Brain Damage With Heart Failure: Cardiac Biomarker Alterations and Gray Matter Decline.

RATIONALE: Heart failure (HF) following heart damage leads to a decreased blood flow due to a reduced pump efficiency of the heart muscle. A consequence can be insufficient oxygen supply to the organism including the brain. While HF clearly shows neurological symptoms, such as fatigue, nausea, and dizziness, the implications for brain structure are not well understood. Few studies show regional gray matter decrease related to HF; however, the underlying mechanisms leading to the observed brain changes remain unclear. OBJECTIVE: To study the relationship between impaired heart function, hampered blood circulation, and structural brain change in a case-control study. METHODS AND RESULTS: Within a group of 80 patients of the Leipzig Heart Center, we investigated a potential correlation between HF biomarkers and the brain's gray matter density (GMD) obtained by magnetic resonance imaging. We observed a significant positive correlation between cardiac ejection fraction and GMD across the whole frontal and parietal medial cortex reflecting the consequence of HF onto the brain's gray matter. Moreover, we also obtained a relationship between GMD and the NT-proBNP (N-terminal prohormone of brain natriuretic peptide)-a biomarker that is used for screening, diagnosis, and prognosis of HF. Here, we found a significant negative correlation between NT-proBNP and GMD in the medial and posterior cingulate cortex but also in precuneus and hippocampus, which are key regions implicated in structural brain changes in dementia. CONCLUSIONS: We obtained significant correlations between brain structure and markers of heart failure including ejection fraction and NT-proBNP. A diminished GMD was found with decreased ejection fraction and increased NT-proBNP in wide brain regions including the whole frontomedian cortex as well as hippocampus and precuneus. Our observations might reflect structural brain damage in areas that are related to cognition; however, whether these structural changes facilitate the development of cognitive alterations has to be proven by further longitudinal studies.

Apathy and Cognitive Deficits in Patients with Transient Global Ischemia After Cardiac Arrest.

BACKGROUND AND OBJECTIVE: Despite the extensive literature on cognitive deficits in the course of transient global ischemia after cardiac arrest with delayed resuscitation, apathy has been studied less frequently and systematically. We aimed to evaluate the frequency of apathy, defined as changes in drive or lack of motivation, and its relation to cognition as well as depression in people with transient global ischemia after cardiac arrest. METHODS: In a retrospective study using the clinical data of 38 cardiac arrest survivors, we analyzed the frequency and severity of deficits in four cognitive domains (attention, memory spans, long-term memory, and executive functions) as well as apathy. RESULTS: As in previous studies, long-term memory problems were predominant, but occurred rarely in isolation. Problems in drive were frequent and correlated with the severity of deficits in all cognitive domains except memory spans (and executive functions only as a trend). Influences of apathy were independent of the presence of a depressive syndrome. CONCLUSIONS: Transient global ischemia after cardiac arrest generally leads to a broad pattern of cognitive decline with predominating memory deficits. Apathy is a frequent sequela and is associated with cognitive deficits, independent of depression. Studies investigating the cognitive profile after cardiac arrest should account for modulating influences of apathy.

Brain dysconnectivity with heart failure.

Structural brain damage associated with heart failure is well described; however, little is known about associated changes in various specific brain functions that bear immediate clinical relevance. A satisfactory pathophysiological link between heart failure and decline in cognitive function is still missing. In the present study, we aim to detect functional correlates of heart failure in terms of alterations in functional brain connectivity (quantified by functional magnetic resonance imaging) related to cognitive performance assessed by neuropsychological testing. Eighty patients were post hoc grouped into subjects with and without coronary artery disease. The coronary artery disease patients were further grouped as presenting with or without heart failure according to the guidelines of the European Society of Cardiology. On the basis of resting-state functional magnetic resonance imaging, brain connectivity was investigated using network centrality as well as seed-based correlation. Statistical analysis aimed at specifying centrality group differences and potential correlations between centrality and heart failure-related measures including left ventricular ejection fraction and serum concentrations of N-terminal fragment of the pro-hormone brain-type natriuretic peptide. The resulting correlation maps were then analysed using a flexible factorial model with the factors 'heart failure' and 'cognitive performance'. Our core findings are: (i) A statistically significant network centrality decrease was found to be associated with heart failure primarily in the precuneus, i.e. we show a positive correlation between centrality and left ventricular ejection fraction as well as a negative correlation between centrality and N-terminal fragment of the pro-hormone brain-type natriuretic peptide. (ii) Seed-based correlation analysis showed a significant interaction between heart failure and cognitive performance related to a significant decrease of precuneus connectivity to other brain regions. We obtained these results by different analysis approaches indicating the robustness of the findings we report here. Our results suggest that the precuneus is a brain region involved in connectivity decline in patients with heart failure, possibly primarily or already at an early stage. Current models of Alzheimer's disease-having pathophysiological risk factors in common with cerebrovascular disorders-also consider reduced precuneus connectivity as a marker of brain degeneration. Consequently, we propose that heart failure and Alzheimer's disease exhibit partly overlapping pathophysiological paths or have common endpoints associated with a more or less severe decrease in brain connectivity. This is further supported by specific functional connectivity alterations between the precuneus and widely distributed cortical regions, particularly in patients showing reduced cognitive performance.

Heart failure decouples the precuneus in interaction with social cognition and executive functions.

Aging increases the risk to develop Alzheimer's disease. Cardiovascular diseases might accelerate this process. Our study aimed at investigating the impact of heart failure on brain connectivity using functional magnetic resonance imaging at resting state. Here we show brain connectivity alterations related to heart failure and cognitive performance. Heart failure decreases brain connectivity in the precuneus. Precuneus dysconnectivity was associated with biomarkers of heart failure-left ventricular ejection fraction and N-terminal prohormone of brain natriuretic peptide-and cognitive performance, predominantly executive function. Meta-analytical data-mining approaches-conducted in the BrainMap and Neurosynth databases-revealed that social and executive cognitive functions are mainly associated with those neural networks. Remarkably, the precuneus, as identified in our study in a mid-life cohort, represents one central functional hub affected by Alzheimer's disease. A long-term follow-up investigation in our cohort after approximately nine years revealed more severe cognitive impairment in the group with heart failure than controls, where social cognition was the cognitive domain mainly affected, and not memory such as in Alzheimer's disease. In sum, our results indicate consistently an association between heart failure and decoupling of the precuneus from other brain regions being associated with social and executive functions. Further longitudinal studies are warranted elucidating etiopathological mechanisms.

Identifying neural correlates of memory and language disturbances in herpes simplex encephalitis: a voxel-based morphometry (VBM) study.

Herpes simplex encephalitis (HSE) is a severe neurological disease that often leads to persistent cognitive deficits in survivors. Memory and naming impairments have been reported most, although direct association between memory and naming performance and disease-related atrophy has not yet been demonstrated in vivo for a larger sample of patients. In the present work, a voxel-based morphometry (VBM) analysis was conducted on 3T magnetic resonance imaging (MRI) of 13 HSE survivors. The gray matter density values were correlated with scores indicating verbal memory decline, as well as errors/omissions in picture naming; both were obtained through neuropsychological assessment. Analysis of individual lesion patterns revealed a considerable inter-individual variability, mainly with atrophy in the basal forebrain, adjacent frontal cortex, medial and lateral temporal cortex, insula and thalamus. The neuropsychological data analysis revealed correlation between verbal memory decline and atrophy especially in the left hippocampal region, whereas naming problems were associated with gray matter loss especially in the lateral temporal lobe, the thalamus and the left insula. These results confirm, for the first time, the assumptions of earlier studies about the considerable variability of individual lesion patterns in HSE in a whole-brain approach in vivo, and thus the anatomical validity of VBM.