Obesity and cognitive dysfunction in heart failure: the role of hypertension, type 2 diabetes, and physical fitness.

BACKGROUND: Cognitive impairment is common in heart failure. Obesity is a known risk factor for cognitive dysfunction in heart failure, though the mechanisms remain unclear. Obesity increases risk for conditions like hypertension and type 2 diabetes mellitus (T2DM) as well as poor fitness levels, and this may serve as one possible pathway accounting for association between obesity and cognitive dysfunction. AIMS: We used structural equation modeling to test whether the combination of hypertension, T2DM, and reduced fitness mediate the association between obesity and cognitive dysfunction. METHODS: Two hundred heart failure patients completed neuropsychological testing and a physical fitness assessment. Hypertension and T2DM were ascertained via self-report and medical records. Body mass index (BMI) was calculated. RESULTS: Forty-three percent of the sample was obese. Hypertension (70%) and T2DM (36%) were common, and fitness levels were reduced. The structural equation model with these factors as mediators between BMI and cognitive function demonstrated excellent fit (comparative fit index = 0.98; root mean-square error of approximations = 0.03). Higher BMI correlated with hypertension, T2DM, and poorer fitness. Each of these factors predicted worse cognition. Models that isolated medical comorbidities and physical fitness as the mediator were weaker than the full model. CONCLUSIONS: Increased risk for medical comorbidities and reduced fitness levels helped to explain the negative effects of obesity on cognitive dysfunction in heart failure. Prospective studies should confirm this pattern and examine how weight loss benefits cognitive function in heart failure.

Better adherence to treatment recommendations in heart failure predicts improved cognitive function at a one-year follow-up.

INTRODUCTION: Treatment nonadherence is common in heart failure (HF) and is associated with poor health outcomes in this population. Recent cross-sectional work in heart failure and past work in other medical populations suggest that cognitive function is a key determinant of a patient's ability to adhere to treatment recommendations. However, it is also possible that treatment adherence is an important modifier and predictor of cognitive function, though no study has examined this possibility, and we sought to do so in a sample of heart failure patients. METHOD: A total of 115 patients with heart failure self-reported adherence to treatment recommendations. The Modified Mini Mental State Examination (3MS), Trail Making Test Parts A and B, and the California Verbal Learning Test-II (CVLT-II) assessed cognitive function. These procedures were performed at baseline and a 12-month follow-up. RESULTS: Global cognition and memory abilities improved over the 12-month period. Regression analyses controlling for baseline and medical and demographic factors showed that better baseline treatment adherence predicted improved 12-month performances on the 3MS and CVLT-II. Adherence to medication and diet regimens and smoking abstinence emerged as the most important contributors. CONCLUSIONS: Better treatment adherence predicted improved cognition one year later in HF. Prospective studies that utilize objective assessments of treatment adherence are needed to confirm our findings and examine whether improved treatment adherence preserves cognitive function in heart failure.

Cardiac rehabilitation is associated with lasting improvements in cognitive function in older adults with heart failure.

OBJECTIVE: Heart failure (HF) is a known risk factor for cognitive impairment. Cardiac rehabilitation (CR) may attenuate poor neurocognitive outcomes in HF via improved physical fitness--a significant promoter of cognitive function. However, no study has examined the possible acute and lasting benefits of CR on cognitive function in persons with HF. METHODS AND RESULTS: Fifty-two patients with HF completed a 12-week Phase II CR program. All participants were administered neuropsychological testing and completed a brief physical fitness assessment at baseline, completion of CR (i.e. 12 weeks), and 12-month follow-up. Repeated measures analyses showed a significant time effect for both attention/executive function and memory (P < 0.05). Attention/executive function performance increased from baseline to 12 weeks and these gains remained up to 12 months; memory was unchanged from baseline to 12 weeks, but then improved between the 12-week and 12-month time points. Physical fitness improved from baseline to 12 weeks and these benefits were maintained 12 months later. Changes in physical fitness and cognitive function over time did not reach a statistically significant association, though poorer physical fitness was associated with decreased cognitive performance at the baseline and 12-month time points. CONCLUSIONS: CR is associated with both acute and lasting cognitive benefits in patients with HF. Prospective studies with extended follow-ups are needed to clarify the mechanisms that underpin cognitive improvements following CR (e.g., improved cerebral perfusion) and whether CR can ultimately reduce risk for cognitive decline and conditions like Alzheimer's disease in HF.

Decreased physical activity predicts cognitive dysfunction and reduced cerebral blood flow in heart failure.

OBJECTIVE: Cognitive impairment in heart failure (HF) is believed to result from brain hypoperfusion subsequent to cardiac dysfunction. Physical inactivity is prevalent in HF and correlated with reduced cardiac and cognitive function. Yet, no longitudinal studies have examined the neurocognitive effects of physical inactivity in HF. The current study examined whether reduced physical activity increases risk for cognitive impairment and brain hypoperfusion over time in HF. METHODS: At baseline and 12 months later, 65 HF patients underwent neuropsychological testing, transcranial Doppler ultrasonography, and were asked to wear an accelerometer for seven days. RESULTS: Lower baseline step count and less time spent in moderate free-living activity best predicted worse attention/executive function and decreased cerebral perfusion at the 12-month follow-up. Decreased baseline cerebral perfusion also emerged as a strong predictor of poorer 12-month attention/executive function. CONCLUSIONS: Lower physical activity predicted worse cognition and cerebral perfusion 12 months later in HF. Physical inactivity in HF may contribute to cognitive impairment and exacerbate risk for conditions such as Alzheimer's disease. Larger studies are needed to elucidate the mechanisms by which physical inactivity leads to cognitive dysfunction in HF, including clarification of the role of cerebral hypoperfusion.

Greater physical activity is associated with better cognitive function in heart failure.

OBJECTIVE: Nearly 6 million Americans have heart failure (HF), up to 80% of which exhibit cognitive deficits on testing. Physical inactivity is common in HF, yet little is known about the possible contribution of physical inactivity to cognitive dysfunction in this population. METHOD: Older adults with HF (N = 93; Mage = 68.5 years, 33.7% women) completed neuropsychological testing, as well as cardiac and physical activity assessment as part of a larger protocol. HF severity was measured via impedance cardiography. Physical activity was assessed via an Actigraph accelerometer and operationalized using daily step count and time engaged in moderate-vigorous activity (minutes/day). RESULTS: Linear regression analyses controlling for sex, high blood pressure, diabetes, depressive symptomatology, and HF severity showed that greater physical activity (both step count and minutes spent in moderate-vigorous activity) was associated with better executive function/attention, processing speed, and scores on a screening measure of cognition. CONCLUSIONS: These findings indicate that physical activity is an independent predictor of cognitive function in persons with HF. Future work is needed to clarify the mechanisms by which physical activity benefits cognitive function in HF and determine whether interventions to promote physical activity can attenuate cognitive decline over time.

Reduced cerebral perfusion predicts greater depressive symptoms and cognitive dysfunction at a 1-year follow-up in patients with heart failure.

OBJECTIVE: Cerebral hypoperfusion is common in heart failure (HF) and believed to underlie poor neurocognitive outcomes in this population. Up to 42% of HF patients also exhibit depressive symptomatology that may stem from reduced cerebral blood flow. However, no study has examined this possibility or whether reduced brain perfusion increases risk for future cognitive dysfunction in older adults with HF. METHODS: One hundred HF patients underwent transcranial Doppler ultrasonagraphy to quantify global cerebral blood flow velocity (CBF-V) and were administered a cognitive test battery to assess global cognition, attention/executive function, and memory abilities. All participants then completed the Beck Depression Inventory-II to assess depressive symptomatology. These procedures were performed at baseline and at 12-month follow-up. RESULTS: Repeated measures revealed that CBF-V declined over the 12-month period. Regression analyses showed that reduced baseline CBF-V predicted worse performances in attention/executive function (p < 0.05 for all) and a trend for memory (p = 0.09) in addition to greater depressive symptomatology (p < 0.05) at the 12-month follow-up, even after controlling for baseline factors and medical and demographic variables. CONCLUSIONS: Cerebral perfusion declined over time and was associated with poorer cognitive function and greater depressive symptoms at a 1-year follow-up in HF. Prospective studies with long-term follow-ups that employ neuroimaging are needed to examine whether cognitive dysfunction and depression in HF stem from the adverse effects of cerebral hypoperfusion on the cerebral structure.

Reduced cognitive function predicts functional decline in patients with heart failure over 12 months.

BACKGROUND: Occurrences of impaired activities of daily living (ADL) are common in heart failure (HF) patients and contribute to the elevated mortality and hospitalization rates in this population. Cognitive impairment is also prevalent in HF, though its ability to predict functional decline over time is unknown. AIMS: This study examined the longitudinal pattern of activities of daily living (ADL) in HF persons and whether reduced baseline cognitive status predicts functional decline in this population. METHODS: Altogether 110 persons with HF completed the Lawton-Brody Instrumental Activities of Daily Living (IADL) scale and were administered the Modified Mini-Mental Status Examination (3MS) at baseline and a 12-month follow-up. Three composite scores were derived from the Lawton-Brody scale, including total, instrumental, and basic ADL. RESULTS: HF patients reported high rates of baseline impairments in instrumental ADL, including shopping, food preparation, housekeeping duties, laundry, among others. Repeated measures analyses showed significant declines in total and instrumental ADL from baseline to the 12-month follow-up in HF (p<0.05). Hierarchical regression analyses showed that poorer baseline performance on the 3MS predicted worse total ADL performance at 12-months (ß=0.15, p=0.049), including greater dependence in shopping, driving, feeding, and physical ambulation (p<0.05 for all). CONCLUSION: The current results show that HF patients report significant functional decline over a 12-month period and brief cognitive tests can identify those patients at highest risk for decline. If replicated, such findings encourage the use of cognitive screening measures to identify HF patients most likely to require assistance with ADL tasks.

Executive dysfunction is independently associated with reduced functional independence in heart failure.

AIMS AND OBJECTIVES: To examine the independent association between executive function with instrumental activities of daily living and health behaviours in older adults with heart failure. BACKGROUND: Executive function is an important contributor to functional independence as it consists of cognitive processes needed for decision-making, planning, organising and behavioural monitoring. Impairment in this domain is common in heart failure patients and associated with reduced performance of instrumental activities of daily living in many medical and neurological populations. However, the contribution of executive functions to functional independence and healthy lifestyle choices in heart failure patients has not been fully examined. DESIGN: Cross-sectional analyses. METHODS: One hundred and seventy-five heart failure patients completed a neuropsychological battery and echocardiogram. Participants also completed the Lawton-Brody Instrumental Activities of Daily Living Scale and reported current cigarette use. RESULTS: Hierarchical regressions revealed that reduced executive function was independently associated with worse instrumental activity of daily living performance with a specific association for decreased ability to manage medications. Partial correlations showed that executive dysfunction was associated with current cigarette use. CONCLUSIONS: Our findings suggest that executive dysfunction is associated with poorer functional independence and contributes to unhealthy behaviours in heart failure. Future studies should examine whether heart failure patients benefit from formal organisation schema (i.e. pill organisers) to maintain independence. RELEVANCE TO CLINICAL PRACTICE: Screening of executive function in heart failure patients may provide key insight into their ability to perform daily tasks, including the management of treatment recommendations.

Cognitive performance in older adults with stable heart failure: longitudinal evidence for stability and improvement.

Cognitive impairment is prevalent in heart failure (HF), though substantial variability in the pattern of cognitive impairment is found across studies. To clarify the nature of cognitive impairment in HF, we examined longitudinal trajectories across multiple domains of cognition in HF patients using latent growth class modeling. 115 HF patients completed a neuropsychological battery at baseline, 3-months and 12-months. Participants also completed the Beck Depression Inventory-II (BDI-II). Latent class growth analyses revealed a three-class model for attention/executive function, four-class model for memory, and a three-class model for language. The slope for attention/executive function and language remained stable, while improvements were noted in memory performance. Education and BDI-II significantly predicted the intercept for attention/executive function and language abilities. The BDI-II also predicted baseline memory. The current findings suggest that multiple performance-based classes of neuropsychological test performance exist within cognitive domains, though case-controlled prospective studies with extended follow-ups are needed to fully elucidate changes and predictors of cognitive function in HF.

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.

The interactive effects of cerebral perfusion and depression on cognitive function in older adults with heart failure.

OBJECTIVE: Depression is common among persons with heart failure (HF) and has been linked to cognitive impairment in this population. The mechanisms of this relationship are unclear, and the current study examined whether cerebral perfusion moderates the association between depressive symptoms and cognitive impairment in patients with HF. METHODS: Persons with HF (n = 89; mean [standard deviation] age = 67.61 [11.78] years) completed neuropsychological testing and impedance cardiography. Depressive symptoms were assessed using the Beck Depression Inventory II, and transcranial Doppler was used to quantify cerebral perfusion. RESULTS: Depression was associated with reduced performance on tasks assessing attention/executive function (r = -0.28), language (r = -0.0.30), and motor function (r = -0.28) in unadjusted models (p values <.05). Global cerebral blood flow was correlated with memory performance (r = 0.22, p = .040) but not with other tasks. A moderation analysis was performed using hierarchical regression models for attention/executive function, memory, language, and motor function. For each model, medical and demographic characteristics were entered into the initial blocks, and the final block consisted of an interaction term between global cerebral blood flow velocity and the Beck Depression Inventory II. The interaction between greater depressive symptoms and decreased global cerebral blood flow velocity was associated with greater deficits in attention/executive function (ß = .32, ΔR(2) = 0.08, p = .003). CONCLUSIONS: Depressive symptoms and cerebral hypoperfusion interact to adversely affect cognitive performance in older adults with HF. Longitudinal studies are needed to clarify this relationship and elucidate subsequent neuropathology.

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.

Dietary habits moderate the association between heart failure and cognitive impairment.

Cognitive impairment is common in heart failure patients. Poor dietary habits are associated with reduced neurocognitive function in other medical populations, including diabetes and Alzheimer's disease. This study examined whether dietary habits help moderate the relationship between heart failure severity and cognitive function. A total of 152 persons with heart failure completed neuropsychological testing and a fitness assessment. Dietary habits were assessed using the Starting the Conversation-Diet questionnaire, a nutrition measure suggested for use in primary care settings. Moderation analyses showed that better dietary habits attenuated the adverse impact of heart failure severity on frontal functioning (b = 1.28, p < 0.05). Follow-up analyses revealed consumption of foods high in sodium was associated with reduced cognitive function (p < 0.05). This study suggests dietary habits can moderate the association between heart failure and performance on tests of attention and executive function. Longitudinal studies are needed to confirm and clarify the mechanisms for our findings.

Cardiovascular fitness associated with cognitive performance in heart failure patients enrolled in cardiac rehabilitation.

BACKGROUND: Reduced cognitive function is common in persons with heart failure (HF). Cardiovascular fitness is a known contributor to cognitive function in many patient populations, but has only been linked to cognition based on estimates of fitness in HF. The current study examined the relationship between fitness as measured by metabolic equivalents (METs) from a standardized stress test and cognition in persons with HF, as well as the validity of office-based predictors of fitness in this population. METHODS: Forty-one HF patients enrolled in cardiac rehabilitation completed a standardized exercise stress test protocol, a brief neuropsychological battery, the 2-minute step test (2MST), and a series of medical history and self-report questionnaires. RESULTS: Maximum METs from stress testing demonstrated incremental predictive validity for attention (ß = .41, p = .03), executive function (ß = .37, p = .04), and memory domains (ß = .46, p = .04). Partial correlations accounting for key medical and demographic characteristics revealed greater METs was associated with the 2MST (r(32) = .41, p = .02) but not with the Duke Activity Status Index (DASI) (r(32) = .24, p = .17). CONCLUSION: The current findings indicate that better fitness levels measured by METs is independently associated with better cognitive function in older adults with HF. Results also showed that METs was closely associated with one office-based measure of fitness (2MST), but not another (DASI). Prospective studies are needed to clarify the mechanisms linking fitness and cognitive function in HF.

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.

Apathy and cognitive test performance in patients undergoing cardiac testing.

Background. Psychiatric comorbidity is common in patients with cardiovascular disease, with the literature indicating that this population may be at risk for apathy. The current study examined the prevalence of apathy in patients with cardiovascular disease and its relation to aspects of cognitive function. Methods. 123 participants from an outpatient cardiology clinic completed a brief neuropsychological battery, a cardiac stress test, and demographic information, medical history, and depression symptomatology self-report measures. Participants also completed the Apathy Evaluation Scale to quantify apathy. Results. These subjects reported limited levels of apathy and depression. Increased depressive symptomatology, history of heart attack, and metabolic equivalents were significantly correlated with apathy (P < 0.05). Partial correlations adjusting for these factors revealed significant correlations between behavioral apathy and a measure of executive function and the other apathy subscale with a measure of attention. Conclusion. Findings revealed that apathy was not prevalent in this sample though associated with medical variables. Apathy was largely unrelated to cognitive function. This pattern may be a result of the mild levels of cardiovascular disease and cognitive dysfunction in the current sample. Future studies in samples with severe cardiovascular disease or neuropsychological impairment may provide insight into these associations.

Depressive symptomatology, exercise adherence, and fitness are associated with reduced cognitive performance in heart failure.

OBJECTIVE: Depression is common in heart failure (HF) and associated with reduced cognitive function. The current study used structrual equation modeling to examine whether depression adversely impacts cognitive function in HF through its adverse affects on exercise adherence and cardiovascular fitness. METHOD: 158 HF patients completed neuropsychological testing, physical fitness test, Beck depression inventory-II (BDI-II), and measures assessing exercise adherence and physical exertion. RESULTS: The model demonstrated excellent model fit and increased scores on the BDI-II negatively affected exercise adherence and cardiovascular fitness. There was a strong inverse association between cardiovascular fitness and cognitive function. Sobel test showed a significant indirect pathway between the BDI-II and cognitive function through cardiovascular fitness. DISCUSSION: This study suggests depression in HF may adversely impact cognitive function through reduced cardiovascular fitness. Prospective studies are needed to determine whether treatment of depression can lead to better lifestyle behaviors and ultimately improve neurocognitive outcomes in HF.

The adverse impact of type 2 diabetes on brain volume in heart failure.

OBJECTIVE: 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. METHODS: Seventy-five older adults with HF underwent an 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). RESULTS: Approximately 30% of HF patients had a comorbid T2DM diagnosis. A series of multivariate analyses of covariance (MANCOVAs) 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 that 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. CONCLUSIONS: 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.