Cerebrospinal fluid proteomic profiling of individuals with mild cognitive impairment and suspected non-Alzheimer's disease pathophysiology.

BACKGROUND: Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker concept that encompasses individuals with neuronal injury but without amyloidosis. We aim to investigate the pathophysiology of SNAP, defined as abnormal tau without amyloidosis, in individuals with mild cognitive impairment (MCI) by cerebrospinal fluid (CSF) proteomics. METHODS: Individuals were classified based on CSF amyloid beta (Aß)1-42 (A) and phosphorylated tau (T), as cognitively normal A-T- (CN), MCI A-T+ (MCI-SNAP), and MCI A+T+ (MCI-AD). Proteomics analyses, Gene Ontology (GO), brain cell expression, and gene expression analyses in brain regions of interest were performed. RESULTS: A total of 96 proteins were decreased in MCI-SNAP compared to CN and MCI-AD. These proteins were enriched for extracellular matrix (ECM), hemostasis, immune system, protein processing/degradation, lipids, and synapse. Fifty-one percent were enriched for expression in the choroid plexus. CONCLUSION: The pathophysiology of MCI-SNAP (A-T+) is distinct from that of MCI-AD. Our findings highlight the need for a different treatment in MCI-SNAP compared to MCI-AD.

The Role of Vascular Risk Factors in Biomarker-Based AT(N) Groups: A German-Dutch Memory Clinic Study.

BACKGROUND: The relation between vascular risk factors (VRFs) and Alzheimer's disease (AD) is important due to possible pathophysiological association. OBJECTIVE: To assess the prevalence of VRFs in biomarker-based AT(N) groups and the associations between VRFs, AD cerebrospinal fluid (CSF) biomarkers, brain magnetic resonance imaging (MRI), and cognition in clinical context. METHODS: We included patients from two memory clinics in University Hospital Aachen (Germany) and Maastricht University Medical Centre (The Netherlands). Subjects were older than 45 years and had available data on demographics, VRFs, CSF AD biomarkers, and MRI. We categorized individuals in normal AD biomarkers, non-AD change, and AD-continuum groups based on amyloid (A), tau (T), and neurodegeneration (N) status in CSF and MRI. Regression models were corrected for age, sex, and site. RESULTS: We included 838 participants (mean age 68.7, 53.2% male, mean MMSE 24.9). The most common VRFs were smoking (60.9%), hypertension (54.6%), and dyslipidemia (37.8%). Alcohol abuse and smoking were most frequent in the non-AD-change group, and coronary heart disease and carotid artery stenosis in the AD continuum group. Higher rates of depression were found in the normal AD biomarkers group. Parietal atrophy and cortical microbleeds were specific for the AD continuum group. Carotid artery stenosis was associated with pathological Aß42 and T-tau values, and diabetes and alcohol abuse were associated with worse medial temporal atrophy and atrial fibrillation, with worse cognition. CONCLUSION: VRFs are common in memory clinic patients, showing differences across the AT(N) biomarker groups. This is important for prevention and individualized treatment of dementia.

Elevated norepinephrine metabolism is linked to cortical thickness in the context of Alzheimer's disease pathology.

Advanced Alzheimer's disease (AD) is characterized by higher noradrenaline metabolite levels that may be associated with AD pathology. The locus coeruleus (LC) is the main site for cerebral noradrenaline synthesis and LC volume loss occurs as early as Braak stage 1. This study investigates the association between noradrenergic turnover and brain morphology, and the modifying effect of AD pathology. The study sample included 77 memory clinic patients (37 cognitively unimpaired and 40 cognitively impaired (mild cognitive impairment or AD dementia)). Cortical thickness and volumetric analyses were performed using FreeSurfer. Cerebrospinal fluid was analyzed for noradrenergic metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), Aß42 and phosphorylated tau. Higher MHPG was associated with lower cortical thickness and hippocampal volume at lower, but subthreshold, levels of Aß42 and at higher p-tau levels. These associations remained significant after adding APOE-E4 or cognitive status as covariates. Our results suggest that greater MHPG together with worse AD pathology contributes to neurodegeneration, possibly before significant amyloidosis. The noradrenergic system may play an important role in early detection of AD-related processes.

Alzheimer's disease pathology: pathways between central norepinephrine activity, memory, and neuropsychiatric symptoms.

The locus coeruleus (LC) supplies norepinephrine to the brain, is one of the first sites of tau deposition in Alzheimer's disease (AD) and modulates a variety of behaviors and cognitive functions. Transgenic mouse models showed that norepinephrine dysregulation after LC lesions exacerbates inflammatory responses, blood-brain barrier leakage (BBB), and cognitive deficits. Here, we investigated relationships between central norepinephrine metabolism, tau and beta-amyloid (Aß), inflammation, BBB-dysfunction, neuropsychiatric problems, and memory in-vivo in a memory clinic population (total n = 111, 60 subjective cognitive decline, 36 mild cognitively impaired, and 19 AD dementia). Cerebrospinal fluid (CSF) and blood samples were collected and analyzed for 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), CSF/plasma albumin ratio (Q-alb), Aß, phosphorylated tau, and interleukins. The verbal word learning task and the neuropsychiatric inventory assessed memory functioning and neuropsychiatric symptoms. Structural equation models tested the relationships between all fluid markers, cognition and behavior, corrected for age, education, sex, and clinical dementia rating score. Our results showed that neuropsychiatric symptoms show strong links to both MHPG and p-tau, whereas memory deficits are linked to MHPG via a combination of p-tau and inflammation-driven amyloidosis (30-35% indirect effect contribution). These results suggest that the LC-norepinephrine may be pivotal to understand links between AD pathology and behavioral and cognitive deficits in AD.

Imaging markers associated with the development of post-stroke depression and apathy: Results of the Cognition and Affect after Stroke - a Prospective Evaluation of Risks study.

INTRODUCTION: It has been suggested that the development of post-stroke apathy (PSA) and depression (PSD) may be more strongly associated with generalised brain pathology, rather than the stroke lesion itself. The present study aimed to investigate associations between imaging markers of lesion-related and generalised brain pathology and the development of PSA and PSD during a one-year follow-up. PATIENTS AND METHODS: In a prospective cohort study, 188 stroke patients received 3-Tesla MRI at baseline (three months post-stroke) for evaluation of lesion-related, vascular, and degenerative brain pathology. Presence of lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces was summed to provide a measure of total cerebral small vessel disease (cSVD) burden (range 0-4). The Mini International Neuropsychiatric Interview and Apathy Evaluation Scale were administered at baseline and repeated at 6- and 12-month follow-up to define presence of PSD and PSA, respectively. RESULTS: Population-averaged logistic regression models showed that global brain atrophy and severe cSVD burden (score 3-4) were significantly associated with the odds of having PSA (ORGEE 5.33, 95% CI 1.99-14.25 and 3.04, 95% CI 1.20-7.69, respectively), independent of stroke lesion volume and co-morbid PSD. Medium cSVD burden (score 2) was significantly associated with the odds of having PSD (ORGEE 2.92, 95% CI 1.09-7.78), independent of stroke lesion volume, co-morbid PSA, and pre-stroke depression. No associations were found with lesion-related markers. CONCLUSIONS: The results suggest that generalised degenerative and vascular brain pathology, rather than lesion-related pathology, is an important predictor for the development of PSA, and less strongly for PSD.

Duration of Care Trajectories in Persons With Dementia Differs According to Demographic and Clinical Characteristics.

OBJECTIVES: To estimate (1) the duration of no formal care, home care, and institutional care after dementia diagnosis, and (2) the effect of age, sex, living situation, dementia medication, migration background, and income on this dementia care duration. DESIGN: Longitudinal retrospective study using routinely recorded general practice electronic health records linked with population-based healthcare and mortality data. SETTING AND PARTICIPANTS: In total, 11,012 community-dwelling persons who received an incident dementia diagnosis and were listed in a Dutch general practitioner database from 448 general practices in the Netherlands. METHODS: Using multistate modeling analyses, we estimated the mean duration of care types (no/home/institutional care) for different ages based on simulations of transition rates and examined the influence of demographic and clinical factors on these durations. RESULTS: From dementia diagnosis onward in 85-year-old men, the mean duration without formal care was 0.7 years, of home care 1.7, and institutional care 1.1 years. In 85-year-old women, the duration without formal care was 0.8 years, of home care 2.3, and institutional care 2.3 years. Total care duration was 3.5 years in 85-year-old men and 5.4 years in 85-year-old women. In men, the duration of home care was longer compared with no formal care and institutional care. The duration of no formal care was longer in persons not living alone, without prescribed dementia medication, with a non‒Western migration background, or with a higher income. The duration of home or institutional care was longer in women, persons without polypharmacy, in those living alone, or those with a Western background. CONCLUSIONS AND IMPLICATIONS: Our findings help to increase understanding of long-term dementia care trajectories and show that demographic and clinical factors determine the duration of care types. Our results can contribute to the organization of healthcare resource planning and monitoring of the effects of healthcare policy and interventions.

Microvascular Dysfunction Is Associated With Worse Cognitive Performance: The Maastricht Study.

Microvascular dysfunction may be associated with worse cognitive performance. Most previous studies did not adjust for important confounders, evaluated only individual measures of microvascular dysfunction, and showed inconsistent results. We evaluated the association between a comprehensive set of measures of microvascular dysfunction and cognitive performance in the population-based Maastricht Study. We used cross-sectional data including 3011 participants (age 59.5±8.2; 48.9% women; 26.5% type 2 diabetes mellitus [oversampled by design]). Measures of microvascular dysfunction included magnetic resonance imaging features of cerebral small vessel disease, plasma biomarkers of microvascular dysfunction, albuminuria, flicker light-induced retinal arteriolar and venular dilation response and heat-induced skin hyperemia. These measures were summarized into a microvascular dysfunction composite score. Cognitive domains assessed were memory, processing speed, and executive function. A cognitive function score was calculated as the sum of the scores on these 3 cognitive domains. The microvascular dysfunction score was associated with a worse cognitive function score (standardized ß, -0.087 [95% CI, -0.127 to -0.047]), independent of age, education level, sex, type 2 diabetes mellitus, smoking, alcohol use, hypertension, total/HDL (high-density lipoprotein) cholesterol ratio, triglycerides, lipid-modifying medication, prior cardiovascular disease, depression and plasma biomarkers of low-grade inflammation. The fully adjusted ß-coefficient of the association between the microvascular dysfunction score and the cognitive function score was equivalent to 2 (range, 1-3) years of aging for each SD higher microvascular dysfunction score. The microvascular dysfunction score was associated with worse memory and processing speed but not with worse executive function. The present study shows that microvascular dysfunction is associated with worse cognitive performance.

Linking APOE-ε4, blood-brain barrier dysfunction, and inflammation to Alzheimer's pathology.

The APOE-ε4 genotype is a risk factor for late-onset Alzheimer's disease (AD) as well as vascular pathology. Given the increased risk of blood-brain barrier (BBB) dysfunction and inflammation among APOE-ε4 carriers, we aimed to examine whether BBB dysfunction and inflammation contribute to the relationship between APOE and AD key pathologies, as measured in the cerebrospinal fluid (CSF). We applied bootstrapped regression and path analyses involving Q-albumin CSF/plasma ratio (a BBB/blood-CSF barrier function marker), interleukins (IL-1ß, IL-6, and IL-12p70; inflammation markers), and CSF p-Tau181 and amyloid-ß1-42 (AD pathology markers) of 97 participants (aged 38-83 years) from a university memory clinic. Our results showed that relationship between BBB dysfunction and AD pathology is modulated by IL-6 and these associations appear to be driven by the APOE-ε4 genotype. This suggests that APOE-ε4-related vascular factors are also part of the pathway to AD pathology, in synergy with an elevated immune response, and could become targets for trials focused on delaying AD.

Dementia awareness and risk perception in middle-aged and older individuals: baseline results of the MijnBreincoach survey on the association between lifestyle and brain health.

BACKGROUND: The total number of people with dementia is increasing worldwide, due to our aging society. Without a disease-modifying drug available, risk reduction strategies are to date the only promising way to reduce dementia incidence in the future. Substantial evidence exists that lifestyle factors contribute to the risk of dementia, such as physical exercise, mental activity and (non-)smoking. Still, most people seem unaware of a relationship between lifestyle and brain health. This paper investigates dementia literacy and knowledge of modifiable risk and protective factors of dementia in a Dutch population-based sample. METHODS: An online-survey was carried out among 590 community-dwelling people between 40 and 75 years old in the Province of Limburg, the Netherlands. The total group comprises both of a provincial sample (n = 381) and a sample of three specific districts within the province (n = 209). Dementia awareness and knowledge about 12 risk and protective factors was assessed with items derived from the British Social Attitudes (BSA) survey, supplemented with custom items developed by the research team. RESULTS: The majority of participants (56%) were unaware of a relationship between lifestyle and dementia risk. Most individuals identified low cognitive activity, physical inactivity and unhealthy diet as dementia risk factors. Particular gaps in knowledge existed with regard to major cardiovascular risk factors such as hypertension, hypercholesterolemia and coronary heart disease. Although the level of awareness varied by age and level of education, most people (70%) were eager to learn more about the topic of brain health, and indicated to be interested in using eHealth (54%) to measure or improve brain health. CONCLUSIONS: Most people still are unaware of the relation between lifestyle and brain health, indicating the need for public health campaigns. Increasing awareness in the general population about the presence of modifiable dementia risk and protective factors is a crucial first step prior to implementation of preventative measures. Targeting specific subgroups, such as individuals with low socioeconomic status and low health literacy, is essential for the reach and effect of a prevention campaign. Outcome of this study was the rationale for an awareness campaign in The Netherlands, called "MijnBreincoach" ("MyBraincoach").

Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort.

INTRODUCTION: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers. METHODS: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis. RESULTS: Eight metabolites were associated with amyloid ß and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory. DISCUSSION: PFAMs have been found increased and associated with amyloid ß burden in CSF and clinical measures.

Personality traits and course of symptoms of depression and apathy after stroke: Results of the CASPER study.

OBJECTIVE: Post-stroke depression (PSD) and post-stroke apathy (PSA) are both associated with adverse outcome after stroke. This study aimed to examine whether personality traits predict the course of PSD and PSA. METHODS: In this prospective cohort study, 240 stroke patients completed the NEO Five Factor Inventory, Montgomery-Åsberg Depression Rating Scale, and Apathy Evaluation Scale at 3 months post-stroke. Neuropsychiatric assessment was repeated at 6- and 12-month follow-up after initial testing. RESULTS: Linear mixed models showed that high neuroticism scores were associated with higher depression levels at baseline, and this association remained stable at follow-up. High extraversion scores and high conscientiousness scores were associated with lower apathy levels at baseline. For neuroticism, a significant interaction with time was found, with higher neuroticism scores at baseline being associated with an increase in apathy scores from 6-month to 12-month follow-up. Prospective analyses showed that high extraversion predicted low apathy levels at 6-month and 12-month follow-up independent of its relations with baseline depression and apathy. High neuroticism predicted high apathy levels at 12-month follow-up, whereas high agreeableness and high openness predicted high apathy levels and low apathy levels, respectively, at 6-month follow-up. None of the personality traits predicted depression scores at follow-up. CONCLUSION: Personality traits are associated with the development and sustainability of PSD and PSA. The traits associated with PSD and PSA were different, providing support for the independence of these constructs. The findings highlight the importance to take personality traits into account as a potential vulnerability factor for PSD and PSA.

Effects of a Medication Review on Delirium in Older Hospitalised Patients: A Comparative Retrospective Cohort Study.

BACKGROUND: Delirium in older hospitalised patients is a common and serious disorder. Polypharmacy and certain medications are risk factors for developing delirium. A medication review could benefit older hospitalised patients with delirium. OBJECTIVES: (1) Evaluate the effects of medication review on length of delirium, length of hospital stay, mortality, and discharge destination; and (2) describe and analyse the proposed changes to medication and its implementation by the treating physician. SETTING: The study was conducted at Maastricht University Medical Centre+. METHODS: We compared two cohorts of older patients with delirium: the first cohort from before introducing the medication review, and a second cohort 5 months after introduction of the medication review. Data were extracted from the patients' digital medical records. RESULTS: A significant interaction effect of cohort and number of medications taken by the patient was found for duration of delirium: patients from the second cohort taking between zero and six medications had significantly shorter delirious episodes than patients in the first cohort. This effect bordered on significance for patients taking between seven and 11 medications, but disappeared for patients taking 12 or more medications. No other statistically significant differences were found between the cohorts. The proposed changes in medication were implemented for 71% of the patients. CONCLUSION: A medication review seems to significantly decrease the length of an older patient's delirious episode. Given the clinical relevance of these findings, we advise medication reviews for all older patients who are delirious or are at risk of developing delirium.

Lack of associations between modifiable risk factors and dementia in the very old: findings from the Cambridge City over-75s cohort study.

OBJECTIVES: To investigate the association between modifiable risk and protective factors and severe cognitive impairment and dementia in the very old. Additionally, the present study tests the predictive validity of the 'LIfestyle for BRAin health' (LIBRA) score, an index developed to assess an individual's dementia prevention potential. METHOD: Two hundred seventy-eight individuals aged 85 years or older from the Cambridge City over-75s cohort study were followed-up until death. Included risk and protective factors were: diabetes, heart disease, hypertension, depression, smoking, low-to-moderate alcohol use, high cognitive activity, and physical inactivity. Incident severe cognitive impairment was based on the Mini-Mental State Examination (score: 0-17) and incident dementia was based on either post-mortem consensus clinical diagnostic assessments or death certificate data. Logistic regressions were used to test whether individual risk and protective factors and the LIBRA score were associated with severe cognitive impairment or dementia after 18 years follow-up. RESULTS: None of the risk and protective factors or the LIBRA score was significantly associated with increased risk of severe cognitive impairment or dementia. Sensitivity analyses using a larger sample, longer follow-up period, and stricter cut-offs for prevalent cognitive impairment showed similar results. CONCLUSION: Associations between well-known midlife risk and protective factors and risk for severe cognitive impairment or dementia might not persist into very old age, in line with suggestions that targeting these factors through lifestyle interventions should start earlier in life.

Baseline Vascular Cognitive Impairment Predicts the Course of Apathetic Symptoms After Stroke: The CASPER Study.

OBJECTIVE: To examine the influence of vascular cognitive impairment (VCI) on the course of poststroke depression (PSD) and poststroke apathy (PSA). METHODS: Included were 250 stroke patients who underwent neuropsychological and neuropsychiatric assessment 3 months after stroke (baseline) and at a 6- and 12-month follow-up after baseline. Linear mixed models tested the influence of VCI in at least one cognitive domain (any VCI) or multidomain VCI (VCI in multiple cognitive domains) at baseline and domain-specific VCI at baseline on levels of depression and apathy over time, with random effects for intercept and slope. RESULTS: Almost half of the patients showed any VCI at baseline, and any VCI was associated with increasing apathy levels from baseline to the 12-month follow-up. Patients with multidomain VCI had higher apathy scores at the 6- and 12-month follow-up compared with patients with VCI in a single cognitive domain. Domain-specific analyses showed that impaired executive function and slowed information processing speed went together with increasing apathy levels from baseline to 6- and 12-month follow-up. None of the cognitive variables predicted the course of depressive symptoms. CONCLUSION: Baseline VCI is associated with increasing apathy levels from baseline to the chronic stroke phase, whereas no association was found between baseline VCI and the course of depressive symptoms. Health professionals should be aware that apathy might be absent early after stroke but may evolve over time in patients with VCI.

Association Between Later Life Lifestyle Factors and Alzheimer's Disease Biomarkers in Non-Demented Individuals: A Longitudinal Descriptive Cohort Study.

BACKGROUND: Lifestyle factors have been associated with the risk of dementia, but the association with Alzheimer's disease (AD) remains unclear. OBJECTIVE: To examine the association between later life lifestyle factors and AD biomarkers (i.e., amyloid-ß 1-42 (Aß42) and tau in cerebrospinal fluid (CSF), and hippocampal volume) in individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). In addition, to examine the effect of later life lifestyle factors on developing AD-type dementia in individuals with MCI. METHODS: We selected individuals with SCD (n = 111) and MCI (n = 353) from the DESCRIPA and Kuopio Longitudinal MCI studies. CSF Aß42 and tau concentrations were assessed with ELISA assay and hippocampal volume with multi-atlas segmentation. Lifestyle was assessed by clinical interview at baseline for: social activity, physical activity, cognitive activity, smoking, alcohol consumption, and sleep. We performed logistic and Cox regression analyses adjusted for study site, age, gender, education, and diagnosis. Prediction for AD-type dementia was performed in individuals with MCI only. RESULTS: Later life lifestyle factors were not associated with AD biomarkers or with conversion to AD-type dementia. AD biomarkers were strongly associated with conversion to AD-type dementia, but these relations were not modulated by lifestyle factors. Apolipoprotein E (APOE) genotype did not influence the results. CONCLUSIONS: Later life lifestyle factors had no impact on key AD biomarkers in individuals with SCD and MCI or on conversion to AD-type dementia in MCI.

Temporal Associations between Fatigue, Depression, and Apathy after Stroke: Results of the Cognition and Affect after Stroke, a Prospective Evaluation of Risks Study.

BACKGROUND: Poststroke fatigue (PSF) is a form of pathological fatigue that can develop after stroke and has a negative impact on functional outcome. PSF is associated with poststroke depression (PSD), which in turn shows similarities with poststroke apathy (PSA). This study aimed at disentangling the temporal associations between PSF and PSD and between PSF and PSA. METHODS: A total of 250 stroke patients were included, of which 243 completed the Fatigue Severity Scale, Montgomery-Åsberg Depression Rating Scale, and Apathy Evaluation Scale at 3 months poststroke, with follow-up measurements at 6 and 12 months after initial testing. Linear mixed models and linear regressions were performed to evaluate the temporal associations between PSF and PSD, and between PSF and PSA. RESULTS: PSF was present in 119 patients (49%), of whom 62 patients also had PSD (26%), and 21 patients (9%) also had PSA. At baseline, PSF patients showed higher depression levels, which remained stable at follow-up. PSD patients had higher fatigue levels compared with no-PSD patients at baseline, which remained stable at follow-up. No association between apathy and fatigue was found at baseline and no interaction with time was found. Change in fatigue from baseline to 12-month follow-up was associated with change in depression and with change in apathy. CONCLUSIONS: Bidirectional associations were found between PSF and PSD. In treatment and rehabilitation programs, early focus on the presence of PSD and PSF is important, since these conditions tend to persist. As there are currently more treatment options for PSD, attention for PSD is important and might also have a beneficial effect on PSF.

Imaging Markers of Post-Stroke Depression and Apathy: a Systematic Review and Meta-Analysis.

Several brain imaging markers have been studied in the development of post-stroke depression (PSD) and post-stroke apathy (PSA), but inconsistent associations have been reported. This systematic review and meta-analysis aims to provide a comprehensive and up-to-date evaluation of imaging markers associated with PSD and PSA. Databases (Medline, Embase, PsycINFO, CINAHL, and Cochrane Database of Systematic Reviews) were searched from inception to July 21, 2016. Observational studies describing imaging markers of PSD and PSA were included. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to examine the association between PSD or PSA and stroke lesion laterality, type, and location, also stratified by study phase (acute, post-acute, chronic). Other imaging markers were reviewed qualitatively. The search retrieved 4502 studies, of which 149 studies were included in the review and 86 studies in the meta-analyses. PSD in the post-acute stroke phase was significantly associated with frontal (OR 1.72, 95% CI 1.34-2.19) and basal ganglia lesions (OR 2.25, 95% CI 1.33-3.84). Hemorrhagic stroke related to higher odds for PSA in the acute phase (OR 2.58, 95% CI 1.18-5.65), whereas ischemic stroke related to higher odds for PSA in the post-acute phase (OR 0.20, 95% CI 0.06-0.69). Frequency of PSD and PSA is modestly associated with stroke type and location and is dependent on stroke phase. These findings have to be taken into consideration for stroke rehabilitation programs, as this could prevent stroke patients from developing PSD and PSA, resulting in better clinical outcome.

Modifiable Risk Factors for Prevention of Dementia in Midlife, Late Life and the Oldest-Old: Validation of the LIBRA Index.

BACKGROUND: Recently, the LIfestyle for BRAin health (LIBRA) index was developed to assess an individual's prevention potential for dementia. OBJECTIVE: We investigated the predictive validity of the LIBRA index for incident dementia in midlife, late life, and the oldest-old. METHODS: 9,387 non-demented individuals were recruited from the European population-based DESCRIPA study. An individual's LIBRA index was calculated solely based on modifiable risk factors: depression, diabetes, physical activity, hypertension, obesity, smoking, hypercholesterolemia, coronary heart disease, and mild/moderate alcohol use. Cox regression was used to test the predictive validity of LIBRA for dementia at follow-up (mean 7.2 y, range 1-16). RESULTS: In midlife (55-69 y, n = 3,256) and late life (70-79 y, n = 4,320), the risk for dementia increased with higher LIBRA scores. Individuals in the intermediate- and high-risk groups had a higher risk of dementia than those in the low-risk group. In the oldest-old (80-97 y, n = 1,811), higher LIBRA scores did not increase the risk for dementia. CONCLUSION: LIBRA might be a useful tool to identify individuals for primary prevention interventions of dementia in midlife, and maybe in late life, but not in the oldest-old.

Supporting clinical rules engine in the adjustment of medication (SCREAM): protocol of a multicentre, prospective, randomised study.

BACKGROUND: In the nursing home population, it is estimated that 1 in every 3 patients is polymedicated and given their considerable frailty, these patients are especially prone to adverse drug reactions. Clinical pharmacist-led medication reviews are considered successful interventions to improve medication safety in the inpatient setting. Due to the limited available evidence concerning the benefits of medication reviews performed in the nursing home setting, we propose a study aiming to demonstrate a positive effect that a clinical decision support system, as a health care intervention, may have on the target population. The primary objective of this study is to reduce the number of patients with at least one event when using the clinical decision support system compared to the regular care. These events consist of hospital referrals, delirium, falls, and/or deaths. METHOD/DESIGN: This study is a multicentre, prospective, randomised study with a cluster group design. The randomisation will be per main nursing home physician and stratified per ward (somatic and psychogeriatric). In the intervention group the clinical decision support system will be used to screen medication list, laboratory values and medical history in order to obtain potential clinical relevant remarks. The remarks will be sent to the main physician and feedback will be provided whether the advice was followed or not. In the control group regular care will be applied. DISCUSSION: We strongly believe that by using a clinical decision support system, medication reviews are performed in a standardised way which leads to comparable results between patients. In addition, using a clinical decision support system eliminates the time factor to perform medication reviews as the major problems related to medication, laboratory values, indications and/or established patient characteristics will be directly available. In this way, and in order to make the medication review process complete, consultation within healthcare professionals and/or the patient itself will be time effective and the medication surveillance could be performed around the clock. TRIAL REGISTRATION: The Netherlands National Trial Register NTR5165 . Registered 2nd April 2015.