Threshold Effects of Total Copper Intake on Cognitive Function in US Older Adults and the Moderating Effect of Fat and Saturated Fatty Acid Intake

Wang, Xiaoxu; Li, Xuelian; Xing, Yufang; Wang, Weijing; Li, Suyun; Zhang, Dongfeng; Zheng, Wei; Shen, Xiaoli

doi:10.1016/j.jand.2021.06.002

Cited by 10 publications

(7 citation statements)

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“…Additionally consistent with most previous studies [ 31 , 48 , 56 ], our study found an inverse association between dietary copper intake and CF, with the level at the top quintile (≥1.8 mg/d) far above the corresponding RDA (0.9 mg/d for adult men and women) [ 50 ]. For instance, Morris et al found that higher dietary copper intake was associated with accelerated cognitive decline among participants with a high intake level of saturated and trans fats [ 57 ].…”

Section: Discussionsupporting

confidence: 92%

Dietary Intake Levels of Iron, Copper, Zinc, and Manganese in Relation to Cognitive Function: A Cross-Sectional Study

et al. 2023

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Previous studies have related circulating levels of trace metal elements, of which dietary intake is the major source, to cognitive outcomes. However, there are still relatively few studies evaluating the associations of dietary intake levels of iron, copper, zinc, and manganese with cognitive function (CF). Methods: We leveraged the data of 6863 participants (mean [standard deviation] age = 66.7 [10.5] years) in the Health and Retirement Study (2013/2014). Dietary intake levels of iron, copper, zinc, and manganese were calculated from a semi-quantitative food frequency questionnaire. CF was assessed using the 27-point modified Telephone Interview for Cognitive Status (TICS). We used linear regression models to calculate the mean differences in global CF scores by quintiles of dietary intake levels of trace metal elements. Results: Among the study participants, the mean (SD) values of daily dietary intake were 13.3 (6.3) mg for iron, 1.4 (0.7) mg for copper, 10.7 (4.6) mg for zinc, and 3.3 (1.6) mg for manganese. Compared with the lowest quintile of dietary iron intake (<8.1 mg), the highest quintile (≥17.7 mg) was associated with a lower cognitive score (−0.50, −0.94 to −0.06, P-trend = 0.007). Higher dietary copper was significantly associated with poorer CF (P-trend = 0.002), and the mean difference in cognitive score between extreme quintiles (≥1.8 vs. <0.8 mg) was −0.52 (95% confidence interval: −0.94 to −0.10) points. We did not observe significant associations for dietary intake of zinc (P-trend = 0.785) and manganese (P-trend = 0.368). Conclusion: In this cross-sectional study, higher dietary intake of iron and copper was related to worse CF, but zinc and manganese intake levels were not significantly associated with CF.

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Section: Discussionsupporting

confidence: 92%

Dietary Intake Levels of Iron, Copper, Zinc, and Manganese in Relation to Cognitive Function: A Cross-Sectional Study

et al. 2023

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“…Regarding executive function and ETEs, the contribution of Cu and Se was particularly noteworthy. Some studies have suggested significant associations of cognitive function with Cu or Se in a single exposure model [42][43][44][45][46]. Wang et al found a positive association between Cu intake and executive function test scores [42].…”

Section: Discussionmentioning

confidence: 99%

Association between Multiple Trace Elements, Executive Function, and Cognitive Impairment with No Dementia in Older Adults

Ryoo,

Choi,

Son

et al. 2024

Nutrients

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Many studies suggest a significant association between individual essential trace elements (ETEs) and cognitive impairment in older adults, but evidence of the synchronized effect of multiple ETEs on cognitive function is lacking. We investigated the association between multiple ETEs, cognitive impairment with no dementia (CIND), and executive function in older Korean adults, using the Bayesian kernel machine regression (BKMR) model. Three hundred and thirty-six older adults were included as the study population and classified as the CIND and control groups. Blood manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), and molybdenum (Mo) were measured as relevant ETEs. The frontal/executive tests included digit symbol coding (DSC), the Korean color word Stroop test (K-CWST), a controlled oral word association test (COWAT), and a trial-making test (TMT). Overall, the BKMR showed a negative association between multiple ETEs and the odds of CIND. Mn was designated as the most dominant element associated with the CIND (PIP = 0.6184), with a U-shaped relationship. Cu and Se levels were positively associated with the K-CWST percentiles (β = 31.78; 95% CI: 13.51, 50.06) and DSC percentiles (β = 25.10; 95% CI: 7.66, 42.53), respectively. Our results suggest that exposure to multiple ETEs may be linked to a protective mechanism against cognitive impairment in older adults.

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“…The National Health and Nutrition Examination Surveys indicated the nonlinear association between copper intake and cognitive performance. They revealed that higher copper intake was associated with better cognitive performance when copper intake was below the inflection point, but not in above inflection point ( Wang et al, 2021 ). Furthermore, a study of AD subjects supported our findings in that plasma copper was positively associated with cognitive performance when excluding those with the highest tertile of copper (i.e., 133–165 μg/dL) ( Pajonk et al, 2005 ).…”

Section: Discussionmentioning

confidence: 99%

“…Preclinical studies have indicated that excessive copper levels are associated with beta-amyloid protein (Aβ) in AD with metal imbalance, ( White et al, 1999 ; Opazo et al, 2002 ) and human studies found similar results in poor cognitive performance ( Oder et al, 1993 ; Smorgon et al, 2004 ; Li et al, 2017 ). In contrast, a couple of studies indicated the positive association between copper level and cognitive performance under conditions below the inflection point of dietary copper intake ( Wang et al, 2021 ) or excluding the highest abnormal blood copper level ( Pajonk et al, 2005 ). Taken together, it is important to investigate the effects of copper on cognitive performance without abnormal copper level in order to understand the precise effects of copper on cognitive function in older adults with normal copper level.…”

Section: Introductionmentioning

confidence: 99%

Association Between Copper and Global Cognition and the Moderating Effect of Iron

Choe

Suh

Lee

et al. 2022

Front. Aging Neurosci.

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BackgroundDespite the known association between abnormal serum copper levels and Alzheimer’s disease (AD) or cognitive decline, the association between copper, iron, and cognition remains poorly investigated. We examined the association between serum copper levels and global cognition measured using the Mini-Mental State Examination (MMSE) in older adults with normal copper levels. We also explored the moderating effect of iron on this association.MethodsThe study enrolled 99 non-demented adults between 65 and 90 years of age. All the participants underwent comprehensive clinical assessments and serum copper measurements. Global cognitive performance was measured by the MMSE. All copper levels were within the normal range and were stratified into three categories: < 87 (low), 87–98 (medium), and > 98 (high: used as a reference category) μg/dL.ResultsSerum copper level (as a continuous variable) was significantly associated with MMSE score (B = 0.065, 95% confidence interval = 0.023–0.108, p = 0.003). Low serum copper group showed significantly decreased MMSE score compared to high copper one (B = −2.643, 95% confidence interval = −4.169 to -1.117, p < 0.001), while middle copper category had no difference (B = −1.211, 95% confidence interval = −2.689 to 0.268, p = 0.107). There was a significant low serum copper ×iron interaction effect on the MMSE score (B = 0.065, 95% confidence interval = 0.016–0.114, p = 0.010). Subgroup analyses showed that low serum copper was significantly associated with a low MMSE score in the low-iron (B = −4.174, 95% confidence interval = −6.607 to −1.741, p = 0.001) but not high-iron subgroup (B = −0.721, 95% confidence interval = −2.852 to 1.409, p = 0.495).ConclusionOur findings from non-demented older adults suggest that a low serum copper level within the normal range was associated with AD or cognitive decline and this is moderated by iron. To prevent AD or cognitive decline, clinicians need to pay attention to avoiding low serum copper and iron levels, even within the clinical normal range.

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Threshold Effects of Total Copper Intake on Cognitive Function in US Older Adults and the Moderating Effect of Fat and Saturated Fatty Acid Intake

Cited by 10 publications

References 54 publications

Dietary Intake Levels of Iron, Copper, Zinc, and Manganese in Relation to Cognitive Function: A Cross-Sectional Study

Dietary Intake Levels of Iron, Copper, Zinc, and Manganese in Relation to Cognitive Function: A Cross-Sectional Study

Association between Multiple Trace Elements, Executive Function, and Cognitive Impairment with No Dementia in Older Adults

Association Between Copper and Global Cognition and the Moderating Effect of Iron

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