[The effect of insomnia on mild cognitive impairment in patients with vascular risks: results of a three-year longitudinal study]. / Vliyanie insomnii na umerennye kognitivnye narusheniya u patsientov s faktorami serdechno-sosudistogo riska: rezul'taty 3-letnego prodol'nogo issledovaniya.

OBJECTIVE: To assess the dynamics of sleep parameters based on the analysis of three items of HDRS-17, designed to measure the severity of insomnia, during 36 months of follow-up and their relationship with indicators of the cognitive phenotype in patients with vascular risk factors. MATERIAL AND METHODS: The longitudinal study included 51 patients (mean age 57.7±6.2 years, 19 (37.3%) men)) who met the inclusion criteria. All participants underwent a general clinical examination with assessment of vascular risks and neuropsychological testing using the Montreal Cognitive Assessment (MoCA) and HDRS-17 at baseline and after 36 months. During the study, patients received stable basic therapy to prevent modifiable vascular risk factors. Sleeping pills were taken sporadically when there were complaints of problems falling asleep. RESULTS: During the 36-month study, as vascular cognitive impairment progressed from 23.7±2.6 to 22.1±2.4 points on the MoCA scale (p=0.01), mainly due to decreased attention (p=0.01), executive functions (EF) (p=0.01), memory (p=0.02), speech (p=0.02), an increase in sleep disturbances was observed (item 4: 0.8±0.02 to 1.9±0.1 points, p=0.01; point 5: 0.6±0.02 to 1.7±0.1 points, p=0.01) and depression (7.5±0.5 to 13.7±3.0 points, p=0.01) in patients with vascular risks. A strong inverse correlation was revealed between the values of items 4, 5, 6 on the HDRS-17 and the average MoCA-total scores (r=-0.85; r=-0.87; r=-0.8 (p<0.05)), memory index (r=-0.8; r=-0.75; r=-0.81 (p<0.05)), attention index (r=-0.88; r=-0.86; r=-0.83 (p<0.05)), index of executive functions (r=-0.87; r=-0.85; r=-0.8 (p<0.05)), respectively. CONCLUSION: The progression of cognitive impairment is associated with worsening insomnia disorders and depression in patients with vascular risks.

Trends in American Indian/Alaskan native self-reported stroke prevalence and associated modifiable risk factors in the United States from 2011-2021.

BACKGROUND: Stroke prevalence varies by race/ethnicity, as do the risk factors that elevate the risk of stroke. Prior analyses have suggested that American Indian/Alaskan Natives (AI/AN) have higher rates of stroke and vascular risk factors. METHODS: We included biyearly data from the 2011-2021 Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults (age ≥18) in the United States. We describe survey-weighted prevalence of stroke per self-report by race and ethnicity. In patients with self-reported stroke (SRS), we also describe the prevalence of modifiable vascular risk factors. RESULTS: The weighted number of U.S. participants represented in BRFSS surveys increased from 237,486,646 in 2011 to 245,350,089 in 2021. SRS prevalence increased from 2.9% in 2011 to 3.3% in 2021 (p<0.001). Amongst all race/ethnicity groups, the prevalence of stroke was highest in AI/AN at 5.4% and 5.6% in 2011 and 2021, compared to 3.0% and 3.4% for White adults (p<0.001). AI/AN with SRS were also the most likely to have four or more vascular risk factors in both 2011 and 2021 at 23.9% and 26.4% compared to 18.2% and 19.6% in White adults (p<0.001). CONCLUSION: From 2011-2021 in the United States, AI/AN consistently had the highest prevalence of self-reported stroke and highest overall burden of modifiable vascular risk factors. This persistent health disparity leaves AI/AN more susceptible to both incident and recurrent stroke.

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: The COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions. METHODS: We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains. RESULTS: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing. CONCLUSION: The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.

Correlation between Morphological and Hemodynamic Parameters of Carotid Arteries and Cerebral Vasomotor Reactivity.

The function of cerebral small vessels can be assessed using cerebral vasomotor reactivity (VMR). Our aim in this retrospective cross-sectional study was to investigate a correlation between carotid artery stenosis measured through ultrasonographic morphological and hemodynamic parameters and cerebral VMR. A total of 285 patients (125 males; mean age 54) were included. The breath-holding index (BHI) was used to evaluate cerebral VMR. Ultrasonographic carotid artery parameters were collected: the presence and characteristics of carotid plaques, the degree of carotid diameter stenosis, intima-media thickness (IMT), peak systolic velocity (PSV), and end diastolic velocity (EDV). Additionally, hemodynamic parameters of the middle cerebral artery (MCA) were evaluated, including the mean flow velocity (MFV) and pulsatility index (PI). The following was collected from patients' medical histories: age, gender, and vascular risk factors. A negative correlation between the BHI and age (r = -0.242, p < 0.01), BHI and the presence of carotid plaques, BHI and IMT (r = -0.203, p < 0.01), and BHI and the PI of MCA on both sides (r = -0.268, p < 0.01) was found. We found a positive correlation between the BHI in the left MCA and EDV in the left internal carotid artery (r = 0.121, p < 0.05). This study shows the correlation between cerebral VMR and carotid stenosis but indicates a higher influence of morphological parameters on VMR values.

An Investigation of Cerebral Vascular Functional Properties in Middle-to-Old Age Community People With High Vascular Risk Profiles.

BACKGROUND: Vascular degeneration is an important cause of brain damage in aging. Assessing the functional properties of the cerebral vascular system may aid early diagnosis and prevention. PURPOSE: To investigate the relationships between potential vascular functional markers and vascular risks, brain parenchymal damage, and cognition. STUDY TYPE: Retrospective. SUBJECTS: Two hundred two general community subjects (42-80 years, males/females: 127/75). FIELD STRENGTH/SEQUENCE: 3 T, spin echo T1W/T2W/FLAIR, resting-state functional MRI with an echo-planar sequence (rsfMRI), pseudo-continuous arterial spin labeling (pCASL) with a three-dimensional gradient-spin echo sequence. ASSESSMENT: Cerebral blood flow (CBF) in gray matter calculated using pCASL, blood transit times calculated using rsfMRI, and the SD of internal carotid arteries signal (ICAstd ) calculated using rsfMRI; visual assessment for lacunes; quantification of white matter hyperintensity volume; permutation test for quality control; collection of demographic and clinical data, Montreal Cognitive Assessment, Mini-Mental State Examination. STATISTICAL TESTS: Kolmogorov-Smirnov test; Spearman rank correlation analysis; Multivariable linear regression analysis controlling for covariates; The level of statistical significance was set at P < 0.05. RESULTS: Age was negatively associated with ICAstd (ß = -0.180). Diabetes was associated with longer blood transit time from large arteries to capillary bed (ß = 0.185, adjusted for age, sex, and intracranial volume). Larger ICAstd was associated with less presence of lacunes (odds ratio: 0.418, adjusted for age and sex). Higher gray matter CBF (ß = 0.154) and larger ICAstd (ß = 0.136) were associated with better MoCA scores (adjusted for age, sex, and education). DATA CONCLUSION: Prolonged blood transit time, decreased ICAstd , and diminished CBF were associated with vascular dysfunction and cognitive impairment. They may serve as vascular functional markers in future studies. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson's disease.

Glypicans are biomarkers for various pathologies, including cardiovascular disease, cancer and diabetes. Increasing evidence suggests that glypicans also play a role in the context of neurodegenerative disorders. Initially described as supporting functionality of synapses via glutamate receptors during CNS development, Glypican 4 (GPC-4) also plays a role in the context of dementia via tau hyperphosphorylation in Alzheimer's disease, which is also a co-pathology in Parkinson's disease dementia. However, clinical evidence of circulating GPC-4 in Parkinson's disease (PD) is missing so far. We therefore investigated GPC-4 in biofluids of PD patients. We analyzed GPC-4 levels in cerebrospinal fluid (CSF, n = 140), serum (n = 80), and tear fluid samples (n = 70) of PD patients and control subjects in a similar age range by ELISA (serum, CSF) and western blot (tear fluid). Expression of circulating GPC-4 was confirmed in all three biofluids, with highest levels in serum. Interestingly, GPC-4 levels were age-dependent, and multiple regression analysis revealed a significant association between GPC-4 serum levels and MoCA score, suggesting an involvement of GPC-4 in PD-associated cognitive decline. Furthermore, stratification of PD patients for vascular risk factors revealed a significant increase of GPC-4 serum levels in PD patients with vascular risk factors. Our results suggest GPC-4 as a clinical biomarker for vascular risk stratification in order to identify PD patients with increased risk of developing dementia.

White matter brain age as a biomarker of cerebrovascular burden in the ageing brain.

As the brain ages, it almost invariably accumulates vascular pathology, which differentially affects the cerebral white matter. A rich body of research has investigated the link between vascular risk factors and the brain. One of the less studied questions is that among various modifiable vascular risk factors, which is the most debilitating one for white matter health? A white matter specific brain age was developed to evaluate the overall white matter health from diffusion weighted imaging, using a three-dimensional convolutional neural network deep learning model in both cross-sectional UK biobank participants (n = 37,327) and a longitudinal subset (n = 1409). White matter brain age gap (WMBAG) was the difference between the white matter age and the chronological age. Participants with one, two, and three or more vascular risk factors, compared to those without any, showed an elevated WMBAG of 0.54, 1.23, and 1.94 years, respectively. Diabetes was most strongly associated with an increased WMBAG (1.39 years, p < 0.001) among all risk factors followed by hypertension (0.87 years, p < 0.001) and smoking (0.69 years, p < 0.001). Baseline WMBAG was associated significantly with processing speed, executive and global cognition. Significant associations of diabetes and hypertension with poor processing speed and executive function were found to be mediated through the WMBAG. White matter specific brain age can be successfully targeted for the examination of the most relevant risk factors and cognition, and for tracking an individual's cerebrovascular ageing process. It also provides clinical basis for the better management of specific risk factors.

Sex steroid and cognitive function among community-dwelling older men with or without vascular risk factors: a cross-sectional study.

BACKGROUND: The relationship of testosterone and estradiol concentrations with cognitive function among community-dwelling older men was inconclusive. To examine the association of serum testosterone and estradiol concentrations with cognitive function in older men with or without vascular risk factors (VRFs). METHODS: This cross-sectional study consisted of 224 community-dwelling men aged 65-90 years in the Songjiang District of Shanghai, China. Serum testosterone and estradiol were measured by electrochemiluminescence immunoassay. The following five factors were defined as VRFs in this study: obesity, history of hypertension, diabetes, stroke, and coronary heart disease. Multivariable linear regression was used to examine the association of testosterone and estradiol with the Mini-Mental State Examination (MMSE) in participants with or without VRF. Restricted cubic spline (RCS) regression was performed to account for the nonlinearity of these associations. RESULTS: An inverted "U" shaped non-linear relationship was found between testosterone concentration and MMSE score in men with one VRF (P overall =.003, non-linear P =.002). Estradiol showed an inverted "U" shaped non-linear relationship with MMSE score independent of VRFs (men without VRF, P overall =.049, non-linear P =.015; men with one VRF, overall P =.007, non-linear P =.003; men with two or more VRFs, overall P =.009, non-linear P =.005). CONCLUSION: In older men, an optimal level of sex steroid concentration may be beneficial to cognitive function and the VRFs should be considered when interpreting the relationship between sex steroid and cognitive function.

Prophylactic Muscle Free Flap for Total Ankle Arthroplasty With Vascular Risk Factors.

Total ankle arthroplasty (TAA) is a treatment for ankle arthritis that preserves the joint's mobility. Conditions causing poor peripheral blood flow are contraindications for TAA. A 63-year-old man with posttraumatic ankle osteoarthritis who was considered high-risk for TAA due to obesity, history of trauma, tobacco usage, chronic venous stasis, lymphedema, and hypertension subsequently underwent TAA followed by a prophylactic muscle free flap to improve peripheral blood flow and soft tissue integrity. He recovered with no pain and excellent ankle mobility. This case highlights the potential usage of prophylactic muscle free flaps to mitigate vascular risk factors in high-risk patients undergoing TAA.

Association of multiple sclerosis with stroke: A comprehensive review.

Background: Multiple sclerosis (MS) is a chronic immune-mediated disorder characterized by the degradation of the myelin sheath in the central nervous system. Research indicates that individuals with MS exhibit a higher susceptibility to stroke compared to the general population. This association is rooted in shared underlying mechanisms, specifically involving neuroinflammatory processes. Methodology: We performed an extensive search on PubMed, MEDLINE, Embase, Scopus, and Google Scholar using specific terms. The search terms included variations of "multiple sclerosis," "stroke," "cerebrovascular disease," "vascular risk factors," "disease-modifying therapies," and "neuroinflammation." The search was limited to articles published from January 1, 2000, up to 31 May, 2023. Results and Discussion: Stroke, a global health burden characterized by significant mortality and adult disability, underscores the critical importance of understanding the link between MS and stroke. Despite a growing body of research establishing an elevated risk of stroke in MS patients, notable information gaps persist. Limited prospective multicenter studies on stroke incidence in MS patients contribute to an incomplete understanding of the precise relationship between these two conditions. Conclusion: In conclusion, this review underscores the critical need for a thorough understanding of the complex relationship between MS and stroke. The identified risk factors and the influence of MS DMTs on stroke risk necessitate further investigation to inform evidence-based preventive and therapeutic strategies. Bridging the existing information gaps through prospective multicenter studies is imperative for a comprehensive understanding of this association. The development of targeted diagnostic and therapeutic approaches for acute stroke risk in MS patients is paramount to mitigate the impact of these debilitating conditions. Ultimately, this review serves as a foundation for future efforts to enhance preventative measures and therapeutic interventions, thereby improving the overall quality of life for individuals with MS susceptible to strokes.

Vascular risk factors, white matter microstructure, and depressive symptoms: a longitudinal analysis in the UK Biobank.

BACKGROUND: Cumulative burden from vascular risk factors (VRFs) has been associated with an increased risk of depressive symptoms in mid- and later life. It has been hypothesised that this association arises because VRFs disconnect fronto-subcortical white matter tracts involved in mood regulation, which puts older adults at higher risk of developing depressive symptoms. However, evidence for the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms from longitudinal studies is scarce. METHODS: This preregistered study analysed longitudinal data from 6,964 middle-aged and older adults from the UK Biobank who participated in consecutive assessments of VRFs, brain imaging, and depressive symptoms. Using mediation modelling, we directly tested to what extend white matter microstructure mediates the longitudinal association between VRF burden and depressive symptoms. RESULTS: VRF burden showed a small association with depressive symptoms at follow-up. However, there was no evidence that fractional anisotropy (FA) of white matter tracts mediated this association. Additional analyses also yielded no mediating effects using alternative operationalisations of VRF burden, mean diffusivity (MD) of single tracts, or overall average of tract-based white matter microstructure (global FA, global MD, white matter hyperintensity volume). CONCLUSIONS: Our results lend no support to the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms, while highlighting the relevance of using longitudinal data to directly test pathways linking vascular and mental health.

Subtypes of major depressive disorders and objectively measured physical activity and sedentary behaviors in the community.

BACKGROUND: Lack of physical activity (PA) and high sedentary behavior (SB) may enhance mental health problems, including depression, and are associated with increased mortality. Aside from a large body of research on major depressive disorder (MDD) assessed as an entity and either PA or SB, few studies have examined associations among subtypes of MDD and both PA and SB simultaneously derived from wrist-worn accelerometers. Accordingly, our aim was to explore the associations among MDD subtypes (atypical, melancholic, combined atypical-melancholic and unspecified) and four actigraphy-derived behaviors combining the levels of PA and SB. METHODS: The sample stemmed from CoLaus|PsyCoLaus, a population-based cohort study, consisting of 2375 participants (55.1% women; mean age: 62.4 years) who wore an accelorometer for 14 days after a physical exam and subsequently completed a semi-structured psychiatric interview. Activity behaviors were defined according to the combination of the levels of moderate-to-vigorous intensity PA and SB. Associations of remitted MDD subtypes, current MDD and physical inactivity behaviors were assessed using multinomial logistic regression, adjusted for socio-demographic characteristics, a history of anxiety, alcohol and drug use disorders and cardiovascular risk factors. RESULTS: In the fully adjusted model, participants with the remitted combined atypical-melancholic subtype had a higher risk of being more physically inactive. CONCLUSIONS: Our findings suggest that low PA and high SB are not restricted to the duration of depressive episodes in people with atypical and melancholic episodes. The lack of PA and high SB in this group of depressive patients exposes them to an additional long-term cardiovascular risk and measures to increase PA may be particularly fruitful in this MDD subgroup.

Effect of Vascular Risk Factors on Blood-Brain Barrier and Cerebrospinal Fluid Biomarkers Along the Alzheimer's Disease Continuum: A Retrospective Observational Study.

BACKGROUND: Blood-brain barrier (BBB) dysfunction could favor the pathogenesis and progression of Alzheimer's disease (AD). Vascular risk factors (VRF) could worsen BBB integrity, thus promoting neurode generation. OBJECTIVE: To investigate BBB permeability and its relation with VRF along the AD continuum (ADc). Cerebrospinal fluid (CSF) Amyloid (A) and p-tau (T) levels were used to stratify patients. METHODS: We compared CSF/plasma albumin ratio (QAlb) of 131 AD patients and 24 healthy controls (HC). APOE genotype and VRF were evaluated for each patient. Spearman's Rho correlation was used to investigate the associations between Qalb and CSF AD biomarkers. Multivariate regression analyses were conducted to explore the relationship between Qalb and AD biomarkers, sex, age, cognitive status, and VRF. RESULTS: QAlb levels did not show significant difference between ADc patients and HC (p = 0.984). However, QAlb was significantly higher in A + T-compared to A + T+ (p = 0.021). In ADc, CSF p-tau demonstrated an inverse correlation with QAlb, a finding confirmed in APOE4 carriers (p = 0.002), but not in APOE3. Furthermore, in APOE4 carriers, sex, hypertension, and hypercholesterolemia were associated with QAlb (p = 0.004, p = 0.038, p = 0.038, respectively), whereas only sex showed an association in APOE3 carriers (p = 0.026). CONCLUSIONS: BBB integrity is preserved in ADc. Among AT categories, A + T-have a more permeable BBB than A + T+. In APOE4 carriers, CSF p-tau levels display an inverse association with BBB permeability, which in turn, seems to be affected by VRF. These data suggest a possible relationship between BBB efficiency, VRF and CSF p-tau levels depending on APOE genotype.

[Luces y sombras de la Guía Europea esc-2021 de Prevención de la Enfermedad Cardiovascular en la Práctica Clínica.] / Lights and shadows of the 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice.

General practitioners see in their consultation a a significant number of patients at high vascular risk (VR). The European Guidelines for Cardiovascular Disease Prevention (2021) recommend a new risk classification and intervention strategies on on vascular risk factors (RF), with the aim of providing a shared decision-making recommendations between professionals and patients. In this document we present a critical analysis of these guidelines, offering possible solutions that can be implemented in Primary Care. It should be noted that there are positive aspects (lights) such as that the SCORE2 (from forty to sixty-nine years) and SCORE2-OP models (from seventy to eighty-nine years) are based on more current cohorts and measure cardiovascular risk in a more accurately manner. In addition, it is proposed to differentiate different risk thresholds according to age-groups. For sake of practicality, cardiovascular risk can be estimated using different websites with the new computer models. However, among the negative aspects (shadows), it seems to be add complexity implementing nine subgroups of subjects according to their age or level of risk, with a defined thresholds that could cause a substantial increase in the potential number of subjects susceptible to treatment without a clear evidence that supports it. In addition, two-step RF interventions could delay achievement of therapeutic goals, especially in very high-risk patients, diabetics, or patients with cardiovascular disease. Given these limitations, in this document we propose practical recommendations in order to simplify and facilitate the implementation of the guideline in primary care.

Los médicos de familia atienden un importante número de pacientes con alto riesgo vascular (RV). Las Guías Europeas de Prevención Cardiovascular (2021) proponen una nueva clasificación del riesgo y estrategias de intervención sobre los factores de riesgo (FRV), orientada a la toma de decisiones compartidas entre profesionales y pacientes. En el presente trabajo realizamos un análisis crítico de dichas guías, ofreciendo posibles soluciones prácticas para la Atención Primaria. Son destacables aspectos positivos (luces) que los modelos de RV SCORE2 (entre cuarenta y sesenta y nueve años) y SCORE2-OP (entre setenta y ochenta y nueve años) se basan en cohortes más actuales y miden con mayor exactitud y discriminación dicho riesgo. Además, se propone actuar diferenciadamente sobre el riesgo según la edad. Pragmáticamente, se presentan nuevos modelos informáticos para calcular el riesgo. Sin embargo, entre los aspectos negativos (sombras), parece colegirse una mayor dificultad de implementación al proponerse nueve subgrupos de sujetos según su edad o nivel de riesgo, con un dintel definitorio de alto RV subjetivo que podría ocasionar un incremento sustancial en el número de sujetos susceptibles de tratar sin una discriminación objetiva que lo sustente. Además, las intervenciones sobre los FRV en dos pasos podrían retrasar la consecución de objetivos terapéuticos, sobre todo en pacientes de muy alto riesgo, diabéticos o con enfermedad cardiovascular. Ante las dificultades que plantea la valoración del riesgo, proponemos unificar criterios y simplificar los mensajes claves para hacer unas guías más atractivas y que realmente ayuden a los profesionales de Atención Primaria en su práctica habitual.

Real-World Incidence of Adverse Clinical Outcomes Among People With Coronary Artery Disease and/or Peripheral Artery Disease in Relation to Vascular Risk in the United States.

Presence of polyvascular disease, diabetes, heart failure, or renal insufficiency in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD) are associated with increased risks of adverse events, including major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). In this retrospective observational study using administrative claims data from Optum's deidentified Clinformatics Data Mart Database from January 2016 to September 2021, we described the incidence rates of MACEs, MALEs, and major thrombotic vascular events in patients with CAD or PAD stratified by the presence of risk factors (i.e., polyvascular disease, diabetes, heart failure, or renal insufficiency). A total of 1,435,241 patients (77% CAD and 34% PAD) met the inclusion and exclusion criteria. Patients with 0 risk factors were deemed the low-risk group (47%; n = 681,333) and patients with ≥1 risk factor were deemed the high-risk group (53%; n = 753,908). The mean age was 71.8 and 73.6 years, and 42% and 44% were female in the low- and high-risk groups, respectively. Compared with the low-risk group, the high-risk group had a 72% higher hazard of developing MACEs (adjusted hazard ratio 1.72, 95% confidence interval 1.70 to 1.74), 82% higher hazard of developing major thrombotic vascular events (1.82, 1.80 to 1.84), and 146% higher hazard of developing MALEs (2.46, 2.39 to 2.53) (all p <0.001). In conclusion, in patients with CAD or PAD, the presence of 1 or more risk factors was associated with higher risks of MACEs, MALEs, and major thrombotic vascular events, underscoring the need to improve management of underlying diseases in this population.

Mediation of the Association Between Vascular Risk Factors and Depressive Symptoms by C-Reactive Protein.

Background: This study examined whether C-reactive protein (CRP), a marker of low-grade systemic inflammation, mediates the association between vascular risk factor (VRF) burden and depressive symptoms. Methods: We drew on the prospective design of the UK Biobank to include participants with longitudinal data on VRF burden, CRP, and depressive symptoms. Total, direct, and indirect effects were estimated using regression-based mediation models while controlling for confounding by sociodemographic factors, baseline CRP, and baseline depression. Sensitivity analyses probed the robustness of results to unmeasured confounding. Results: We analyzed data from 10,470 participants from the UK Biobank (mean age = 56.75 years at baseline). Net of covariates, VRFs at baseline were associated with higher depressive symptoms at follow-up (total effect = 0.099; 95% CI, 0.002-0.163). CRP mediated this association (indirect effect = 0.010; 95% CI, 0.004-0.017), accounting for 10.0% (95% CI, 0.3%-30.0%) of the total effect of VRF burden on depressive symptoms. Exploratory analyses suggested that the total and indirect effects pertained to somatic depressive symptoms (tiredness and appetite). Conclusions: These results suggest that inflammation-promoting effects of VRFs may contribute to depressive symptoms in mid- and later life. However, the mediating pathway via CRP explains only a small part of the association between VRFs and depression after accounting for important covariates and may pertain to specific depressive symptoms. Future studies leveraging similar longitudinal designs are needed to further disentangle the time-varying effects between VRFs, inflammation, and certain depressive symptoms while addressing important confounders.

Recruitment methods and yield rates for a multisite clinical trial exploring risk reduction for Alzheimer's disease (rrAD).

INTRODUCTION: The risk reduction for Alzheimer's disease (rrAD) trial was a multisite clinical trial to assess exercise and intensive vascular pharmacological treatment on cognitive function in community-dwelling older adults at increased risk for Alzheimer's disease. METHODS: Eligibility, consent, and randomization rates across different referral sources were compared. Informal interviews conducted with each site's project team were conducted upon study completion. RESULTS: Initially, 3290 individuals were screened, of whom 28% were eligible to consent, 805 consented to participate (87.2% of those eligible), and 513 (36.3% of those consented) were randomized. Emails sent from study site listservs/databases yielded the highest amount (20.9%) of screened individuals. Professional referrals from physicians yielded the greatest percentage of consented individuals (57.1%). Referrals from non-professional contacts (ie, friends, family; 75%) and mail/phone contact from a site (73.8%) had the highest yield of randomization. DISCUSSION: Professional referrals or email from listservs/registries were most effective for enrolling participants. The greatest yield of eligible/randomized participants came from non-professional and mail/phone contacts. Future trials should consider special efforts targeting these recruitment approaches. Highlights: Clinical trial recruitment is commonly cited as a significant barrier to advancing our understanding of cognitive health interventions.The most cited referral source was email, followed by interviews/editorials on the radio, television, local newspapers, newsletters, or magazine articles.The referral method that brought in the largest number of contacts was email but did not result in the greatest yield of consents or eligible participants.The sources that yielded the greatest likelihood of consent were professional referrals (ie, physician), social media, and mail/phone contact from study site.The greatest yield of eligible/randomized participants came from non-professional contacts and mail/phone contact from a site.Findings suggest that sites may need to focus on more selective referral sources, such as using contact mailing and phone lists, rather than more widely viewed recruitment sources, such as social media or TV/radio advertisements.

Diabetes Mellitus Is a Strong Independent Negative Prognostic Factor in Patients with Brain Metastases Treated with Radiotherapy.

BACKGROUND: Brain metastases (BM) cause relevant morbidity and mortality in cancer patients. The presence of cerebrovascular diseases can alter the tumor microenvironment, cellular proliferation and treatment resistance. However, it is largely unknown if the presence of distinct cerebrovascular risk factors may alter the prognosis of patients with BM. METHODS: Patients admitted for the radiotherapy of BM at a large tertiary cancer center were included. Patient and survival data, including cerebrovascular risk factors (diabetes mellitus (DM), smoking, arterial hypertension, peripheral arterial occlusive disease, hypercholesterolemia and smoking) were recorded. RESULTS: 203 patients were included. Patients with DM (n = 39) had significantly shorter overall survival (OS) (HR 1.75 (1.20-2.56), p = 0.003, log-rank). Other vascular comorbidities were not associated with differences in OS. DM remained prognostically significant in the multivariate Cox regression including established prognostic factors (HR 1.92 (1.20-3.06), p = 0.006). Furthermore, subgroup analyses revealed a prognostic role of DM in patients with non-small cell lung cancer, both in univariate (HR 1.68 (0.97-2.93), p = 0.066) and multivariate analysis (HR 2.73 (1.33-5.63), p = 0.006), and a trend in melanoma patients. CONCLUSION: DM is associated with reduced survival in patients with BM. Further research is necessary to better understand the molecular mechanisms and therapeutic implications of this important interaction.

Do cerebrovascular risk factors impact the clinical expression of idiopathic isolated adult-onset dystonia?

BACKGROUND: Although acquired dystonia may develop following ischaemic/haemorrhagic stroke, the relationship between cerebrovascular disease and idiopathic dystonia has been poorly investigated. This cross sectional study aimed at evaluating the impact of cerebrovascular risk factors on the clinical expression of idiopathic adult onset dystonia (IAOD), with reference to dystonia localization and dystonia-associated features. METHODS: Data were obtained from the Italian Dystonia Registry. Patients with IAOD were stratified into two groups according to the presence of diabetes mellitus and/or arterial hypertension and/or dyslipidemia and/or heart disease. The two groups were compared for demographic features, dystonia phenotype, and dystonia-associated features (sensory trick, tremor, eye symptoms in blepharospasm, and neck pain in cervical dystonia). RESULTS: A total of 1108 patients participated into the study. Patients who reported one cerebrovascular factor or more (n = 555) had higher age and longer disease duration than patients who did not. On multivariable logistic regression analysis, blepharospasm was the only localization, and sensory trick was the only dystonia-associated feature that was significantly associated with cerebrovascular risk factors. Linear regression analysis showed that the strength of the association between cerebrovascular factors and blepharospasm/sensory trick increased with increasing the number of cerebrovascular factors per patient. CONCLUSIONS: Results of the present study showed that cerebrovascular risk factors may be associated with specific features of IAOD that is development of blepharospasm and sensory trick. Further studies are needed to better understand the meaning and the mechanisms underlying this association.

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: the COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMH) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well-documented in populations of different ethnicities and/or from different geographical regions. METHOD: Magnetic resonance imaging data of five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1,946) were examined for WMH and their associations with vascular risk factors and cognition. RESULT: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake and insufficient physical activity. Participants with moderate or higher physical activity had less WMH than those who never exercised, but the former two groups did not differ. Hypertension and stroke had stronger associations with WMH volumes in the White, compared to Asian subsample. DISCUSSION: The current study highlighted the ethnic differences in the contributions of vascular risk factors to WMH.