2024.100211","url":null,"abstract":"<div><h3>Background</h3><p>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of hereditary cerebral small vessel disease (SVD), currently lacks disease-modifying treatments. Adrenomedullin (AM), a vasoactive peptide with angiogenic, vasodilatory, anti-inflammatory, and anti-oxidative properties, shows potential effects on the neuro-glial-vascular unit.</p></div><div><h3>Objective</h3><p>The AdrenoMedullin for CADASIL (AMCAD) study aims to assess the efficacy and safety of AM in patients with CADASIL.</p></div><div><h3>Sample size</h3><p>Overall, 60 patients will be recruited.</p></div><div><h3>Methods</h3><p>The AMCAD is a multicenter, investigator-initiated, single-arm phase II trial. Patients with a confirmed CADASIL diagnosis, based on <em>NOTCH3</em> genetic testing, will receive an 8-h AM treatment (15 ng/kg/min) for 14 days following a baseline assessment (from day 1 to day 14). Follow-up evaluations will be performed on days 15, 28, 90, and 180.</p></div><div><h3>Study outcomes</h3><p>The primary endpoint is the cerebral blood flow change rate in the frontal cortex, evaluated using arterial spin labeling magnetic resonance imaging, from baseline to day 28. Summary statistics, 95% confidence intervals, and a one-sample <em>t</em>-test will be used for analysis.</p></div><div><h3>Conclusion</h3><p>The AMCAD study aims to represent the therapeutic potential of AM in patients with CADASIL, addressing an unmet medical need in this challenging condition.</p></div><div><h3>Clinical Trial Registration</h3><p>jRCT 2,051,210,117 (<span>https://jrct.niph.go.jp/en-latest-detail/jRCT2051210117</span><svg><path></path></svg>).</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100211"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245024000126/pdfft?md5=792cfc81ff75c70058dcb56ad28b0418&pid=1-s2.0-S2666245024000126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139726271","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":"Brain health assessment. An exploratory review of tools related to its cognitive dimension","authors":"Alessia Nicotra ,&nbsp;Giorgia Maestri ,&nbsp;Emilia Salvadori ,&nbsp;Leonardo Pantoni","doi":"10.1016/j.cccb.2023.100188","DOIUrl":"10.1016/j.cccb.2023.100188","url":null,"abstract":"<div><h3>Background</h3><p>Brain health is an evolving concept and relates to physical and mental health, social well-being, productivity, creativity. Brain health has several dimensions (cognitive, motor, functional, social, and emotional), and should be recognized as one top global priorities of health policies. The purpose of this paper is to provide a summary of tools developed for assessing the cognitive dimension of brain health in the out-patient services.</p></div><div><h3>Methods</h3><p>A literature search on PubMed was performed (from inception to May 31, 2023). We identified cognitive tests, functional and psychological scales, and focused on screening tools specifically proposed to characterize cognition within the construct of brain health, comparing them with common global screening tests.</p></div><div><h3>Results</h3><p>Among 1947 records, we identified 17 cognitive screening tools used in the context of brain health assessment, of which four were ad hoc developed: Brain Health Assessment (BHA), Brain Health Test (BHT), Brain Health Test-7 (BHT-7), and The Cogniciti Brain Health Assessment. The four tests have administration time ranging from 4 to 30 min, and different administration methods (paper-and-pencil or tablet-based). All four tools assess memory and other cognitive domains. Specific cut-offs have been identified for BHT and BHT-7, while the other tools have automated scoring systems. All but one test also assess other dimensions. Compared to commonly used cognitive screening tests, the brain health tools are less widely used, translated, and validated.</p></div><div><h3>Conclusions</h3><p>The concept of brain health is new and requires further validation of tools for its assessment, especially for the cognition dimension.</p></div>","PeriodicalId":72549,"journal":{"name":"Cerebral circulation - cognition and behavior","volume":"6 ","pages":"Article 100188"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666245023000326/pdfft?md5=b8a6a9a186c5ced90376a50ae701ec2c&pid=1-s2.0-S2666245023000326-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135407902","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}