Karin F. Hoth

Early Life Stress and Morphometry of the Adult Anterior Cingulate Cortex and Caudate Nuclei

BACKGROUND Early life stress (ELS) is linked to adult psychopathology and may contribute to long-term brain alterations, as suggested by studies of women who suffered childhood sexual abuse. We examine whether reported adverse ELS defined as stressful and/or traumatic adverse childhood events (ACEs) is associated with smaller limbic and basal ganglia volumes. METHOD 265 healthy Australian men and women without psychopathology or brain disorders were studied. ACEs were assessed by the ELSQ and current emotional state by the DASS. Anterior cingulate cortex (ACC), hippocampus, amygdala, and caudate nucleus volumes were measured from T1-weighted MRI. Analyses examined ROI volumetric associations with reported ACEs and DASS scores. RESULTS Participants with greater than two ACEs had smaller ACC and caudate nuclei than those without ACEs. A significant association between total ACEs and ROI volumes for these structures was observed. Regression analysis also revealed that ELS was more strongly associated than current emotional state (DASS) with these ROI volumes. CONCLUSIONS Reported ELS is associated with smaller ACC and caudate volumes, but not the hippocampal or amygdala volumes. The reasons for these brain effects are not entirely clear, but may reflect the influence of early stress and traumatic events on the developing brain.

Endothelial function and white matter hyperintensities in older adults with cardiovascular disease.

Background and Purpose— The presence of white matter hyperintensities on brain MRI is common among elderly individuals. Previous research suggests that cardiovascular risk factors are associated with increased white matter hyperintensities. Examining the role of direct physiological measures of vascular function will help to clarify the vascular mechanisms related to white matter hyperintensities. The aim of the present study was to examine the association between endothelial-dependent and endothelial-independent vasodilatation and white matter hyperintensity volume. Methods— Twenty-five older adults with a range of cardiovascular diseases underwent brain MRI and completed assessments of blood vessel integrity using endothelial-dependent and independent flow-mediated dilation of the brachial artery. A semi-automated pixel-based method was used to quantify total brain volume and white matter hyperintensity volume, with white matter hyperintensity volume corrected for total brain volume. The association between measures of flow-mediated dilation and log-transformed white matter hyperintensities was examined. Results— Correlation analysis revealed that endothelial-dependent vasodilatation was significantly and inversely associated with white matter hyperintensity volume. In contrast, endothelial-independent vasodilatation was not associated with white matter hyperintensities. Neither endothelial-dependent nor endothelial-independent vasodilatation was associated with total brain volume. Conclusions— These data provide preliminary evidence that the integrity of the vascular endothelium is associated with white matter hyperintensities in older adults with cardiovascular disease. Impaired vascular function may be one mechanism that contributes to the development of white matter hyperintensities in the brain. Additional longitudinal research combining measures of vessel function, neuroimaging and cognition will be helpful in clarifying this potential mechanism.

Patients with Huntington's disease have impaired awareness of cognitive, emotional, and functional abilities

The clinical literature in Huntingtons disease (HD) suggests that unawareness of deficits is prevalent among HD patients. However, few studies have characterized unawareness of different types of impairment within this neuropsychiatric disorder. The purpose of the current study was to examine self-awareness of functioning across symptom domains in HD patients and to explore the association between impaired awareness and cognitive dysfunction. A total of 66 pairs of HD patients and collaterals of the patients completed symptom-rating measures regarding both the patients’ and the collaterals’ behavior. A subset of 19 patients also underwent neurological and neuropsychological assessments. The results indicated that patients lacked awareness across symptom domains (i.e., behavioral control, emotional control, activities of daily living), which was significantly greater for their perception of their own behavior than for their perception of their collaterals behavior. Exploratory analyses revealed associations between impaired self-awareness, global cognition, and deficits in executive functioning and memory. The current findings underscore the importance of examining different types of impaired awareness including both over- and underreporting of abilities. Future studies will benefit also from examining the association between awareness and cognition in larger samples.

Vascular and cognitive functions associated with cardiovascular disease in the elderly.

This study examines the relationship between systemic vascular function, neurocognitive performance, and structural brain abnormalities on magnetic resonance imaging (MRI) among geriatric outpatients with treated, stable cardiovascular disease and no history of neurological illness (n = 88, ages 56–85 years). Vascular function was assessed by cardiac ejection fraction and output, sequential systolic and diastolic blood pressures, flow mediated brachial artery reactivity (BAR), and carotid intima media thickness (IMT). White matter hyperintensities (WMH) on MRI were quantified and examined relative to cognitive and vascular function. Principal component analysis revealed two primary vascular components: one associated with cardiac function, the other with atherosclerotic burden/endothelial dysfunction. Both factors were significantly associated with cognitive function and WMH volume. Reduced systolic variability and increased IMT were most strongly related to reduced attention, executive function, and information-processing speed. These findings suggest the possibility that systemic vascular indices may provide proxy measures of cerebrovascular dysfunction and reinforce the importance of achieving greater understanding of interaction between systemic vascular disease and brain dysfunction among elderly people with cardiovascular disease.

Cardiac dysfunction and cognition in older adults with heart failure.

ObjectivesTo characterize cognition in patients with moderate to severe heart failure and examine the association between 2 measures of systemic perfusion (ie, ejection fraction and cardiac index) and cognition. BackgroundDecreased systemic perfusion has been implicated as an etiologic factor in the development of cognitive deficits in cardiovascular disease. MethodThirty-one patients with moderate to severe heart failure and 31 patients with cardiovascular disease and no heart failure completed a medical history interview and neuropsychologic assessment. Participants with heart failure additionally underwent an echocardiogram to assess cardiac function. ResultsPatients with heart failure performed significantly worse than the cardiovascular disease-no heart failure group on several measures of executive functioning and psychomotor speed. Among the heart failure group, lower ejection fraction was associated with weaker global cognition, performance on several, but not all, measures of executive functioning, and was marginally associated with delayed memory. Decreased cardiac index was associated with poorer immediate memory and weakly associated with global cognition. ConclusionsFindings suggest that depressed systemic perfusion is associated with cognitive deficits among patients with heart failure. Research including measures of cardiac function, cerebral perfusion, and cognition will be necessary to clarify the causal nature of the suggested mechanism.

C-reactive protein, but not homocysteine, is related to cognitive dysfunction in older adults with cardiovascular disease

Cardiovascular disease (CVD) is a risk factor for cognitive impairment and dementia. Recent studies implicate homocysteine (HCY) and C-reactive protein (CRP) in this increased risk, as both are associated with cognitive dysfunction in demented and non-demented patients. However, it remains unclear whether they confer added risk in older adults with CVD. A total of 126 older CVD patients underwent blood and neuropsychological evaluation as part of a prospective examination of the neurocognitive consequences of CVD. A subset of these participants (n=37) also underwent neuroimaging to quantify the degree of white matter disease. After adjusting for demographic and medical factors, no significant relationship emerged between HCY and cognitive performance. In contrast, CRP showed significant independent relationships to test performance, including global cognitive performance, attention/psychomotor function, executive function, memory, and visuospatial abilities. Neither HCY nor CRP was related to extent of white matter disease or whole brain volume on magnetic resonance imaging. Further study is needed to identify mechanisms by which inflammatory processes impact on cognitive function and to determine whether reducing circulating levels of inflammatory markers results in improved cognition.

Subjective cognitive complaints relate to white matter hyperintensities and future cognitive decline in patients with cardiovascular disease.

OBJECTIVE Elderly patients with cardiovascular disease (CVD) often report cognitive difficulties including reduced cognitive processing speed and attention. On cross-sectional examination, such reports relate more closely to mood than to objective measures of cognitive performance, thus questioning the validity of subjective cognitive complaints as a marker of neurodegenerative processes. This study examined the longitudinal relationship among self-reported cognitive difficulties, depression, and performance on objective tests of global cognition in patients with CVD. PARTICIPANTS AND METHODS Forty-seven patients with CVD (aged 55-85 years) completed a measure of perceived cognitive dysfunction (Cognitive Difficulties Scale [CDS]), a medical history questionnaire, the Dementia Rating Scale (DRS), and the Beck Depression Inventory (BDI) at baseline and 12 months later. Baseline brain imaging was available on a small subsample (N = 17). RESULTS Hierarchical linear regression revealed that increased report of cognitive difficulties at baseline was significantly associated with poorer DRS performance at follow-up (F[3, 43] = 4.45, p = 0.008, CDS partial r = -0.30, p = 0.048), independent of age, education, baseline DRS, and BDI scores. Greater perceived cognitive dysfunction at baseline also related to higher level of white matter lesions (r = 0.53, df = 15, p = 0.028). CONCLUSIONS Self-reported cognitive difficulties may reflect early changes in cognitive aging that are difficult to detect using global cognitive screening measures at a single time point. However, these perceived difficulties relate to objectively measured cognitive decline over time. Thus, they may provide important clinical information about early neurodegenerative processes that should be carefully monitored.

Elevated C-Reactive Protein Is Related to Cognitive Decline in Older Adults with Cardiovascular Disease

OBJECTIVES: To prospectively relate C‐reactive protein (CRP), a systemic marker of inflammation, to cognitive change over a 1‐year follow‐up period.

A Longitudinal Examination of Social Support, Agreeableness and Depressive Symptoms in Chronic Kidney Disease

Research examining the role of social support in patient adjustment to chronic illness has been inconsistent suggesting that patient individual differences play a moderating role. This study examined the hypothesis that the relationship between social support and depressive symptoms would differ as a function of individual differences in trait Agreeableness. Fifty-nine patients with chronic kidney disease were assessed using the Social Provisions Scale, Beck Depression Inventory and NEO-Five-Factor Inventory and were followed-up a year and a half later. After controlling for baseline depressive symptoms and clinical characteristics, regression analyses revealed a significant interaction between social support and Agreeableness predicting change in depressive symptoms. Greater social support among individuals high in Agreeableness was associated with a decrease in depressive symptoms over time, while support had little effect on depression change for individuals low in Agreeableness. These findings underscore the importance of individual difference variables in understanding adjustment to chronic illness.

Blood pressure variability and white matter hyperintensities in older adults with cardiovascular disease.

The present study examined the relationship between multiple blood pressure (BP) indices and white matter hyperintensities (WMH) in a sample of 39 older adults with cardiovascular disease (CVD). Resting BP was measured using an automated monitor every 10 min for 2 h. WMH were quantified on FLAIR images and separate indices were generated for neocortical, periventricular and subcortical brain regions. Correlation analyses revealed systolic BP variability was related to neocortical and total WMH. A function of systolic BP variability and average diastolic pressure showed the strongest relationships, including significant correlation to neocortical, subcortical and total WMH. No BP index was related to WMH in periventricular regions. Exploratory analyses showed only the function of systolic BP variability and average diastolic pressure predicted total WMH, whereas as age, CVD conditions and psychosocial factors did not. These findings demonstrate BP variability is an important contributor to WMH in older adults with CVD and suggests it may have differential relationships to WMH in different brain regions. Additional studies are needed to examine the role of autoregulatory systems in the development of WMH, particularly those using beat‐to‐beat measures of BP.