Serum lipid traits and the risk of dementia: A cohort study of 254,575 women and 214,891 men in the UK Biobank

Gong, Jessica; Peters, Sanne; Woodward, Mark

doi:10.1016/j.eclinm.2022.101695

Cited by 15 publications

(21 citation statements)

References 46 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9,37,38,41 The findings suggest that the prognostic implication of triglycerides on neurocognitive outcomes differs depending on whether they are measured during early life, midlife, or late life. 5,42 Based on our assumption regarding the varying neurocognitive impacts of triglycerides measured at different time points in life, one plausible explanation for our study findings is that lower triglycerides in older people may be attributable to their poorer nutritional intake and absorption, which are known predictors of cognitive decline and dementia. 43,44 By contrast, higher triglycerides within the normal to normal-high range may indicate plentiful food sources and healthy lifestyle, therefore a lower dementia risk.…”

Section: Discussionmentioning

confidence: 87%

“…4 A recent study using data of more than 500,000 participants from the UK Biobank cohort who were aged between 40 and 69 years (mean age: 56.5 years) reported a U-shaped relationship between low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), total cholesterol levels, and dementia risk, but an inverse relationship between triglyceride levels and dementia risk over 12 years of follow-up. 5 Triglyceride levels were proposed to be less affected by wasting diseases (sarcopenia and other end-stage diseases) and aging processes that are known to cause cholesterol decline in late life (explaining the observed U-shaped relationship of cholesterol metrics with dementia risk in previous studies). 6 Thus, triglyceride levels may be a more stable biomarker of dementia risk in older populations.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association Between Triglycerides and Risk of Dementia in Community-Dwelling Older Adults

Zhou,

Ryan,

Tonkin

et al. 2023

Neurology

View full text Add to dashboard Cite

Background and Objectives:It has been suggested that higher triglyceride levels were associated with a lower risk of Alzheimer's disease. This study aimed to examine the association of triglycerides with dementia and cognition change in community-dwelling older adults.Methods:This prospective longitudinal study used data from the ASPREE randomized trial of adults aged ≥65 years without dementia or previous cardiovascular events at enrolment. The main outcome was incident dementia. Other outcomes included changes in composite cognition and domain-specific cognition (global cognition, memory, language and executive function, and psychomotor speed). The association between baseline triglycerides and dementia risk was estimated using Cox proportional-hazard models adjusting for relevant risk factors. Linear mixed models were used to investigate cognitive change. The analysis was repeated in a sub-cohort of participants with availableAPOE-ε4 genetic data with additional adjustment forAPOE-ε4 carrier status, and an external cohort (UK Biobank) with similar selection criteria applied.Results:The study included 18,294 ASPREE participants and 68,200 UK Biobank participants (mean age: 75.1 & 66.9 years; female: 56.3% & 52.7%; median [IQR] triglyceride:106 [80-142]mg/dl & 139 [101-193]mg/dl), with dementia recorded in 823 and 2,778 individuals over a median follow-up of 6.4 and 12.5 years, respectively. Higher triglyceride levels were associated with lower dementia risk in the entire ASPREE cohort (HR with doubling of TG: 0.82, 95% CI 0.72-0.94). Findings were similar in the sub-cohort of participants with APOE-ε4 genetic data (n=13,976), and in the UK Biobank cohort (HR was 0.82 and 0.83, respectively, all p≤0.01). Higher triglycerides were also associated with slower decline in global, composite cognition, and memory over time (p≤0.05).Discussion:Older adults with higher triglyceride levels within the normal to high-normal range had a lower dementia risk and slower cognitive decline over time compared to individuals with lower triglyceride levels. Higher triglyceride levels may be reflective of better overall health and/or lifestyle behaviors that would protect against dementia development. Future studies are warranted to investigate whether specific components within the total circulating pool of plasma triglycerides may promote better cognitive function, with the hope of informing the development of new preventive strategies.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Association Between Triglycerides and Risk of Dementia in Community-Dwelling Older Adults

Zhou,

Ryan,

Tonkin

et al. 2023

Neurology

View full text Add to dashboard Cite

show abstract

“…The most interesting findings are the associations of higher L‐LDL‐CE% and L‐LDL‐C% with lower risk of incident dementia, AD, and better AD phenotypes, but not VD. However, some previous studies found that higher circulating LDL‐C was associated with increased risk of AD and VD (Gong et al., 2022; Wu et al., 2019; Zhou et al., 2020), which may be caused by the association with its greater atherogenic potential and proinflammatory properties (Ivanova et al., 2017). Despite this, there was still some literature that yielded similar results to the present study, demonstrating that a higher level of LDL‐C was inversely associated with prevalent dementia and cognitive decline (Lv et al., 2016; Zhou et al., 2018).…”

Section: Discussionmentioning

confidence: 96%

“…We found that higher S‐HDL‐CE concentrations were significantly associated with lower risk of all‐cause dementia and VD, but were not associated with AD, cognition, or brain structure. This finding is unexpected because, among previous studies, many have suggested that the association of higher circulating HDL‐C levels with lower risk of dementia and AD (Pedrini, Chatterjee, et al., 2020; Reitz et al., 2010; Wolf et al., 2004), better cognitive function (Singh‐Manoux et al., 2008), and increased brain volume (Ward et al., 2010; Wolf et al., 2004), and that HDL‐C levels were not associated with risk of VD (Gong et al., 2022; Schilling et al., 2017). These studies did not examine HDL subclasses, however, and changes in the levels of these subclasses may have been missed.…”

Section: Discussionmentioning

confidence: 99%

Circulating metabolites and risk of incident dementia: A prospective cohort study

Huang,

Zhang,

Yang

et al. 2023

Journal of Neurochemistry

View full text Add to dashboard Cite

Identifying circulating metabolites associated with dementia, cognition, and brain volume may improve the understanding of dementia pathogenesis and provide novel insights for preventive and therapeutic interventions. This cohort study included a total of 87 885 participants (median follow‐up of 9.1 years, 54% female) without dementia at baseline from the UK Biobank. A total of 249 plasma metabolites were measured using nuclear magnetic resonance spectroscopy at baseline. Cox proportional regression was used to examine the associations of each metabolite with incident dementia (cases = 1134), Alzheimer's disease (AD; cases = 488), and vascular dementia (VD; cases = 257) during follow‐up. Dementia‐associated metabolites were further analyzed for association with cognitive deficits (N = 87 885) and brain volume (N = 7756) using logistic regression and linear regression. We identified 26 metabolites associated with incident dementia, of which 6 were associated with incident AD and 5 were associated with incident VD. These 26 dementia‐related metabolites were subfractions of intermediate‐density lipoprotein, large low‐density lipoprotein (L‐LDL), small high‐density lipoprotein (S‐HDL), very‐low‐density lipoprotein, fatty acids, ketone bodies, citrate, glucose, and valine. Among them, the cholesterol percentage in L‐LDL (L‐LDL‐C%) was associated with lower risk of AD (HR [95% CI] = 0.92 [0.87–0.97], p = 0.002), higher brain cortical (β = 0.047, p = 3.91 × 10−6), and hippocampal (β = 0.043, p = 1.93 × 10−4) volume. Cholesteryl ester–to–total lipid ratio in L‐LDL (L‐LDL‐CE%) was associated with lower risk of AD (HR [95% CI] = 0.93 [0.90–0.96], p = 1.48 × 10−4), cognitive deficits (odds ratio = 0.98, p = 0.009), and higher hippocampal volume (β = 0.027, p = 0.009). Cholesteryl esters in S‐HDL (S‐HDL‐CE) were associated with lower risk of VD (HR [95% CI] = 0.81 [0.71–0.93], p = 0.002), but not AD. Taken together, circulating levels of L‐LDL‐CE% and L‐LDL‐C% were robustly associated with risk of AD and AD phenotypes, but not with VD. S‐HDL‐CE was associated with lower risk of VD, but not with AD or AD phenotypes. These metabolites may play a role in the advancement of future intervention trials. Additional research is necessary to gain a complete comprehension of the molecular mechanisms behind these associations.image

show abstract

“…Conversely, there is debate as to whether high lipoprotein(a) levels could be protective of dementia, as a in Finish study (N ¼ 2532) individuals with high lipoprotein(a) had lower risk of dementia [19]. These findings were however not replicated in a recent study from the UK biobank (N ¼ 469 466) [20]. It has also been hypothesized that lipoprotein(a) may have both neoplastic and antineoplastic properties, and a study using the UK biobank and the PRACTICAL consortium found an association of LPA genetic variants with increased risk of prostate cancer [21].…”

Section: Andandmentioning

confidence: 98%

Measuring lipoprotein(a) for cardiovascular disease prevention – in whom and when?

Thomas,

Vedel-Krogh,

Nordestgaard

2023

Current Opinion in Cardiology

View full text Add to dashboard Cite

Purpose of review The aim of this study is to summarize major cardiovascular guideline recommendations on lipoprotein(a) and highlighting recent findings that emphasize how measuring lipoprotein(a) once in all adults is meaningful regardless of age, sex, comorbidities, or ethnicity. Recent findings Many international guidelines now recommend once in a lifetime measurement of lipoprotein(a) in all adult individuals to facilitate accurate risk prediction. Lipoprotein(a)-lowering therapy to reduce cardiovascular disease is on the horizon, with results from the first phase 3 trial expected in 2025. Summary Elevated lipoprotein(a) is an independent causal risk factor for atherosclerotic cardiovascular disease and aortic valve stenosis and measuring lipoprotein(a) once in all individuals regardless of age, sex, comorbidities, or ethnicity is meaningful to aid in risk stratification.

show abstract

Serum lipid traits and the risk of dementia: A cohort study of 254,575 women and 214,891 men in the UK Biobank

Cited by 15 publications

References 46 publications

Association Between Triglycerides and Risk of Dementia in Community-Dwelling Older Adults

Association Between Triglycerides and Risk of Dementia in Community-Dwelling Older Adults

Circulating metabolites and risk of incident dementia: A prospective cohort study

Measuring lipoprotein(a) for cardiovascular disease prevention – in whom and when?

Contact Info

Product

Resources

About