The association of high sensitivity C-reactive protein and incident Alzheimer disease in patients 60 years and older: The HUNT study, Norway

Abstract

BackgroundWith ageing, long-standing inflammation can be destructive, contributing to development of several disorders, among these Alzheimer’s disease (AD). C-reactive protein (CRP) is a relatively stable peripheral inflammatory marker, but in previous studies the association between highly sensitive CRP (hsCRP) and AD have shown inconsistent results. This study examines the association between AD and hsCRP in blood samples taken up to 15 years prior to the diagnoses of 52 persons with AD amongst a total of 2150 persons ≥60 years of age.ResultsData from Norway’s Nord-Trøndelag Health Study (HUNT 2) and the Health and Memory Study (HMS) were linked. The participants had an average age of 73 years, and diagnosed with AD up to 15 years [mean 8.0 (±3.9)] following hsCRP measurement. Logistic regression models showed an adverse association between hsCRP and AD in participants aged 60-70.5 (odds ratio: 2.37, 95% CI: 1.01-5.58). Conversely, in participants aged 70.6-94, there was an inverse association between hsCRP and AD (odds ratio: 0.39, 95% CI: 0.19-0.84). When applying multivariate models the findings were significant in individuals diagnosed 0.4-7 years after the hsCRP was measured; and attenuated when AD was diagnosed more than seven years following hsCRP measurement.ConclusionsOur study is in line with previous studies indicating a shift in the association between hsCRP and AD by age: in adults (60-70.5 years) there is an adverse association, while in seniors (>70.6 years) there is an inverse association. If our findings can be replicated, a focus on why a more active peripheral immune response may have a protective role in individuals ≥70 years should be further examined.

Inherited risk of dementia and the progression of cerebral small vessel disease and inflammatory markers in cognitively healthy midlife adults: the PREVENT-Dementia study

“…Inflammation is increasingly implicated in neurodegenerative diseases such as AD ( Gabin et al., 2018 ; Gong et al., 2016 ; Heneka et al., 2015 ; Kinney et al., 2018 ; Tao et al., 2018 ). Under normal circumstances, inflammation is a protective biological response to infections and injuries.…”

“…Chronic systemic inflammation can compromise the integrity of the blood–brain barrier, thereby allowing the entry of toxins and pathogens into the brain, and activating glial cells ( Bendorius et al., 2018 ; Kempuraj et al., 2017 ). Blood markers of inflammation have been linked to neurodegenerative conditions including AD ( Gabin et al., 2018 ; Gong et al., 2016 ; Tao et al., 2018 ), cognitive decline ( Noble et al., 2010 ; Watanabe et al., 2016 ), and SVD ( Low et al., 2019 ). However, there has been a lack of research considering longitudinal changes in systemic inflammation in relation to heritable AD risk.…”

APOE4 Copy Number-Dependent Proteomic Changes in the Cerebrospinal Fluid1

“…CRP is an acute phase reactant [40] and acts as a mediator of inflammatory and apoptotic processes, including activation of the classical complement pathway [41] and opsonization of atherosclerotic plaques [42]. Recent prospective studies have found that elevated serum CRP levels in midlife may predict increased AD risk, though there is paradoxical shift in which CRP levels decline with advancing age and before clinical AD symptoms appear [43][44][45]. Further, reduced CRP levels in peripheral blood [46][47][48][49] and in CSF [50,51] correlate with increased cognitive dysfunction and further AD progression in an APOE4-dependent manner.…”

A Stress Syndrome Prototype Reflects Type 3 Diabetes and Ischemic Stroke Risk: The SABPA Study

“…The following dementia-related risk markers indicating cardiometabolic perturbations [ 1 , 2 , 3 , 4 , 5 , 6 ], neurodegeneration [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ] and vascular dysregulation [ 14 , 15 , 27 ] were specified and included in the current investigation (in no particular order): poorer cognitive executive functioning control [ 30 ]; neuronal glia injury (increased S100B and NSE) [ 19 ]; increased central obesity or waist circumference (WC) [ 32 ]; endothelial dysfuntion (increased von Willebrand factor (VWF)) [ 33 ]; depressed time domain heart rate variability (HRV) ( Supplementary Methodology ) [ 34 ]; increased insulin resistance/HOMA-IR [ 8 ] and inflammation (C-reactive protein/CRP) [ 35 ]; and shorter telomeres [ 21 ].…”