A Mixed-Effects Model of Associations Between Interleukin-6 and Hippocampal Volume

Overview

Journal J Gerontol A Biol Sci Med Sci

Specialty Geriatrics

Date 2021 Oct 12

PMID 34637514

Citations 1

Authors

Erin R Harrell

Chuong Bui

Sharlene D Newman

Affiliations

Soon will be listed here.

Abstract

Previous studies report hippocampal volume loss can help predict conversion from normative aging to mild cognitive impairment to dementia. Additionally, a growing literature indicates that stress-related allostatic load may increase disease vulnerability. The current study examined the relationship between stress-related cytokines (ie, interleukin-6 [IL-6]), cognition as measured by Mini-Mental State Examination (MMSE) scores, and hippocampal volume. Mixed models were employed to examine both within- (across time) and between-subject effects of IL-6 and hippocampal volume on MMSE score among 566 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The within-subject analysis found left hippocampal volume significantly (p = .009) predicted MMSE score. Between-subject analysis found the effect of IL-6 on MMSE was moderated by right hippocampal volume (p = .001). These results replicate previous findings and also extend prior work demonstrating stress-related cytokines may play a role in Alzheimer's disease progression.

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References

Miller G, Chen E, Parker K . Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving toward a model of behavioral and biological mechanisms. Psychol Bull. 2011; 137(6):959-97. PMC: 3202072. DOI: 10.1037/a0024768. View

Turner A, James B, Capuano A, Aggarwal N, Barnes L . Perceived Stress and Cognitive Decline in Different Cognitive Domains in a Cohort of Older African Americans. Am J Geriatr Psychiatry. 2017; 25(1):25-34. PMC: 5327822. DOI: 10.1016/j.jagp.2016.10.003. View

Godbout J, Johnson R . Interleukin-6 in the aging brain. J Neuroimmunol. 2004; 147(1-2):141-4. DOI: 10.1016/j.jneuroim.2003.10.031. View

Dhabhar F . Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation. 2009; 16(5):300-17. PMC: 2790771. DOI: 10.1159/000216188. View

Yaffe K, Lindquist K, Penninx B, Simonsick E, Pahor M, Kritchevsky S . Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology. 2003; 61(1):76-80. DOI: 10.1212/01.wnl.0000073620.42047.d7. View

Marsland A, Gianaros P, Abramowitch S, Manuck S, Hariri A . Interleukin-6 covaries inversely with hippocampal grey matter volume in middle-aged adults. Biol Psychiatry. 2008; 64(6):484-90. PMC: 2562462. DOI: 10.1016/j.biopsych.2008.04.016. View

Alley D, Crimmins E, Karlamangla A, Hu P, Seeman T . Inflammation and rate of cognitive change in high-functioning older adults. J Gerontol A Biol Sci Med Sci. 2008; 63(1):50-5. PMC: 2952346. DOI: 10.1093/gerona/63.1.50. View

Williams D, Mohammed S, Leavell J, Collins C . Race, socioeconomic status, and health: complexities, ongoing challenges, and research opportunities. Ann N Y Acad Sci. 2010; 1186:69-101. PMC: 3442603. DOI: 10.1111/j.1749-6632.2009.05339.x. View

Saleh A, Potter G, McQuoid D, Boyd B, Turner R, MacFall J . Effects of early life stress on depression, cognitive performance and brain morphology. Psychol Med. 2016; 47(1):171-181. PMC: 5195852. DOI: 10.1017/S0033291716002403. View

10.

Treadway M, Waskom M, Dillon D, Holmes A, Park M, Chakravarty M . Illness progression, recent stress, and morphometry of hippocampal subfields and medial prefrontal cortex in major depression. Biol Psychiatry. 2014; 77(3):285-294. PMC: 4277904. DOI: 10.1016/j.biopsych.2014.06.018. View

11.

Engelhart M, Geerlings M, Meijer J, Kiliaan A, Ruitenberg A, Van Swieten J . Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch Neurol. 2004; 61(5):668-72. DOI: 10.1001/archneur.61.5.668. View

12.

Mueller S, Schuff N, Yaffe K, Madison C, Miller B, Weiner M . Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer's disease. Hum Brain Mapp. 2010; 31(9):1339-47. PMC: 2943433. DOI: 10.1002/hbm.20934. View

13.

Barnes J, Scahill R, Schott J, Frost C, Rossor M, Fox N . Does Alzheimer's disease affect hippocampal asymmetry? Evidence from a cross-sectional and longitudinal volumetric MRI study. Dement Geriatr Cogn Disord. 2005; 19(5-6):338-44. DOI: 10.1159/000084560. View

14.

Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei X . IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest. 1998; 101(2):311-20. PMC: 508569. DOI: 10.1172/JCI1368. View

15.

Scheef L, Spottke A, Daerr M, Joe A, Striepens N, Kolsch H . Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment. Neurology. 2012; 79(13):1332-9. DOI: 10.1212/WNL.0b013e31826c1a8d. View

16.

Zimmerman M, Ezzati A, Katz M, Lipton M, Brickman A, Sliwinski M . Perceived Stress Is Differentially Related to Hippocampal Subfield Volumes among Older Adults. PLoS One. 2016; 11(5):e0154530. PMC: 4856349. DOI: 10.1371/journal.pone.0154530. View

17.

Elderkin-Thompson V, Irwin M, Hellemann G, Kumar A . Interleukin-6 and memory functions of encoding and recall in healthy and depressed elderly adults. Am J Geriatr Psychiatry. 2012; 20(9):753-63. PMC: 3690956. DOI: 10.1097/JGP.0b013e31825d08d6. View

18.

Wang L, Swank J, Glick I, Gado M, Miller M, Morris J . Changes in hippocampal volume and shape across time distinguish dementia of the Alzheimer type from healthy aging. Neuroimage. 2003; 20(2):667-82. DOI: 10.1016/S1053-8119(03)00361-6. View

19.

Sabuncu M, Desikan R, Sepulcre J, Yeo B, Liu H, Schmansky N . The dynamics of cortical and hippocampal atrophy in Alzheimer disease. Arch Neurol. 2011; 68(8):1040-8. PMC: 3248949. DOI: 10.1001/archneurol.2011.167. View

20.

Juster R, McEwen B, Lupien S . Allostatic load biomarkers of chronic stress and impact on health and cognition. Neurosci Biobehav Rev. 2009; 35(1):2-16. DOI: 10.1016/j.neubiorev.2009.10.002. View