Association Between Anemia and Dementia: A Nationwide, Populationbased Cohort Study in Taiwan

Author(s): Chien-Tai Hong, Yi-Chen Hsieh, Hung-Yi Liu, Hung-Yi Chiou, Li-Nien Chien*.

Journal Name: Current Alzheimer Research

Volume 17 , Issue 2 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Background: In addition to the traditional risk predictors, whether anemia is an early biomarker of dementia, needs to be confirmed.

Objective: This population-based cohort study aimed to investigate the dementia risk in patients with newly diagnosed anemia using data from the Taiwan National Health Insurance Research Database.

Methods: All newly diagnosed anemia patients (n = 26,343) with no history of stroke hospitalization, central nervous disease other than dementia, psychiatric disorders, traumatic brain injury, major operations, or blood loss diseases, were enrolled. A group of non-anemic controls, 1:4 matched with anemic patients on the basis of demographics and comorbidities, was also included. A competing risk analysis was used to evaluate the dementia risk in anemic patients compared to that of their matched controls.

Results: The adjusted subdistribution hazard ratio (SHR) of dementia risk in anemic patients was 1.14 (95% confidence interval [CI]: 1.08~1.21, p<0.001). Patients with iron supplements tended to exhibit a lower dementia risk (adjusted SHR: 0.84; 95% CI: 0.75~0.94, p=0.002) compared to patients without iron supplement. A subgroup analysis showed that a positive association between dementia and anemia existed in females, those aged 70 years and older, and patients without hypertension, diabetes, or hyperlipidemia.

Conclusion: The present population-based cohort study identified that newly diagnosed anemia is a risk factor for dementia and also that iron supplementation was able to reduce the risk of dementia in people with iron deficiency anemia.

Keywords: Dementia, anemia, population-based cohort study, competing risk analysis, subdistribution hazard ratio, apolipoprotein E4 (ApoE4).

[1]
Prince M, Ali GC, Guerchet M, Prina AM, Albanese E, Wu YT. Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther 8(1): 23-3. (2016).
[http://dx.doi.org/10.1186/s13195-016-0188-8] [PMID: 27473681]
[2]
Dyer SM, Harrison SL, Laver K, Whitehead C, Crotty M. An overview of systematic reviews of pharmacological and non-pharmacological interventions for the treatment of behavioral and psychological symptoms of dementia. Int Psychogeriatr 30(3): 295-309. (2018).
[http://dx.doi.org/10.1017/S1041610217002344] [PMID: 29143695]
[3]
Deckers K, van Boxtel MPJ, Schiepers OJG, et al. Target risk factors for dementia prevention: a systematic review and Delphi consensus study on the evidence from observational studies. Int J Geriatr Psychiatry 30(3): 234-46. (2015).
[http://dx.doi.org/10.1002/gps.4245] [PMID: 25504093]
[4]
Smith JA. Exercise, training and red blood cell turnover. Sports Med 19(1): 9-31. (1995).
[http://dx.doi.org/10.2165/00007256-199519010-00002] [PMID: 7740249]
[5]
Mohanty JG, Nagababu E, Rifkind JM. Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging. Front Physiol 5: 84-4. (2014).
[http://dx.doi.org/10.3389/fphys.2014.00084] [PMID: 24616707]
[6]
Hong CT, Huang YH, Liu HY, Chiou HY, Chan L, Chien LN. Newly diagnosed anemia increases risk of Parkinson’s disease: a Population-Based Cohort Study. Sci Rep 6: 29651. (2016).
[http://dx.doi.org/10.1038/srep29651] [PMID: 27412825]
[7]
Savica R, Grossardt BR, Carlin JM, et al. Anemia or low hemoglobin levels preceding Parkinson disease: a case-control study. Neurology 73(17): 1381-7. (2009).
[http://dx.doi.org/10.1212/WNL.0b013e3181bd80c1] [PMID: 19858460]
[8]
Wu T-Y, Majeed A, Kuo KN. An overview of the healthcare system in Taiwan. London J Prim Care (Abingdon) 3(2): 115-9. (2010).
[http://dx.doi.org/10.1080/17571472.2010.11493315] [PMID: 25949636]
[9]
Cheng TM. Taiwan’s new national health insurance program: genesis and experience so far. Health Aff (Millwood) 22(3): 61-76. (2003).
[http://dx.doi.org/10.1377/hlthaff.22.3.61] [PMID: 12757273]
[10]
Little RJ, Rubin DB. Causal effects in clinical and epidemiological studies via potential outcomes: concepts and analytical approaches. Annu Rev Public Health 21: 121-45. (2000).
[http://dx.doi.org/10.1146/annurev.publhealth.21.1.121] [PMID: 10884949]
[11]
Austin PC. A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003. Stat Med 27(12): 2037-49. (2008).
[http://dx.doi.org/10.1002/sim.3150] [PMID: 18038446]
[12]
Austin PC, Grootendorst P, Anderson GM. A comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study. Stat Med 26(4): 734-53. (2007).
[http://dx.doi.org/10.1002/sim.2580] [PMID: 16708349]
[13]
Chen JH, Lin KP, Chen YC. Risk factors for dementia. J Formos Med Assoc 108(10): 754-64. (2009).
[http://dx.doi.org/10.1016/S0929-6646(09)60402-2] [PMID: 19864195]
[14]
Baumgart M, Snyder HM, Carrillo MC, Fazio S, Kim H, Johns H. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective. Alzheimers Dement 11(6): 718-26. (2015).
[http://dx.doi.org/10.1016/j.jalz.2015.05.016] [PMID: 26045020]
[15]
Roe CM, Fitzpatrick AL, Xiong C, et al. Cancer linked to Alzheimer disease but not vascular dementia. Neurology 74(2): 106-12. (2010).
[http://dx.doi.org/10.1212/WNL.0b013e3181c91873] [PMID: 20032288]
[16]
Lin TM, Chen WS, Sheu JJ, Chen YH, Chen JH, Chang CC. Autoimmune rheumatic diseases increase dementia risk in middle-aged patients: A nationwide cohort study. PLoS One 13(1): e0186475 (2018).
[http://dx.doi.org/10.1371/journal.pone.0186475] [PMID: 29304089]
[17]
Chiang CJ, Yip PK, Wu SC, et al. Midlife risk factors for subtypes of dementia: a nested case-control study in Taiwan. Am J Geriatr Psychiatry 15(9): 762-71. (2007).
[http://dx.doi.org/10.1097/JGP.0b013e318050c98f] [PMID: 17623813]
[18]
Chilcot J, Guirguis A, Friedli K, et al. Depression symptoms in haemodialysis patients predict all-cause mortality but not kidney transplantation: a cause-specific outcome analysis. Ann Behav Med 52(1): 1-8. (2018).
[http://dx.doi.org/10.1007/s12160-017-9918-9] [PMID: 28762106]
[19]
Austin PC, Lee DS, Fine JP. Introduction to the analysis of survival data in the presence of competing risks. Circulation 133(6): 601-9. (2016).
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.017719] [PMID: 26858290]
[20]
Andersen PK, Geskus RB, de Witte T, Putter H. Competing risks in epidemiology: possibilities and pitfalls. Int J Epidemiol 41(3): 861-70. (2012).
[http://dx.doi.org/10.1093/ije/dyr213] [PMID: 22253319]
[21]
Jack CR Jr, Knopman DS, Jagust WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol 9(1): 119-28. (2010).
[http://dx.doi.org/10.1016/S1474-4422(09)70299-6] [PMID: 20083042]
[22]
Carmel R. Anemia and aging: an overview of clinical, diagnostic and biological issues. Blood Rev 15(1): 9-18. (2001).
[http://dx.doi.org/10.1054/blre.2001.0146] [PMID: 11333135]
[23]
Bissinger R, Bhuyan AAM, Qadri SM, Lang F. Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases. FEBS J 286(5): 826-54. (2019).
[http://dx.doi.org/10.1111/febs.14606] [PMID: 30028073]
[24]
Jeong SM, Shin DW, Lee JE, Hyeon JH, Lee J, Kim S. Anemia is associated with incidence of dementia: a national health screening study in Korea involving 37,900 persons. Alzheimers Res Ther 9(1): 94. (2017).
[http://dx.doi.org/10.1186/s13195-017-0322-2] [PMID: 29212527]
[25]
Chung SD, Sheu JJ, Kao LT, Lin HC, Kang JH. Dementia is associated with iron-deficiency anemia in females: a population-based study. J Neurol Sci 346(1-2): 90-3. (2014).
[http://dx.doi.org/10.1016/j.jns.2014.07.062] [PMID: 25127441]
[26]
Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 352(10): 1011-23. (2005).
[http://dx.doi.org/10.1056/NEJMra041809] [PMID: 15758012]
[27]
Nakabeppu Y, Tsuchimoto D, Furuichi M, Sakumi K. The defense mechanisms in mammalian cells against oxidative damage in nucleic acids and their involvement in the suppression of mutagenesis and cell death. Free Radic Res 38(5): 423-9. (2004).
[http://dx.doi.org/10.1080/10715760410001688348] [PMID: 15293549]
[28]
Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr 85(1): 193-200. (2007).
[http://dx.doi.org/10.1093/ajcn/85.1.193] [PMID: 17209196]
[29]
Cevik B, Solmaz V, Yigitturk G, Cavusoğlu T, Peker G, Erbas O. Neuroprotective effects of erythropoietin on Alzheimer’s dementia model in rats. Adv Clin Exp Med 26(1): 23-9. (2017).
[http://dx.doi.org/10.17219/acem/61044] [PMID: 28397428]
[30]
Dehejia RH, Wahba S. Propensity score-matching methods for nonexperimental causal studies. Rev Econ Stat 84(1): 151-61. (2002).
[http://dx.doi.org/10.1162/003465302317331982]
[31]
Johnson SR, Tomlinson GA, Hawker GA, Granton JT, Feldman BM. Propensity score methods for bias reduction in observational studies of treatment effect. Rheum Dis Clin North Am 44(2): 203-13. (2018).
[http://dx.doi.org/10.1016/j.rdc.2018.01.002] [PMID: 29622292]
[32]
McAfee AT, Ming EE, Seeger JD, et al. The comparative safety of rosuvastatin: a retrospective matched cohort study in over 48,000 initiators of statin therapy. Pharmacoepidemiol Drug Saf 15(7): 444-53. (2006).
[http://dx.doi.org/10.1002/pds.1281] [PMID: 16761308]
[33]
Prada-Ramallal G, Takkouche B, Figueiras A. Bias in pharmacoepidemiologic studies using secondary health care databases: a scoping review. BMC Med Res Methodol 19(1): 53-3. (2019).
[http://dx.doi.org/10.1186/s12874-019-0695-y] [PMID: 30871502]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 2
Year: 2020
Page: [196 - 204]
Pages: 9
DOI: 10.2174/1567205017666200317101516
Price: $65

Article Metrics

PDF: 11