Prospective associations of interleukin-6 and APOE allele with cognitive decline in biracial community-dwelling older adults: The Chicago Health and Aging Project (CHAP).

Autor: Ng TKS; Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA., Beck T; Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA., Desai P; Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA., Dhana K; Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA., Wilson RS; Rush Alzheimer's Disease Research Center Rush University Medical Center Chicago Illinois USA., Evans DA; Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA., Rajan KB; Rush Institute for Healthy Aging Department of Internal Medicine Rush University Medical Center Chicago Illinois USA.; Rush Alzheimer's Disease Research Center Rush University Medical Center Chicago Illinois USA.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia (Amsterdam, Netherlands) [Alzheimers Dement (Amst)] 2024 Oct 21; Vol. 16 (4), pp. e70002. Date of Electronic Publication: 2024 Oct 21 (Print Publication: 2024).
DOI: 10.1002/dad2.70002
Abstrakt: Introduction: It is unclear whether inflammation, that is, high interleukin-6 (IL-6) levels, and genetic risk, that is, apolipoprotein E ( APOE ) ε4 allele, have a compounding effect on cognitive decline (CD).
Methods: We analyzed a subset of participants from the longitudinal cohort study, Chicago Health and Aging Project, comprising 1120 biracial community-dwelling older adults (60% Black and 62% women), and mean follow-up = 6.4 years. We ran adjusted mixed-effects models on2 longitudinal CD.
Results: In APOE ε4 carriers, higher serum IL-6 was not associated with the rate of CD (β = -0.0091 [standard deviation (SD) = 0.0165, p  = 0.5800]). Conversely, in non-ε4 carriers, compared to the lower tertile, those with the upper tertile of serum IL-6 levels experienced significantly accelerated CD (β = -0.0257 [SD = 0.0084, p  = 0.0023]).
Discussion: Even without the largest genetic risk factor for late-onset Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD), elevated serum IL-6 still accelerate the rate of CD in non- APOE ε4 carriers. Hence, interventions ameliorating inflammation may prevent AD/ADRD.
Highlights: Interleukin-6 (IL-6) and the apolipoprotein E ( APOE ) ε4 allele have been separately associated with an increased risk for cognitive decline, but their interaction remains unclear.In ε4 carriers, IL-6 was not associated with cognitive decline. However, even without the biggest genetic risk factor for Alzheimer's disease (AD), that is, APOE ε4, elevated serum IL-6 still could confer accelerated rate of cognitive decline, with a detrimental effect half of that imposed by APOE ε4 alone.We found no racial differences in these associations.These findings contribute complementary evidence on non- APOE ε4-dependent and non-AD biological pathways through which cognitive decline can still be accelerated in non- APOE ε4 carriers and highlight a specific subgroup of older adults who are at a higher risk of AD and thus may benefit from anti-inflammatory interventions.
Competing Interests: K.D. and K.B.R. are funded by NIH research grants and report no conflicts of interest. All other authors report no conflicts of interest. Author disclosures are available in the journal. Author disclosures are available in the supporting information.
(© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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