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Peripheral inflammation in mild cognitive impairment with possible and probable Lewy body disease and Alzheimer’s disease

  • Eleanor King (a1), John Tiernan O’Brien (a2), Paul Donaghy (a1), Christopher Morris (a1), Nicola Barnett (a1), Kirsty Olsen (a1), Carmen Martin-Ruiz (a1), John Paul Taylor (a1) and Alan J. Thomas (a1)...


Objectives and design:

To Investigate the peripheral inflammatory profile in patients with mild cognitive impairment (MCI) from three subgroups – probable Lewy body disease (probable MCI-LB), possible Lewy body disease, and probable Alzheimer’s disease (probable MCI-AD) – as well as associations with clinical features.


Memory clinics and dementia services.


Patients were classified based on clinical symptoms as probable MCI-LB (n = 38), possible MCI-LB (n = 18), and probable MCI-AD (n = 21). Healthy comparison subjects were recruited (n = 20).


Ten cytokines were analyzed from plasma samples: interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor (TNF)-alpha. C-reactive protein levels were investigated.


There was a higher level of IL-10, IL-1beta, IL-2, and IL-4 in MCI groups compared to the healthy comparison group (p < 0.0085). In exploratory analyses to understand these findings, the MC-AD group lower IL-1beta (p = 0.04), IL-2 (p = 0.009), and IL-4 (p = 0.012) were associated with increasing duration of memory symptoms, and in the probable MCI-LB group, lower levels of IL-1beta were associated with worsening motor severity (p = 0.002). In the possible MCI-LB, longer duration of memory symptoms was associated with lower levels of IL-1beta (p = 0.003) and IL-4 (p = 0.026).


There is increased peripheral inflammation in patients with MCI compared to healthy comparison subjects regardless of the MCI subtype. These possible associations with clinical features are consistent with other work showing that inflammation is increased in early disease but require replication. Such findings have importance for timing of putative therapeutic strategies aimed at lowering inflammation.


Corresponding author

Correspondence should be addressed to: Eleanor King, Institute of Neuroscience, Biomedical Research Building, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE4 5PL, United Kingdom. Phone: 0191 208 1318; Fax: 0191 208 1301. Email:


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Albert, M. S. et al. (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7, 270279. doi: 10.1016/j.jalz.2011.03.008.
Bettcher, B. M. et al. (2018). Cerebrospinal fluid and plasma levels of inflammation differentially relate to CNS markers of Alzheimer’s disease pathology and neuronal damage. Journal of Alzheimer’s Disease, 62, 385397. doi: 10.3233/JAD-170602.
Cooper, C., Sommerlad, A., Lyketsos, C. G. and Livingston, G. (2015). Modifiable predictors of dementia in mild cognitive impairment: a systematic review and meta-analysis. American Journal of Psychiatry, 172, 323334. doi: 10.1176/appi.ajp.2014.14070878.
Cummings, J. L. et al. (1994). The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology, 44, 23082314. doi: 10.1212/WNL.44.12.2308.
Dantzer, R. et al. (1999). Mechanisms of the behavioural effects of cytokines. Advances in Experimental Medicine and Biology, 461, 83105. doi: 10.1007/b102345.
de Waal Malefyt, R., Abrams, J., Bennett, B., Figdor, C. G. and De Vries, J. E. (1991). Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. Journal of Experimental Medicine, 174, 12091220. doi: 10.1084/jem.174.5.1209.
Donaghy, P.C. et al. (2018). Neurophsychiatric symptoms and cognitive profile in mild cognitive impairment with Lewy bodies. Psychological Medicine 24, 17. doi: 10.1017/S0033291717003956.
Dufek, M. et al. (2009). Serum inflammatory biomarkers in Parkinson’s disease. Parkinsonism and Related Disorders, 15, 318320. doi: 10.1016/j.parkreldis.2008.05.014.
Engelhart, M. J. et al. (2004). Inflammatory proteins in plasma and the risk of dementia: the Rotterdam study. Archives of Neurology, 61, 668672. doi: 10.1001/archneur.61.5.668.
Furney, S. J. et al. (2011). Combinatorial markers of mild cognitive impairment conversion to Alzheimer’s disease – cytokines and MRI measures together predict disease progression. Journal of Alzheimer’s Disease, 26, 395405. doi: 10.3233/JAD-2011-0044.
Galimberti, D. et al. (2006). Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. Archives of Neurology, 63, 538543. doi: 10.1001/archneur.63.4.538.
Goetz, C. G. et al. (2008). Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Movement Disorders, 23, 21292170. doi: 10.1002/mds.v23:15.
Heneka, M. T. et al. (2015). Neuroinflammation in Alzheimer’s disease. Lancet Neurology, 14, 388405. doi: 10.1016/S1474-4422(15)70016-5.
Holmes, C. (2013). Review: systemic inflammation and Alzheimer’s disease. Neuropathology and Applied Neurobiology, 39, 5168. doi: 10.1111/nan.2013.39.issue-1.
King, E. et al. (2017). Peripheral inflammation in prodromal Alzheimer’s and Lewy body dementias. Journal of Neurology, Neurosurgery, and Psychiatry, 89, 339345. doi: 10.1136/jnnp-2017-317134.
King, E. and Thomas, A. (2017). Systemic inflammation in Lewy body diseases: a systematic review. Alzheimer Disease and Associated Disorders, 31, 346356. doi: 10.1097/WAD.0000000000000211.
Koyama, A., O’Brien, J., Weuve, J., Blacker, D., Metti, A. L. and Yaffe, K. (2013). The role of peripheral inflammatory markers in dementia and Alzheimer’s disease: a meta-analysis. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 68, 433440. doi: 10.1093/gerona/gls187.
Lawton, M. P. and Brody, E. M. (1969). Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist, 9, 179186. doi: 10.1093/geront/9.3_Part_1.179.
Magaki, S., Mueller, C., Dickson, C. and Kirsch, W. (2007). Increased production of inflammatory cytokines in mild cognitive impairment. Experimental Gerontology, 42, 233240. doi: 10.1016/j.exger.2006.09.015.
Marcos, G. et al. (2016). Conversion to dementia in mild cognitive impairment diagnosed with DSM-5 criteria and with Petersen’s criteria. Acta Psychiatrica Scandinavica, 133, 378385. doi: 10.1111/acps.12543.
McKeith, I. et al. (2007). Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurology, 6, 305313. doi: 10.1016/S1474-4422(07)70057-1.
McKeith, I. G. (2002). Dementia with Lewy bodies. British Journal of Psychiatry, 180, 144147. doi: 10.1192/bjp.180.2.144.
McKeith, I. G. et al. (2017). Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology, 89, 88100. doi: 10.1212/WNL.0000000000004058.
McKhann, G. M. et al. (2011). The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7, 263269. doi: 10.1016/j.jalz.2011.03.005.
Miguel-Alvarez, M. et al. (2015). Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer’s disease: a systematic review and meta-analysis of treatment effect. Drugs Aging, 32, 139147. doi: 10.1007/s40266-015-0239-z.
Miller, M. D. et al. (1992). Rating chronic medical illness burden in geropsychiatric practice and research: application of the cumulative illness rating scale. Psychiatry Research, 41, 237248. doi: 10.1016/0165-1781(92)90005-N.
Mioshi, E., Dawson, K., Mitchell, J., Arnold, R. and Hodges, J. R. (2006). The Addenbrooke’s Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. International Journal of Geriatric Psychiatry, 21, 10781085. doi: 10.1002/(ISSN)1099-1166.
Monsonego, A., Maron, R., Zota, V., Selkoe, D. J. and Weiner, H. L. (2001). Immune hyporesponsiveness to amyloid beta-peptide in amyloid precursor protein transgenic mice: implications for the pathogenesis and treatment of Alzheimer’s disease. Proceedings of the National Academy of Sciences of the USA, 98, 1027310278. doi: 10.1073/pnas.191118298.
Motta, M., Imbesi, R., Di Rosa, M., Stivala, F. and Malaguarnera, L. (2007). Altered plasma cytokine levels in Alzheimer’s disease: correlation with the disease progression. Immunology Letters, 114, 4651. doi: 10.1016/j.imlet.2007.09.002.
O’Brien, J. T. et al. (2009). Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies. British Journal of Psychiatry, 194, 3439. doi: 10.1192/bjp.bp.108.052050.
Reale, M. et al. (2009). Peripheral cytokines profile in Parkinson’s disease. Brain, Behavior, and Immunity, 23, 5563. doi: 10.1016/j.bbi.2008.07.003.
Song, D. K., Im, Y. B., Jung, J. S., Cho, J., Suh, H. W. and Kim, Y. H. (2001). Central beta-amyloid peptide-induced peripheral interleukin-6 responses in mice. Journal of Neurochemistry, 76, 13261335. doi: 10.1046/j.1471-4159.2001.00121.x.
Swardfager, W., Lanctot, K., Rothenburg, L., Wong, A., Cappell, J. and Herrmann, N. (2010). A meta-analysis of cytokines in Alzheimer’s disease. Biological Psychiatry, 68, 930941. doi: 10.1016/j.biopsych.2010.06.012.
Thomas, A. J. et al. (2018). Diagnostic accuracy of dopaminergic imaging in prodromal dementia with Lewy bodies. Psychological Medicine (in press). doi: 10.1017/S0033291718000995.
Verghese, J., Crystal, H. A., Dickson, D. W. and Lipton, R. B. (1999). Validity of clinical criteria for the diagnosis of dementia with Lewy bodies. Neurology, 53, 19741974. doi: 10.1212/WNL.53.9.1974.
Walker, Z. et al. (2016). Evolution of clinical features in possible DLB depending on FP-CIT SPECT result. Neurology, 87, 10451051. doi: 10.1212/WNL.0000000000003076.


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Peripheral inflammation in mild cognitive impairment with possible and probable Lewy body disease and Alzheimer’s disease

  • Eleanor King (a1), John Tiernan O’Brien (a2), Paul Donaghy (a1), Christopher Morris (a1), Nicola Barnett (a1), Kirsty Olsen (a1), Carmen Martin-Ruiz (a1), John Paul Taylor (a1) and Alan J. Thomas (a1)...


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