C-reactive protein and familial risk for dementia

Silverman, Jeremy M.; Schmeidler, James; Beeri, Michal Schnaider; Rosendorff, Clive; Sano, Mary; Grossman, Hillel; Carrión-Baralt, José R.; Bespalova, Irina N.; West, Rebecca; Haroutunian, Vahram

doi:10.1212/wnl.0b013e3182698c89

Cited by 27 publications

(30 citation statements)

References 39 publications

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“…The survivor effect model states that such groups comprise a higher proportion of individuals who are resilient against certain risk factors, as evidenced by their maintenance of physical or cognitive health in the face of these risk factors. [28] Thus, the presence of risk factors in subgroups of the healthiest older adults may reflect a correlate of successful cognitive aging rather than a protective factor.…”

Section: Discussionmentioning

confidence: 99%

Dementia Risk and Protective Factors Differ in the Context of Memory Trajectory Groups

Zahodne

Schupf

Brickman

et al. 2016

JAD

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Background Previous research has identified multiple risk and protective factors for late onset Alzheimer’s disease (LOAD). However, it is not known whether these risk and protective factors differ for individuals who are cognitively stable versus those already experiencing declines. Objective This study examined how dementia risk factors differ across subgroups of older adults defined by memory trajectory. This line of research may lead to more individualized risk profiles. Methods Risk factors for incident LOAD were compared across previously-validated groups of older adults exhibiting different memory trajectories (“Stable-High,” “Stable-Low,” “Decliner,” “Rapid Decliner”) using stratified Cox regressions. Participants included 2,593 racially/ethnically diverse older adults (mean age of 76 at study entry) in the Washington Heights-Inwood Columbia Aging Project. Results Predictors of incident dementia differed across trajectory groups: older age only incurred independent risk in stable groups, education did not incur independent risk in the rapidly declining group, depression only incurred independent risk in the stable-low group, stroke incurred independent risk in the two extreme groups, and APOE-ε4 only incurred independent risk in the rapidly declining group. Conclusion The finding that different risk factors for LOAD were associated with specific memory trajectories may reflect the existence of resilience or vulnerability factors that modify the individual influences of risk/protective factors. This study highlights the utility of considering interactions between dementia risk factors and a patient’s unique cognitive history.

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Section: Discussionmentioning

confidence: 99%

Dementia Risk and Protective Factors Differ in the Context of Memory Trajectory Groups

Zahodne

Schupf

Brickman

et al. 2016

JAD

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“…47 A recent study of cognitively intact adults aged 75 and older found lower dementia risk in relatives of those with high CRP, suggesting that familial, possibly genetic, factors may contribute to resiliency. 48 …”

Section: Discussionmentioning

confidence: 99%

Long‐Term Systemic Inflammation and Cognitive Impairment in a Population‐Based Cohort

Wichmann

Cruickshanks

Carlsson

et al. 2014

J American Geriatrics Society

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OBJECTIVES Evidence suggests inflammation is associated with cognitive impairment, but previous epidemiological studies have reported conflicting results. DESIGN Prospective population-based cohort. SETTING Epidemiology of Hearing Loss Study participants. PARTICIPANTS Individuals without cognitive impairment in 1998–2000 (N = 2,422; 1,947 with necessary data). MEASUREMENTS Cognitive impairment (Mini-Mental State Examination score <24 or diagnosis of dementia) was ascertained in 1998–2000, 2003–2005, and 2009– 2010. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) were measured in 1988–1990, 1998–2000, and 2009–2010; tumor necrosis factor-alpha was measured from 1998–2000. RESULTS Participants with high CRP in 1988–1990 and 1998–2000 had lower risk of cognitive impairment than those with low CRP at both time points (hazard ratio (HR) = 0.46, 95% confidence interval (CI) = 0.26–0.80). Risk did not differ according to 10-year IL-6 profile or baseline inflammation category in the whole cohort. In sensitivity analyses restricted to statin nonusers, those with high IL-6 at both times had greater risk of cognitive impairment than those with low IL-6 at both times (HR = 3.35, 95% CI = 1.09–10.30). In secondary analyses, each doubling of IL-6 change over 20 years was associated with greater odds of cognitive impairment in 2009–2010 in the whole cohort (odds ratio (OR) = 1.40, 95% CI = 1.04–1.89), whereas a doubling of CRP change over 20 years was associated with cognitive impairment only in statin nonusers (OR = 1.32, 95% CI = 1.06–1.65). CONCLUSION With data collected over 20 years, this study demonstrated greater likelihood of cognitive impairment in individuals with repeated high or increasing IL-6. The inconsistent CRP findings may reflect effects of statin medications, survival effects, or adverse effects associated with chronically low CRP. Further studies of long-term inflammation and cognitive impairment are needed.

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“…To explain such a reversal, in a survivor effect model for successful cognitive aging, there is a risk factor for both mortality and dementia, but a relatively small group has protection against it (10). At increasing ages, the proportion of protected survivors among those remaining free of dementia increases.…”

Section: Discussionmentioning

confidence: 99%

Association of Apolipoprotein E-e4 and Dementia Declines with Age

Valerio

Raventós

Schmeidler

et al. 2014

The American Journal of Geriatric Psychiatry

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Objective To study the association of dementia with APOE-e4 and its interaction with age in a nonagenarian Costa Ricans (N-sample) and a general elderly contrast group (GE-sample). Methods In both case-control studies, participants were cognitively intact or demented. The N-sample (N=112) was at least age 90; the GE-sample (N=98) was at least age 65. Results Dementia and APOE-e4 were not significantly associated in the N-sample, but were in the GE-sample. There was a significant interaction of age with APOE-e4 in the N-sample, but not in the GE-sample. Descriptively dividing the N-sample at the median (age 93) showed a group interaction: APOE-e4 was more associated with dementia in the younger N-sample than in the older N-sample, where six of seven APOE-e4 carriers were cognitively intact. Conclusions The results support the reduction in association of APOE-e4 with dementia in extreme old age, consistent with a survivor effect model for successful cognitive aging.

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C-reactive protein and familial risk for dementia

Cited by 27 publications

References 39 publications

Dementia Risk and Protective Factors Differ in the Context of Memory Trajectory Groups

Dementia Risk and Protective Factors Differ in the Context of Memory Trajectory Groups

Long‐Term Systemic Inflammation and Cognitive Impairment in a Population‐Based Cohort

Association of Apolipoprotein E-e4 and Dementia Declines with Age

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