The Association between Pulse Wave Velocity and Cognitive Function: The Sydney Memory and Ageing Study

Objectives

Pulse wave velocity (PWV) is a measure of arterial stiffness and its increase with ageing has been associated with damage to cerebral microvessels and cognitive impairment. This study examined the relationship between carotid-femoral PWV and specific domains of cognitive function in a non-demented elderly sample.

Method

Data were drawn from the Sydney Memory and Ageing Study, a cohort study of non-demented community-dwelling individuals aged 70–90 years, assessed in successive waves two years apart. In Wave 2, PWV and cognitive function were measured in 319 participants. Linear regression was used to analyse the cross-sectional relationship between arterial stiffness and cognitive function in the whole sample, and separately for men and women. Analysis of covariance was used to assess potential differences in cognition between subjects with PWV measurements in the top and bottom tertiles of the cohort. Covariates were age, education, body mass index, pulse rate, systolic blood pressure, cholesterol, depression, alcohol, smoking, hormone replacement therapy, apolipoprotein E ε4 genotype, use of anti-hypertensive medications, history of stroke, transient ischemic attack, myocardial infarction, angina, diabetes, and also sex for the whole sample analyses.

Results

There was no association between PWV and cognition after Bonferroni correction for multiple testing. When examining this association for males and females separately, an association was found in males, with higher PWV being associated with lower global cognition and memory, however, a significant difference between PWV and cognition between males and females was not found.

Conclusion

A higher level of PWV was not associated with lower cognitive function in the whole sample.     

Cognitive function in adolescence and the risk for premature diabetes and cardiovascular mortality in adulthood

Background

Epidemiological studies have demonstrated a relationship between cognitive function in youth and the future risk of death. Less is known regarding the relationship with diabetes related death. This study assessed the relationship between cognitive function in late adolescence and the risk for diabetes, cardiovascular- (CVD) and all-cause mortality in adulthood.

Methods

This retrospective study linked data from 2,277,188 16–19 year olds who had general intelligence tests (GIT) conducted during pre-military recruitment assessment with cause of death as coded by the Israel Central Bureau of Statistics. The associations between cognitive function and cause-specific mortality were assessed using Cox models.

Results

There were 31,268 deaths that were recorded during 41,916,603 person-years of follow-up, with a median follow-up of 19.2 (IQR 10.7, 29.5) years. 3068, 1443, 514 and 457 deaths were attributed to CVD, CHD, stroke, and diabetes, respectively. Individuals in the lowest GIT vs. highest GIT quintiles in unadjusted models had the highest risk for all-cause mortality (HR 1.84, 95% CI 1.78, 1.91), total CVD (HR 3.32, 95% CI 2.93, 3.75), CHD (HR 3.49 95% CI 2.92, 4.18), stroke (HR 3.96 95% CI 2.85, 5.5) and diabetes-related (HR 6.96 95% CI 4.68, 10.36) mortality. These HRs were attenuated following adjustment for age, sex, birth year, body-mass index, residential socioeconomic status, education and country of origin for all-cause (HR 1.23, 95% CI 1.17, 1.28), CVD (HR 1.76, 95% CI 1.52, 2.04), CHD (HR 1.7 95% CI 1.37, 2.11), stroke (HR 2.03, 95% CI 1.39, 2.98) and diabetes-related (HR 3.14 95% CI 2.00, 4.94) mortality. Results persisted in a sensitivity analyses limited to participants with unimpaired health at baseline and that accounted competing risk.

Conclusions

This analysis of over 2 million demonstrates a strong relationship between cognitive function at youth and the risk for diabetes, all-cause and CVD-related mortality independent of adolescent obesity.

     

Cardiovascular Disease Risk Models and Longitudinal Changes in Cognition: A Systematic Review

Background

Cardiovascular disease and its risk factors have consistently been associated with poor cognitive function and incident dementia. Whether cardiovascular disease prediction models, developed to predict an individual''s risk of future cardiovascular disease or stroke, are also informative for predicting risk of cognitive decline and dementia is not known.

Objective

The objective of this systematic review was to compare cohort studies examining the association between cardiovascular disease risk models and longitudinal changes in cognitive function or risk of incident cognitive impairment or dementia.

Materials and Methods

Medline, PsychINFO, and Embase were searched from inception to March 28, 2014. From 3,413 records initially screened, 21 were included.

Results

The association between numerous different cardiovascular disease risk models and cognitive outcomes has been tested, including Framingham and non-Framingham risk models. Five studies examined dementia as an outcome; fourteen studies examined cognitive decline or incident cognitive impairment as an outcome; and two studies examined both dementia and cognitive changes as outcomes. In all studies, higher cardiovascular disease risk scores were associated with cognitive changes or risk of dementia. Only four studies reported model prognostic performance indices, such as Area Under the Curve (AUC), for predicting incident dementia or cognitive impairment and these studies all examined non-Framingham Risk models (AUC range: 0.74 to 0.78).

Conclusions

Cardiovascular risk prediction models are associated with cognitive changes over time and risk of dementia. Such models are easily obtainable in clinical and research settings and may be useful for identifying individuals at high risk of future cognitive decline and dementia.     

Cognitive impairment and risk of future stroke: a systematic review and meta-analysis

Background:

Several studies have assessed the link between cognitive impairment and risk of future stroke, but results have been inconsistent. We conducted a systematic review and meta-analysis of cohort studies to determine the association between cognitive impairment and risk of future stroke.

Methods:

We searched MEDLINE and Embase (1966 to November 2013) and conducted a manual search of bibliographies of relevant retrieved articles and reviews. We included cohort studies that reported multivariable adjusted relative risks and 95% confidence intervals or standard errors for stroke with respect to baseline cognitive impairment.

Results:

We identified 18 cohort studies (total 121 879 participants) and 7799 stroke events. Pooled analysis of results from all studies showed that stroke risk increased among patients with cognitive impairment at baseline (relative risk [RR] 1.39, 95% confidence interval [CI] 1.24–1.56). The results were similar when we restricted the analysis to studies that used a widely adopted definition of cognitive impairment (i.e., Mini-Mental State Examination score < 25 or nearest equivalent) (RR 1.64, 95% CI 1.46–1.84). Cognitive impairment at baseline was also associated with an increased risk of fatal stroke (RR 1.68, 95% CI 1.21–2.33) and ischemic stroke (RR 1.65, 95% CI 1.41–1.93).

Interpretation:

Baseline cognitive impairment was associated with a significantly higher risk of future stroke, especially ischemic and fatal stroke.Cognitive impairment is a major contributor to disability and dependence worldwide. Globally, stroke is the leading cause of long-term disability among adults and the second leading cause of death.¹ The high cumulative risk of dementia or stroke or both conditions has been shown by the Framingham study,² and the urgent need to improve knowledge regarding cognition and vascular conditions has been emphasized in a specific meeting providing harmonized standards.³ Beyond their personal tolls, both of these conditions carry substantial social and economic burdens. These conditions also correlate strongly with increasing age. Given the projected substantial rise in the number of older people around the world, prevalence rates of cognitive impairment and stroke are expected to soar over the next several decades, especially in high-income countries.^4,5Shared pathophysiologic mechanisms seem to exist between cognitive impairment and cerebrovascular disease.⁶ Indeed, risk factors for stroke (hypertension, hyperlipidemia, diabetes, obesity and physical inactivity) have been shown to play a role in the onset and progression of cognitive impairment,⁷ and it is well established that stroke itself increases the risk of future cognitive impairment.⁸ However, whether cognitive impairment increases the risk of future stroke remains unclear. Early identification and regular surveillance for cognitive impairment could potentially enable prompt initiation of treatment aimed at not only potentially limiting further deterioration of cognitive function (if mild), but also possibly reducing the risk of future stroke through timely and optimal control of risk factors.Several published studies have assessed the association between cognitive impairment and subsequent risk of stroke, but the results have not been consistent. We performed a systematic review and meta-analysis to determine the qualitative and quantitative association between baseline cognitive impairment and risk of future stroke.     

Mood after stroke: a case control study of biochemical,neuro-imaging and socio-economic risk factors for major depression in stroke survivors

Background  

Though vascular factors may be important in the aetiology of late-life depression, it is not clear whether they have a major effect on the risk of depression after a stroke. We investigated the relationship between physiological, biochemical, neuro-imaging and socio-economic factors and late-phase post-stroke depression in a cross-sectional case-control study.     

Validation of multi-stage telephone-based identification of cognitive impairment and dementia

Background  

Many types of research on dementia and cognitive impairment require large sample sizes. Detailed in-person assessment using batteries of neuropyschologic testing is expensive. This study evaluates whether a brief telephone cognitive assessment strategy can reliably classify cognitive status when compared to an in-person "gold-standard" clinical assessment.     

Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study

Objectives

Cognitive impairment, predominantly affecting processing speed and executive function, is an important consequence of cerebral small vessel disease (SVD). To date, few longitudinal studies of cognition in SVD have been conducted. We determined the pattern and rate of cognitive decline in SVD and used the results to determine sample size calculations for clinical trials of interventions reducing cognitive decline.

Methods

121 patients with MRI confirmed lacunar stroke and leukoaraiosis were enrolled into the prospective St George’s Cognition And Neuroimaging in Stroke (SCANS) study. Patients attended one baseline and three annual cognitive assessments providing 36 month follow-up data. Neuropsychological assessment comprised a battery of tests assessing working memory, long-term (episodic) memory, processing speed and executive function. We calculated annualized change in cognition for the 98 patients who completed at least two time-points.

Results

Task performance was heterogeneous, but significant cognitive decline was found for the executive function index (p<0.007). Working memory and processing speed decreased numerically, but not significantly. The executive function composite score would require the smallest samples sizes for a treatment trial with an aim of halting decline, but this would still require over 2,000 patients per arm to detect a 30% difference with power of 0.8 over a three year follow-up.

Conclusions

The pattern of cognitive decline seen in SVD over three years is consistent with the pattern of impairments at baseline. Rates of decline were slow and sample sizes would need to be large for clinical trials aimed at halting decline beyond initial diagnosis using cognitive scores as an outcome measure. This emphasizes the importance of more sensitive surrogate markers in this disease.     

Risk Factors of Dilated Virchow-Robin Spaces Are Different in Various Brain Regions

Background and Purpose

Few studies have reported on the risk factors of dilated Virchow-Robin Spaces (dVRS) in large samples of ischemic stroke patients. Little evidence exists regarding the relationship between dVRS and etiologic subtype of ischemic stroke or lacune. We aimed to investigate the risk factors associated with the severity of dVRS in a large sample of ischemic stroke patients.

Methods

We consecutively enrolled 1,090 patients who experienced an ischemic stroke within the past seven days and underwent a 3.0 T MRI scan in the Chinese IntraCranial AtheroSclerosis Study (ICAS). Clinical data and cranial MRI information of patients included age, sex, vascular risk factors, dVRS, leukoaraiosis, lacune, and etiologic subtype of ischemic stroke. Analyses were performed regarding the risk factors associated with the severity of dVRS by univariate analysis and multivariable ordinal logistic regression analysis.

Results

Through multivariable ordinal logistic regression analysis, age, the severity of leukoaraiosis, lacune, admission National Institutes of Health Stroke Scale (NIHSS) ≤3, and the severity of dVRS in the white matter (WM) and hippocampus (Hip) were correlated with the severity of dVRS in basal ganglia (BG); male, history of hypertension, admission NIHSS ≤3, and the severity of dVRS in BG and Hip were correlated with the severity of dVRS in WM; female, the severity of leukoaraiosis, admission NIHSS >3, small artery occlusion subtype of ischemic stroke, and the severity of dVRS in BG and WM were correlated with the severity of dVRS in Hip.

Conclusion

dVRS is an indicator of cerebral small vessel diseases such as leukoaraiosis and lacune. However, the risk factors of dVRS differ in various brain regions.     

Dysregulation of MicroRNAs in cancer

Background

The association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample.

Methods

We examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke.

Results

There was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively.

Conclusions

This is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke.     

SALGOT - <Emphasis Type="Underline">S</Emphasis>troke <Emphasis Type="Underline">A</Emphasis>rm <Emphasis Type="Underline">L</Emphasis>ongitudinal study at the University of <Emphasis Type="Underline">Got</Emphasis>henburg,prospective cohort study protocol

Background  

Recovery patterns of upper extremity motor function have been described in several longitudinal studies, but most of these studies have had selected samples, short follow up times or insufficient outcomes on motor function. The general understanding is that improvements in upper extremity occur mainly during the first month after the stroke incident and little if any, significant recovery can be gained after 3-6 months. The purpose of this study is to describe the recovery of upper extremity function longitudinally in a non-selected sample initially admitted to a stroke unit with first ever stroke, living in Gothenburg urban area.     

Cardiovascular risk factors and cognitive function in middle aged and elderly Lithuanian urban population: results from the HAPIEE study

Background

The purpose of this study was to examine associations between cardiovascular risk factors and cognitive ability in middle aged and elderly Lithuanian urban population.

Methods

Data from the survey performed in the framework of the HAPIEE (Health, Alcohol, Psychosocial Factors in Eastern Europe) study were presented. A random sample of 7,087 individuals aged 45–72 years was screened in 2006–2008.

Results

The scores of immediate recall and delayed verbal recall, cognitive speed and attention were significantly lower in men than in women; yet numerical ability scores were higher in men. Significant associations between lowered cognitive functions and previous stroke (in male OR?=?2.52; 95% CI?=?1.75-3.64; in female OR?=?2.45; 95% CI?=?1.75, 3.64) as well as ischemic heart disease history (among male OR?=?1.28; 95% CI?=?1.03-1.60) have been determined. Higher level of physical activity in leisure time (among female OR?=?1.32; 95% CI?=?1.03-1.69), poor self-rated health (among male OR?=?1.57; 95% CI?=?1.15-2.14) and poor quality of life (in male OR?=?1.67; 95% CI?=?1.07-2.61; in female OR?=?2.81; 95% CI?=?1.92-4.11) were related to lowered cognitive function.

Conclusions

The findings of the study suggest that associations between cardiovascular risk factors and lowered cognitive function among healthy middle-aged and elderly adults strongly depend on gender.

     

To what degree does cognitive impairment in Alzheimer's disease predict dependence of patients on caregivers?

Background  

Patients with Alzheimer's disease experience a progressive loss of cognitive function, and the ability to independently perform activities of daily life. Sometimes a dependent stage is reached quite early in the disease, when caregivers decide that the patients can no longer be left alone safely. This is an important aspect of Alzheimer's for patients, their families, and also health care providers. Understanding the relationship between a patient's current cognitive status and their need for care may assist clinicians when recommending an appropriate management plan. In this study, we investigated the relationship of cognitive function to dependence on caregivers before the patients reach a severe stage of the disease.     

White matter fractional anisotropy is related to processing speed in metabolic syndrome patients: a case-control study

Background  

Metabolic Syndrome (MetSd) is a cluster of vascular risk factors that may influence cerebrovascular pathology during aging. Recently, microstructural white matter (WM) changes detected by diffusion tensor imaging (DTI) and processing speed deficits have been reported in MetSd patients. We aimed to test the relationship between WM alteration and cognitive impairment in these patients.     

Can cognitive enhancers reduce the risk of falls in older people with Mild Cognitive Impairment? A protocol for a randomised controlled double blind trial

Background  

Older adults with cognitive problems have a higher risk of falls, at least twice that of cognitively normal older adults. The consequences of falls in this population are very serious: fallers with cognitive problems suffer more injuries due to falls and are approximately five times more likely to be admitted to institutional care. Although the mechanisms of increased fall risk in cognitively impaired people are not completely understood, it is known that impaired cognitive abilities can reduce attentional resource allocation while walking. Since cognitive enhancers, such as cholinesterase inhibitors, improve attention and executive function, we hypothesise that cognitive enhancers may reduce fall risk in elderly people in the early stages of cognitive decline by improving their gait and balance performance due to an enhancement in attention and executive function.     

Association of childhood trauma with cognitive function in healthy adults: a pilot study

Background  

Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults.     

Estimating the probability of stroke in Korean hypertensive patients visiting tertiary hospitals using a risk profile from the framingham study

Background  

Hypertension is the most important single modifiable risk factor for stroke. We investigated the distribution of stroke risk factors and 10-year probability of stroke in Korean hypertensive patients.     

Body Mass Index and Decline of Cognitive Function

Background

The association between body mass index (BMI) and cognitive function is a public health issue. This study investigated the relationship between obesity and cognitive impairment which was assessed by the Korean version of the Mini-mental state examination (K-MMSE) among mid- and old-aged people in South Korea.

Methods

A cohort of 5,125 adults, age 45 or older with normal cognitive function (K-MMSE≥24) at baseline (2006), was derived from the Korean Longitudinal Study of Aging (KLoSA) 2006~2012. The association between baseline BMI and risk of cognitive impairment was assessed using multiple logistic regression models. We also assessed baseline BMI and change of cognitive function over the 6-year follow-up using multiple linear regressions.

Results

During the follow-up, 358 cases of severe cognitive impairment were identified. Those with baseline BMI≥25 kg/m² than normal-weight (18.5≤BMI<23 kg/m²) were marginally less likely to experience the development of severe cognitive impairment (adjusted odds ratio [aOR] = 0.73, 95% CI = 0.52 to 1.03; P_trend = 0.03). This relationship was stronger among female (aOR = 0.63, 95% CI = 0.40 to 1.00; P_trend = 0.01) and participants with low-normal K-MMSE score (MMSE: 24–26) at baseline (aOR = 0.59, 95% CI = 0.35 to 0.98; P_trend<0.01). In addition, a slower decline of cognitive function was observed in obese individuals than those with normal weight, especially among women and those with low-normal K-MMSE score at baseline.

Conclusion

In this nationally representative study, we found that obesity was associated with lower risk of cognitive decline among mid- and old-age population.     

The Ischemic Stroke Genetics Study (ISGS) Protocol

Background  

The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype.     

Increased risk of cognitive and functional decline in patients with atrial fibrillation: results of the ONTARGET and TRANSCEND studies

Background:

The role of atrial fibrillation in cognitive impairment and dementia, independent of stroke, is uncertain. We sought to determine the association of atrial fibrillation with cognitive and physical impairment in a large group of patients at high cardiovascular risk.

Methods:

We conducted a post-hoc analysis of two randomized controlled trials involving 31 546 patients, the aims of which were to evaluate the efficacy of treatment with ramipril plus telmisartan (ONTARGET) or telmisartan alone (TRANSCEND) in reducing cardiovascular disease. We evaluated the cognitive function of participants at baseline and after two and five years using the Mini–Mental State Examination (MMSE). In addition, we recorded incident dementia, loss of independence in activities of daily living and admission to long-term care facilities. We used a Cox regression model adjusting for main confounders to determine the association between atrial fibrillation and our primary outcomes: a decrease of three or more points in MMSE score, incident dementia, loss of independence in performing activities of daily living and admission to long-term care.

Results:

We enrolled 31 506 participants for whom complete information on atrial fibrillation was available, 70.4% of whom were men. The mean age of participants was 66.5 years, and the mean baseline MMSE score was 27.7 (standard deviation 2.9) points. At baseline, 1016 participants (3.3%) had atrial fibrillation, with the condition developing in an additional 2052 participants (6.5%) during a median follow-up of 56 months. Atrial fibrillation was associated with an increased risk of cognitive decline (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.03–1.26), new dementia (HR 1.30, 95% CI 1.14–1.49), loss of independence in performing activities of daily living (HR 1.35, 95% CI 1.19–1.54) and admission to long-term care facilities (HR 1.53, 95% CI 1.31–1.79). Results were consistent among participants with and without stroke or receiving antihypertensive drugs.

Interpretation:

Cognitive and functional decline are important consequences of atrial fibrillation, even in the absence of overt stroke.A trial fibrillation is an important and modifiable cause of ischemic stroke, which may result in considerable physical and cognitive disability.¹ In addition, atrial fibrillation is associated with an increased risk of covert cerebral infarction, which is reported in about one-quarter of patients with atrial fibrillation who undergo magnetic resonance imaging of the brain.² Thus, atrial fibrillation may be an important determinant of cognitive and functional decline, even in the absence of clinical ischemic stroke. However, previous epidemiologic studies evaluating atrial fibrillation’s association with cognitive function have been inconsistent,^3–13 and very few have evaluated its association with functional outcomes.¹⁴A recent systematic review showed convincing evidence of an association between atrial fibrillation and dementia in patients with a history of stroke, but it concluded that there was considerable uncertainty of a link between atrial fibrillation and dementia in patients with no history of stroke.¹⁵ Large prospective cohort studies are required to determine a true association between atrial fibrillation and cognitive outcomes.In this study, we sought to determine the prospective association between atrial fibrillation and cognitive decline, loss of independence in activities of daily living and admission to long-term care facilities, using data from a large group of patients included in the ONTARGET and TRANSCEND trials.^16,17     

Perception of stroke and knowledge of potential risk factors among Omani patients at increased risk for stroke

Background  

Previous studies have demonstrated poor knowledge of stroke among patients with established risk factors. This study aims to assess the baseline knowledge, among patients with increased risk for stroke in Oman, of warning symptoms of stroke, impending risk factors, treatment, and sources of information.