Mechanism of an Intrinsic Oscillation in Rat Geniculate Interneurons.

Depolarizing current injections produced a rhythmic bursting of action potentials - a bursting oscillation - in a set of local interneurons in the lateral geniculate nucleus (LGN) of rats. The current dynamics underlying this firing pattern have not been determined, though this cell type constitutes an important cellular component of thalamocortical circuitry, and contributes to both pathologic and non-pathologic brain states. We thus investigated the source of the bursting oscillation using pharmacological manipulations in LGN slices in vitro and in silico. 1. Selective blockade of calcium channel subtypes revealed that high-threshold calcium currents I L and I P contributed strongly to the oscillation. 2. Increased extracellular K+ concentration (decreased K+currents) eliminated the oscillation. 3. Selective blockade of K+ channel subtypes demonstrated that the calcium-sensitive potassium current ( I A H P ) was of primary importance. A morphologically simplified, multicompartment model of the thalamic interneuron characterized the oscillation as follows: 1. The low-threshold calcium current I T provided the strong initial burst characteristic of the oscillation. 2. Alternating fluxes through high-threshold calcium channels and I A H P then provided the continuing oscillation's burst and interburst periods respectively. This interplay between I L and I A H P contrasts with the current dynamics underlying oscillations in thalamocortical and reticularis neurons, which primarily involve I T and I H , or I T and I A H P respectively. These findings thus point to a novel electrophysiological mechanism for generating intrinsic oscillations in a major thalamic cell type. Because local interneurons can sculpt the behavior of thalamocortical circuits, these results suggest new targets for the manipulation of ascending thalamocortical network activity.

Data-driven multiscale model of macaque auditory thalamocortical circuits reproduces in vivo dynamics.

We developed a detailed model of macaque auditory thalamocortical circuits, including primary auditory cortex (A1), medial geniculate body (MGB), and thalamic reticular nucleus, utilizing the NEURON simulator and NetPyNE tool. The A1 model simulates a cortical column with over 12,000 neurons and 25 million synapses, incorporating data on cell-type-specific neuron densities, morphology, and connectivity across six cortical layers. It is reciprocally connected to the MGB thalamus, which includes interneurons and core and matrix-layer-specific projections to A1. The model simulates multiscale measures, including physiological firing rates, local field potentials (LFPs), current source densities (CSDs), and electroencephalography (EEG) signals. Laminar CSD patterns, during spontaneous activity and in response to broadband noise stimulus trains, mirror experimental findings. Physiological oscillations emerge spontaneously across frequency bands comparable to those recorded in vivo. We elucidate population-specific contributions to observed oscillation events and relate them to firing and presynaptic input patterns. The model offers a quantitative theoretical framework to integrate and interpret experimental data and predict its underlying cellular and circuit mechanisms.

Detecting Spontaneous Neural Oscillation Events in Primate Auditory Cortex.

Electrophysiological oscillations in the brain have been shown to occur as multicycle events, with onset and offset dependent on behavioral and cognitive state. To provide a baseline for state-related and task-related events, we quantified oscillation features in resting-state recordings. We developed an open-source wavelet-based tool to detect and characterize such oscillation events (OEvents) and exemplify the use of this tool in both simulations and two invasively-recorded electrophysiology datasets: one from human, and one from nonhuman primate (NHP) auditory system. After removing incidentally occurring event-related potentials (ERPs), we used OEvents to quantify oscillation features. We identified ∼2 million oscillation events, classified within traditional frequency bands: δ, θ, α, ß, low γ, γ, and high γ. Oscillation events of 1-44 cycles could be identified in at least one frequency band 90% of the time in human and NHP recordings. Individual oscillation events were characterized by nonconstant frequency and amplitude. This result necessarily contrasts with prior studies which assumed frequency constancy, but is consistent with evidence from event-associated oscillations. We measured oscillation event duration, frequency span, and waveform shape. Oscillations tended to exhibit multiple cycles per event, verifiable by comparing filtered to unfiltered waveforms. In addition to the clear intraevent rhythmicity, there was also evidence of interevent rhythmicity within bands, demonstrated by finding that coefficient of variation of interval distributions and Fano factor (FF) measures differed significantly from a Poisson distribution assumption. Overall, our study provides an easy-to-use tool to study oscillation events at the single-trial level or in ongoing recordings, and demonstrates that rhythmic, multicycle oscillation events dominate auditory cortical dynamics.

Enhanced Long-Term Brain Magnetic Resonance Imaging Evaluation of Children with Sickle Cell Disease after Hematopoietic Cell Transplantation.

Progressive neurovasculopathy in children with sickle cell disease (SCD) results in decreased cognitive function and quality of life (QoL). Hematopoietic cell transplantation (HCT) is believed to halt progression of neurovasculopathy. Quantitative analysis of T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) for white matter hyperintensity (WMH) burden provides a meaningful estimate of small vessel cerebrovascular disease. We asked if quantitative analysis of WMH could complement standardized clinical assessment of MRI/magnetic resonance angiography (MRA) for assessing SCD central nervous system vasculopathy before and after HCT. Retrospective longitudinal clinical examination of scheduled annual MRI/MRA and quantitative analysis of WMH were performed before and 1 to 7 years after HCT at scheduled annual intervals, along with QoL measurements, in children who had engrafted after HCT. Of 18 patients alive and persistently engrafted (median age, 9.1 years), pretransplantation MRI demonstrated that 9 and 5 had sickle-related stroke and/or small infarcts, respectively. Patients were divided into WMH severity tertiles based on pretransplantation WMH volumes. MRI and WMH were assessed 1 to 7 years after HCT. MRI/MRA and WMH volume were stable or slightly better in 17 of 18 patients. By parent- and self-report, post-HCT QoL improved for children in the lowest WMH tertile significantly more than in the other groups. Based on this single-institution retrospective sample, we report that WMH appears to quantitatively support MRI-based findings that HCT stabilizes long-term small and large vessel cerebrovascular changes and is associated with the degree of improved QoL. While confirmation in larger prospective studies and evaluation by neurocognitive testing are needed, these findings suggest that WMH is a useful biomarker of neurovasculopathy after transplantation for SCD.

Low episodic memory performance in cognitively normal elderly subjects is associated with increased posterior cingulate gray matter N-acetylaspartate: a 1H MRSI study at 7 Tesla.

Low episodic memory performance characterizes elderly subjects at increased risk for Alzheimer's disease (AD) and may reflect neuronal dysfunction within the posterior cingulate cortex and precuneus (PCP) region. To investigate a potential association between cerebral neurometabolism and low episodic memory in the absence of cognitive impairment, tissue-specific magnetic resonance spectroscopic imaging at ultrahigh field strength of 7 Tesla was used to investigate the PCP region in a healthy elderly study population (n = 30, age 70 ± 5.7 years, Mini-Mental State Examination 29.4 ± 4.1). The Verbal Learning and Memory Test (VLMT) was administered as part of a neuropsychological battery for assessment of episodic memory performance. Significant differences between PCP gray and white matter could be observed for glutamate-glutamine (p = 0.001), choline (p = 0.01), and myo-inositol (p = 0.02). Low Verbal Learning and Memory Test performance was associated with high N-acetylaspartate in PCP gray matter (p = 0.01) but not in PCP white matter. Our data suggest that subtle decreases in episodic memory performance in the elderly may be associated with increased levels of N-acetylaspartate as a reflection of increased mitochondrial energy capacity in PCP gray matter.

Is the Alzheimer's disease cortical thickness signature a biological marker for memory?

Recent work suggests that analysis of the cortical thickness in key brain regions can be used to identify individuals at greatest risk for development of Alzheimer's disease (AD). It is unclear to what extent this "signature" is a biological marker of normal memory function - the primary cognitive domain affected by AD. We examined the relationship between the AD signature biomarker and memory functioning in a group of neurologically healthy young and older adults. Cortical thickness measurements and neuropsychological evaluations were obtained in 110 adults (age range 21-78, mean = 46) drawn from the Brain Resource International Database. The cohort was divided into young adult (n = 64, age 21-50) and older adult (n = 46, age 51-78) groups. Cortical thickness analysis was performed with FreeSurfer, and the average cortical thickness extracted from the eight regions that comprise the AD signature. Mean AD-signature cortical thickness was positively associated with performance on the delayed free recall trial of a list learning task and this relationship did not differ between younger and older adults. Mean AD-signature cortical thickness was not associated with performance on a test of psychomotor speed, as a control task, in either group. The results suggest that the AD signature cortical thickness is a marker for memory functioning across the adult lifespan.

Reduced Gray Matter Volume Is Associated With Poorer Instrumental Activities of Daily Living Performance in Heart Failure.

BACKGROUND: Heart failure patients require assistance with instrumental activities of daily living in part because of the high rates of cognitive impairment in this population. Structural brain insult (eg, reduced gray matter volume) is theorized to underlie cognitive dysfunction in heart failure, although no study has examined the association among gray matter, cognition, and instrumental activities of daily living in heart failure. OBJECTIVES: The aim of this study was to investigate the associations among gray matter volume, cognitive function, and functional ability in heart failure. METHODS: A total of 81 heart failure patients completed a cognitive test battery and the Lawton-Brody self-report questionnaire to assess instrumental activities of daily living. Participants underwent magnetic resonance imaging to quantify total gray matter and subcortical gray matter volume. RESULTS: Impairments in instrumental activities of daily living were common in this sample of HF patients. Regression analyses controlling for demographic and medical confounders showed that smaller total gray matter volume predicted decreased scores on the instrumental activities of daily living composite, with specific associations noted for medication management and independence in driving. Interaction analyses showed that reduced total gray matter volume interacted with worse attention/executive function and memory to negatively impact instrumental activities of daily living. CONCLUSIONS: Smaller gray matter volume is associated with greater impairment in instrumental activities of daily living in persons with heart failure, possibly via cognitive dysfunction. Prospective studies are needed to clarify the utility of clinical correlates of gray matter volume (eg, cognitive dysfunction) in identifying heart failure patients at risk for functional decline and determine whether interventions that target improved brain and cognitive function can preserve functional independence in this high-risk population.

Daily Physical Activity Is Associated with Subcortical Brain Volume and Cognition in Heart Failure.

Cognitive impairment in heart failure (HF) is believed to in part stem from structural brain alterations, including shrinkage of subcortical regions. Fortunately, neurocognitive dysfunction in HF can be mitigated by physical activity (PA), though mechanisms for this phenomenon are unclear. PA is protective against age-related cognitive decline that may involve improved structural integrity to brain regions sensitive to aging (e.g., subcortical structures). Yet, no study has examined the benefits of PA on the brain in HF and we sought to do so and clarify related cognitive implications. Fifty older adults with HF completed a neuropsychological battery and wore an accelerometer for 7 days. All participants underwent brain MRI. This study targeted subcortical brain volume given subcortical alterations are often observed in HF and the sensitivity of PA to subcortical structures in other patient populations. Participants averaged 4348.49 (SD=2092.08) steps per day and greater daily steps predicted better attention/executive function, episodic memory, and language abilities, p's<.05. Medical and demographically adjusted regression analyses revealed higher daily steps per day predicted greater subcortical volume, with specific effects for the thalamus and ventral diencephalon, p's<.05. Greater subcortical volume was associated with better attention/executive function, p<.05. Higher daily PA was associated with increased subcortical brain volume and better cognition in older adults with HF. Longitudinal work is needed to clarify whether daily PA can attenuate brain atrophy in HF to reduce accelerated cognitive decline in this population.

Is residual memory variance a valid method for quantifying cognitive reserve? A longitudinal application.

Cognitive reserve describes the mismatch between brain integrity and cognitive performance. Older adults with high cognitive reserve are more resilient to age-related brain pathology. Traditionally, cognitive reserve is indexed indirectly via static proxy variables (e.g., years of education). More recently, cross-sectional studies have suggested that reserve can be expressed as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). The present study extends these methods to a longitudinal framework in a community-based cohort of 244 older adults who underwent two comprehensive neuropsychological and structural magnetic resonance imaging sessions over 4.6 years. On average, residual memory variance decreased over time, consistent with the idea that cognitive reserve is depleted over time. Individual differences in change in residual memory variance predicted incident dementia, independent of baseline residual memory variance. Multiple-group latent difference score models revealed tighter coupling between brain and language changes among individuals with decreasing residual memory variance. These results suggest that changes in residual memory variance may capture a dynamic aspect of cognitive reserve and could be a useful way to summarize individual cognitive responses to brain changes. Change in residual memory variance among initially non-demented older adults was a better predictor of incident dementia than residual memory variance measured at one time-point.

Neuropsychiatric effects of neurodegeneration of the medial versus lateral ventral prefrontal cortex in humans.

Animal evidence suggests that a brain network involving the medial and rostral ventral prefrontal cortex (PFC) is central for threat response and arousal and a network involving the lateral and caudal PFC plays an important role in reward learning and behavioral control. In this study, we contrasted the neuropsychiatric effects of degeneration of the medial versus lateral PFC in 43 patients with Frontotemporal dementia (FTD) and 11 patients with Corticobasal Syndrome (CBS) using MRI, the Neuropsychiatric Inventory (NPI), and the Sorting, Tower, Twenty Questions, and Fluency tests of the Delis-Kaplan Executive Function System (D-KEFS). Deviations in MRI grey matter volume from 86 age-matched healthy control subjects were determined for the patients using FreeSurfer. Multivariate regression was used to determine which brain areas were associated with specific neuropsychiatric and cognitive symptoms. Decreased grey matter volume of the right medial ventral PFC was associated with increased anxiety and apathy, decreased volume of the right lateral ventral PFC with apathy and inappropriate repetitive behaviors, and of the left lateral ventral PFC with poor performance on the sorting and Twenty Questions task in patients with FTD and CBS. Similar to in animal studies, damage to the medial OFC appears to be associated with a disruption of arousal, and damage to the lateral OFC appears to be associated with deficits in trial-and-error learning and behavioral dysregulation. Studies of brain dysfunction in humans are valuable to bridge animal and human neuropsychiatric research.

Structural MRI Predictors of Late-Life Cognition Differ Across African Americans, Hispanics, and Whites.

BACKGROUND: Structural magnetic resonance imaging (MRI) provides key biomarkers to predict onset and track progression of Alzheimer's disease (AD). However, most published reports of relationships between MRI variables and cognition in older adults include racially, ethnically, and socioeconomically homogenous samples. Racial/ethnic differences in MRI variables and cognitive performance, as well as health, socioeconomic status and psychological factors, raise the possibility that brain-behavior relationships may be stronger or weaker in different groups. The current study tested whether MRI predictors of cognition differ in African Americans and Hispanics, compared with non-Hispanic Whites. METHODS: Participants were 638 non-demented older adults (29% non-Hispanic White, 36% African American, 35% Hispanic) in the Washington Heights-Inwood Columbia Aging Project. Composite scores of memory, language, speed/executive functioning, and visuospatial function were derived from a neuropsychological battery. Hippocampal volume, regional cortical thickness, infarcts, and white matter hyperintensity (WMH) volumes were quantified with FreeSurfer and in-house developed procedures. Multiple-group regression analysis, in which each cognitive composite score was regressed onto MRI variables, demographics, and cardiovascular health, tested which paths differed across groups. RESULTS: Larger WMH volume was associated with worse language and speed/executive functioning among African Americans, but not among non-Hispanic Whites. Larger hippocampal volume was more strongly associated with better memory among non-Hispanic Whites compared with Hispanics. Cortical thickness and infarcts were similarly associated with cognition across groups. CONCLUSION: The main finding of this study was that certain MRI predictors of cognition differed across racial/ethnic groups. These results highlight the critical need for more diverse samples in the study of cognitive aging, as the type and relation of neurobiological substrates of cognitive functioning may be different for different groups.

The right insula contributes to memory awareness in cognitively diverse older adults.

Unawareness of memory loss is a challenging characteristic of Alzheimer's disease (AD) and other age-related neurodegenerative conditions at their earliest stages, adversely affecting important outcomes such as patient decision making and safety. The basis of this metacognitive disturbance has been elusive; however it is almost certainly determined in part by compromise to brain regions critical for self-assessment. The subjectivity of traditional measurements of self-awareness in dementia has likely limited the rigor with which its neuroanatomic correlates can be established. Here we objectively measure memory awareness (metamemory) using a Feeling of Knowing (FOK) task in a group of cognitively diverse older adults, including 14 with mild AD and 20 cognitively healthy older adults. Performance on the metamemory task was examined in relation to the structural integrity of 14 bilateral neuroanatomic regions hypothesized to support self-awareness. Less accurate metamemory was associated only with reduced right insular volume (r=.41, p=.019). Implications of the current findings for models of metacognitive aging are discussed, with attention to the role of the insula in the conscious detection of errors.

Reconsidering harbingers of dementia: progression of parietal lobe white matter hyperintensities predicts Alzheimer's disease incidence.

Accumulating evidence implicates small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging, in the pathogenesis and diagnosis of Alzheimer's disease (AD). Cross-sectional volumetric measures of WMH, particularly in the parietal lobes, are associated with increased risk of AD. In the present study, we sought to determine whether the longitudinal regional progression of WMH predicts incident AD above-and-beyond traditional radiological markers of neurodegeneration (i.e., hippocampal atrophy and cortical thickness). Three hundred three nondemented older adults (mean age = 79.24 ± 5.29) received high-resolution magnetic resonance imaging at baseline and then again 4.6 years (standard deviation = 1.01) later. Over the follow-up interval 26 participants progressed to AD. Using structural equation modeling, we calculated latent difference scores of parietal and nonparietal WMH, hippocampus volumes, and cortical thickness values in AD-related regions. Within the structural equation modeling framework, we determined whether baseline or change scores or both predicted AD conversion, while controlling for several time-invariant relevant variables. Smaller baseline hippocampus volume, change in hippocampus volume (i.e., atrophy), higher baseline parietal lobe WMH, and increasing parietal lobe WMH volume but not WMH in other regions or measures of cortical thickness, independently predicted progression to AD. The findings provide strong evidence that regionally accumulating WMH predict AD onset in addition to hallmark neurodegenerative changes typically associated with AD.

Preliminary observations on MRI correlates of driving independence and performance in persons with heart failure.

PURPOSE/AIM: Heart failure patients often require assistance with activities of daily living, including driving. Recent work shows heart failure patients commit more errors on a simulated driving task relative to controls and cognitive dysfunction contributed to these errors. We sought to extend these findings by examining whether structural magnetic resonance imaging indices correlate with driving independence and performance in heart failure. MATERIALS AND METHODS: Forty-nine heart failure patients underwent brain magnetic resonance imaging and performed a battery assessing attention/executive function and memory. A self-report instrument was used to assess independence in transportation. A subset of heart failure participants (N = 8) completed a validated driving simulator scenario. RESULTS: Among the larger sample (N = 49), reduced gray matter correlated with greater dependence in transportation and worse attention/executive function; in turn, worse attention/executive function predicted greater assistance with transportation (p < 0.05). Among the subset that completed the driving simulator (N = 8), reduced gray matter correlated with more stop signs missed and increased white matter hyperintensities correlated with greater collisions, centerline crossings and time out of lane (p < 0.05). Poorer attention/executive function was also associated with more time over the speed limit on the driving simulation (p < 0.05). Follow-up analyses showed the above effects were largely independent of age. CONCLUSIONS: Reduced structural brain integrity is associated with poorer reported and simulated driving in persons with heart failure. Larger prospective studies that employ on-road testing are needed to clarify brain changes and risk for unsafe driving in heart failure.

Soluble amyloid beta levels are elevated in the white matter of Alzheimer's patients, independent of cortical plaque severity.

Alzheimer's disease (AD) is the most common neurodegenerative disease and the leading cause of dementia. In addition to grey matter pathology, white matter changes are now recognized as an important pathological feature in the emergence of the disease. Despite growing recognition of the importance of white matter abnormalities in the pathogenesis of AD, the causes of white matter degeneration are still unknown. While multiple studies propose Wallerian-like degeneration as the source of white matter change, others suggest that primary white matter pathology may be due, at least in part, to other mechanisms, including local effects of toxic Aß peptides. In the current study, we investigated levels of soluble amyloid-beta (Aß) in white matter of AD patients (n=12) compared with controls (n=10). Fresh frozen white matter samples were obtained from anterior (Brodmann area 9) and posterior (Brodmann area 1, 2 and 3) areas of post-mortem AD and control brains. ELISA was used to examine levels of soluble Aß -42 and Aß -40. Total cortical neuritic plaque severity rating was derived from individual ratings in the following areas of cortex: mid-frontal, superior temporal, pre-central, inferior parietal, hippocampus (CA1), subiculum, entorhinal cortex, transentorhinal cortex, inferior temporal, amygdala and basal forebrain. Compared with controls, AD samples had higher white matter levels of both soluble Aß -42 and Aß -40. While no regional white matter differences were found in Aß -40, Aß -42 levels were higher in anterior regions than in posterior regions across both groups. After statistically controlling for total cortical neuritic plaque severity, differences in both soluble Aß -42 and Aß -40 between the groups remained, suggesting that white matter Aß peptides accumulate independent of overall grey matter fibrillar amyloid pathology and are not simply a reflection of overall amyloid burden. These results shed light on one potential mechanism through which white matter degeneration may occur in AD. Given that white matter degeneration may be an early marker of disease, preceding grey matter atrophy, understanding the mechanisms and risk factors that may lead to white matter loss could help to identify those at high risk and to intervene earlier in the pathogenic process.

Higher BMI is associated with reduced brain volume in heart failure.

BACKGROUND: Heart failure (HF) patients are at risk for structural brain changes due to cerebral hypoperfusion. Past work shows obesity is linked with reduced cerebral blood flow and associated with brain atrophy in healthy individuals, although its effects on the brain in HF are unclear. This study examined the association among body mass index (BMI), cerebral perfusion, and brain volume in HF patients. RESULTS: Eighty HF patients underwent transcranial Doppler sonography to quantify cerebral blood flow velocity of the middle cerebral artery (CBF-V of the MCA) and brain magnetic resonance imaging (MRI) to quantify total brain, total and subcortical gray matter, white matter volume, and white matter hyperintensities. Body mass index (BMI) operationalized weight status. Nearly 45% of HF patients exhibited a BMI consistent with obesity. Regression analyses adjusting for medical variables, demographic characteristics, and CBF-V of the MCA, showed increased BMI was associated with reduced white matter volume (p <.05). BMI also interacted with cerebral perfusion to impact total gray matter volume, but this pattern did not emerge for any other MRI indices (p < 0.05). CONCLUSIONS: Our findings suggest increased BMI negatively affects brain volume in HF, and higher BMI interacts with cerebral perfusion to impact gray matter volume. The mechanisms for these findings remain unclear and likely involve multiple physiological processes. Prospective studies are needed to elucidate the exact pattern and rates of brain changes in obese HF persons.

Reduced cerebral blood flow and white matter hyperintensities predict poor sleep in heart failure.

BACKGROUND: Poor sleep is common in heart failure (HF), though mechanisms of sleep difficulties are not well understood. Adverse brain changes among regions important for sleep have been demonstrated in patients with HF. Cerebral hypoperfusion, a correlate of sleep quality, is also prevalent in HF and a likely contributor to white matter hyperintensities (WMH). However, no study to date has examined the effects of cerebral blood flow, WMH, and brain volume on sleep quality in HF. METHODS: Fifty-three HF patients completed the Pittsburgh Sleep Quality Index and underwent brain magnetic resonance imaging to quantify brain and WMH volume. Transcranial Doppler ultrasonography assessed cerebral blood flow velocity of the middle cerebral artery (CBF-V of the MCA). RESULTS: 75.5% of HF patients reported impaired sleep. Regression analyses adjusting for medical and demographic factors showed decreased CBF-V of the MCA and greater WMH volume were associated with poor sleep quality. No such pattern emerged on total brain or regional volume indices. CONCLUSIONS: Decreased cerebral perfusion and greater WMH may contribute to sleep difficulties in HF. Future studies are needed to confirm these findings and clarify the effects of cerebral blood flow and WMH on sleep in healthy and patient samples.

Independent and interactive effects of blood pressure and cardiac function on brain volume and white matter hyperintensities in heart failure.

BACKGROUND: Reduced systemic perfusion and comorbid medical conditions are key contributors to adverse brain changes in heart failure (HF). Hypertension, the most common co-occurring condition in HF, accelerates brain atrophy in aging populations. However, the independent and interactive effects of blood pressure and systemic perfusion on brain structure in HF have yet to be investigated. METHODS: Forty-eight older adults with HF underwent impedance cardiography to assess current systolic blood pressure status and cardiac index to quantify systemic perfusion. All participants underwent brain magnetic resonance imaging to quantify total brain, total and subcortical gray matter volume, and white matter hyperintensities (WMH) volume. RESULTS: Regression analyses adjusting for medical and demographic factors showed decreased cardiac index was associated with smaller subcortical gray matter volume (P < .01), and higher systolic blood pressure predicted reduced total gray matter volume (P = .03). The combination of higher blood pressure and lower cardiac index exacerbated WMH (P = .048). CONCLUSIONS: Higher blood pressure and systemic hypoperfusion are associated with smaller brain volume, and these factors interact to exacerbate WMH in HF. Prospective studies are needed to clarify the effects of blood pressure on the brain in HF, including the role of long-term blood pressure fluctuations.

Poorer physical fitness is associated with reduced structural brain integrity in heart failure.

OBJECTIVE: Physical fitness is an important correlate of structural and functional integrity of the brain in healthy adults. In heart failure (HF) patients, poor physical fitness may contribute to cognitive dysfunction and we examined the unique contribution of physical fitness to brain structural integrity among patients with HF. METHODS: Sixty-nine HF patients performed the Modified Mini Mental State examination (3MS) and underwent brain magnetic resonance imaging. All participants completed the 2-minute step test (2MST), a brief measure of physical fitness. We examined the associations between cognitive performance, physical fitness, and three indices of global brain integrity: total cortical gray matter volume, total white matter volume, and whole brain cortical thickness. RESULTS: Regression analyses adjusting for demographic characteristics, medical variables (e.g., left ventricular ejection fraction), and intracranial volume revealed reduced performance on the 2MST were associated with decreased gray matter volume and thinner cortex (p<.05). Follow up analyses showed that reduced gray matter volume and decreased cortical thickness were associated with poorer 3MS scores (p<.05). CONCLUSIONS: Poor physical fitness is common in HF and associated with reduced structural brain integrity. Prospective studies are needed to elucidate underlying mechanisms for the influence of physical fitness on brain health in HF.

Cerebral perfusion is associated with white matter hyperintensities in older adults with heart failure.

Cognitive impairment is common in heart failure (HF) and believed to be the result of cerebral hypoperfusion and subsequent brain changes including white matter hyperintensities (WMHs). The current study examined the association between cerebral blood flow and WMHs in patients with HF and the relationship between WMHs and cognitive impairment. Sixty-nine patients with HF completed the Mini-Mental State Examination (MMSE) and underwent echocardiography, transcranial Doppler sonography for cerebral blood flow velocity of the middle cerebral artery, and brain magnetic resonance imaging. Multivariable hierarchical regression analyses controlling for medical and demographic characteristics as well as intracranial volume showed reduced cerebral blood flow velocity of the middle cerebral artery was associated with greater WMHs (ß=-0.34, P=.02). Follow-up regression analyses adjusting for the same medical and demographic factors in addition to cerebral perfusion also revealed marginal significance between increased WMHs and poorer performance on the MMSE (ß=-0.26, P=.05). This study suggests that reduced cerebral perfusion is associated with greater WMHs in older adults with HF. These findings support the widely proposed mechanism of cognitive impairment in HF patients and prospective studies are needed to confirm these results.