Dement Neurocogn Disord.  2012 Dec;11(4):131-135. 10.12779/dnd.2012.11.4.131.

A Clinical Significance of High-Sensitivity C-reactive Protein Level in Alzheimer's Disease and Vascular Dementia

• Wang MJ
• Lim EY
• Kim YD
• Song IU
• Chung SW
• Yang YS

• KMID: 2052196
• DOI: http://doi.org/10.12779/dnd.2012.11.4.131

Abstract

BACKGROUND
There is increasing evidence about inflammatory processes in the development of dementia. Therefore, inflammation has been believed to play a pivot role in cognitive decline, Alzheimer's disease (AD), and vascular dementia. High-sensitivity C-reactive protein (hs-CRP) is a sensitive systemic marker of inflammation, and increased levels of hs-CRP are associated with inflammatory reactions. It is important to identify modifiable risk factors, which could be used in preventing or delaying the onset of dementia. Therefore, we studied to clarify a clinical role of hs-CRP in AD and VaD.
METHODS
This study population consisted of a sample of 102 patients with dementia (54 patients of AD and 48 patients of VaD) and 91 controls. We have investigated hs-CRP levels and cognitive function of each group. Cognitive function was evaluated with Mini-Mental State Examination (MMSE), Global Deterioration Scale (GDS), Clinical Dementia Rating (CDR) with Sum of Box and Activities of Daily Living (ADL).
RESULTS
All subjects with dementia showed higher hs-CRP levels than subjects without dementia. But, there was no significant difference of hs-CRP levels between patients with AD and those with VaD. The odds ratio of patients with AD and VaD by hs-CRP is 2.250 (95% Cl 1.670-3.032) for Alzheimer's disease and 4.0 (95% Cl 2.451-6.529) for vascular dementia.
CONCLUSIONS
The result of our study suggests the presence of inflammatory activity is related with dementia, not only AD known to degenerative disease but also VaD associated with cerebrovascular disease. However, we could suggest that dementia with cerebrovascular lesions is more related with inflammatory activity than AD.

Keyword

Inflammation; High-sensitivity C-reactive protein; Alzheimer's disease; Vascular dementia

MeSH Terms

Activities of Daily Living
Alzheimer Disease
C-Reactive Protein
Dementia
Dementia, Vascular
Humans
Inflammation
Odds Ratio
Risk Factors
C-Reactive Protein

Figure

• 

  Fig. 1 Mean hs-CRP value of patients with Alzheimer's disease (AD) and Vascular dementia (VaD) compared with normal controls. Mean hs-CRP value of AD and VaD patients are higher than normal controls (AD: 2.53±7.42, VaD: 1.39±1.77, Normal control: 0.074±0.06). The differences of hs-CRP value between AD and VaD patients are not significant statistically (p=0.768).

• 

  Fig. 2 Odds Ratio and 95% confidence interval (CI) of patients with Alzheimer's disease (AD) and Vascular dementia (VaD) compared with normal controls for high-sensitivity C-reactive protein (hs-CRP). Values are expressed as odd ratio (95% CI). Rectangles indicate odds ratio and vertical lines represent 95% CIs.

Reference

1. Skoog I, Lernfelt B, Landahl S, Palmertz B, Andreasson LA, Nilsson L, et al. 15-year longitudinal study of blood pressure and dementia. Lancet. 1996. 347:1141–1145.

2. Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, et al. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000. 21:49–55.

3. Hofman A, Ott A, Breteler MM, Bots ML, Slooter AJ, van Harskamp F, et al. Athero-sclerosis apolipoprotein E, and prevalence of dementia and Alzheimers disease in the Rotterdam Study. Lancet. 1997. 349:151–154.

4. Ott A, Breteler MM, de Bruyne MC, van Harskamp FC, Grobbee DE, Hofman A. Atrial fibrillation and dementia in a popula-tion-based study. The Rotterdam Study. Stroke. 1997. 28:316–321.

5. Yoshitake T, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, et al. Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study. Neurology. 1995. 45:1161–1168.

6. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and risk of dementia: the Rotterdam Study. Neurology. 1999. 53:1937–1942.

7. Gustafson D, Rotenberg E, Blennow K, Steen B, Skoog I. An 18-year follow-up of over-weight and risk of Alzheimer disease. Arch Intern Med. 2003. 163:1524–1528.

8. Honig LS, Tang MX, Albert S, Costa R, Luchsinger J, Manly J, et al. Stroke and the risk of Alzheimer's disease. Arch Neurol. 2003. 60:1707–1712.

9. Bassuk SS, Rifai N, Ridker PM. High sensitive C-reactive protein: clinical importance. Curr Probl Cardiol. 2004. 29:439–493.

10. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002. 347:1557–1565.

11. Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, et al. Low grade inflammation and coronary heart disease: prospective study and updated metaanalyses. BMJ. 2000. 321:199–204.

12. Praticó D, Trojanowski JQ. Inflammatory hypotheses: novel mechanisms of Alzheimer's neurodegeneration and new therapeutic targets? Neurobiol Aging. 2000. 21:441–445.

13. Breteler MBB. Vascular involvement in cognitive decline and dementia: epidemiologic evidence from the Rotterdam Study and the Rotterdam Scan Study. Ann N Y Acad Sci. 2000. 903:457–465.

14. Kuo HS, Yen CJ, Chang CH, Kuo CK, Chen JH, Sorond F. Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet Neurol. 2005. 4:371–380.

15. Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, Launer LJ. Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging study. Ann Neurol. 2002. 52:168–174.

16. Ravaglia G, Forti P, Maioli F, Bastagli L, Chiappelli M, Montesi F, et al. Blood inflammatory markers and risk of dementia: the Conselice Study of brain aging. Neurobiol Aging. 2007. 28:1810–1820.

17. Nilsson K, Gustafson L, Hultberg B. The lack of association between plasma homocysteine and inflammation in psychogeriatric patients. Dement Geriatr Cogn Disord. 2002. 14:151–155.

18. Nilsson K, Gustafson L, Hultberg B. C-reactive protein: vascular risk marker in elderly patients with mental illness. Dement Geriatr Cogn Disord. 2008. 26:251–256.

19. Locascio JJ, Fukumoto H, Yap L, Bottiglieri T, Growden JH, Hyman BT, et al. Plasma amyloid beta-protein and C-reactive protein in relation to the rate of progression of Alzheimer disease. Arch Neurol. 2008. 65:776–778.

20. Rost NS, Wolf PA, Kase CS, Kelly-Hayes M, Silbershatz H, Massaro JM, et al. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke. 2001. 32:2575–2579.

21. Yaffe K, Lindquist K, Penninx BW, Simonsick EM, Pahor M, Kritchevsky S, et al. Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology. 2003. 61:76–80.

22. McGeer EG, Yasojima K, Schwab C, McGeer PL. The pentraxins: possible role in Alzheimer's disease and other innate inflammatory diseases. Neurobiol Aging. 2001. 22:843–848.

23. Luchsinger JA, Mayeux R. Cardiovascular risk factors and Alzheimer's disease. Curr Atheroscler Rep. 2004. 6:261–266.

24. Casserly I, Topol E. Convergence of atherosclerosis and Alzheimer's disease: inflammation, cholesterol, and misfolded proteins. Lancet. 2004. 363:1139–1146.

25. O'Bryant SE, Waring SC, Hobson V, Hall JR, Moore CB, Bottiglieri T, et al. Decreased C-reactive protein levels in Alzheimer disease. J Geriatr Psychiatry Neurol. 2010. 23:49–53.

26. White L, Petrovitch H, Hardman J, Nelson J, Davis DG, Ross GW, et al. Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants. Ann NY Acad Sci. 2002. 977:9–23.

27. Kravitz BA, Corrada MM, Kawas CH. Elevated C-reactive protein levels are associated with prevalent dementia in the oldest-old. Alzheimers Dement. 2009. 5:318–323.

28. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al. Inflammation and Alzheimer's disease. Neurobiol Aging. 2000. 21:383–421.