BACKGROUND: Studies that have investigated the association between markers of inflammation and risk of dementia are conflicting. Therefore, the researchers conducted a systematic review and meta-analysis of observational studies with the hypothesis that an increased level of peripheral proinflammatory markers would be associated with risk of all-cause dementia or Alzheimer's disease (AD). METHODS: The researchers conducted a literature search of observational studies indexed in the PubMed and PsycInfo databases. Selected studies included those with at least one peripheral inflammatory biomarker and its association with risk of all-cause dementia or AD. Random effects models were used to generate pooled hazard ratios (HRs) comparing the top versus bottom quantile of inflammatory marker level. Heterogeneity was assessed using the I (2) statistic. RESULTS: Seven studies were identified, combining for a total 5,717 participants, 746 cases of all-cause dementia and 565 cases of AD. An increased level of C-reactive protein was associated with a 45% increased risk of all-cause dementia (HR: 1.45; 95% CI: 1.10, 1.91). Similarly, a higher level of interleukin-6 was associated with a 32% increased risk (HR: 1.32; 95% CI: 1.06, 1.64) of all-cause dementia. For AD alone, the association with C-reactive protein was less pronounced (HR: 1.21; 95% CI: 1.03, 1.42) and interleukin-6 was not associated with risk of AD (HR: 1.06; 95% CI: 0.83, 1.35). No significant heterogeneity was found in any of the meta-analyses (I (2) = 0%-40%, p ≥ .16). CONCLUSIONS: An increased peripheral level of inflammatory markers is associated with a modest increase in risk of all-cause dementia. Evidence for an association with risk of AD alone is limited.
BACKGROUND: Studies that have investigated the association between markers of inflammation and risk of dementia are conflicting. Therefore, the researchers conducted a systematic review and meta-analysis of observational studies with the hypothesis that an increased level of peripheral proinflammatory markers would be associated with risk of all-cause dementia or Alzheimer's disease (AD). METHODS: The researchers conducted a literature search of observational studies indexed in the PubMed and PsycInfo databases. Selected studies included those with at least one peripheral inflammatory biomarker and its association with risk of all-cause dementia or AD. Random effects models were used to generate pooled hazard ratios (HRs) comparing the top versus bottom quantile of inflammatory marker level. Heterogeneity was assessed using the I (2) statistic. RESULTS: Seven studies were identified, combining for a total 5,717 participants, 746 cases of all-cause dementia and 565 cases of AD. An increased level of C-reactive protein was associated with a 45% increased risk of all-cause dementia (HR: 1.45; 95% CI: 1.10, 1.91). Similarly, a higher level of interleukin-6 was associated with a 32% increased risk (HR: 1.32; 95% CI: 1.06, 1.64) of all-cause dementia. For AD alone, the association with C-reactive protein was less pronounced (HR: 1.21; 95% CI: 1.03, 1.42) and interleukin-6 was not associated with risk of AD (HR: 1.06; 95% CI: 0.83, 1.35). No significant heterogeneity was found in any of the meta-analyses (I (2) = 0%-40%, p ≥ .16). CONCLUSIONS: An increased peripheral level of inflammatory markers is associated with a modest increase in risk of all-cause dementia. Evidence for an association with risk of AD alone is limited.
Authors: Ulrika K Eriksson; Nancy L Pedersen; Chandra A Reynolds; Mun-Gwan Hong; Jonathan A Prince; Margaret Gatz; Paul W Dickman; Anna M Bennet Journal: J Alzheimers Dis Date: 2011 Impact factor: 4.472
Authors: John C Breitner; Laura D Baker; Thomas J Montine; Curtis L Meinert; Constantine G Lyketsos; Karen H Ashe; Jason Brandt; Suzanne Craft; Denis E Evans; Robert C Green; M Saleem Ismail; Barbara K Martin; Michael J Mullan; Marwan Sabbagh; Pierre N Tariot Journal: Alzheimers Dement Date: 2011-07 Impact factor: 21.566
Authors: Piet Eikelenboom; Erik van Exel; Jeroen J M Hoozemans; Rob Veerhuis; Annemieke J M Rozemuller; Willem A van Gool Journal: Neurodegener Dis Date: 2010-02-13 Impact factor: 2.977
Authors: Reinhold Schmidt; Helena Schmidt; J David Curb; Kamal Masaki; Lon R White; Lenore J Launer Journal: Ann Neurol Date: 2002-08 Impact factor: 10.422
Authors: Johan Sundelöf; Lena Kilander; Johanna Helmersson; Anders Larsson; Elina Rönnemaa; Malin Degerman-Gunnarsson; Hans Basun; Lars Lannfelt; Samar Basu Journal: J Alzheimers Dis Date: 2009 Impact factor: 4.472
Authors: Daniel J Raiten; Fayrouz A Sakr Ashour; A Catharine Ross; Simin N Meydani; Harry D Dawson; Charles B Stephensen; Bernard J Brabin; Parminder S Suchdev; Ben van Ommen Journal: J Nutr Date: 2015-04-01 Impact factor: 4.798
Authors: Margarete A Wichmann; Karen J Cruickshanks; Cynthia M Carlsson; Rick Chappell; Mary E Fischer; Barbara E K Klein; Ronald Klein; Michael Y Tsai; Carla R Schubert Journal: J Am Geriatr Soc Date: 2014-08-14 Impact factor: 5.562
Authors: Jennifer S Yokoyama; Yunpeng Wang; Andrew J Schork; Wesley K Thompson; Celeste M Karch; Carlos Cruchaga; Linda K McEvoy; Aree Witoelar; Chi-Hua Chen; Dominic Holland; James B Brewer; Andre Franke; William P Dillon; David M Wilson; Pratik Mukherjee; Christopher P Hess; Zachary Miller; Luke W Bonham; Jeffrey Shen; Gil D Rabinovici; Howard J Rosen; Bruce L Miller; Bradley T Hyman; Gerard D Schellenberg; Tom H Karlsen; Ole A Andreassen; Anders M Dale; Rahul S Desikan Journal: JAMA Neurol Date: 2016-06-01 Impact factor: 18.302
Authors: Ferenc Deak; Willard M Freeman; Zoltan Ungvari; Anna Csiszar; William E Sonntag Journal: J Gerontol A Biol Sci Med Sci Date: 2015-11-20 Impact factor: 6.053