Serum inflammatory proteins and cognitive decline in older persons

Dik, Miranda G.; Jonker, Cees; Hack, C. E.; Smit, Johannes H.; Comijs, Hannie C.; Eikelenboom, Piet

doi:10.1212/01.wnl.0000158281.08946.68

Cited by 314 publications

(245 citation statements)

References 35 publications

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“…Our finding that CRP is lower among those with any APOE4 is consistent with most reports for other populations. Another published study in a population-based study of the association between dementia incidence and CRP [Dik, Jonker, et al 2005 ], found no association between CRP and dementia but, in a recent analysis of three CRP genotypes [van Oijen, de Maat, et al 2006 ] the authors found one haplotype that was associated with increased rate of dementia. This was not evaluated in relation to APOE.…”

Section: Discussionmentioning

confidence: 95%

“…This was not evaluated in relation to APOE. Other research relating CRP to cognition [Kuo, Yen, et al 2005 ] [Yaffe, Lindquist, et al 2003 ] [Dik, Jonker, et al 2005 ] [Tilvis, Kahonen-Vare, et al 2004 ] [Yaffe, Lindquist, et al 2003 ] has produced conflicting results. Elevated CRP has been linked to cardiovascular disease, atherosclerosis and ischemic stroke [Ridker, Haughie 1998 ] [Kuo, Yen, et al 2005 ] [van Dijk, Prins, et al 2005 ] which are themselves associated with higher risk of cognitive impairments.…”

Section: Discussionmentioning

confidence: 99%

“…Although immune and inflammatory factors such as CRP may influence the development of dementia and cognitive impairment, research examining the influence on dementia risk of this acute phase reactant has produced varied results [Ravaglia, Forti, et al 2006] [Dik, Jonker, et al 2005 ] [van Oijen, de Maat, et al 2006]. APOE is often found to modify the effects of exposure on neurodegenerative processes [Haan, Shemanski, et al 1999 ].…”

Section: Introductionmentioning

confidence: 99%

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C-reactive protein and rate of dementia in carriers and non carriers of Apolipoprotein APOE4 genotype

Haan

Aiello

West

et al. 2008

Neurobiology of Aging

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Background-Those with an apolipoprotein APOE4 allele (APOE4) have lower C-reactive protein (CRP) than those without APOE4. Whether APOE4 modifies the effects of CRP on rate of all cause dementia, cognitive impairment or Alzheimer's disease (AD) is not established.Methods-All cause dementia and cognitive impairment without dementia (CIND) was determined over five follow up visits from 1998-2006 in an ongoing cohort of older Latinos. The association between high sensitivity CRP and dementia/CIND, all cause dementia and Alzheimer's disease by APOE4 status was examined in semi-parametric survival models with covariate adjustments.Results-CRP was significantly lower among those with APOE4 than in those without. Among those with APOE4, CRP was associated with lower rates of combined dementia/CIND (HR: 0.60, 95% CL: 0.20-0.91, p=0.03) from a fully adjusted model. Among those with no APOE4, there was no effect of CRP on dementia/CIND rates (HR: 0.94, 95% CL:0.67-1.33).Conclusions-Lower CRP in those with APOE4 may reflect immune effects of the APOE4 genotype. Higher CRP in those with APOE4 may be a marker of better immune function, leading to lower rate of dementia and AD.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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C-reactive protein and rate of dementia in carriers and non carriers of Apolipoprotein APOE4 genotype

Haan

Aiello

West

et al. 2008

Neurobiology of Aging

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“…Two large population-based studies in older adults observed that participants with high IL-6 levels had higher rates of cognitive decline after 2.5, 3, and 7 years of follow-up, independent of race, other vascular risk factors, and Creactive protein levels (Economos et al 2013;Weaver et al 2002). However, no association for IL-6 levels and cognitive decline was reported in two other studies of middle-aged or older adults (Dik et al 2005;Gimeno et al 2008). However, these inconsistent associations could be because of age differences.…”

Section: Discussionmentioning

confidence: 97%

Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study

Adriaensen

Matheï

Vaes

et al. 2014

AGE

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The chronic inflammatory state at old age may contribute to the pathophysiology of or reflect chronic conditions resulting in loss of physical and mental functioning. Therefore, our objective was to examine the predictive value of a large battery of serum inflammatory markers as risk indicators for global functional decline and its specific physical and mental determinants in the oldest old. Global functional decline and specific aspects of physical and mental functional decline were assessed during an average of 1.66 years (±0.21) in a sample of 303 persons aged 80 years or older of the BELFRAIL study. Serum levels of 14 inflammatory proteins, including cytokines, growth factors, and acute phase proteins, were measured at baseline. Almost 20 % of the participants had a significant global functional decline over time. Interleukin (IL)-6 serum levels were uniquely positively associated with global functional decline, even after correcting for multiple confounders (odds ratio 1.51). Odds ratios for the individual aspects (physical dependency, physical performance, cognition, and depression) of functioning were lower, and composite scores of physical or mental decline were not significant. The proportion of global functional decline exhibited a dose-response curve with increasing levels of IL-6. Thus, IL-6 is an independent risk indicator for accelerated global functional decline in the oldest old. Our results suggest that simple serum levels of IL-6 may be very useful in short-term identification or evaluation of global functional status in the oldest old.

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“…The relationship between immune markers, such as IL-1β, IL-6, IL-8, TNF-α, and CRP, and cognitive functioning has been described in several population studies on older persons (Singh and Newman 2011;Holmes et al 2003;Baune et al 2008;Weaver et al 2002;Bruunsgaard et al 1999;Dik et al 2005;van Exel et al 2003).…”

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confidence: 99%

Significance of serum immune markers in identification of global functional impairment in the oldest old: cross-sectional results from the BELFRAIL study

Adriaensen

Matheï

Pottelbergh

et al. 2013

AGE

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The large burden and coexistence of physical disability, cognitive impairment, and depression in the oldest old makes summary markers of global functioning of great value, allowing for risk stratification. Inflammation may be a common underlying cause or represents a final common pathway. The present study investigated the association between elevated serum inflammatory markers and global functioning and its underlying aspects. A representative sample of 415 communitydwelling elderly subjects participating in the BELFRAIL study, with a mean age of 85 years, was included in the present analysis. Data on physical performance, dependence, and mental aspects of functioning and serum levels of 15 inflammatory proteins, including cytokines, chemokines, and acute-phase proteins, were assessed. Interleukin (IL)-6 was negatively associated with global functioning (odds ratio (OR) 4.35). The odds ratios for C-reactive protein (CRP) (OR 2.37) and the combined score of IL-6 and CRP (OR 2.59) were lower or not significant. IL-6 was significantly associated with physical dependence and cognitive function, and only a highly elevated serum level was associated with physical performance. Physical dependence was associated with a highly elevated CRP serum level. The proportion of functionally impaired older persons with elevated IL-6 was 81.93 %, giving a low positive predictive value (0.38), but a high negative predictive value (0.87). So, IL-6 is strongly associated with global functioning and all of the individual aspects of functioning, except suspected depression, in communitydwelling persons 80 years and older.

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Serum inflammatory proteins and cognitive decline in older persons

Abstract: This population-based study showed that the serum inflammatory protein alpha1-antichymotrypsin is associated with cognitive decline in older persons, whereas C-reactive protein, interleukin-6, and albumin are not.

Cited by 314 publications

References 35 publications

C-reactive protein and rate of dementia in carriers and non carriers of Apolipoprotein APOE4 genotype

C-reactive protein and rate of dementia in carriers and non carriers of Apolipoprotein APOE4 genotype

Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study

Significance of serum immune markers in identification of global functional impairment in the oldest old: cross-sectional results from the BELFRAIL study

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