Long-Term Levels of LDL-C and Cognitive Function: The CARDIA Study

Mefford, Matthew T.; Chen, Ligong; Lewis, Cora E.; Muntner, Paul; Launer, Lenore J.; Monda, Keri L.; Ruzza, Andrea; Rosenson, Robert S.; Carson, April P

doi:10.1017/s1355617721000059

Cited by 9 publications

(9 citation statements)

References 55 publications

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“…We found higher LDL-C was greater cognitive impairment. This result is consistent with a previous cross-sectional analysis from four U.S. cities which found a positive association between LDL-C levels and cognitive measures (10,36). Additionally, ndings from the Northern Manhattan Stroke Study showed that higher LDL-C was associated with the risk of incident vascular dementia (10,37).…”

Section: Discussionsupporting

confidence: 93%

“…This result is consistent with a previous cross-sectional analysis from four U.S. cities which found a positive association between LDL-C levels and cognitive measures (10,36). Additionally, ndings from the Northern Manhattan Stroke Study showed that higher LDL-C was associated with the risk of incident vascular dementia (10,37). The mechanisms underlying the association between LDL-C and cognitive impairment are unknown, and different explanations have been proposed (8,38,39).…”

Section: Discussionsupporting

confidence: 93%

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Prevalence and Predictors of Post-stroke Cognitive Impairment among Stroke Survivors in Uganda

Kaddumukasa

Katabira

et al. 2023

Preprint

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Background Little is known about the characteristics and determinants of post-stroke cognitive impairments in low- and middle-income countries. The objective of this study was to determine the frequencies, patterns, and risk factors for cognitive impairment in a cross-sectional study of consecutive stroke patients cared for at Uganda’s Mulago Hospital, located in sub-Saharan Africa. Methods From August 2019 to July 2020, patients were enrolled a minimum of 3-months post-stroke hospital admission. We collected data on their demographics, vascular risk factors and clinical factors using a questionnaire, clinical examination findings, and test results. Independent predictor variables associated with cognitive impairment were ascertained. Stroke impairments, disability, and handicap were assessed using the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin scale (mRS), respectively. The Montreal Cognitive Assessment (MoCA) was used to assess participants’ cognitive function. Stepwise multiple logistic regression was used to identify variables independently associated with cognitive impairment. Results The overall mean MoCA score was 11.7-points (range 0.0–28.0-points) for 128 patients with available data of whom 66.4% were categorized as cognitively impaired (MoCA < 19-points). Increasing age (OR 1.04, 95% CI 1.00-1.07; p = 0.026), low level of education (OR 3.23, 95% CI 1.25–8.33; p = 0.016), functional handicap (mRS 3–5; OR 1.84, 95% CI 1.28–2.63; p < 0.001) and high LDL cholesterol (OR 2.74, 95% CI 1.14–6.56; p = 0.024) were independently associated with cognitive impairment. Discussion Further longitudinal, prospective studies are required to confirm these findings and identify strategies for reducing the risk of post-stroke cognitive impairment in this population.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Prevalence and Predictors of Post-stroke Cognitive Impairment among Stroke Survivors in Uganda

Kaddumukasa

Katabira

et al. 2023

Preprint

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“…LDL‐C levels have been implicated in neuropsychiatric disorders, 57 , 58 , 59 and because LDL‐C is the primary biomarker measured with PCSK9i, 44 we also evaluated the relationships of LDL‐C levels and neuropsychiatric outcomes using a polygenic LDL‐C instrument. To proxy LDL‐C levels, we extracted 400 independent (linkage disequilibrium R 2 < 0.001) variants associated with LDL‐C at conventional genome‐wide significance, irrespective of their genomic position, from the GLGC meta‐analysis (N≤1 320 016).…”

Section: Methodsmentioning

confidence: 99%

Comparing the Relationships of Genetically Proxied PCSK9 Inhibition With Mood Disorders, Cognition, and Dementia Between Men and Women: A Drug‐Target Mendelian Randomization Study

Bell

Rosoff

Mavromatis

et al. 2022

JAHA

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Background PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are important therapeutic options for reducing cardiovascular disease risk; however, questions remain regarding potential differences in the neuropsychiatric impact of long‐term PCSK9 inhibition between men and women. Methods and Results Using PCSK9 gene single‐nucleotide polymorphisms from European ancestry–based genome‐wide association studies of low‐density lipoprotein cholesterol (N=1 320 016), circulating PCSK9 protein levels (N=10 186), tissue‐specific PCSK9 gene expression, sex‐specific genome‐wide association studies of anxiety, depression, cognition, insomnia, and dementia (ranging from 54 321 to 194 174), we used drug‐target inverse variance–weighted Mendelian randomization (MR) and complementary MR methods (MR Egger, weighted median, and weighted mode) to investigate potential neuropsychiatric consequences of genetically proxied PCSK9 inhibition in men and women. We failed to find evidence surpassing correction for multiple comparisons of relationships between genetically proxied PCSK9 inhibition and the risk for the 12 neuropsychiatric end points in either men or women. Drug‐target analyses were generally well‐powered to detect effect estimates at several hypothesized thresholds for both combined‐sex and sex‐specific end points, especially analyses using PCSK9 instruments derived from protein and expression quantitative trait loci. Further, MR estimates across complementary MR methods and additional models using genetic instruments derived from circulating PCSK9 protein levels and tissue‐specific PCSK9 expression were in alignment, strengthening causal inference. Conclusions Genetically proxied PCSK9 inhibition showed a neutral neuropsychiatric side effect profile with no major sex‐specific differences. Given statistical power considerations, replication with larger samples, as well as data from other ancestral populations, are necessary. These findings may have important clinical implications for lipid‐lowering drug‐prescribing practices and side effect monitoring of approved and future PCSK9 therapies.

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“…The DSST, which is a performance module from the Wechsler Adult Intelligence Scale, assesses sustained attention, processing speed, and working memory [14]. The test form had a key at the top, containing nine numbers paired with symbols.…”

Section: Measurement Of Dsstmentioning

confidence: 99%

“…A cross-sectional study in China showed that subjects with high levels of TC and lowdensity lipoprotein cholesterol (LDL), but not HDL and TG, were at risk for cognitive impairment [13]. Another prospective cohort study in the United States indicated that LDL levels were associated with good performance in cognitive memory [14]. Although the above-mentioned studies have suggested that multiple serum lipid parameters are a risk factor for cognitive impairment, the results are inconsistent.…”

Section: Introductionmentioning

confidence: 99%

Association between Serum Lipid Parameters and Cognitive Performance in Older Adults

Lee

Min

et al. 2021

JCM

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(1) Background: Previous studies have suggested the association between lipid profiles and cognitive function in older adults. However, they generated inconsistent results. We aim to determine the relationship between lipid profiles and cognitive performance in older adults. (2) Methods: We used the 2011–2014 National Health and Nutrition Examination Survey. This study included 2215 participants who were aged more than 60 years old and free of coronary heart disease or stroke. Lipid profiles included total cholesterol (TC), low density lipid cholesterol (LDL), high density lipid cholesterol (HDL), and triglyceride (TG). Cognitive function was assessed using the digit symbol substitution test (DSST). (3) Results: Positive correlations of DSST were observed with TC (r = 0.111; p < 0.0001), HDL (r = 0.127; p < 0.0001), and LDL (r = 0.107; p = 0.0005). However, there was no significant relationship between TG and DSST. A one-unit increase in HDL was associated with an increase in DSST score (beta coefficient: 0.036; p = 0.018); but the association was not significant for LDL, TG, and TC. In the categorical analysis, the high HDL group had a higher DSST score than the low HDL group (beta = 3.113; p < 0.0001) and the low TG group was more likely to show a lower DSST score than the high TC group (beta = −1.837; p = 0.0461). However, LDL and TC showed no statistically significant associations. Moreover, HDL was only associated with a 0.701 times increased risk of cognitive impairment (95% CI = 0.523–0.938) in the logistic regression analysis. (4) Conclusions: Higher blood concentrations of HDL levels were positively associated with DSST scores in older adults. We suggest that the high levels of HDL may be a protective factor against cognitive impairment.

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Long-Term Levels of LDL-C and Cognitive Function: The CARDIA Study

Cited by 9 publications

References 55 publications

Prevalence and Predictors of Post-stroke Cognitive Impairment among Stroke Survivors in Uganda

Prevalence and Predictors of Post-stroke Cognitive Impairment among Stroke Survivors in Uganda

Comparing the Relationships of Genetically Proxied PCSK9 Inhibition With Mood Disorders, Cognition, and Dementia Between Men and Women: A Drug‐Target Mendelian Randomization Study

Association between Serum Lipid Parameters and Cognitive Performance in Older Adults

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