Cognitive Disorders and Dementia in CKD

Age-related Changes in Renal Arterio-Arteriolosclerosis in Kidney Disease: Renal Biopsy-based Study

Epidemiologic data suggest that individuals at all stages of chronic kidney disease (CKD) have a higher risk of developing neuropsychiatric disorders, cognitive impairment, and dementia. This risk is generally explained by the high prevalence of both symptomatic and subclinical ischemic cerebrovascular lesions. However, other potential mechanisms, including cytokine/chemokine release, production of reactive oxygen species (ROS), circulating and local formation of trophic factors and of renin-angiotensin system (RAS) molecules, could also be involved, especially in the absence of obvious cerebrovascular disease. In this review, we discuss experimental and clinical evidence for the role of these mechanisms in kidney-brain cross-talk. In addition, we hypothesize potential pathways for the interactions between kidney and brain and their pathophysiological role in neuropsychiatric and cognitive changes found in patients with CKD. Understanding the pathophysiologic interactions between renal impairment and brain function is important in order to minimize the risk for future cognitive impairment and to develop new strategies for innovative pharmacological treatment.

With successful antiretroviral therapy, patients infected with the human immunodeficiency virus (HIV) are living longer; however, recent reports suggest increased rates of coronary heart disease (CHD) among HIV-infected patients,1 and cardiovascular disease has become an important cause of morbidity and mortality in this population.2 Increased CHD rates in the HIV population may relate to traditional risk factors, including advancing age, higher smoking rates, dyslipidemia, insulin resistance, and impaired glucose tolerance. Cardiovascular disease may also be due to nontraditional factors, including changes in body composition with loss of subcutaneous fat and/or accumulation of visceral fat in some patients, inflammation, and direct effects of the virus on the vasculature, as well as to direct effects of specific antiretroviral drugs. Important questions remain as to the pathogenesis, detection, and treatment of cardiovascular disease and related risk factors in HIV-infected patients. These questions concern, among other things, the design of adequate trials to determine CHD incidence and the utility of existing CHD guidelines for screening, prevention, treatment, and risk stratification. To ascertain the state of the science with respect to these and related questions, a multidisciplinary conference with interested HIV specialists, cardiologists, endocrinologists, primary care physicians, National Institutes of Health representatives, and patient advocates was convened June 28–30, 2007, in Chicago, Ill, and chaired by Drs Steven Grinspoon and Robert Eckel. The discussions focused on 6 areas of interest, each with its own working group, including the following: (1) the contribution of metabolic and anthropometric abnormalities to cardiovascular disease risk factors (chaired by Drs Carl Grunfeld and Donald Kotler); (2) the epidemiological evidence for cardiovascular disease and its relationship to highly active antiretroviral therapy (HAART; chaired by Drs Judy Currier and Jens Lundgren); (3) the effects of HIV infection and antiretroviral therapy on the heart and vasculature (chaired by Drs Michael Dube …

Complications of Progression of CKD

Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.

Reverters from PD-MCI to cognitively intact are at risk for future cognitive impairment: Analysis of the PPMI cohort

Trends in Risk Factor Prevalence and Incidence of Acute Myocardial Infarction in Young Adults

Exercise improves cardiovascular health, but high-volume high-intensity exercise is associated with increased coronary artery calcification (CAC). We aimed to identify predictors of CAC in athletes. We assessed the association of traditional and non-traditional cardiovascular risk factors with CAC using linear and logistic regression. A total of 289 male athletes from the MARC-2 study were included, with a median age of 60 (Q1-3 56-66) years, lifelong weekly training load of 26 (17-35) metabolic equivalent of task hours, body mass index of 24.5 (22.9-26.6) kg/m2, systolic blood pressure of 139 ± 18 mmHg, and reported 0.0 (0.0-8.0) smoking pack years. Thirty-one per cent had a CAC score > 100 and 13% > 400. Among traditional cardiovascular risk factors, higher age, systolic blood pressure, smoking pack years, and family history of coronary artery disease independently predicted greater CAC scores, while body mass index, low-density lipoprotein cholesterol, and diabetes mellitus did not. Among non-traditional risk factors, higher training loads, serum phosphate, and lower adjusted energy intake and fat percentage of energy intake independently predicted greater CAC scores. The full model with all traditional and non-traditional risk factors had higher accuracy in predicting CAC > 100 [receiver operating characteristic area under the curve 0.76, 95% confidence interval (0.70-0.82)] and CAC > 400 [0.85 (0.77-0.92)] than traditional cardiovascular risk factors alone [0.72 (0.65-0.78), P = 0.012, and 0.81 (0.74-0.90), P = 0.038, respectively]. Non-traditional risk factors, including training load, dietary patterns, and serum phosphate, were independently associated with CAC in aging male athletes. Prediction accuracy for CAC increased when including these variables in a prediction model with traditional risk factors.

Despite women having fewer traditional risk factors (eg, hypertension, diabetes), strokes are more common in women than men aged ≤45 years. This study examined the contributions of traditional and nontraditional risk factors (eg, migraine, thrombophilia) in the development of strokes among young adults. This retrospective case-control study used Colorado's All Payer Claims Database (2012-2019). We identified index stroke events in young adults (aged 18-55 years), matched 1:3 to stroke-free controls, by (1) sex, (2) age±2 years, (3) insurance type, and (4) prestroke period. All traditional and nontraditional risk factors were identified from enrollment until a stroke or proxy-stroke date (defined as the prestroke period). Conditional logistic regression models stratified by sex and age group first assessed the association of stroke with counts of risk factors by type and then computed their individual and aggregated population attributable risks. We included 2618 cases (52% women; 73.3% ischemic strokes) and 7827 controls. Each additional traditional and nontraditional risk factors were associated with an increased risk of stroke in all sex and age groups. In adults aged 18 to 34 years, more strokes were associated with nontraditional (population attributable risk: 31.4% men and 42.7% women) than traditional risk factors (25.3% men and 33.3% women). The contribution of nontraditional risk factors declined with age (19.4% men and 27.9% women aged 45-55 years). The contribution of traditional risk factors peaked among patients aged 35 to 44 years (32.8% men and 39.7% women). Hypertension was the most important traditional risk factor and increased in contribution with age (population attributable risk: 27.8% men and 26.7% women aged 45 to 55 years). Migraine was the most important nontraditional risk factor and decreased in contribution with age (population attributable risk: 20.1% men and 34.5% women aged 18-35 years). Nontraditional risk factors were as important as traditional risk factors in the development of strokes for both young men and women and have a stronger association with the development of strokes in adults younger than 35 years of age.

Chronic kidney disease (CKD) is a growing public health problem. The incidence of kidney failure is rising in all age groups but particularly in older adults. Individuals in all stages of CKD are at higher risk for development of cognitive impairment and this may be a major determinant in their quality of life. Furthermore, cognitive impairment is associated with an increased risk of death in dialysis patients. Cerebrovascular disease is a strong risk factor for development of cognitive impairment and vascular disease is a more likely cause of cognitive impairment than Alzheimer’s disease in patients with CKD. Both traditional and nontraditional vascular risk factors are more common in CKD and dialysis patients may also be at risk for cognitive impairment via nonvascular risk factors and the hemodialysis procedure itself. Unfortunately, because risk factors for cognitive impairment in CKD have not been thoroughly ascertained, evaluation of potential treatments has been limited. Given the high prevalence of cognitive impairment in all stages of CKD, additional studies are needed to evaluate potential risk factors and treatments in this vulnerable population.

Brain and behavior in the Framingham Heart Study

INTRODUCTIONNeighborhood‐level socioeconomic status (nSES) is associated with risk for cognitive impairment, but prior studies assessed nSES within an individual's own residential area without considering the distribution of nSES among adjacent areas.METHODSUsing up to 14 years of data from the Study of Women's Health Across the Nation (N = 1391, mean age = 54), we examined whether geographic clustering of concentrated neighborhood poverty was associated with cognitive decline over midlife.RESULTSGreater neighborhood concentrated poverty was associated with faster decline in episodic memory but not in processing speed or working memory. Living in high concentrated poverty areas was linked to a 7% episodic memory decline per decade (both immediate and delayed recall), with Black women experiencing the steepest decline at 10% per decade (delayed recall).DISCUSSIONWomen living in concentrated poverty areas exhibited accelerated decline in episodic memory during midlife. Neighborhood concentrated poverty may impact risk for future cognitive impairment and ADRD.HighlightsLiving in concentrated poverty areas predicted a more rapid episodic memory decline.This pattern was most pronounced among Black women.The cohort was a racially/ethnically diverse cohort of midlife women across the US.Neighborhood concentrated poverty may contribute to the risk of ADRD.

Nontraditional Risk Factors as Mediators of Racial Differences in Diabetes Risk

Cardiovascular and cerebrovascular diseases are prevalent in individuals with type 2 diabetes (T2D). Among people with T2D aged over 70 years, up to 45% might have cognitive dysfunction. Cardiorespiratory fitness (V˙O2max) correlates with cognitive performances in healthy younger and older adults, and individuals with cardiovascular diseases (CVD). The relationship between cognitive performances, V˙O2max, cardiac output and cerebral oxygenation/perfusion responses during exercise has not been studied in patients with T2D. Studying cardiac hemodynamics and cerebrovascular responses during a maximal cardiopulmonary exercise test (CPET) and during the recovery phase, as well as studying their relationship with cognitive performances could be useful to detect patients at greater risk of future cognitive impairment. Purposes: (1) to compare cerebral oxygenation/perfusion during a CPET and during its post-exercise period (recovery); (2) to compare cognitive performances in patients with T2D to those in healthy controls; and (3) to examine if V˙O2max, maximal cardiac output and cerebral oxygenation/perfusion are associated with cognitive function in individuals with T2D and healthy controls. Nineteen patients with T2D (61.9 ± 7 years old) and 22 healthy controls (HC) (61.8 ± 10 years old) were evaluated on the following: a CPET test with impedance cardiography and cerebral oxygenation/perfusion using a near-infrared spectroscopy. Prior to the CPET, the cognitive performance assessment was performed, targeting: short-term and working memory, processing speed, executive functions, and long-term verbal memory. Patients with T2D had lower V˙O2max values compared to HC (34.5 ± 5.6 vs. 46.4 ± 7.6 mL/kg fat free mass/min; p < 0.001). Compared to HC, patients with T2D showed lower maximal cardiac index (6.27 ± 2.09 vs. 8.70 ± 1.09 L/min/m2, p < 0.05) and higher values of systemic vascular resistance index (826.21 ± 308.21 vs. 583.35 ± 90.36 Dyn·s/cm5·m2) and systolic blood pressure at maximal exercise (204.94 ± 26.21 vs. 183.61 ± 19.09 mmHg, p = 0.005). Cerebral HHb during the 1st and 2nd min of recovery was significantly higher in HC compared to T2D (p < 0.05). Executive functions performance (Z score) was significantly lower in patients with T2D compared to HC (-0.18 ± 0.7 vs. -0.40 ± 0.60, p = 0.016). Processing speed, working and verbal memory performances were similar in both groups. Brain tHb during exercise and recovery (-0.50, -0.68, p < 0.05), and O2Hb during recovery (-0.68, p < 0.05) only negatively correlated with executive functions performance in patients with T2D (lower tHb values associated with longer response times, indicating a lower performance). In addition to reduced V˙O2max, cardiac index and elevated vascular resistance, patients with T2D showed reduced cerebral hemoglobin (O2Hb and HHb) during early recovery (0-2 min) after the CPET, and lower performances in executive functions compared to healthy controls. Cerebrovascular responses to the CPET and during the recovery phase could be a biological marker of cognitive impairment in T2D.

BackgroundIt is known that patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are characterized with a variability of traditional and non-traditional cardiovascular risk factors for the early development...