Bridges, J. M.

Objectives: Determine relationships between calcification and cognitive function. Background: Dementia affects over 5.4 million Americans; prevalence will quadruple in the next 50 years. Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, may affect cognitive function through microvascular brain effects. Abdominal aortoiliac calcification (AAC) generally precedes CAC and may provide earlier risk determination. Effects of calcification on cognition have not been studied in African Americans (AA). Methods: The 2008-2011 GENOA CAC cohort consists of AA sibships (n=657, mean age 69 [range 40-98], 74% women, 82% hypertensive) enriched with hypertension from Jackson, MS with computed tomography (CT) Agatston calcification measures. Cognition was assessed in 4 domains: global cognitive function (Mini-Mental State Examination); processing speed (Digit Symbol Substitution and Trail Making A); memory (RAVLT and WAIS-III Incidental Learning); and executive function (Trail Making B). Relationships of cognition (standardized) and calcification (log base 2 scale accounting for skewness) were examined using linear regressions with GEE to account for sibship clustering, adjusting parsimoniously for age, sex, and education. Results: Doublings of CAC were significantly associated with poorer processing speed (ß=-0.049 [-0.072, -0.025] p=0.000) and executive function (ß=-0.037 [-0.070, -0.003] p=0.031) in younger subjects and with poorer global function (ß=-0.0648 [-0.096, -0.020] p=0.000), memory (ß=-0.034 [-0.060, -0.007] p=0.013), and processing speed (ß=-0.051 [-0.076, -0.025] p=0.000) in older subjects. Doublings of AAC were significantly associated with poorer processing speed (ß=-0.0381 [-0.056, -0.020] p=0.000) and executive function (ß=-0.045 [-0.070, -0.020] p=0.000) in younger subjects and poorer processing speed (ß=-0.050 [-0.075, -0.025] p=0.000) in older subjects. Conclusions: Calcification is associated with processing speed in young and old AA with prevalent cardiovascular risk factors and may be differentially associated with other cognitive domains by age. Processing speed in particular may be a domain affected early in the calcification process, warranting further study. This supports existing literature addressing the relationship between calcification and cognitive function in ethnically diverse cohorts. Further studies can focus on the temporal and causal relationships between calcification and cognition across age in AA samples enriched for hypertension to identify predictive factors associated with future cognitive decline.

Dementia affects approximately 5 million people in the United States and cost $183 billion in 2011, with African Americans (AA) experiencing a disproportionate burden of dementia compared to European Americans (EA). Inflammation is considered by many to be a potential mediator in the development of cognitive dysfunction. High sensitivity C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α), increasingly measured by the soluble TNF receptors 1 & 2 (sTNFRI1, sTNFR2), are among the most frequently cited inflammatory markers associated with dementia and are also elevated in vascular disease. Few studies have compared associations of inflammatory markers with cognitive function in EA and AA. We examined the association of CRP, sTNFR1 and sTNFR2 with cognitive function using detailed neuropsychological assessments in the Genetic Epidemiology Network of Arteriopathy (GENOA)-Genetics of Microangiopathic Brain Injury (GMBI) participants, a cohort considered at high risk of vascular disease due to family history (> 2 individuals in sibships with hypertension at age <60 years) and high prevalence rates of hypertension (74%), diabetes (27%), and obesity (51%). Cognitive function was measured across 5 cognitive domains: global cognitive function, processing speed, language, memory, and executive function. In AA, higher sTNFR2 was associated with poorer performance across all five domains. Higher sTNFR1 and CRP were associated with slower processing speed. In EA, higher sTNFR1 was associated with slower processing speed. CRP and sTNFR2 were not associated with cognitive function in EA. Inflammatory markers in this cohort were associated differentially across cognitive domains in AA and EA, and may reflect racial differences in vascular responses to inflammation.

Objectives To examine associations between specific inflammatory biomarkers and cognitive function in African Americans (AAs) and European Americans (EAs) with prevalent vascular risk factors. Design Cross‐sectional analysis using generalized estimating equations to account for familial clustering; standardized β‐coefficients, adjusted for age, sex, and education are reported. Setting Community cohort study in Jackson, Mississippi, and Rochester, Minnesota. Participants Genetic Epidemiology Network of Arteriopathy (GENOA)–Genetics of Microangiopathic Brain Injury (GMBI) Study participants. Measurements Associations between inflammation (high‐sensitivity C‐reactive protein (CRP), interleukin (IL)‐6, soluble tumor necrosis factor (TNF) receptor 1 and 2 (sTNFR1, sTNFR2)) and cognitive function (global, processing speed, language, memory, and executive function) were examined in AAs and EAs (N = 1,965; aged 26–95, 64% women, 52% AA, 75% with hypertension). Results In AAs, higher sTNFR2 was associated with poorer cognition in all domains (global: −0.11, P = .009; processing speed: −0.11, P < .001; language: −0.08, P = .002; memory: −0.09, P = .008; executive function: −0.07, P = .03); sTNFR1 was associated with slower processing speed (−0.08, P < .001) and poorer executive function (−0.08, P = .008); higher CRP was associated with slower processing speed (−0.04, P = .024), and higher IL6 was associated with poorer executive function (−0.07, P = .02). In EA, only higher sTNFR1 was associated with slower processing speed (−0.05, P = .007). Associations were not found between cognition and sTNFR2, CRP, or IL6 in EA. Conclusion In a population with high vascular risk, adverse associations between inflammation and cognitive function were especially apparent in AAs, primarily involving markers of TNFα activity.