Cognitive changes in prevalent and incident cardiovascular disease: a 12-year follow-up in the Maastricht Aging Study (MAAS).

AIMS: Cardiovascular disease (CVD) has been suggested to accelerate cognitive decline and to be a risk factor for dementia, but still little is known about the cognitive course after a first cardiovascular event. Therefore, the present study aims to investigate the cognitive trajectories in both prevalent and incident CVD over a 12-year time period in the general population. METHODS AND RESULTS: Cognitively healthy participants (age 24-82 years, n = 1823) of a prospective cohort study were serially assessed at baseline, 6 and 12 years. Verbal memory, executive function, and information processing speed were analysed in adults with prevalent, incident, and no CVD. Random effects models were used to test the association between CVD and change in cognitive function over time. At baseline, participants with prevalent CVD showed more decline in memory and information processing speed than healthy controls. Participants with incident CVD also showed more decline in these cognitive domains, but this was only significant in the follow-up period from 6 to 12 years. Associations were more pronounced in participants aged younger than 65 years at baseline, and in sub-analyses with angina pectoris or myocardial infarction as the most prevalent CVD conditions. CONCLUSION: Prevalent and incident CVD predict cognitive decline in middle-aged individuals. Findings for incident CVD suggest that the onset of decline is linked in time with the vascular event itself. Timely CVD management may delay the onset of decline.

Co-occurrence of depressive symptoms and executive dysfunction after stroke: associations with brain pathology and prognosis.

OBJECTIVE: To examine, first, whether the co-occurrence of executive dysfunction (ED) and poststroke depression (PSD) shows different associations with neuroimaging markers and the course of depression and executive function, and second, whether it is associated with a different course on other cognitive domains and quality of life. METHODS: The present study included 245 stroke patients (35.9% female, mean age 67.5 years (SD=11.9). All patients completed neuropsychological and neuropsychiatric assessment 3 months poststroke, which were repeated at 6-month and 12-month follow-up. A subset (n=186) received 3-Tesla brain MRI at baseline to evaluate lesion-related imaging markers, white matter hyperintensity volume, global brain atrophy and total cerebral small vessel disease burden. RESULTS: Patients with 'depression-executive dysfunction syndrome' (DES) showed higher white matter hyperintensity volumes compared with all other groups and more frequently showed left-sided lesions compared with ED only and PSD only. They also had more frequently old infarcts and higher total cerebral small vessel disease burden compared with PSD only and patients with neither ED nor PSD, and more global brain atrophy compared with PSD only. Longitudinal analyses showed that patients with DES had a more chronic course of depressive symptoms relative to PSD only, and a stable pattern of worse cognitive performance similar to patients with ED only. CONCLUSIONS: The co-occurrence of ED and PSD is associated with a worse prognosis of depression, persistent cognitive impairment and a higher amount of vascular and degenerative brain pathology. Future studies are needed to examine whether these patients represent a more severe subtype within the PSD spectrum. CLINICAL TRIAL REGISTRATION: NCT02585349;Results.

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.

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.

The Cognition and Affect after Stroke - a Prospective Evaluation of Risks (CASPER) study: rationale and design.

BACKGROUND: Cognitive impairment and neuropsychiatric syndromes, like depression and apathy, are frequent residual consequences of stroke. These have a large impact on quality of life and long-term prognosis. Several factors are involved in the development of these residual syndromes, although their exact role and their interrelationships remain still rather unclear. The Cognition and Affect after Stroke: a Prospective Evaluation of Risks (CASPER) study has been primarily designed to examine whether stroke-specific (e.g. lesion location, volume, type, severity), cerebrovascular and neurodegenerative (e.g. white matter changes, atrophy, microbleeds, perivascular spaces), inflammatory, endothelial, and (epi)genetic markers are associated with cognitive impairment, post-stroke depression, and post-stroke apathy, and whether they predict their course over 12 months. The secondary aims are to investigate how the above-mentioned markers interact with each other, and to determine if patients with apathy and depression after stroke differ in pathogenesis, course, and outcome (e.g. functional outcome, neurocognitive performance, quality of life). METHODS/DESIGN: CASPER is a 1-year prospective clinical cohort follow-up study in 250 stroke patients recruited at the neurological in- and outpatient services at Maastricht University Medical Center (MUMC+, Maastricht, The Netherlands), and Zuyderland Medical Center (Sittard and Heerlen, The Netherlands). At baseline (3 months post-stroke), a neuropsychological assessment, neuropsychiatric interview, blood sample, and brain magnetic resonance imaging (MRI) scan are conducted. Assessment of neuropsychiatric and neurocognitive status are repeated 6 and 12 months later. DISCUSSION: The CASPER study investigates stroke-specific, vascular, neurodegenerative, inflammatory, and genetic markers of the development of vascular cognitive impairment, depression, and apathy after stroke. This creates the possibility to study not only the contribution of these individual markers but also their joint contribution, which differentiates this study from earlier stroke cohorts who lacked long-term follow-up data, a large sample size, an extensive MRI protocol, and markers from the blood. The knowledge we derive from this study might help in identifying markers that are associated with, or can predict the onset, maintenance, and progression of vascular cognitive impairment, depression, and apathy after stroke, and could provide new insights into possibilities for treatment and rehabilitation that result in better functional outcome after stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT02585349.

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.

Coronary heart disease and risk for cognitive impairment or dementia: Systematic review and meta-analysis.

AIMS/HYPOTHESIS: Accumulating evidence suggests an association between coronary heart disease and risk for cognitive impairment or dementia, but no study has systematically reviewed this association. Therefore, we summarized the available evidence on the association between coronary heart disease and risk for cognitive impairment or dementia. METHODS: Medline, Embase, PsycINFO, and CINAHL were searched for all publications until 8th January 2016. Articles were included if they fulfilled the inclusion criteria: (1) myocardial infarction, angina pectoris or coronary heart disease (combination of both) as predictor variable; (2) cognition, cognitive impairment or dementia as outcome; (3) population-based study; (4) prospective (≥1 year follow-up), cross-sectional or case-control study design; (5) ≥100 participants; and (6) aged ≥45 years. Reference lists of publications and secondary literature were hand-searched for possible missing articles. Two reviewers independently screened all abstracts and extracted information from potential relevant full-text articles using a standardized data collection form. Study quality was assessed with the Newcastle-Ottawa Scale. We pooled estimates from the most fully adjusted model using random-effects meta-analysis. RESULTS: We identified 6,132 abstracts, of which 24 studies were included. A meta-analysis of 10 prospective cohort studies showed that coronary heart disease was associated with increased risk of cognitive impairment or dementia (OR = 1.45, 95%CI = 1.21-1.74, p<0.001). Between-study heterogeneity was low (I2 = 25.7%, 95%CI = 0-64, p = 0.207). Similar significant associations were found in separate meta-analyses of prospective cohort studies for the individual predictors (myocardial infarction, angina pectoris). In contrast, meta-analyses of cross-sectional and case-control studies were inconclusive. CONCLUSION/INTERPRETATION: This meta-analysis suggests that coronary heart disease is prospectively associated with increased odds of developing cognitive impairment or dementia. Given the projected worldwide increase in the number of people affected by coronary heart disease and dementia, insight into causal mechanisms or common pathways underlying the heart-brain connection is needed.