@article {Higgins, title = {Systemic inflammation is associated with dementia status in the health and retirement study}, year = {2023}, abstract = {BackgroundThe prevalence of dementia is expected to increase in the coming decades. The highest burden of this chronic condition will likely be borne by racial/ethnic minorities. Systemic inflammation is associated with dementia. This effect may be modified by race/ethnicity, since racial minorities are more likely to have elevated levels of systemic inflammation due to the accumulation of compounded negative experiences (e.g., discrimination, racism, and marginalization). Our goal was to test baseline systemic inflammation in relation to cognitive function in a racially/ethnically representative cohort of US adults.MethodsIn a cross-sectional analysis of the Health and Retirement Study (2006 and 2008 waves, n=9,983), highly sensitive C-reactive protein (hsCRP) was measured in dried blood spots. Cognitive status (dementia, cognitive impairment non-dementia (CIND), and normal cognition) was measured and categorized using the Langa-Weir classification of a modified telephone interview for cognition scale. We estimated the adjusted associations between hsCRP and cognitive status, using multivariable logistic regression. We stratified models by race/ethnicity to explore race-dependent associations.ResultsOur study prevalence of dementia and CIND is 3.5\% and 15.8\%, respectively. Similarly, 26.7\% of dementia and 30.1\% of CIND cases occurred among participants with circulating hsCRP levels above the 75th quartile. We observed a racial and gender gradient in the levels of hsCRP in our cohort. For example, Black females had the highest average concentration of hsCRP (7.53 mg/L, SD =15.1) and Whites males the lowest (3.95 mg/L, SD = 7.42). Among participants with hsCRP >75th we observed higher odds of CIND (OR = 1.45; 95\%CI: 1.22, 1.72) with respect to those in the . Similarly, elevated hsCRP >75th was associated with dementia (OR= 1.21; 95\%CI: 0.86, 1.69), in comparison to the reference lower quartile. We did not observe a race-dependent relationship between hsCRP and cognitive status.ConclusionsSystemic inflammation, as represented by high levels of hsCRP, was associated with concurrent cognitive status. Despite racial minorities exhibiting higher levels of hsCRP; in our study, the association between inflammation on cognition did not differ by race. Further studies should explore whether the established relationship is causal, seek larger sample sizes in diverse populations, and examine longitudinal relationships Peer Reviewed}, issn = {1552-5260 1552-5279}, doi = {10.1002/alz.053316}, author = {Higgins, Cesar and Ware, Erin B and Hicken, Margaret and Zawistowski, Matthew and Bakulski, Kelly M} } @article {11732, title = {Mendelian Randomization of Dyslipidemia on Cognitive Impairment Among Older Americans}, journal = {Frontiers in Neurology}, volume = {12}, year = {2021}, abstract = {Background: Altered lipid metabolism may be a risk factor for dementia, and blood cholesterol level has a strong genetic component. We tested the hypothesis that dyslipidemia (either low levels of high-density lipoprotein cholesterol (HDL-C) or high total cholesterol) is associated with cognitive status and domains, and assessed causality using genetic predisposition to dyslipidemia as an instrumental variable. Methods: Using data from European and African genetic ancestry participants in the Health and Retirement Study, we selected observations at the first non-missing biomarker assessment (waves 2006-2012). Cognition domains were assessed using episodic memory, mental status, and vocabulary tests. Overall cognitive status was categorized in three levels (normal, cognitive impairment non-dementia, dementia). Based on 2018 clinical guidelines, we compared low HDL-C or high total cholesterol to normal levels. Polygenic scores for dyslipidemia were used as instrumental variables in a Mendelian randomization framework. Multivariable logistic regressions and Wald-type ratio estimators were used to examine associations. Results: Among European ancestry participants (n = 8,781), at risk HDL-C levels were associated with higher odds of cognitive impairment (OR = 1.20, 95\% CI: 1.03, 1.40) and worse episodic memory, specifically. Using cumulative genetic risk for HDL-C levels as a valid instrumental variable, a significant causal estimate was observed between at risk low HDL-C levels and higher odds of dementia (OR = 2.15, 95\% CI: 1.16, 3.99). No significant associations were observed between total cholesterol levels and cognitive status. No significant associations were observed in the African ancestry sample (n = 2,101). Conclusion: Our study demonstrates low blood HDL-C is a potential causal risk factor for impaired cognition during aging in non-Hispanic whites of European ancestry. Dyslipidemia can be modified by changing diets, health behaviors, and therapeutic strategies, which can improve cognitive aging. Studies on low density lipoprotein cholesterol, the timing of cholesterol effects on cognition, and larger studies in non-European ancestries are needed.}, keywords = {blood cholesterol, cognitive domain, Dementia, Mendelian randomization, polygenic score}, doi = {10.3389/fneur.2021.660212}, author = {Fu, Mingzhou and Kelly M Bakulski and Higgins, Cesar and Erin B Ware} }