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1.  Decreased Default Network Connectivity is Associated with Early Life Stress in Medication-Free Healthy Adults 
Early life stress (ELS) is a significant risk factor for psychopathology, although there are few functional imaging studies investigating its effects. Previous literature suggests that ELS is associated with changes in structure and function in the medial prefrontal cortex (MPFC), which forms the main anterior node of the default network (DN). This study investigated the impact of ELS history on resting state DN connectivity, using seed-based correlation analyses (SCA) involving the posterior cingulate cortex (PCC). Data were analyzed from 22 adult subjects without psychiatric or medical illness (13 with and 9 without ELS); none were taking psychotropic medication. Relative to controls, the ELS group had significant decreases in DN connectivity, observed between the PCC seed and the MPFC and inferior temporal cortex. Further analyses revealed a trend-level increase in connectivity between the amygdala and MPFC associated with ELS history. In conclusion, this study found that subjects with ELS, in the absence of psychiatric illness and medication exposure, demonstrated decreased DN connectivity, and trend-level increases in connectivity between the amygdala and MPFC. These findings suggest that altered resting state connectivity is a correlate of stress exposure, rather than a product of medication or psychiatric morbidity.
PMCID: PMC3581700  PMID: 23141153
Default Network; Early Life Stress; Resilience; Functional Connectivity; Post Traumatic Stress Disorder; Medial Prefrontal Cortex
2.  The Adverse Impact of Type 2 Diabetes on Brain Volume in Heart Failure 
Heart failure (HF) is associated with structural brain abnormalities, including atrophy in multiple brain regions. Type 2 diabetes mellitus (T2DM) is a prevalent comorbid condition in HF and is associated with abnormalities on neuroimaging in other medical and elderly samples. The current study examined whether comorbid T2DM exacerbates brain atrophy in older adults with HF.
Seventy-five older adults with HF underwent echocardiogram, and completed a brief cognitive test battery. Participants then underwent brain magnetic resonance imaging (MRI) to quantify total brain volumes, cortical lobar volumes, and white matter hyperintensities (WMH).
Approximately 30% of HF patients had a comorbid T2DM diagnosis. A series of MANCOVA analyses adjusting for medical and demographic characteristics and intracranial volume showed that HF patients with T2DM had smaller total brain, gray matter, and subcortical gray matter volume than those without such history. No between group differences emerged for WMH. Persons with T2DM also had smaller cortical lobar volumes, including in frontal, temporal, and parietal lobes. Follow-up analyses revealed smaller total and cortical lobar brain volumes and WMH were associated with poorer performance on measures of global cognitive status, attention, executive functions, and memory.
T2DM is associated with smaller total and cortical lobar brain volumes in patients with HF and these structural brain indices were associated with cognitive test performance. Prospective studies that directly monitor glucose levels are needed to confirm our findings and clarify the mechanisms by which T2DM adversely impacts brain atrophy in this population.
PMCID: PMC3633205  PMID: 23419083
Brain; cognitive function; heart failure; type 2 diabetes; neuroimaging
3.  The Independent Association of Hypertension with Cognitive Function Among Older Adults with Heart Failure 
Journal of the neurological sciences  2012;323(1-2):216-220.
Hypertension is the most common comorbidity among heart failure (HF) patients and has been independently linked with cognitive impairment. Cognitive impairment is prevalent among HF patients, though the extent to which hypertension contributes to cognitive function in this population is unclear.
116 HF patients (31.0% women, 67.68 ± 11.16 years) completed neuropsychological testing and impedance cardiography. History of physician diagnosed hypertension, along with other medical characteristics, was ascertained through a review of participants’ medical charts.
69.8% of the HF patients had a diagnostic history of hypertension. After adjustment for demographic and medical characteristics (i.e., cardiac index, medication status, and resting blood pressure), hypertension was independently associated with attention/executive function/psychomotor speed (ΔF(1,103) = 10.85, ΔR2 = .07, p < .01) and motor functioning (ΔF(1,103) = 4.46, ΔR2 = .04, p < .05). HF patients with a diagnosed history of hypertension performed worse in these domains than those without such history.
The current findings indicate that diagnostic history of hypertension is an important contributor to cognitive impairment in HF. Hypertension frequently precedes HF and future studies should examine whether sustained hypertension compromises cerebral autoregulatory mechanisms to produce brain damage and exacerbate cognitive impairment in this population.
PMCID: PMC3483380  PMID: 23026535
Cognitive function; cardiac index; heart failure; hypertension; blood pressure
4.  Cognitive Function and Treatment Adherence in Older Adults with Heart Failure 
Psychosomatic medicine  2012;74(9):965-973.
Treatment recommendation and guidelines for patients with heart failure (HF) can be complex, and past work has shown HF patients to demonstrate low rates of adherence to recommended health behaviors. While previous work has identified several medical, demographic, and psychosocial predictors of HF persons’ capacity to adhere to treatment recommendations, little is known about the contribution of cognitive impairment to reported treatment adherence in this population.
149 persons with HF (68.08 years; SD = 10.74) completed a brief fitness assessment and neuropsychological testing. Treatment adherence was assessed using the Heart Failure Compliance Questionnaire, a brief measure that asks participants to report their adherence to a variety of recommended health behaviors (i.e., medication management, diet, exercise, among others).
16.1% of participants reported poor overall adherence, with particularly high rates of non-adherence to dietary and exercise recommendations. Hierarchical regression analyses adjusting for possible confounds revealed reduced performance on attention (β = .26, p = .01), executive function (β = .18, p = .04), and language (β = .22, p = .01) were associated with poorer overall adherence. Follow-up analyses showed these cognitive domains were associated with behaviors such as keeping doctor appointments, medication management, and dietary recommendations (p < .05 for all).
The current findings demonstrate that cognitive function is an independent contributor to adherence in older adults with HF. Prospective studies that objectively measure treatment adherence are needed to clarify these findings and identify possible strategies to improve outcomes in this population.
PMCID: PMC3498588  PMID: 23115344
attention; executive function; heart failure; treatment adherence; cognitive impairment
5.  Depression is Associated with Reduced Physical Activity in Persons with Heart Failure 
Reduced physical activity is common in persons with heart failure (HF). However, studies of correlates and modifiers of physical activity in this population rarely employ objective measures. Motivational and mood related factors that may exacerbate inactivity in HF patients are also rarely investigated. In this study, we examined the relationship between physical activity as assessed by accelerometry, and depression in older adults with HF.
At baseline, older adults with HF (N = 96; 69.81 ± 8.79) wore an accelerometer for seven days, and completed a brief fitness assessment, neuropsychological testing, and psychosocial measures including the Beck Depression Inventory-II (BDI-II). Medical and demographic history was obtained through record review and self-report.
Accelerometer measures showed that HF patients averaged 587 minutes of sedentary time and just 0.31 minutes of vigorous activity per day. Lower daily step count was associated with poorer quality of life and reduced cognitive function. A multiple linear regression adjusting for important demographic and medical variables found that greater number of depressive symptoms on the BDI-II independently predicted lower physical activity levels.
Consistent with past work, the current study found that low physical activity is common in older adults with HF. Depression is an independent predictor of physical activity in older adults with HF and reduced physical activity is associated with numerous adverse psychosocial outcomes. Future studies need to determine whether treatment of depression can boost physical activity and thus improve health outcomes in this population.
PMCID: PMC3610332  PMID: 22924448
Physical Activity; heart failure; depression; psychosocial outcomes; step count
6.  The adverse effects of reduced cerebral perfusion on cognition and brain structure in older adults with cardiovascular disease 
Brain and Behavior  2013;3(6):626-636.
It is well established that aging and vascular processes interact to disrupt cerebral hemodynamics in older adults. However, the independent effects of cerebral perfusion on neurocognitive function among older adults remain poorly understood. We examined the associations among cerebral perfusion, cognitive function, and brain structure in older adults with varying degrees of vascular disease using perfusion magnetic resonance imaging (MRI) arterial spin labeling (ASL).
Materials and methods
52 older adults underwent neuroimaging and were administered the Mini Mental State Examination (MMSE), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and measures of attention/executive function. ASL and T1-weighted MRI were used to quantify total brain perfusion, total brain volume (TBV), and cortical thickness.
Regression analyses showed reduced total brain perfusion was associated with poorer performance on the MMSE, RBANS total index, immediate and delayed memory composites, and Trail Making Test B. Reduced frontal lobe perfusion was associated with worse executive and memory function. A similar pattern emerged between temporal lobe perfusion and immediate memory. Regression analyses revealed that decreased total brain perfusion was associated with smaller TBV and mean cortical thickness. Regional effects of reduced total cerebral perfusion were found on temporal and parietal lobe volumes and frontal and temporal cortical thickness.
Reduced cerebral perfusion is independently associated with poorer cognition, smaller TBV, and reduced cortical thickness in older adults.
Prospective studies are needed to clarify patterns of cognitive decline and brain atrophy associated with cerebral hypoperfusion.
PMCID: PMC3868168  PMID: 24363966
Arterial spin labeling; cardiovascular disease; cerebral blood flow; cerebrovascular disease; cognitive function; magnetic resonance imaging; neuroimaging
7.  Reduced cerebral blood flow and white matter hyperintensities predict poor sleep in heart failure 
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.
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).
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.
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.
PMCID: PMC3816301  PMID: 24171759
Sleep quality; Heart failure; MRI; Brain perfusion; White matter hyperintensity
8.  Reduced memory in fat mass and obesity-associated allele carriers among older adults with cardiovascular disease 
Much attention has been paid to the prevalence and predisposition of the fat mass and obesity-associated (FTO) gene to obesity, although only a few studies have characterized the extent to which this affects cognitive function. This study examined differences between risk allele carriers (i.e. FTO-AC/AA) and non-carriers (i.e. FTO-CC) on indices of attention/executive function/psychomotor speed, memory, language, and visual-spatial ability in a sample of older patients with cardiovascular disease.
We recruited 120 older adults from an outpatient cardiology clinic who underwent blood draw and completed neuropsychological testing. Participants were classified into two groups: one for those who were homozygous for the non-risk-conferring allele (i.e. FTO-CC) (n = 49) and the other for those who had at least one copy of the obesity risk-conferring A allele (i.e. FTO-AC/AA) (n = 71).
Mancova analyses adjusting for age and years of education revealed the FTO-AC/AA group performed significantly worse on indices of memory (λ = 0.94, F(2, 115) = 3.58, P = 0.03, partial η2 = 0.06). Follow-up tests revealed a significant effect for the FTO-AC/AA group, relative to the non-carrier group, on encoding (i.e. California Verbal Learning Test Total Learning) and California Verbal Learning Test long-delay free recall (P < 0.05). No such differences between FTO carriers and non-carriers emerged on tests of attention/executive function/psychomotor speed, language, or visual-spatial ability (P > 0.05 for all).
These findings suggest that the FTO risk allele is associated with reduced memory performance, particularly on aspects of memory encoding and delayed recall. To elucidate underlying mechanisms, these findings will need to be replicated in larger samples that utilize neuroimaging.
PMCID: PMC3806216  PMID: 23551410
cardiovascular disease; cognitive function; FTO risk allele; memory; obesity
10.  Effects of HIV and Early Life Stress on Amygdala Morphometry and Neurocognitive Function 
Both HIV infection and high levels of early life stress (ELS) have been related to abnormalities in frontal-subcortical structures, yet the combined effects of HIV and ELS on brain structure and function have not been previously investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+) and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N = 20); HC High-ELS (N = 27); HIV+ Low-ELS (N = 24); HIV+ High-ELS (N = 25). An automated segmentation tool measured volumes of brain structures known to show HIV-related or ELS-related effects; a brief neurocognitive battery was administered. A significant HIV-ELS interaction was observed for amygdala volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+ High-ELS group also demonstrated significant reductions in psychomotor/processing speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed that amygdala enlargements were associated with higher ELS, lower nadir CD4 counts, and reduced psychomotor/processing speed. Our results suggest that HIV infection and high ELS interact to increase amygdala volume, which is associated with neurocognitive dysfunction in HIV+ patients. These findings highlight the lasting neuropathological influence of ELS and suggest that high ELS may be a significant risk factor for neurocognitive impairment in HIV-infected individuals.
PMCID: PMC3575741  PMID: 22621973
HIV; Stress; Amygdala; Neuroimaging; Cognition
11.  Cognitive Profiles in Heart Failure: A Cluster Analytic Approach 
Cognitive impairment is common among individuals with heart failure (HF), but the exact nature of these impairments remains unclear. The current study examined 140 older adults with heart failure and sought to determine whether there are distinct cognitive profiles using a cluster analytic approach. Results indicated three unique profiles comprising of individuals who were cognitively intact, memory impaired, and globally impaired. Clusters differed on several important demographic and clinical characteristics. These findings suggest cognitive impairment in persons with HF is more heterogeneous than commonly believed and have important implications for treatment recommendations.
PMCID: PMC3341622  PMID: 22375800
heart failure; cognitive function; cognitive profiles; older adults; cluster analysis
12.  The neuroeconomics of nicotine dependence: A preliminary study of delay discounting of monetary and cigarette rewards in smokers using fMRI 
Psychiatry research  2012;202(1):20-29.
Neuroeconomics integrates behavioral economics and cognitive neuroscience to understand the neurobiological basis for normative and maladaptive decision making. Delay discounting is a behavioral economic index of impulsivity that reflects capacity to delay gratification and has been consistently associated with nicotine dependence. This preliminary study used functional magnetic resonance imaging to examine delay discounting for money and cigarette rewards in 13 nicotine dependent adults. Significant differences between preferences for smaller immediate rewards and larger delayed rewards were evident in a number of regions of interest (ROIs), including the medial prefrontal cortex, anterior insular cortex, middle temporal gyrus, middle frontal gyrus, and cingulate gyrus. Significant differences between money and cigarette rewards were generally lateralized, with cigarette choices associated with left hemisphere activation and money choices associated with right hemisphere activation. Specific ROI differences included the posterior parietal cortex, medial and middle frontal gyrus, ventral striatum, temporoparietal cortex, and angular gyrus. Impulsivity as measured by behavioral choices was significantly associated with both individual ROIs and a combined ROI model. These findings provide initial evidence in support of applying a neuroeconomic approach to understanding nicotine dependence.
PMCID: PMC3530421  PMID: 22633679
Nicotine dependence; smoking; tobacco; behavioral economics; neuroeconomics; delay discounting; impulsivity
13.  Cortical thickness of the cognitive control network in obesity and successful weight loss maintenance: A preliminary MRI study 
Psychiatry Research  2012;202(1):77-79.
Cortical thickness of the cognitive control network was contrasted between obese (OB), successful weight loss maintainers (SWLM), and lean individuals. OB had significant thinning, most notably in the anterior cingulate and posterior parietal cortices. SWLM exhibited trends towards thicker cortex than OB, which may be important in future studies.
PMCID: PMC3380138  PMID: 22595506
obese; magnetic resonance imaging; Freesurfer
14.  Brain response to food stimulation in obese, normal weight, and successful weight loss maintainers 
Obesity (Silver Spring, Md.)  2012;20(11):2220-2225.
As many people struggle with maintenance of weight loss, the study of successful weight loss maintainers (SWLM) can yield important insights into factors contributing to weight loss maintenance. However, little research has examined how SWLM differ from people who are obese or normal weight (NW) in brain response to orosensory stimulation. The goal of this study was to determine if SWLM exhibit different brain responses to orosensory stimulation. Brain response to one-minute orosensory stimulation with a lemon lollipop was assessed using functional magnetic resonance imaging (FMRI) among 49 participants, including SWLM (n=17), NW (n=18) and obese (n=14) controls. Significant brain responses were observed in nine brain regions, including the bilateral insula, left inferior frontal gyrus, left putamen, and other sensory regions. All regions also exhibited significant attenuation of this response over one minute. The SWLM exhibited greater response compared to the other groups in all brain regions. Findings suggest that the response to orosensory stimulation peaks within 40 seconds and attenuates significantly between 40-60 seconds in regions associated with sensation, reward, and inhibitory control. Greater reactivity among the SWLM suggests that greater sensory reactivity to orosensory stimulation, increased anticipated reward, and subsequently greater inhibitory processing are associated with weight loss maintenance.
PMCID: PMC3483466  PMID: 22569002
Functional Magnetic Resonance Imaging; Functional Neuroimaging; Weight Loss Maintenance
15.  A fMRI Study of Verbal Working Memory, Cardiac Output, and Ejection Fraction in Elderly Patients with Cardiovascular Disease 
Brain imaging and behavior  2009;3(4):350-357.
Cardiovascular disease (CVD) is associated with cognitive deficits even in the absence of stroke. We examined the relationship between cardiac performance, as measured by cardiac output (CO) and ejection fraction (EF), and brain activity during a verbal working memory (VWM) task in elderly CVD patients who tend to be at increased risk for vascular cognitive impairments. Seventeen patients were recruited from a cohort participating in an ongoing prospective study examining the effects of CVD on cognitive function in the elderly. Participants were diagnosed with CVD (age 68±8) and completed a 2-back VWM task in a 1.5T fMRI paradigm. CO and EF were calculated from echocardiogram measures. Task-related activation was averaged in a priori regions of interest. The relationship between CO, EF, and 2-back-related activity was modeled using partial correlations (two-tailed p<.05) controlling for age and 2-back accuracy. All participants were globally cognitively intact as indicated by Mini-Mental Status Exam and Dementia Rating Scale scores. Mean accuracy on the 2-back was 78±9% while reaction time averaged 1,027±192 ms. Mean CO and EF values showed a large range (CO: 3.55 to 6.31; EF: 0.36 to 0.76) but average values were within the normal range. After controlling for age and 2-back accuracy, lower EF was related to decrease in left insula activity (r=0.61, p=0.03). There were trends for EF to be related to accuracy (r=0.47, p=0.09) and reaction time (r=−0.48, p=0.09). CO was also related to insula activity (r=0.60, p=0.04) and activity in the supplementary motor area activity (r=0.66, p=0.01). Cardiac performance was related to decreased efficiency in task related brain areas and tended to be related to performance on a VWM task in elderly patients with CVD. Results have implications for a line of investigation indicating that cardiac and systemic vascular indices could be used as proxy measures to examine mechanisms of cerebrovascular dysfunction in the elderly.
PMCID: PMC3514458  PMID: 23227137
Functional magnetic resonance imaging; FMRI; Functional neuroimaging; Verbal working memory; Cardiovascular disease; Heart disease; Ejection fraction; Cardiac output
16.  Neural correlates of inhibitory control in adult ADHD: Evidence from the Milwaukee longitudinal sample 
Psychiatry research  2011;194(2):119-129.
Only a few studies have investigated the neural substrate of response inhibition in adult ADHD using Stop-Signal and Go/No-Go tasks. Inconsistencies and methodological limitations in the existing literature have resulted in limited conclusions regarding underlying pathophysiology. We examined the neural basis of response inhibition in a group of adults diagnosed with ADHD in childhood and who continue to meet criteria for ADHD while addressing limitations present in earlier studies. Adults with ADHD (n=12) and controls (n=12) were recruited from an ongoing longitudinal study and were matched for age, IQ, and education. Individuals with comorbid conditions were excluded. Functional MRI was used to identify and compare the brain activation patterns during correct trials of a response inhibition task (Go/No-Go). Our results showed that the control group recruited a more extensive network of brain regions than the ADHD group during correct inhibition trials. Adults with ADHD showed reduced brain activation in the right frontal eye field, pre-supplementary motor area, left precentral gyrus, and the inferior parietal lobe bilaterally. During successful inhibition of an inappropriate response, adults with ADHD display reduced activation in fronto-parietal networks previously implicated in working memory, goal-oriented attention, and response selection. This profile of brain activation may be specifically associated with ADHD in adulthood.
PMCID: PMC3196255  PMID: 21937201
functional magnetic resonance imaging (fMRI); attention deficit hyperactivity disorder; response inhibition; adult psychiatry; attention; impulsivity
17.  Obesity Interacts with Cerebral Hypoperfusion to Exacerbate Cognitive Impairment in Older Adults with Heart Failure 
Cerebral hypoperfusion accompanies heart failure (HF) and is associated with reduced cognitive performance. Obesity is prevalent in persons with HF and is also a likely contributor to cognitive function, as it has been independently linked to cognitive impairment in healthy individuals. The current study examined the association between obesity and cognitive performance among older adults with HF and whether obesity interacts with cerebral hypoperfusion to exacerbate cognitive impairment.
Patients with HF (n = 99, 67.46 ± 11.36 years of age) completed neuropsychological testing and impedance cardiography. Cerebral blood flow velocity (CBF-V) measured by transcranial Doppler sonography quantified cerebral perfusion and body mass index (BMI) operationalized obesity.
A hierarchical regression analysis showed that lower CBF-V was associated with reduced performance on tests of attention/executive function and memory. Elevated BMI was independently associated with reduced attention/executive function and language test performance. Notably, a significant interaction between CBF-V and BMI indicated that a combination of hypoperfusion and high BMI has an especially adverse influence on attention/executive function in HF patients.
The current findings suggest that cerebral hypoperfusion and obesity interact to impair cognitive performance in persons with HF. These results may have important clinical implications, as HF patients who are at high risk for cerebral hypoperfusion may benefit from weight reduction.
PMCID: PMC3507266  PMID: 23272007
Body mass index; Cerebral perfusion; Cognitive function; Heart failure; Obesity
18.  Delayed reward discounting and addictive behavior: a meta-analysis 
Psychopharmacology  2011;216(3):305-321.
Delayed reward discounting (DRD) is a behavioral economic index of impulsivity and numerous studies have examined DRD in relation to addictive behavior. To synthesize the findings across the literature, the current review is a meta-analysis of studies comparing DRD between criterion groups exhibiting addictive behavior and control groups.
The meta-analysis sought to characterize the overall patterns of findings, systematic variability by sample and study type, and possible small study (publication) bias.
Literature reviews identified 310 candidate articles from which 46 studies reporting 64 comparisons were identified (total N=56,013).
From the total comparisons identified, a small magnitude effect was evident (d=.15; p<.00001) with very high heterogeneity of effect size. Based on systematic observed differences, large studies assessing DRD with a small number of self-report items were removed and an analysis of 57 comparisons (n=3,329) using equivalent methods and exhibiting acceptable heterogeneity revealed a medium magnitude effect (d=.58; p<.00001). Further analyses revealed significantly larger effect sizes for studies using clinical samples (d=.61) compared with studies using nonclinical samples (d=.45). Indices of small study bias among the various comparisons suggested varying levels of influence by unpublished findings, ranging from minimal to moderate.
These results provide strong evidence of greater DRD in individuals exhibiting addictive behavior in general and particularly in individuals who meet criteria for an addictive disorder. Implications for the assessment of DRD and research priorities are discussed.
PMCID: PMC3201846  PMID: 21373791
Delay discounting; Impulsivity; Addiction; Substance dependence; Alcohol; Tobacco; Nicotine; Stimulant; Opiate; Gambling; Meta-analysis
19.  The Additive Effects of Type-2 Diabetes on Cognitive Function in Older Adults with Heart Failure 
Background. Medical comorbidity has been theorized to contribute to cognitive impairment in heart failure (HF) patients. Specifically, type-2 diabetes mellitus (T2DM), a common coexisting condition among HF patients, may be an independent predictor of cognitive impairment. Nonetheless, the relationships between T2DM and other risk factors for cognitive impairment among persons with HF are unclear. Methods. Persons with HF (N = 169, 34.3% women, age 68.57 ± 10.28 years) completed neuropsychological testing within a framework of an ongoing study. History of T2DM, along with other medical characteristics, was ascertained through a review of participants' medical charts and self-report. Results. Many participants (34.9%) had a comorbid T2DM diagnosis. After adjustment for demographic and medical characteristics, HF patients with T2DM evidenced significantly greater impairments across multiple cognitive domains than HF patients without T2DM: λ = .92, F(5, 156) = 2.82, P = .018. Post hoc tests revealed significant associations between T2DM and attention (P = .003), executive function (P = .032), and motor functioning (P = .008). Conclusion. The findings suggest additive contributions of T2DM and HF to impairments in attention, executive function, and motor function. Future work is needed to elucidate the mechanisms by which T2DM exacerbates cognitive impairment in HF.
PMCID: PMC3371669  PMID: 22701196
Patients with amnestic mild cognitive impairment (MCI) demonstrate decline in everyday function. In this study, we investigated whether whole brain atrophy and apolipoprotein E (APOE) genotype are associated with the rate of functional decline in MCI.
Participants were 164 healthy controls, 258 MCI patients, and 103 patients with mild Alzheimer’s disease (AD), enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). They underwent brain MRI scans, APOE genotyping, and completed up to 6 biannual Functional Activities Questionnaire (FAQ) assessments. Random effects regressions were used to examine trajectories of decline in FAQ across diagnostic groups, and to test the effects of ventricle-to-brain ratio (VBR) and APOE genotype on FAQ decline among MCI patients.
Rate of decline in FAQ among MCI patients was intermediate between that of controls and mild AD patients. Patients with MCI who converted to mild AD declined faster than those who remained stable. Among MCI patients, increased VBR and possession of any APOE ε4 allele were associated with faster rate of decline in FAQ. In addition, there was a significant VBR by APOE ε4 interaction such that patients who were APOE ε4 positive and had increased atrophy experienced the fastest decline in FAQ.
Functional decline occurs in MCI, particularly among patients who progress to mild AD. Brain atrophy and APOE ε4 positivity are associated with such declines, and patients who have elevated brain atrophy and are APOE ε4 positive are at greatest risk of functional degradation. These findings highlight the value of genetic and volumetric MRI information as predictors of functional decline, and thus disease progression, in MCI.
PMCID: PMC2950092  PMID: 20813341
MRI; Brain atrophy; APOE ε4; activities of daily living; MCI
21.  Blood Pressure and Cognitive Function in Older adults with Cardiovascular Disease 
Past studies link elevated blood pressure (BP) and BP variability to adverse neurocognitive changes in community samples. However, little is known about the relationship between BP indices and cognitive function in older CVD patients.
A total of 99 older adults with CVD completed a comprehensive neuropsychological test battery. Resting BP measurements were collected every 10 minutes for two hours during a separate cardiac assessment. Five BP indices were generated: average and standard deviation of systolic blood pressure, average and standard deviation of diastolic blood pressure, and a function of systolic variability and average diastolic pressure. We examined the relationship between these BP indices and cognitive function.
Partial correlation adjusting for age and education revealed that the function of systolic variability and average diastolic pressure (systolic BP standard deviation divided by the average diastolic BP) was most closely related to test performance, showing significant associations to both Learning/Memory (r = 0.25) and Language functioning (r = 0.22). Systolic BP indices were also related to Language functioning (SBP avg, r = 0.22; SBP sd, r = 0.25), though diastolic BP indices were unrelated to performance in any cognitive domain.
The current findings indicate that BP is modestly related to cognitive function in older CVD patients. Contrary to expectations, greater BP variability was associated with better, not poorer, cognitive test performance. Such findings suggest that the relationship between BP and cognitive function is more complicated than typically hypothesized and requires further examination.
PMCID: PMC2899480  PMID: 19916851
Blood Pressure; Cognitive Function; Heart Disease
22.  Neuroanatomical Correlates of Malingered Memory Impairment: Event-related fMRI of Deception on a Recognition Memory Task 
Brain injury : [BI]  2008;22(6):481-489.
Primary objective
Event-related, functional magnetic resonance imaging (fMRI) data were acquired in healthy participants during purposefully malingered and normal recognition memory performances to evaluate the neural substrates of feigned memory impairment.
Methods and procedures
Pairwise, between-condition contrasts of neural activity associated with discrete recognition memory responses were conducted to isolate dissociable neural activity between normal and malingered responding while simultaneously controlling for shared stimulus familiarity and novelty effects. Response timing characteristics were also examined for any association with observed between-condition activity differences.
Outcomes and results
Malingered recognition memory errors, regardless of type, were associated with inferior parietal and superior temporal activity relative to normal performance, while feigned recognition target misses produced additional dorsomedial frontal activation and feigned foil false alarms activated bilateral ventrolateral frontal regions. Malingered response times were associated with activity in the dorsomedial frontal, temporal, and inferior parietal regions. Normal memory responses were associated with greater inferior occipitotemporal and dorsomedial parietal activity, suggesting greater reliance upon visual/attentional networks for proper task performance.
The neural substrates subserving feigned recognition memory deficits are influenced by response demand and error type, producing differential activation of cortical regions important to complex visual processing, executive control, response planning, and working memory processes.
PMCID: PMC2875084  PMID: 18465389
fMRI; MRI, Functional; forensic psychiatry; deception; malingering; Deficits, Memory
23.  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.
PMCID: PMC2739675  PMID: 18608677
Cardiovascular disease; Cerebrovascular disease; White matter hyperintensities; Magnetic resonance imaging; Flow mediated dilatation intima lamina thickness; Blood pressure variability; Cardiac output; Cognition; Attention; Executive function; Psychomotor function
24.  Sustained attention is associated with left ventricular ejection fraction in older adults with heart disease 
Poor cardiac pumping efficiency has shown to lead to cognitive impairments in patients with cardiovascular disease (CVD). The current study examined the relationship between left ventricular ejection fraction and sustained attention and inhibitory processes measured by the Adaptive Rate Continuous Performance Task and the Go/No-go test. Participants were 67 older outpatients (age 68.5 ± 7.4) with a range of CVD. Associations between cognition and ejection fraction were examined via linear regression analysis. Results were consistent with the hypothesis that lower ejection fraction is significantly associated with decrements in sustained attention and vigilance. Overall, the results provide support for the hypothesis that a change in cardiac pumping leads to decrements in some aspects of attention; however, inhibitory processes are relatively spared.
PMCID: PMC2719846  PMID: 19128537
Cardiovascular disease; Ejection fraction; Sustained attention; Vigilance; ARCPT; Go/No-go
25.  Carotid Artery Intima-Media Thickness and Cognition in Cardiovascular Disease 
International journal of cardiology  2006;121(2):148-154.
Increased carotid artery intima-media thickness (IMT) is a non-invasive marker of systemic arterial disease. Increased IMT has been associated with atherosclerosis, abnormal arterial mechanics, myocardial infarction, and stroke. Given evidence of a relationship between cardiovascular health and attention-executive-psychomotor functioning, the purpose of this study was to examine IMT in relation to neuropsychological test performance in patients with a variety of cardiovascular diagnoses.
One hundred and nine participants, ages 55 to 85, underwent neuropsychological assessment and B-mode ultrasound of the left common carotid artery. IMT was calculated using an automated algorithm based on a validated edge-detection technique. The relationship between IMT and measures of language, memory, visual-spatial abilities and attention-executive-psychomotor functioning was modeled using hierarchical linear regression analyses adjusted for age, education, sex, cardiovascular risk, current systolic blood pressure, and history of coronary artery disease (CAD).
Increased IMT was associated with significantly lower performance in the attention-executive-psychomotor domain (IMT beta = −0.26, p < .01), independent of age, education, sex, cardiovascular risk, current systolic blood pressure, and CAD (F(10,100) = 3.61, p < .001). IMT was not significantly related to language, memory, or visual-spatial abilities.
Our findings suggest that, in patients with cardiovascular disease, IMT may be associated with the integrity of frontal subcortical networks responsible for attention-executive-psychomotor performance. Future studies are needed to clarify the mechanisms by which IMT affects cognition and examine potential interactions between increased IMT and other measures of cardiovascular health such as blood pressure variability, cardiac systolic performance, and systemic perfusion.
PMCID: PMC2042538  PMID: 17196687
Cognition; Cardiovascular Diseases; Carotid Arteries; Atherosclerosis; IMT; B-mode Ultrasound

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