Cytokines are associated with longitudinal changes in cognitive performance among urban adults.

BACKGROUND: Chronic systemic inflammation has been positively associated with structural and functional brain changes representing early markers of Alzheimer's Disease (AD) and cognitive decline. The current study examined associations between systemic inflammation and cognitive performance among African-Americans and Whites urban adults. METHODS: Participants were selected from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (2004-2013, baseline age: 30-64 y, mean ±â€¯SD follow-up time of 4.64 ±â€¯0.93 y, N = 189-222, k = 1.5-1.7 observations/participant). Cytokines known to be positively linked to AD incidence among others were tested against cross-sectional and longitudinal cognitive function, stratifying by age group (≤50 y vs. >50 y), sex and race. A series of mixed-effects regression models were conducted, adjusting for key confounders. RESULTS: Among key findings, IL1ß was positively associated with a faster rate of decline on a test of executive functioning, among older adults (age >50 y, γ11 = +2.49 ±â€¯0.89, p = 0.005), while in the total population, IL-6 was linked to a faster decline on a test of verbal memory (γ11 = -0.011 ±â€¯0.004, p = 0.009). Among younger participants, IL-18 was linked to a poorer performance on a test of attention at baseline (age ≤50 y, γ01 = -0.007 ±â€¯0.0025, p = 0.004) though a slower rate of decline with higher IL-18 was detected for a test of psychomotor speed in older adults (age >50 y, γ11 = +0.0010 ±â€¯0.0004, p = 0.008). Finally, among Whites, unlike among African-Americans, IL-6 was associated with a better baseline performance on two tests of verbal and working memory. CONCLUSIONS: Cytokines were shown to be associated with age-related cognitive decline among middle-aged and older urban adults in an age group and race-specific manner. Further longitudinal studies are needed to replicate our findings and mediation through relevant biological and psychosocial factors need to be studied as well.

Systemic Inflammation Is Associated With Longitudinal Changes in Cognitive Performance Among Urban Adults.

Objectives/Background: Systemic inflammation can affect cognitive performance over time. The current study examined associations between systemic inflammation and cognitive performance among African Americans and Whites urban adults, stratifying by sex, and age group and by race. Patients/Methods: Among 1,555-1,719 White and African-American urban adults [Agebase: 30-64y, 2004-2013, mean±SD follow-up time(y): 4.64 ± 0.93y], conducted linear mixed-effects regression models were conducted to test associations of inflammatory markers [C-reactive protein, Erythrocyte Sedimentation Rate (ESR), albumin, iron, and an inflammation composite score (ICS)] with longitudinal cognitive performance. Results: Among key findings, CRP was linked to poorer baseline mental status among younger women (≤50y, γ01 = -0.03 ± 0.01, p = 0.002) and poorer attention in older women (>50y, γ01 = -0.024 ± 0.007, p < 0.004) and African-Americans (γ01 = -0.029 ± 0.008, p < 0.001). ESR was related to faster decline on verbal memory among older men (>50y, γ11 = -0.008 ± 0.003, P = 0.009); with poorer performance on attention tests overall (γ01 = -0.010 ± 0.003, P = 0.003) and among African-Americans (γ01 = -0.013 ± 0.004, P = 0.002); on verbal fluency among older women (>50y,γ01 = -0.037 ± 0.013, P = 0.004) and on executive function: overall (γ01 = +0.62 ± 0.21, P = 0.004), older men (>50y, γ01 = +1.69 ± 0.53, P = 0.001) and African-Americans (γ01 = +0.84 ± 0.28, P = 0.002). Albumin was linked to slower attention decline among older men (>50y, γ11 = +0.329 ± 0.103, P = 0.009), over-time improvement in executive function overall (γ11 = -6.00 ± 2.26, P = 0.008), and better baseline psychomotor speed among African-Americans (γ01 = +0.56 ± 0.19, P = 0.003). Finally, ICS predicted faster decline on visual memory/visuo-constructive abilities among older men (>50y, γ11 = +0.17 ± 0.06, p = 0.003). Conclusion: In sum, strong associations between systemic inflammation and longitudinal cognitive performance were detected, largely among older individuals (>50y) and African-Americans. Randomized trials targeting inflammation are warranted.

Helicobacter pylori seropositivity and its association with incident all-cause and Alzheimer's disease dementia in large national surveys.

INTRODUCTION: Infectious agents were recently implicated in Alzheimer's disease (AD) and etiology of other dementias, notably Helicobacter pylori. METHODS: We tested associations of H. pylori seropositivity with incident all-cause and AD dementia and with AD-related mortality among US adults in a retrospective cohort study. Data from the National Health and Nutrition Surveys III, phase 1 (1988-1991) and 1999-2000 linked with Medicare and National Death Index registries, were used (baseline age ≥45 y, follow-up to 2013, Npooled = 5927). RESULTS: A positive association between H. pylori seropositivity and AD mortality was found in men (hazard ratioadj, pooled = 4.33, 95% confidence interval: 1.51-12.41, P = .006), which was replicated for incident AD and all-cause dementia, with hazard ratioadj, pooled = 1.45 (95% confidence interval: 1.03-2.04, P = .035) and hazard ratioadj, III = 1.44 (95% confidence interval: 1.05-1.98, P = .022), respectively. These associations were also positive among higher socioeconomic status groups. DISCUSSION: In sum, H. pylori seropositivity's direct association with AD mortality, all-cause dementia, and AD dementia was restricted to men and to higher socioeconomic status groups.

Age modifies the relation between intraindividual measurement-to-measurement variation in blood pressure and cognitive function: the Maine-Syracuse Study.

BACKGROUND: There is evidence to suggest that intraindividual variability in blood pressure (BP IIV) may be superior to mean BP for predicting cognitive function, taken from both within a single visit and between-visits. BP IIV increases with age in studies of persons middle-aged and older. The aim was therefore to investigate age by BP IIV (SBP and DBP) interactions with regard to cognitive functioning while considering medication class and polypharmacy, which may also affect BP IIV with advancing age. METHOD AND RESULTS: Cross-sectional analyses were performed on 980 community-dwelling individuals from the Maine-Syracuse Longitudinal Study. Automated BP measures were taken 15 times (five times each in sitting, reclining, and standing positions). Cognitive function was assessed using a thorough neuropsychological test battery following the BP assessment. A significant age by BP IIV interaction was observed. For individuals aged over age 60 years, IIV in SBP and DBP was inversely associated with Global Composite, Scanning and Tracking, and the Similarities test. IIV in SBP was additionally associated with Verbal Memory and the Mini-Mental State Examination. DBP IIV was additionally related to the Visual-Spatial Memory and Organization composite. There were no significant associations between BP IIV and cognitive function in those aged less than 60 years. CONCLUSION: BP IIV is an important predictor of cognition with advancing age.

Intimate Partner Violence Victimization and Cognitive Function in a Mixed-Sex Epidemiological Sample of Urban Adults.

Intimate partner violence (IPV) victimization is associated with a wide range of mental and physical health problems, but little is known about the effect of IPV on cognitive decline. Previous research suggests an association between IPV victimization and cognitive dysfunction, but the few studies that have examined this phenomenon were cross-sectional in design and focused only on female victims of IPV. This study examined cognitive function over time among a diverse population of both male and female victims of IPV. Regression analyses indicated increased completion time on Trail Making Test (TMT) A for both male and female victims of IPV living below poverty as well as for female victims of IPV without previously depressive symptomatology. Results also indicated increased completion time on TMT B for male victims of IPV. Our findings support an association between IPV victimization and increased cognitive decline that is moderated by poverty status and previous depressive symptomatology.

Systolic orthostatic hypotension is related to lowered cognitive function: Findings from the Maine-Syracuse Longitudinal Study.

The aim of the present study was to examine the relationship between orthostatic changes in blood pressure (BP) and cognition, with consideration given to cardiovascular risk factors and lifestyle variables. The cross-sectional analysis included 961 community-dwelling participants of the Maine-Syracuse Longitudinal Study, for whom BP clinic measures (five sitting, five recumbent, and five standing) were obtained. Eighteen percent of participants had orthostatic hypotension (fall in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg upon standing) and 6% had orthostatic hypertension (rise in systolic BP ≥20 mm Hg). Orthostatic hypotension and hypertension defined using traditional criteria were unrelated to cognition with covariate adjustment. However, an examination of systolic and diastolic BP change independently revealed that participants with systolic orthostatic hypotension had poorer global cognition, verbal memory, and scanning and tracking scores than those with normal systolic BP change. The authors conclude that systolic orthostatic hypotension is significantly associated with reduced cognitive function.

Differential Associations of Socioeconomic Status With Global Brain Volumes and White Matter Lesions in African American and White Adults: the HANDLS SCAN Study.

OBJECTIVE: The aim of the study was to examine interactive relations of race and socioeconomic status (SES) to magnetic resonance imaging (MRI)-assessed global brain outcomes with previously demonstrated prognostic significance for stroke, dementia, and mortality. METHODS: Participants were 147 African Americans (AAs) and whites (ages 33-71 years; 43% AA; 56% female; 26% below poverty) in the Healthy Aging in Neighborhoods of Diversity across the Life Span SCAN substudy. Cranial MRI was conducted using a 3.0 T unit. White matter (WM) lesion volumes and total brain, gray matter, and WM volumes were computed. An SES composite was derived from education and poverty status. RESULTS: Significant interactions of race and SES were observed for WM lesion volume (b = 1.38; η = 0.036; p = .028), total brain (b = 86.72; η = 0.042; p < .001), gray matter (b = 40.16; η = 0.032; p = .003), and WM (b = 46.56; η = 0.050; p < .001). AA participants with low SES exhibited significantly greater WM lesion volumes than white participants with low SES. White participants with higher SES had greater brain volumes than all other groups (albeit within normal range). CONCLUSIONS: Low SES was associated with greater WM pathology-a marker for increased stroke risk-in AAs. Higher SES was associated with greater total brain volume-a putative global indicator of brain health and predictor of mortality-in whites. Findings may reflect environmental and interpersonal stressors encountered by AAs and those of lower SES and could relate to disproportionate rates of stroke, dementia, and mortality.

Serum Uric Acid and Its Association with Longitudinal Cognitive Change Among Urban Adults.

Uric acid, a waste metabolite among humans, was linked to various cognitive outcomes. We describe sex and age-group specific associations of baseline serum uric acid (SUAbase) and significant change in SUA (ΔSUA: 1 versus 0 = decrease versus no change; 2 versus 0 = increase versus no change) with longitudinal annual rate of cognitive change among a large sample of urban adults. Data from the Healthy Aging in Neighborhoods of Diversity across the Life Span study, 2004-2009 (visit 1) and 2009-2013 (visit 2) were used. Of 3,720 adults selected at baseline (age range: 30-64 y), complete data were available for N = 1,487-1,602 with a mean repeat of 1.5-1.7 visits/participant. Cognitive test domains spanned attention, processing speed, learning/memory, executive function, visuo-spatial/visuo-construction ability, language/verbal, and global cognitive function. SUA was measured at both visits. Multiple mixed-effects regression analyses were conducted. In the total population, a higher SUAbase was associated with a faster annual rate of decline on a measure of visual memory/visuo-construction ability (the Benton Visual Retention Test) by γ= 0.07 with a standard error of 0.02, p < 0.001. Among older men, a significant increase in SUA was associated with slower decline on a test of attention/processing speed, namely Trailmaking test, Part A, measured in seconds to completion (γ= -6.91 ± 1.73, p < 0.001). In sum, a higher SUAbase was associated with faster cognitive decline over-time in a visual memory/visuo-construction ability test. ΔSUA had particular beneficial effects of an increasing ΔSUA on the domain of attention/processing speed among older men. More longitudinal studies are needed to examine cognitive domain-specific effects of over-time change in SUA within sex and age groups.

Associations Between Diabetes and Cognitive Function in Socioeconomically Diverse African American and White Men and Women.

OBJECTIVES: To examine whether race and poverty (income <125% of the federal poverty limit), modifies associations between diabetes and cognition in a biracial, urban-dwelling sample. METHODS: Cross-sectional data for 2066 participants (mean age = 47.6 years, 56.8% women, 56.2% African American, 38.6% below poverty) from the first wave of the Healthy Aging in Neighborhoods of Diversity across the Life Span study were used for analyses. Eleven tests measured cognitive function. Interactions among diabetes, race, and poverty status with cognition were assessed in multiple regression analyses. RESULTS: Significant interactions among diabetes, race, and poverty status were observed. Among African Americans below poverty, diabetic individuals performed lower than nondiabetic individuals on California Verbal Learning Test Free Recall Short Delay (z = -0.444 [0.123] versus z = -0.137 [0.045]) and Long Delay (z = -0.299 [0.123] versus z = -0.130 [0.045]), Digit Span Backward (z = -0.347 [0.109] versus z = -0.072 [0.041]), and the Brief Test of Attention (z = -0.452 [-0.099] versus z = -0.099 [0.047]), and higher on Category Fluency (z = 0.114 [0.117] versus z = -0.118 [0.044]). No consistent differences between diabetic and nondiabetic individuals were found for African American and white participants above poverty. CONCLUSIONS: Diabetes was associated with poorer verbal memory, working memory, and attention among African Americans living in poverty. Diabetic African Americans below poverty may have increased risk of cognitive deficit at a younger age. Improving health literacy, doctor-patient communication, and multidisciplinary medical care for impoverished individuals may reduce differences. Additional research is needed to clarify mechanisms underlying these associations.

Measurement-to-measurement blood pressure variability is related to cognitive performance: the Maine Syracuse study.

The objective was to investigate the association between variability in blood pressure (BP) and cognitive function for sitting, standing, and reclining BP values and variability derived from all 15 measures. In previous studies, only sitting BP values have been examined, and only a few cognitive measures have been used. A secondary objective was to examine associations between BP variability and cognitive performance in hypertensive individuals stratified by treatment success. Cross-sectional analyses were performed on 972 participants of the Maine Syracuse Study for whom 15 serial BP clinic measures (5 sitting, 5 recumbent, and 5 standing) were obtained before testing of cognitive performance. Using all 15 measures, higher variability in systolic and diastolic BP was associated with poorer performance on multiple measures of cognitive performance, independent of demographic factors, cardiovascular risk factors, and pulse pressure. When sitting, reclining, and standing systolic BP values were compared, only variability in standing BP was related to measures of cognitive performance. However, for diastolic BP, variability in all 3 positions was related to cognitive performance. Mean BP values were weaker predictors of cognition. Furthermore, higher overall variability in both systolic and diastolic BP was associated with poorer cognitive performance in unsuccessfully treated hypertensive individuals (with BP ≥140/90 mm Hg), but these associations were not evident in those with controlled hypertension.

Risk of dementia after fluctuating mild cognitive impairment: when the yo-yoing stops.

Friends, family members, and medical caretakers notice that sometimes we have good days and sometimes we have bad days. If we are older, the bad days may involve making poor judgments, acting impulsively, forgetting information we just heard, or repeating ourselves in conversations. If these oscillations persist, then someone we know well may suggest consulting a physician because our bad days are interfering with our daily activities. Presented with variable symptoms on different occasions, physicians legitimately may diagnose us with mild cognitive impairment (MCI) on one occasion and then equally legitimately retract the diagnosis on another occasion. Many in the field have observed that patients and study participants may yo-yo between normal cognitive performance and MCI, but until now, the import of these diagnostic fluctuations was unclear.

Deterioration in renal function is associated with increased arterial stiffness.

BACKGROUND: Higher levels of baseline pulse wave velocity (PWV) have been associated with longitudinal decline in renal function in patients with kidney disease. We examined longitudinal decline in renal function in relation to levels of PWV. We hypothesized that longitudinal decline in renal function in a community-based, nonclinic sample would be associated with higher levels of PWV. METHODS: We conducted a 4-5 year longitudinal study with 482 community-living individuals free from acute stroke, dementia, and end-stage renal disease (mean age = 60.9 years; 59% women; 93.2% white; 10% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) = 79.2 ml/min/1.73 m2). Multiple linear regression analyses were used to examine the association between changes in renal function (eGFR and serum creatinine) from baseline to follow-up and PWV levels at follow-up, the outcome measure. Regression coefficients were adjusted for age, sex, education, race/ethnicity, weight, activity level, mean arterial pressure, treatment of hypertension, and cardiovascular risk factors. RESULTS: With adjustment for covariables, decline in renal function was associated with higher levels of PWV over a mean follow-up of 4.68 years. CONCLUSIONS: Decline in renal functioning from baseline levels measured 4-5 years before measurement of PWV is related to higher levels of PWV in a community sample.

Kidney disease and cognitive function.

UNLABELLED: We provide a brief review of research on chronic kidney disease and cognitive performance, including dementia. We touch briefly on the literature relating end-stage-renal disease to cognitive function, but focus on studies of modest and moderate forms of chronic kidney disease (CKD) that precede dialysis and transplantation. We summarize previous reviews dealing with case control studies of patients but more fully examine community-based studies with large samples and necessary controls for demographic risk factors, cardiovascular variables, and other confounds such as depression. In addition we suggest potential biological and social-psychological mediators between CKD and cognition. Studies follow in two categories of design: (1) cross-sectional studies, and (2) longitudinal studies. In each, CKD is related to a wide range of deficits in cognitive functioning including verbal and visual memory and organization, and components of executive functioning and fluid intellect. In general, prior to the need to treat with hemodialysis (HD) or kidney transplant (KT), magnitude of effect with relation to CKD and function are small or modest in persons free from acute stroke and dementia. However, HD and KT can result in major impairment. We discuss needed controls, the greater demand on controls after the start of HD and KT, and suggest that mechanisms intervening relations between hypertension, or diabetes, and cognitive performance may be similar to those intervening between hypertension and cognitive performance and the hypertension and diabetes literature on cognition provides a good model for the study of early stage kidney disease and cognitive ability. We posit that the mechanisms linking CKD and cognition may be similar to those linking hypertension or diabetes to cognition. We identify the need for more studies with multiple cognitive test batteries, measures of every-day cognitive abilities relevant to patient understanding of the disease and treatments, and more studies with prevalent and incident dementia outcomes. DESCRIPTORS: kidney disease, chronic kidney disease, cognitive function, dementia and cardiovascular risk factors.

Decline in renal functioning is associated with longitudinal decline in global cognitive functioning, abstract reasoning and verbal memory.

BACKGROUND: Decreased estimated glomerular filtration rate (eGFR) and higher serum creatinine (sCR) levels have been associated with longitudinal decline in global mental status measures. Longitudinal data describing change in multiple domains of cognitive functioning are needed in order to determine which specific abilities are most affected in individuals with impaired renal function. METHODS: We conducted a 5-year longitudinal study with 590 community-living individuals (mean age 62.1 years, 60.2% female, 93.2% white, 11.4% with diabetes mellitus, mean eGFR 78.4 mL/min/1.73 m²) free from dementia, acute stroke and end-stage renal disease. To measure longitudinal change-over-time, cognitive performance measures were regressed on eGFR adjusting for baseline eGFR and cognitive performance, comorbidity and vascular risk factors. Outcome measures were scores from 17 separate tests of cognitive abilities that were used to index 5 theoretically relevant domains: verbal episodic memory, visual-spatial organization and memory, scanning and tracking, working memory and similarities (abstract reasoning). RESULTS: Declines in eGFR values were associated with cognitive declines, when adjusted for eGFR and cognitive function scores at baseline. Change in renal functioning over time was related to change observed in global cognitive ability [b=0.21SD decline per unit ln(eGFR), 95% CI: 0.04-0.38, P=.018], verbal episodic memory [b=0.28 SD decline per unit ln(eGFR), 95% CI: 0.02-0.54, P=0.038] and abstract reasoning [b=0.36 SD decline per unit ln(eGFR), 95% CI: 0.04-0.67, P=0.025]. Decline in cognitive functioning in association with declining renal functioning was observed despite statistical adjustment for demographic variables and CVD risk factors and the exclusion of persons with dementia or a history of acute stroke. CONCLUSIONS: Early detection of mild to moderate kidney disease is an important public health concern with regard to cognitive decline.

Relations between dairy food intake and arterial stiffness: pulse wave velocity and pulse pressure.

Modifiable risk factors, such as diet, are becomingly increasingly important in the management of cardiovascular disease, one of the greatest major causes of death and disease burden. Few studies have examined the role of diet as a possible means of reducing arterial stiffness, as measured by pulse wave velocity, an independent predictor of cardiovascular events and all-cause mortality. The aim of this study was to investigate whether dairy food intake is associated with measures of arterial stiffness, including carotid-femoral pulse wave velocity and pulse pressure. A cross-sectional analysis of a subset of the Maine-Syracuse Longitudinal Study sample was performed. A linear decrease in pulse wave velocity was observed across increasing intakes of dairy food consumption (ranging from never/rarely to daily dairy food intake). The negative linear relationship between pulse wave velocity and intake of dairy food was independent of demographic variables, other cardiovascular disease risk factors, and nutrition variables. The pattern of results was very similar for pulse pressure, whereas no association between dairy food intake and lipid levels was found. Further intervention studies are needed to ascertain whether dairy food intake may be an appropriate dietary intervention for the attenuation of age-related arterial stiffening and reduction of cardiovascular disease risk.

Diabetes mellitus in centenarians.

OBJECTIVES: To describe the prevalence of diabetes mellitus (DM) in centenarians. DESIGN: Cross-sectional, population-based. SETTING: Forty-four counties in northern Georgia. PARTICIPANTS: Two hundred forty-four centenarians (aged 98-108, 15.8% male, 20.5% African American, 38.0% community dwelling) from the Georgia Centenarian Study (2001-2009). MEASUREMENTS: Nonfasting blood samples assessed glycosylated hemoglobin (HbA(1c)) and relevant clinical parameters. Demographic, diagnosis, and DM complication covariates were assessed. RESULTS: 12.5% of centenarians were known to have DM. DM was more prevalent in African Americans (27.7%) than whites (8.6%, P < .001). There were no differences between men (16.7%) and women (11.7%, P = .41) or between centenarians living in the community (10.2%) and in facilities (13.9%, P = .54). DM was more prevalent in overweight and obese (23.1%) than nonoverweight (7.1%, P = .002) centenarians. Anemia (78.6% vs 48.3%, P = .004) and hypertension (79.3% vs 58.6%, P = .04) were more prevalent in centenarians with DM than in those without, and centenarians with DM took more nonhypoglycemic medications (8.6 vs 7.0, P = .02). No centenarians with HbA(1c) of less than 6.5% had random serum glucose levels greater than 200 mg/dL. DM was not associated with 12-month all-cause mortality, visual impairment, amputations, cardiovascular disease, or neuropathy. Thirty-seven percent of centenarians reported onset before age 80 (survivors), 47% between age 80 and 97 (delayers), and 15% aged 98 and older (escapers). CONCLUSION: Diabetes mellitus is a risk factor for cardiovascular disease and mortality but is seen in persons who live into very old age. Aside from higher rates of anemia and use of more medications, few clinical correlates of DM were observed in centenarians.

Normative data for elderly adults: the Maine-Syracuse study.

The primary objective of this study was to provide supplementary normative data on aging and cognition from an ongoing community-based study. This dementia- and stroke-free sample (age range = 70-89; mean = 77.5) consisted of 228 women and 155 men participating in the Maine-Syracuse Longitudinal Study at waves 6 to 7 (2001-2009). The authors employed a battery of 23 widely utilized clinical cognitive tests. In this cross-sectional study, the authors focus on subjects 70 to 79 (n = 248) and 80 to 89 (n = 135) years old, and provide preliminary data for a smaller number of subjects aged 90 to 98 years old (n = 14). More highly educated and younger participants exhibited better performance on cognitive tests. Education was not significantly associated with every cognitive outcome, nor was age cohort membership. The addition of cardiovascular disease (CVD)/health variables to a model including age, education, and gender main effects provided statistically significant increases in R² (range = .021-.084) of performance on some tests. Results are discussed in relation to this study's value with respect to determining cognitive impairment in individuals free from probable dementia or stroke.