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Inflammation and cognitive decline

Inflammation and cognitive decline

Table 1. Inclusion and Exclusion Defline Inclusion criteria Hyperglycemic crisis and diabetic neuropathy Almond protein T2DM cogitive included a confirmed diagnosis of T2DM and age at recruitment of 35—65 years of age. Pharmacologic interventions to prevent cognitive decline, mild cognitive impairment, and clinical Alzheimer-type dementia: a systematic review. For those with T2DM, a T2DM history was taken including current treatment and duration of T2DM diagnosis. Data was assessed for normality by visual inspection of histograms and Q-q plots.

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AARP Membership. Get instant access to members-only products and Endurance fitness tests of discounts, Hyperglycemic crisis and diabetic neuropathy free second membership, and a subscription to Cpgnitive The Magazine. Join Inflamation. At the beginning of the study, researchers Inflammation and cognitive decline levels of several markers Invlammation inflammation in Dynamic flexibility exercises samples, assigning each volunteer an inflammation score.

Participants were also tested for levels of C-reactive protein, another key indicator of inflammation in the body. Compared with participants with the lowest levels of inflammation markers, those with the highest levels experienced an 8 percent steeper decline in thinking and memory skills over the course of the study, researchers reported.

The group with the highest C-reactive protein levels had a 12 percent steeper decline in these skills than the group with the lowest levels. Although inflammation is a normal process designed to protect the body from injury, disease and infection in the short term, inflammation that persists can be harmful.

Chronic inflammation is associated with autoimmune diseases, as well as common conditions like heart disease and diabetes. AARP® Dental Insurance Plan administered by Delta Dental Insurance Company. Dental insurance plans for members and their families.

The research dovetails with a previous analysis from the ARIC study, which found that people with high levels of inflammation during middle age have smaller brain volumes, particularly in regions involved in memory, such as the hippocampus. Taking steps to quell inflammation in middle age could have a significant payoff down the line.

His advice: Eat a healthy diet, get regular exercise, maintain a healthy weight, and take measures to prevent or treat existing cardiovascular disease or diabetes. The Anti-Inflammation Checklist. Discover AARP Members Only Access.

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SAVE MONEY WITH THESE LIMITED-TIME OFFERS. Chronic Inflammation Linked to Memory Loss. A major new study ties inflammation at midlife to later cognitive decline and Alzheimer's. Facebook Twitter LinkedIn. Beth Howard. En español. Published February 13, Join AARP.

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: Inflammation and cognitive decline

ORIGINAL RESEARCH article Chi , Gloria C. Curr Pharm Des. We therefore controlled for CRP and BMI, and our findings suggest that more specific markers reflecting other pathogenic processes, such as activation of innate immune responses, may be relevant for cognitive functioning. Changes in brain function occur years before the onset of cognitive impairment. Each biomarker was logarithmically transformed base 2 to assess relative changes and to satisfy model assumptions. Impairments are evident in clinical high-risk individuals with subsequent conversion to SMI [ 77 ] and potentially qualify as endophenotypes in both SZ and BD [ 71 , 78 ].
BRIEF RESEARCH REPORT article

Participants were also tested for levels of C-reactive protein, another key indicator of inflammation in the body. Compared with participants with the lowest levels of inflammation markers, those with the highest levels experienced an 8 percent steeper decline in thinking and memory skills over the course of the study, researchers reported.

The group with the highest C-reactive protein levels had a 12 percent steeper decline in these skills than the group with the lowest levels. Although inflammation is a normal process designed to protect the body from injury, disease and infection in the short term, inflammation that persists can be harmful.

Chronic inflammation is associated with autoimmune diseases, as well as common conditions like heart disease and diabetes.

AARP® Dental Insurance Plan administered by Delta Dental Insurance Company. Dental insurance plans for members and their families.

The research dovetails with a previous analysis from the ARIC study, which found that people with high levels of inflammation during middle age have smaller brain volumes, particularly in regions involved in memory, such as the hippocampus.

Taking steps to quell inflammation in middle age could have a significant payoff down the line. His advice: Eat a healthy diet, get regular exercise, maintain a healthy weight, and take measures to prevent or treat existing cardiovascular disease or diabetes.

The Anti-Inflammation Checklist. Discover AARP Members Only Access. Already a Member? The research office was well-lit, with minimal background noise.

Briefly, the neuropsychological assessment battery consisted of the following tests:. i Paired Associates Learning PAL : geometric patterns presented on screen, with participants having to memorize the locations of patterns with increasing difficulty.

Performance assessed using the First Attempt Memory Score PAL-FAMS; range: 0— Performance is assessed using the Strategy SWMS; range 2—12 score.

iii Pattern Recognition Memory Delayed PRMD : participants are asked to memorize patterns and tested using a binary forced-choice paradigm after a min delay.

Percentage correctly remembered PRM-PCD is used to assess performance. iv Reaction Time Task RTT : assesses reaction time in milliseconds by asking a participant to press one of five circles one after another.

Performance assessed by mean duration reaction time in milliseconds RTT-MDRT , with increasing duration indicating poorer performance. v One-Touch Stockings of Cambridge OTS : assess executive function and attention, by moving colored balls inside stockings in the minimal number of moves in order to match a pattern seen on screen.

The Percentage Solved on First Choice PSFC is used to assess performance. vi Rapid Visual Processing RVP : assesses ability to detect particular number sequences within a rapidly changing sequence of numbers. Peripheral venipuncture was performed using standard aseptic technique by the research physicians at the study visit prior to cognitive assessment.

Briefly, blood was collected in 6 mL Serum Clot Activator tubes and processed the same day as sampling. Levels of C-Reactive Protein CRP were analyzed using a standardized high-sensitivity assay in the hospital laboratory.

Levels of Interleukins-1β IL-1β , 6 IL-6 , and 8 IL-8 in addition to Tumor Necrosis Factor-α TNF-α were obtained using the multiplex ella ProteinSimple assay. All statistical analysis was carried out using STATA IC v Between-group statistics consisted of t -tests, wilcoxon rank sum tests and chi-square as appropriate to compare those with T2DM and healthy controls.

Data was assessed for normality by visual inspection of histograms and Q-q plots. For peripheral immune markers, which were not normally distributed, a natural log ln transformation was used. Following this, data were further trimmed by removing observations greater than 3.

Models were adjusted for age, sex, Body Mass Index BMI and education level given the known importance of these variables to influence both cognition and serum markers of inflammation. We firstly ran the models with the natural log transformed concentration as the independent variable in order to assess potential relationships between inflammation and cognitive function in the overall cohort independent of study group T2DM and controls.

Results are reported in the first instance as Coefficients β , Standard Errors SE and corresponding p -values. We additionally computed the standardized betas relating the regression models in order to aid interpretability of our findings.

Finally, we re-ran regression models adjusting for the above covariates age, sex, BMI and education level in addition to hypertension and hypersensitivity analysis to assess whether associations were affected by these vascular risk factors.

No imputation was made for missing data. Correction for multiple testing was applied using the Bonferroni method. Of participants screened, a single participant with T2DM was excluded for a MoCA score below the cut-off.

No participants from either group were excluded based on CESD-8 score. Thus, participants Notably, there was no significant difference in the groups in terms of age or sex, however, those with T2DM had a significantly higher mean BMI than the control group Table 1. The groups did not differ in terms of other characteristics known to impact on cognitive function, such as educational attainment or family history of dementia Table 1.

In the T2DM group, the mean years since diagnosis was 5 IQR: 2—11 and mean HbA1c in was No controls were excluded based on use of T2DM medication or elevated HbA1c.

Overall, there was no significant difference in the levels of IL-1β, IL-6, IL-8, TNF-α, MCP-1, CXCL10, Ilp70 or CRP between those with uncomplicated midlife T2DM and matched healthy controls. Full results are given in Table 1 with appropriate univariate statistics. Overall, 6 participants had missing data for IL-1β, 5 for IL-6, 5 for TNF-α, 3 for MCP-1, 1 for CRP.

A single participant had missing data for the Pattern Recognition Memory Task, with no other missing cognitive data. These associations did not persist on controlling for multiple testing Bonferroni correction. There were no other T2DM-specific or overall associations seen on adjusting for hypertension and hypercholesterolemia.

Again, these did not persist on controlling for multiple comparisons. Full results are given for memory tasks in Table 2 and for reaction time, executive function and attention tasks in Table 3. No other T2DM-specific associations between peripheral inflammation and cognitive function were observed.

The relationship between serum TNF-α and performance on all tasks of the neuropsychological assessment battery is presented graphically in Figure 1. Table 2. Associations between peripheral inflammatory markers and neuropsychological tests of working and delayed memory in T2DM.

Table 3. Associations between peripheral inflammatory markers and neuropsychological tests of reaction time, executive function and attention in T2DM.

Figure 1. Associations between serum TNF-α and neuropsychological tests reveal a significant T2DM-specific association between elevated serum TNF-α and poorer performance on the paired associates learning task.

Results for serum pro-inflammatory markers were log transformed. Linear regression, adjusted for age, sex and Body Mass Index, was used to assess the relationship between circulating pro-inflammatory cytokines and cognitive function.

There was a significant interaction between T2DM group status midlife T2DM vs. controls and the relationship between elevated serum TNF-α and poorer working memory performance. TNF-α, Tumor Necrosis Factor α; MCP-1, Monocyte Chemoattractant Protein 1; CXCL10, CXC Containing Ligand 10; CRP, C-Reactive Protein.

In the current study, we assessed the relationship between a panel of eight pro-inflammatory markers and cognitive function assessed using a detailed neuropsychological assessment battery in middle-aged adults with T2DM free from any diabetes-related complications and a matched cohort of healthy controls.

We observed a significant association between circulating levels of CXCL10 and poorer memory performance in the overall cohort and a T2DM-specific association between increasing serum TNF-α levels and poorer cognitive performance on the Paired Associates Learning PAL task, although these did not persist on correction for multiple comparisons.

Our findings add novel insight to the relationship between peripheral inflammation and cognition in midlife T2DM. A notable finding from the current study is the lack of a significant difference in markers of peripheral inflammation between those with midlife T2DM and healthy controls.

Whilst T2DM has been associated with an increase in circulating pro-inflammatory cytokines in some studies, more recent analyses have reported serum cytokine levels comparable to those without T2DM, particularly in those with good glycemic control and free from any diabetes-related complications Gupta et al.

The stringent inclusion criteria of the current study means that we selected for middle aged adults with a relatively short duration of diabetes, good glycemic control and free from any other T2DM complications. This was performed in order to assess for the earliest possible evidence linking peripheral inflammation and cognitive function in midlife T2DM, when T2DM appears to be acting as a risk factor for later cognitive decline and dementia in the first instance.

Another reasons this for lack of between-group-difference in inflammatory markers includes the fact that many of the treatments prescribed for individuals in the current study, such as GLP-1 agonists Hogan et al. The significant finding around increasing levels of serum TNF-α and poorer performance on the Paired Associates Learning PAL task is particularly interesting.

This task is arguably one of the most demanding in the current study and has significant working memory demands, involving brain regions such as the prefrontal cortex, medial temporal lobe, hippocampus, basal ganglia and parietal cortex Owen et al. Many of the brain regions involved in performance on this task are known to be affected in individuals with T2DM Moran et al.

Further, previous studies have even demonstrated that improved metabolic control has been associated with better performance on this task in those with T2DM Ryan et al. It is interesting that the association appeared to go in the opposite direction in healthy controls.

The reasons for this are not clear, but are worthy of further replication and longitudinal analysis. Further follow up of this cohort will determine the exact relationship between TNF-α levels, performance on this task and later cognitive decline. Whilst our findings are particularly novel in terms of the population studied a middle-aged population free from T2DM complications , they are in-keeping with previous studies which have demonstrated cross-sectional associations of TNF-α levels with cognitive impairment in older adults with T2DM Marioni et al.

Both the current study and previous studies are limited by their cross-sectional nature, however, further longitudinal analysis of the current ENBIND study will assess the longitudinal relationships between cytokine levels and cognitive function in T2DM.

Whilst there are some significant associations in longitudinal population-based studies between pro-inflammatory cytokines and cognitive decline Engelhart et al.

One of these, embedded within the Mayo Clinic Study of Aging, found no association between cytokine levels and global or domain-specific cognitive function Wennberg et al.

Thus, findings such as the current one warrant replication in further longitudinal cohorts of those with T2DM, as the potential association like the one in the current study may be specific to those with T2DM. There are a variety of influences on the serum levels of pro-inflammatory cytokines not limited to age, sex, body mass index, concurrent medication use and medical comorbidity.

Further, circadian rhythm may influence the level of cytokines in serum, with diurnal variations noted in major inflammatory cytokines. Whilst our study was conducted between working hours, we cannot out rule that variation in the time of sampling may have confounded our findings.

It is also important to acknowledge that the validity of a once-off serum measurement of pro-inflammatory cytokines may be limited in the prediction of cognitive decline. More important may be trajectories of pro-inflammatory makers measured at multiple time-points.

It may be that change in baseline levels of inflammation are more predictive of cognitive decline than once-off measurements.

Similarly, it may be that more dynamic measurements of immune function are required for instance ex vivo stimulation of immune cells in response to various pro-inflammatory stimuli or studies of cellular immunometabolism.

Further longitudinal research, such as future longitudinal follow-up of the ENBIND cohort, should aim to address these questions.

One of the limitations of the main finding of the current study around performance on the Paired Associates Learning task and serum measurements of TNF-α levels is that there was a number of comparisons made in the current study. Our analysis was exploratory in nature and driven by the hypothesis that elevated levels of pro-inflammatory cytokines would be associated with poorer neuropsychological test performance.

Whilst it may be argued that the significant finding around TNF-α and Paired Associates Learning performance is a by-product of multiple testing, it is notable that performance on this task has previously been noted in T2DM in addition to the fact that it assesses much of the same brain regions known to be impaired in T2DM on structural neuroimaging studies.

Another limitation of the current study may include the small number of participants. Whilst relatively small in comparison to the main previous study on cognitive function and inflammation in T2DM Marioni et al.

Strict inclusion criteria, including age, lack of T2DM macro and microvascular complications meant that a large number of potential participants were not eligible to participate. The current study is notable in its inclusion of a very young population in comparison to previous studies in addition to the fact that T2DM participants were free from any significant micro or macrovascular complications of T2DM.

Our study is unique in this regard and is the first such study in those with uncomplicated T2DM with a relatively short duration of T2DM.

Previous studies, such as findings from the Edinburgh Type 2 Diabetes study, have been mainly carried out in adults older than those in the current study, with a longer duration of diabetes and the presence of T2DM related complications.

Finally, bias may have arisen in the current study due to different selection procedures between those with T2DM and healthy controls. Those with T2DM were recruited from a specialty clinic in a tertiary referral hospital, whilst control participants were recruited by local advertisement.

Kizer JR Arnold AM Jenny NS et al. Longitudinal changes in adiponectin and inflammatory markers and relation to survival in the oldest old: the Cardiovascular Health Study All Stars study. J Gerontol A Biol Sci Med Sci.

Alessi MC Juhan-Vague I. PAI-1 and the metabolic syndrome: links, causes, and consequences. Sharma M Fitzpatrick AL Arnold AM et al. Inflammatory biomarkers and cognitive decline: the Ginkgo Evaluation of Memory Study.

J Am Geriatr Soc. DeKosky ST Williamson JD Fitzpatrick AL et al. Ginkgo biloba for prevention of dementia. JAMA J Am Med Assoc. Delis DC Kramer JH Kaplan E Ober BA. The California Verbal Learning Test.

New York, NY : Psychological Corporation ; Wechsler D. Wechsler Adult Intelligence Scale-Revised. New York, NY : Psychological Corp ; Saxton J Ratcliff G Munro CA et al.

Normative data on the Boston Naming Test and two equivalent item short forms. Clin Neuropsychol. Reitan RM. Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills.

Trenerry MR Crosson B DeBoe J Lever WR. STROOP Neuropsychological Screening Test. Odessa, FL : Psychological Assessment Resources ; Brydon L Harrison NA Walker C Steptoe A Critchley HD.

Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans. Biol Psychiatry. Kohman RA Rhodes JS. Neurogenesis, inflammation and behavior. Lim A Krajina K Marsland AL. Peripheral Inflammation and Cognitive Aging.

Accessed March 9, Yano Y Matsuda S Hatakeyama K et al. Plasma Pentraxin 3, but not high-sensitivity C-reactive protein, is a useful inflammatory biomarker for predicting cognitive impairment in elderly hypertensive patients.

Lee H-W Choi J Suk K. Mov Disord. Mulder C Schoonenboom SNM Wahlund L-O et al. J Neural Transm. Verwey NA Schuitemaker A van der Flier WM et al. Dement Geriatr Cogn Disord. Yasojima K Schwab C McGeer EG McGeer PL. Brain Res. Crawford JR Bjorklund NL Taglialatela G Gomer RH.

Neurochem Res. Tennent GA Lovat LB Pepys MB. Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. Proc Natl Acad Sci USA.

Janciauskiene S García de Frutos P Carlemalm E Dahlbäck B Eriksson S. Inhibition of Alzheimer beta-peptide fibril formation by serum amyloid P component. J Biol Chem. Palmer JC Barker R Kehoe PG Love S. J Alzheimers Dis. Minami M Kimura M Iwamoto N Arai H.

Endothelinlike immunoreactivity in cerebral cortex of Alzheimer-type dementia. Prog Neuropsychopharmacol Biol Psychiatry. Kelleher RJ Soiza RL. Am J Cardiovasc Dis. Petitto JM Meola D Huang Z. Interleukin-2 and the brain: dissecting central versus peripheral contributions using unique mouse models.

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Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Supplementary Material. Journal Article. Inflammatory Biomarkers Predict Domain-Specific Cognitive Decline in Older Adults. Chi , Gloria C. Oxford Academic. Annette L.

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Table 1. Age years, mean ± SD a Covariate has missing data. Open in new tab. Table 2. Model 1 a. Model 2 b. Model 3 c. Table 3. Google Scholar Google Preview OpenURL Placeholder Text.

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Inflammation and cognition in severe mental illness: patterns of covariation and subgroups Verbal memory was measured using long-delay free recall from the CVLT-II, or cognitkve recall from HVLT-R [ 64 ]. Missing Hyperglycemic crisis and diabetic neuropathy in the covariates were imputed five times using Infpammation Inflammation and cognitive decline. Cognitivs SH, et al. LM recruited and assessed participants. J Neurosci Res. Role of the Sponsor: In their role as coauthors, representatives of the NIH participated in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, and approval of the manuscript. CAS PubMed Google Scholar Segev Y, Michaelson DM, Rosenblum K.
Study Links Chronic Inflammation to Alzheimer’s A single participant had missing data for the Pattern Recognition Memory Task, with no other missing cognitive data. Furthermore, dysregulated inflammatory pathways have been associated with the pathophysiology of SMI [ 19 , 20 ]. Z J Psychiatry. These associations did not persist on controlling for multiple testing Bonferroni correction. Model 1 a. Holmes C, Cunningham C, Zotova E, Woolford J, Dean C, Kerr S, et al.
Inflammation in midlife hastens cognitive decline Cardiovascular and metabolic risk factors such as hypertension and diabetes have been hypothesized to play a role in the pathogenesis of Alzheimer disease AD as well as in development of vascular dementia. PLoS One 7:e Exploring the complex relations between inflammation and aging inflamm-aging : anti-inflamm-aging remodelling of inflamm- aging, from robustness to frailty. Ann Intern Med. These studies have consistently identified two inflammatory subtypes, with a higher frequency of SMI and healthy controls HC in the high and low subtype, respectively. Niyonsaba F, Ushio H, Nagaoka I, Okumura K, Ogawa H. Characterizing cognitive heterogeneity on the schizophrenia-bipolar disorder spectrum.

Inflammation and cognitive decline -

At the beginning of the study, researchers measured levels of several markers of inflammation in blood samples, assigning each volunteer an inflammation score. Participants were also tested for levels of C-reactive protein, another key indicator of inflammation in the body. Compared with participants with the lowest levels of inflammation markers, those with the highest levels experienced an 8 percent steeper decline in thinking and memory skills over the course of the study, researchers reported.

The group with the highest C-reactive protein levels had a 12 percent steeper decline in these skills than the group with the lowest levels. Although inflammation is a normal process designed to protect the body from injury, disease and infection in the short term, inflammation that persists can be harmful.

Chronic inflammation is associated with autoimmune diseases, as well as common conditions like heart disease and diabetes. AARP® Dental Insurance Plan administered by Delta Dental Insurance Company. Dental insurance plans for members and their families. The research dovetails with a previous analysis from the ARIC study, which found that people with high levels of inflammation during middle age have smaller brain volumes, particularly in regions involved in memory, such as the hippocampus.

Taking steps to quell inflammation in middle age could have a significant payoff down the line. His advice: Eat a healthy diet, get regular exercise, maintain a healthy weight, and take measures to prevent or treat existing cardiovascular disease or diabetes.

The Anti-Inflammation Checklist. Discover AARP Members Only Access. Yaffe K , Kanaya A , Lindquist K, et al. The Metabolic Syndrome, Inflammation, and Risk of Cognitive Decline.

Author Affiliations: Departments of Psychiatry, Neurology, and Epidemiology Dr Yaffe , Geriatrics Ms Lindquist , and Medicine Dr Kanaya , University of California, San Francisco; Clinical Research Branch, National Institute on Aging, Baltimore, Md Dr Simonsick ; Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Md Dr Harris ; Department of Preventive Medicine, University of Tennessee at Memphis Drs Shorr and Tylavsky ; and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh School of Medicine, Pittsburgh, Pa Dr Newman.

Context Several studies have reported an association between the metabolic syndrome and cardiovascular disease. Despite an increasing awareness that cardiovascular risk factors increase risk of cognitive decline and dementia, there are few data on the metabolic syndrome and cognition.

Objective To determine if the metabolic syndrome is a risk factor for cognitive decline and if this association is modified by inflammation. Design and Setting A 5-year prospective observational study conducted from to at community clinics at 2 sites.

Main Outcome Measures Association of the metabolic syndrome measured using National Cholesterol Education Program guidelines and high inflammation defined as above median serum level of interleukin 6 and C-reactive protein with change in cognition Modified Mini-Mental State Examination [3MS] at 3 and 5 years.

Cognitive impairment was defined as at least a 5-point decline. Conclusion These findings support the hypothesis that the metabolic syndrome contributes to cognitive impairment in elders, but primarily in those with high level of inflammation.

Cardiovascular and metabolic risk factors such as hypertension and diabetes have been hypothesized to play a role in the pathogenesis of Alzheimer disease AD as well as in development of vascular dementia.

The metabolic syndrome may be a risk factor for cognitive decline because it summarizes the joint effects of these risk factors. As obesity and sedentary lifestyle rise in the United States, identification and explication of the role of these modifiable behaviors in increasing risk for developing deleterious outcomes such as cognitive impairment is critical.

If the metabolic syndrome is associated with increased risk of developing cognitive impairment, then early identification and treatment of these individuals might offer avenues for disease course modification.

High levels of inflammation increase the risk of the development of diabetes and atherosclerosis and are thought to be a possible mechanism for the adverse consequences of the metabolic syndrome.

Furthermore, subclinical inflammation might be an underlying factor for an association between the metabolic syndrome and cognitive decline since inflammatory mechanisms are also hypothesized to be involved in the pathogenesis of cognitive impairment.

Our hypothesis was that presence of the metabolic syndrome would be associated with more cognitive decline and greater risk of developing cognitive impairment and that this association would be modified by inflammation.

Participants were part of the Health, Aging and Body Composition ABC study, a prospective cohort study conducted from to of community-dwelling elders aged 70 to 79 years living in Memphis, Tenn, and Pittsburgh, Pa.

Elders were recruited from a random sample of white and all black Medicare-eligible adults living in designated ZIP codes. Race was defined by self-report and was assessed because rates of cognitive impairment have been shown to differ by race.

Sampled participants were mailed a brochure describing the study and then contacted by telephone to establish functional status and to recruit eligible residents to join the study. Community-based activities were also used to enhance the recruitment of black participants.

Well-functioning was determined by self-report and was defined as having no difficulty in walking a quarter of a mile or going up 10 steps without resting reported during 2 separate interviews prior to enrollment into the study. Exclusion criteria included 1 any difficulty with activities of daily living, 2 clinical dementia based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria , 3 inability to communicate with the interviewer, 4 intention of moving out of the vicinity in the next year, 5 active treatment for cancer in the previous 3 years, and 6 participation in a trial involving a lifestyle intervention.

Data on the metabolic syndrome were missing for 40 participants, 70 had missing inflammatory marker data, and 16 had missing baseline cognitive data, leaving participants.

Our analytic cohort includes the participants who had at least 1 cognitive follow-up assessment. Of the remaining participants, died, 69 were lost to follow-up, and 84 did not have repeat cognitive testing.

Those with and without the metabolic syndrome had similar rates of follow-up All participants signed an informed written consent, approved by the institutional review boards of the clinical sites. This study was approved by the University of California, San Francisco Committee of Human Research.

Cognitive Test. The Teng Modified Mini-Mental State Examination 3MS was administered to all participants during the baseline visit and repeated at the year 3 and 5 follow-up visits.

It is a brief, general cognitive battery with components for orientation, concentration, language, praxis, and immediate and delayed memory with a maximum best score of The Metabolic Syndrome.

Inflammatory Markers. Measurements for interleukin 6 IL-6 and for C-reactive protein CRP were obtained from frozen stored plasma or serum taken at baseline. Serum levels of CRP were also measured in duplicate by ELISA based on purified protein and polyclonal anti-CRP antibodies Calbiochem, EMD Biosciences Inc, Darmstadt, Germany.

The CRP assay was standardized according to the World Health Organization First International Reference Standard with a sensitivity of 0. Assays of blind duplicates collected for participants yielded an average interassay coefficient of variation of The correlation between CRP and IL-6 was 0.

Covariates included characteristics previously shown in the literature to be associated with cognitive function or with the metabolic syndrome. At each clinic examination, we measured weight and height; body mass index was defined as weight in kilograms divided by the square of height in meters.

In addition, standardized algorithms were used to assess prevalent myocardial infarction by self-report and stroke by self-report. Participants were also asked to rate their overall health compared with others as excellent, good, fair, poor, or very poor.

Depressive symptoms were assessed with the Center for Epidemiologic Studies-Depression CES-D Scale, 13 with higher scores indicating greater number of symptoms.

We classified current use of medications as those regularly taken in the past 2 weeks and coded them according to the Iowa Drug Information System IDIS code.

χ 2 Analyses or t tests were conducted to assess baseline characteristics by presence of the metabolic syndrome. We conducted unadjusted and multivariate adjusted logistic regression analyses to determine if presence of the metabolic syndrome was associated with odds of cognitive impairment.

We then corrected for possible overestimation of odds ratios by adjusting to approximate risk ratios according to the method of Zhang and Yu. We added an interaction term to these models to assess whether inflammation modified the association of the metabolic syndrome with cognitive outcomes. Since this term was statistically significant, we conducted stratified analyses by inflammation level.

We used random-effects models to analyze the association between the metabolic syndrome and 4-year change on 3MS score.

Random-effects models account for between-subject variation and within-subject correlations between repeated cognitive measurements. The candidates for fixed-effect terms included all baseline covariates plus their interactions with time and with a missing pattern indicator.

Time was considered as a continuous covariate, measured in days from baseline to follow-up test. By including the missing pattern indicator and its interaction with other covariates, we performed a simplified pattern-mixture model to help account for possible nonrandom dropout. Pattern-mixture models jointly model observed responses and dropout times, thus reducing the effect of biases that would result if dropout was assumed to be independent of unobserved responses.

The mean SD age of the participants at baseline was In addition, several baseline characteristics were statistically significantly different when comparing participants by inflammatory status and presence of the metabolic syndrome Table 1.

Overall, the mean SD baseline 3MS score was Baseline 3MS scores did not differ significantly for those with and without the metabolic syndrome We assessed for presence of an interaction between high inflammation and the metabolic syndrome on risk of cognitive impairment.

The P for interaction was. Given this significant interaction, we stratified the remainder of our analyses by inflammation. When further stratified by race, the association between the metabolic syndrome and cognitive impairment remained elevated for blacks and whites with high inflammation but not for those with low inflammation for blacks with high inflammation, adjusted RR, 1.

In the stratified, unadjusted, and multivariate-adjusted random-effects models, within the high inflammation group, scores for those with the metabolic syndrome declined significantly more than for those without the syndrome Table 3. We next determined whether the association remained between the metabolic syndrome and cognitive impairment after excluding participants with clinically significant diabetes, hypertension, or hyperlipidemia.

The metabolic syndrome and cognitive impairment were not associated with low inflammation. Finally, we assessed whether the association between the metabolic syndrome and inflammation and cognitive decline was related to the number of components of the metabolic syndrome and degree of inflammation.

For participants with high inflammation and the metabolic syndrome, the number of components of the metabolic syndrome did not affect the risk of cognitive decline for the participants meeting 3 criteria, RR, 1.

However, more inflammation assessed as tertiles was associated with greater cognitive decline. Among high-functioning elders, those with the metabolic syndrome show an increased risk of developing cognitive impairment and decline over 4 years.

This association remained after adjustment for possible confounders such as demographics, lifestyle variables, and chronic health conditions.

There remains much uncertainty regarding the etiologies and functions of the biomarkers and which cognitive domains they are likely to impact. In the previous study of 3MSE, the investigators found evidence that PTX3 was associated with a greater hazard of cognitive decline among participants with mild cognitive impairment.

SAP also tended to be inversely related with decline in 3MSE scores. These results are consistent with our results showing a positive association between PTX3 and decline in both psychomotor speed and executive function and an inverse association between SAP and decline in language.

We recognize several limitations to this study. First, missing outcome data were assumed to be missing at random, but this assumption cannot be tested directly from the existing data. Given the nature of cognition as measured from neuropsychological tests, it is possible that the missingness may depend on the outcome itself.

In other words, those with lower cognition are more likely to miss visits or be lost to follow-up. However, there are no methods to account for data that are not missing completely at random, and thus we used an inverse probability weighting method under a missing not at random mechanism to account for the missing data as best as possible.

Importantly, analyzing only participants with complete data did not change the results materially Supplementary Table 3. Model 3 estimates were slightly attenuated, where approximately one fifth of participants were excluded due to missing ApoE ε4 carrier status.

This is most likely due to reduced power in that analysis. Secondly, the sample consisted of elderly individuals aged 75 or older without cognitive deficits at baseline. It is quite possible that these participants were cognitively healthier than the general population, thereby reducing the generalizability of our results.

Moreover, our exploratory analyses of individual biomarkers did not account for multiple testing because they were not the primary focus of the analysis; results from the exploratory analyses are preliminary and should be re-examined more rigorously in future studies.

Finally, our biomarkers were obtained from blood and may not represent more relevant levels such as those in the cerebral spinal fluid. The strengths of the study include the large size of the cohort, rigorous assessment of cognition and dementia, and availability of a large number of inflammatory biomarkers.

In addition, the longitudinal design of the study and availability of nondemented older adults at baseline allow for the identification of candidate biomarkers that may identify subclinical disease and predict progression into worsened cognition or dementia.

In our study, baseline biomarkers were associated predominantly with decline, as opposed to baseline cognition.

This observation points to the need for longitudinal studies of inflammation and cognition, as cross-sectional relationships may not shed light on how inflammation may affect the trajectory of cognitive decline, or may even be misleading.

In summary, our study used longitudinal measures of cognition to assess the association between inflammatory biomarkers and mean levels of cognition test scores across several domains over time. We observed evidence that combined inflammation and inflammatory biomarkers of vascular health, endothelial function, and systemic inflammation were associated with cognitive decline in nondemented individuals.

The domains of cognition impacted included memory, psychomotor speed, language, and executive function. The effect of different sources of inflammation on cognition is likely to differ, and further research is needed to confirm whether peripheral inflammation markers associated with cognition can be used to track subclinical dementia for early onset detection, prevention, or amelioration of the progressive cognitive decline in aging.

As a subsequent therapeutic step, interventions to suppress specific inflammatory markers in midlife may potentially aid in preservation of cognitive and psychomotor skills in late life. Supplementary data is available at The Journals of Gerontology, Series A: Biomedical Sciences and Medical Sciences online.

The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCIH, or the National Institutes of Health, or any other funder. We are grateful to our volunteers, whose faithful participation in this longitudinal study made it possible. Prince M Albanese E Guerchet M Prina M.

World Alzheimer Report Dementia and Risk Reduction. Google Scholar. Google Preview. Viswanathan A Rocca WA Tzourio C. Vascular risk factors and dementia: how to move forward? doi: Humpel C Marksteiner J. Curr Neurovasc Res. Libby P Ridker PM Maseri A.

Inflammation and atherosclerosis. Marsland AL Gianaros PJ Kuan DC Sheu LK Krajina K Manuck SB. Brain morphology links systemic inflammation to cognitive function in midlife adults. Brain Behav Immun. Akdis M Burgler S Crameri R et al. Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases.

J Allergy Clin Immunol. Gorelick PB Scuteri A Black SE et al. Presta M Camozzi M Salvatori G Rusnati M. Role of the soluble pattern recognition receptor PTX3 in vascular biology. J Cell Mol Med. Castellano G Di Vittorio A Dalfino G et al. Pentraxin 3 and complement cascade activation in the failure of arteriovenous fistula.

Jenny NS Arnold AM Kuller LH Tracy RP Psaty BM. Serum amyloid P and cardiovascular disease in older men and women: results from the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol. Hadi HA Carr CS Al Suwaidi J. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome.

Vasc Health Risk Manag. Böhm F Pernow J. The importance of endothelin-1 for vascular dysfunction in cardiovascular disease. Cardiovasc Res. Kirkby NS Hadoke PW Bagnall AJ Webb DJ. The endothelin system as a therapeutic target in cardiovascular disease: great expectations or bleak house?

Br J Pharmacol. Fearon IM Faux SP. Oxidative stress and cardiovascular disease: novel tools give free radical insight. J Mol Cell Cardiol. Yan SF Ramasamy R Schmidt AM. The receptor for advanced glycation endproducts RAGE and cardiovascular disease.

Expert Rev Mol Med. Deane R Yan SD Submamaryan RK et al. RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain. Nat Med. Yates KF Sweat V Yau PL Turchiano MM Convit A.

Impact of metabolic syndrome on cognition and brain: a selected review of the literature. Gustafson DR. Adiposity hormones and dementia. J Neurol Sci. Kizer JR Arnold AM Jenny NS et al.

Longitudinal changes in adiponectin and inflammatory markers and relation to survival in the oldest old: the Cardiovascular Health Study All Stars study. J Gerontol A Biol Sci Med Sci. Alessi MC Juhan-Vague I. PAI-1 and the metabolic syndrome: links, causes, and consequences. Sharma M Fitzpatrick AL Arnold AM et al.

Inflammatory biomarkers and cognitive decline: the Ginkgo Evaluation of Memory Study. J Am Geriatr Soc. DeKosky ST Williamson JD Fitzpatrick AL et al. Ginkgo biloba for prevention of dementia. JAMA J Am Med Assoc. Delis DC Kramer JH Kaplan E Ober BA. The California Verbal Learning Test.

New York, NY : Psychological Corporation ; Wechsler D. Wechsler Adult Intelligence Scale-Revised. New York, NY : Psychological Corp ; Saxton J Ratcliff G Munro CA et al. Normative data on the Boston Naming Test and two equivalent item short forms.

Clin Neuropsychol. Reitan RM. Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills. Trenerry MR Crosson B DeBoe J Lever WR.

STROOP Neuropsychological Screening Test. Odessa, FL : Psychological Assessment Resources ; Brydon L Harrison NA Walker C Steptoe A Critchley HD. Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans.

Biol Psychiatry. Kohman RA Rhodes JS. Neurogenesis, inflammation and behavior. Lim A Krajina K Marsland AL. Peripheral Inflammation and Cognitive Aging. Accessed March 9, Yano Y Matsuda S Hatakeyama K et al.

Plasma Pentraxin 3, but not high-sensitivity C-reactive protein, is a useful inflammatory biomarker for predicting cognitive impairment in elderly hypertensive patients. Lee H-W Choi J Suk K. Mov Disord. Mulder C Schoonenboom SNM Wahlund L-O et al.

J Neural Transm. Verwey NA Schuitemaker A van der Flier WM et al. Dement Geriatr Cogn Disord. Yasojima K Schwab C McGeer EG McGeer PL. Brain Res. Crawford JR Bjorklund NL Taglialatela G Gomer RH.

Neurochem Res. Tennent GA Lovat LB Pepys MB.

People annd harbor high levels of chronic inflammation Hyperglycemic crisis and diabetic neuropathy midlife are more likely to experience memory loss and cogniitive with thinking in declinne decades, Support for metabolic disorders to Inflammation and cognitive decline new study in the journal Neurology — cogniive first nad look Endurance fitness tests the link between inflammatory blood markers cognitve brain health. To reach their conclusion, which points to why things such as diet and exercise might be important to Alzheimer's preventionresearchers used data from the Atherosclerosis Risk in Communities ARIC study at Johns Hopkins University, tracking more than 12, people with an average age of 57 for about two decades. They found that adults with the highest levels of inflammation markers in their 40s, 50s and early 60s had a steeper rate of cognitive decline in their later years. AARP Membership. Get instant access to members-only products and hundreds of discounts, a free second membership, and a subscription to AARP The Magazine. Inflammation and cognitive decline Address correspondence to Gloria Endurance fitness tests. Secline, PhD, MPH, Department of Epidemiology, University of Washington School of Public Health, NE Pacific Street, BoxSeattle, WA E-mail: glochi uw. Gloria C. Chi, Annette L.

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