Cerebral circulation - cognition and behavior最新文献

Introduction

The Kazakh population has been increasing in age over the last two decades. Life expectancy in Kazakhstan in 2022 was 73.8 years (y). Noncommunicable diseases (NCDs) accounted for ∼84% of deaths, particularly among men, and included cardiovascular disease, diabetes, chronic respiratory disease and cancer. It is anticipated that life expectancy trends will be similar among People Living With HIV (PLWH) who are virally suppressed in Kazakhstan. However, the prevalence and types of aging-related NCDs among Kazakh PLWH are unknown, despite ∼40% of Kazakh PLWH being age >40 years (y). In addition, and limited knowledge exists about the NCD-HIV care continuum.

Methods

An ongoing cross-sectional study is being conducted among PLWH, >40y at the Almaty AIDS center. Cardiovascular, clinical, sociodemographic, mental health, medical history, health behavior, and HIV measures are collected. The Montreal Cognitive Assessment was included (range: 0-30).

Results

113 PLWH were interviewed over ∼6 months (43.4% females; 54.9% age 40-49y, 30.1%, 11.5% and 3.5% age 50-59, 60-69, >70 years, respectively; gender: 58.3% cis men, 41.7% cis women; 20.4% self-reported Asian (Kazakh) race, 56.6% White (Russian), 23.0% unknown; 55.4% were employed; 25.7% reported education beyond college; 65.5% consumed alcohol; 76.1% were current smokers and 26.5% drug users. 54% had healthy BMI (18.5- <25 kg/m2). Systolic blood pressure range was 90-140mmHg (median 120); diastolic blood pressure range, 60-100mmHg (median 80). Median oxygen saturation was 98%. 76.7% participants had undetectable HIV viral load (<50 copies/ml), and 16.7% exhibited CD4 cell count <200 cells/mm3. However, 36.3% had high NT-pro-BNP (≥125 pg/ml), which was accompanied by a higher mean HIV viral load (p=0.026). Mean plasma glucose (mmol/l) and triglycerides were higher (p<0.10) among those with NT- proBNP ≥125 pg/ml. Among those taking antiretroviral therapies over a longer time period, there was higher NT-proBNP, however p>0.05. The MoCA indicated that 61.9% scored <26 (raw score); average 23.1. Comparing those with MoCA <26 versus ≥26, there were no differences in pro-BNP or lipid levels, HIV viral load or CD4+ count. However, diastolic blood pressure was higher among those with MoCA<26 (p=0.043).

Discussion

Further investigation to understand cardiovascular contributors to cognitive impairment among PLWH is necessary.

Introduction

Cerebral small vessel disease (cSVD) is a major contributor to stroke and vascular cognitive impairment. However, other potential physical and psychological consequences have been described. Our aim was to provide an overview of systematic reviews describing clinical phenotypes associated with cSVD.

Methods

We searched four multidisciplinary databases from inception to December 2022. We included reviews describing concurrent clinical phenotypes in individuals with neuroimaging evidence of cSVD, defined using the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE-1) criteria. We broadly classified phenotypes into cognitive, mood and neuropsychiatric, respiratory, cardiovascular, renal-urinary, peripheral nervous system, locomotor, and gastrointestinal. We included studies assessing multiple cSVD features or using a summary cSVD score, and studies examining individual cSVD markers. We extracted risk-factor adjusted effect estimates, where possible, and assessed methodological quality using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool.

Results

We included 24 systematic reviews reporting on 685 original studies and >1,135,940 participants. Cognitive and neuropsychiatric phenotypes were examined most often, particularly in relation to white matter hyperintensities (range of risk ratios for neurocognitive phenotypes, 1.21-1.49; and for neuropsychiatric, 1.02-5.71). Two reviews focused solely on perivascular spaces. No reviews assessed lacunes or small subcortical infarcts separately from other cSVD features. Reviews on peripheral nervous system, urinary or gastrointestinal phenotypes were lacking. Fourteen reviews had high methodological quality. Heterogeneity in cSVD definitions and phenotypic assessments was substantial.

Discussion

Neuroimaging markers of cSVD are associated with various concurrent clinical conditions. Cognitive and neuropsychiatric phenotypes have been reviewed most extensively, while few reviews assessed gait and mobility. Reviews for many body systems were lacking. Similarly, while white matter hyperintensities were relatively well studied, there were limited data on phenotypes associated with perivascular spaces and lacunes. Future studies should characterize the full clinical spectrum of cSVD, and explore clinical associations beyond neurocognitive and neuropsychiatric presentations.

Introduction

HCHS/SOL is a representative study of Hispanic/Latinos living in the US. SOL-INCA examines cognition amongst those of HCHS/SOL over age 50 and SOL-INCA-MRI obtains quantitative MRI measures on a subgroup of these individuals. Prior research in SOL-INCA found that vascular risk factors summarized by the Framingham Cardiovascular Risk Score (Fram CVD) is associated with Mild Cognitive Impairment (MCI)1. We hypothesize that the extent of white matter hyperintensities (WMH) will partially mediate this impact of Fram CVD on MCI prevalence in this cohort.

Methods

SOL-INCA-MRI consists of 2366 individuals of Hispanic/Latino Heritage from 4 centers across the US. Demographics of the cohort are summarized in the Table. High resolution MRI were acquired and WMH burden measured by previously reported methods2. WMH volumes were natural log transformed and corrected for scanner type using NeuroCombat. General linear models were used to test the associated between diagnosis (normal, questionable impairment and MCI) and Fram CVD and WMH adjusting for age, gender, education, heritage, and center. Casual mediation analysis was also performed to assess the extent to which WMH mediated the association between Fram CVD and diagnosis.

Results

Subjects were 64.6 + 6.8 years of age at MRI, 68.5% were female, 16% had questionable impairment and 13% had MCI. Mean Fram CVD risk was 11.4 + 0.9%. Mean log WMH was -0.13 +1.55. Diagnosis was significantly associated with Fram CVD (beta= 780, p <0.0001) and WMH (beta =34, p <0.0001). Fram CVD was also strongly associated with WMH (beta = 2.6, p <0.0001). Causal mediation analysis found that WMH significantly mediated the association of Fram CVD to Diagnosis (p < 0.0001) by a proportion of 10%.

Discussion

These results indicate that at least part of the impact of Fram CVD of MCI prevalence is mediated by the impact of Fram CVD on white matter injury suggesting that microvascular disease is a strong predictor of cognitive impairment amongst Hispanic/Latinos in the US.

Introduction

To investigate the psychometric properties, administration efficiency and implementational feasibility of a previously piloted voice recognition- based digital cognitive screener for dementia detection in a large-scale community of elderly participants.

Methods

Eligible participants completed the demographic, lifestyle investigations and the DCS. Domain-specific and global cognition was assessed by a comprehensive neuropsychological test battery. Diagnosis of mild cognitive impairment(MCI) and dementia was made based on the clinical dementia rating. Completion rate and administration time for the DCS were recorded. Correlation between the DCS and domain-specific and global cognitive performance were assessed. Receiver operating characteristic (ROC) analyses examined the discriminate validity of the DCS in detecting MCI and dementia. A cost-consequences analysis was conducted to compare the screening efficacy of DCS with two traditionally administered cognitive assessment tools, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), was conducted.

Results

Among a total of 11,186 participants, the completion rate of the DCS was 97·5% with a conduction time of 5·6–6·1 minutes, regardless of gender, age and education stratifications. DCS total score was significantly associated with domain-specific and global cognitive z-scores. Area under the curves (AUCs) of the DCS were 0·95 (0·92, 0·99) and 0·83 (0·79, 0·88) for dementia and MCI detection, respectively. There was no significant difference on the AUCs among different age- and education-stratified subgroups. Comparing with the MoCA and MMSE, DCS resulted in time savings of 35·4%–36·0% and 30·7%–31·2% for identifying dementia cases, as well as 22·6%–22·8% and 16·2%–16·4% for identifying MCI cases.

Discussion

Our findings demonstrated that the DCS was an effective and efficient tool for case-finding of dementia and MCI in a Chinese community. The large-scale implementation of the DCS among older Chinese adults could be a practical cognitive screening strategy to improve the management of healthcare resources.

Introduction

Nutrition, a modifiable risk factor, presents a low-cost prevention strategy to reduce the burden of cognitive impairment and dementia. However, studies examining the effects of dietary patterns on cognition are lacking in multi-ethnic Asian populations. We investigate the association between diet quality, measured with the Alternative Healthy Eating Index (AHEI)-2010, and cognitive impairment in middle-and old-aged adults of different ethnicities (Chinese, Malay, Indian) in Singapore.

Methods

This cross-sectional study (n=3138) was based on data from the Singapore Multi-Ethnic Cohort. Dietary intake collected with a validated semi-quantitative Food Frequency Questionnaire were converted into AHEI-2010 scores, where trans-fat and sodium consumption were not considered and a score range of 0-90 was allowed. Higher AHEI-2010 score indicates better compliance to recommended dietary pattern. Cognition, assessed with the Mini-Mental State Examination (MMSE), was analysed as a continuous or binary outcome (cognitively impaired is defined using education-based cut-offs of <23, 25 or 27 for participants with no education, primary school education and secondary school education and above). Multivariable linear and logistic regression models were used to examine associations between AHEI-2010 and cognition, adjusting for covariates.

Results

Participants have a mean age of 56.6 (SD = 9.3) years, and 41.6% were male. Participants have a mean AHEI-2010 score of 52.4 (SD = 9.8) and 988 (31.5%) participants had cognitive impairment. Ethnic Chinese (mean = 51.3, SD = 9.6) and Indians (mean = 51.3, SD = 9.7) had higher AHEI-2010 score than Malays (mean = 47.6, SD = 9.9). Higher AHEI-2010 scores were significantly associated with higher MMSE score (p trend < 0.001) and lower odds of cognitive impairment (p trend = 0.01). Compared with lowest quartile, participants from highest quartile had 0.44 (95%CI 0.22, 0.67) higher MMSE score and 31% less cognitive impairment odds (OR = 0.69, 95%CI 0.54, 0.88) after adjusting for all the covariates. However, no significant associations were observed for individual dietary components of the AHEI-2010 with MMSE or cognitive impairment.

Discussion

Healthier dietary patterns were associated with better cognitive function in middle- aged and older Singaporeans. These findings could inform better support to promote healthier dietary patterns in Asian populations.

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.

Background

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).

Methods

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.

Results

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 (n = 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; p < 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.

Conclusions

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.

Introduction

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.

Methods

As part of the Nor-COAST study, 373 stroke patients were screened for delirium using the Confusion Assessment

Methods

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.

Results

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.

Discussion

Patients with delirium in the acute phase of stroke may be particularly vulnerable to developing cognitive and psychiatric symptoms in the chronic phase.

Introduction

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.

Methods

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.

Results

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.

Discussion

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.

Introduction

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.

Methods

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).

Results

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).

Discussion

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.

International Clinical Trials Registry Platform reference: ISRCTN15483452 (http://isrctn.com/ISRCTN15483452)