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Cited by 31Dementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration MechanismsAging and Gerontology Research

C-reactive protein and memory function suggest antagonistic pleiotropy in very old nondemented subjects

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Silverman, J. M., Beeri, M. S., Schmeidler, J., Rosendorff, C., Angelo, G., Mavris, R. S., Grossman, H. T., Elder, G. A. +2 more·2008·Age and Ageing
DOI 10.1093/ageing/afn278PMC PMC2724888
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Abstract

SIR—A possible role of inflammation in the development of dementia [1] has led to investigations examining whether C-reactive protein (CRP), a systemic marker of inflammation, is associated with worse cognitive function and decline in old age. Elevated CRP has been associated with worse global and specific cognitive functioning [2–7], although other studies have found no relationship between CRP and cognition [8–10]. Most studies have examined samples averaging <75 years [3–6, 9, 10]. We hypothesised that elevated CRP would be related to worse cognitive function in very old cognitively healthy subjects. Cognitively healthy subjects with no other preconditions beyond their age being 75 years or more were recruited from the Bronx Veterans Affairs Medical Center (BxVAMC) and senior centres in New York metropolitan area for a project investigating cardiovascular risk factors and cognition. The Mount Sinai School of Medicine and the BxVAMC both provided IRB approval and all subjects gave written informed consent. We evaluated overall cognitive functioning by direct assessments and informant interviews using the Clinical Dementia Rating scale (CDR) [11] and included only subjects with CDR = 0 (not demented). In addition, subjects with a history of a neurological, medical or psychiatric disorder potentially affecting cognition (e.g. stroke, schizophrenia)—by self-report, informant report or medical charts—were excluded. The subjects received a neuropsychological test battery, described previously [12]: the Mini Mental State Exam (MMSE), tests of memory (sum of immediate recall trials 1, 2 and 3), delayed recall, recognition and savings (100*delayed recall/immediate recall trial 3), executive functions (Trail making A, Trail making B), intelligence (Shipley) and language (word fluency). The subjects’ blood samples were sent to the BxVAMC haematology laboratory and wide-range CRP, possessing near-perfect correlation with high-sensitivity CRP [13], was measured from plasma using the ADVIA 1650 Chemistry System with a CRP latex reagent. Also, apolipoprotein E (APOE) genotyping and other values relevant to cardiovascular risk factors (e.g. cholesterol, haemoglobin A1C) were measured. Subjects were first categorised into conventionally identified ‘low’ (≤1.0 mg/l), ‘normal’ (>1.0 mg/l and ≤3.0 mg/l) and ‘high’ (>3.0 mg/l) CRP groups [14]. Logarithmic transformation of the non-normally distributed CRP was applied for all other statistical analyses. The MMSE was used to examine global cognitive function. To summarise the other neuropsychological tests, we conducted a factor analysis using varimax rotation. Stepwise regression assessed the linear and quadratic associations of CRP with each factor and MMSE, controlling for age, sex and education, for the entire sample, and divided by sex, or by the presence of an APOE-e4 allele. Two-sided tests were employed. Of the 189 nondemented subjects with CRP measurements, 13 subjects did not have neuropsychological test data allowing for the factor analysis, and were excluded. This left 176 subjects (112 men, 64 women) with full neuropsychological test data [mean age: 85 ± 6 years; mean years of education: 15 (±3)]. The preponderance of males reflects the many subjects recruited through the BxVAMC. There were 123 subjects with no APOE-e4 allele (3/3: n = 92; 2/3: n = 31), 50 subjects with an e4 allele (3/4: n = 35; 2/4: n = 10; 4/4: n = 5) and three missing DNA. The factor analysis produced a model with two factors, one primarily including memory functions (high weights from delayed recall, savings and recognition) and one primarily including executive/language functions (high weights from Trail making B, word fluency, Trail making A, immediate recall and Shipley). Untransformed mean CRP level was 2.5 mg/l ± 5.2 mg/l (ranging from 0.00 to 41.50) with 97 having ‘low’, 40 ‘normal’ and 39 ‘high’ CRP levels. Memory scores were significantly different [F(2, 170) = 4.34, P = 0.01] across groups, where the low-CRP group had worse memory scores than the other two groups. The groups did not differ in executive/language score or MMSE. As indicated in Table 1, we found that higher CRP values were significantly associated with lower (worse) executive/language function scores and also with higher (better) memory scores. The CRP relationship with MMSE was not significant. No quadratic associations were significant. Demographics and partial correlations for total sample and APOE-e4 non-carriers and carriers aIncludes three subjects not genotyped for APOE. bControlling for age, sex and years of education in multiple regression analysis. *P < 0.05, **P < 0.005, ***P < 0.001 Demographics and partial correlations for total sample and APOE-e4 non-carriers and carriers aIncludes three subjects not genotyped for APOE. bControlling for age, sex and years of education in multiple regression analysis. *P < 0.05, **P < 0.005, ***P < 0.001 There were no differences in CRP, memory, executive/language or MMSE s

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  • In the very old, higher CRP has also been linked to better memory performance.

    “However, higher CRP levels in very old people have also been associated with better memory function (59).”

    From Frailty in elderly people (2013) · cites this paper as [59]

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Authors
Silverman, J. M., Beeri, M. S., Schmeidler, J., Rosendorff, C., Angelo, G., Mavris, R. S., Grossman, H. T., Elder, G. A., Carrion-Baralt, J., & West, R.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • James J. Peters VA Medical Center (US)
Corresponding author
Silverman, J. M.
ORCID
Venue
Age and Ageing
Publisher
Oxford University Press (OUP)
Published
2008-11-13
Volume
38
Issue
2
Pages
237-241
ISSN
  • 0002-0729 (ISSN-L)
  • 1468-2834
DOI
10.1093/ageing/afn278
PMC
PMC2724888
OpenAlex
W1970832547
Cited by
31
References
28
Citations by year
2024: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 4 · 2012: 3
FWCI
1.64
Type
journal article
Language
en
Open access
Locations
  • Age and Ageing (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5k01ag023515-04)
  • National Institute on Aging (P50 AG 05138, P01 AG 02219, P50AG005138, K01-AG023515, P01AG002219)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
Keywords
C-reactive protein, memory function, antagonistic pleiotropy, oldest old, cognitive function, inflammation, dementia, apolipoprotein E, cardiovascular risk factors, executive function, older adults, cognitive decline, sex differences, diabetes mellitus, alcohol consumption, physical activity, body mass index, sleep apnea
MeSH terms
Aged, Aged, 80 and over, C-Reactive Protein, Cognition, Cross-Sectional Studies, Dementia, Female, Humans, Inflammation, Male, Memory, Psychiatric Status Rating Scales

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