Skip to main content

Advertisement

Log in

Endothelial dysfunction associated with mild cognitive impairment in elderly population

  • Original Article
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

Background and aims

According to the original Petersen criteria, we investigated the association between endothelial dysfunction and mild cognitive impairment (MCI) by flow-mediated dilation (FMD). We aimed to verify if endothelial dysfunction occurs in MCI and whether vascular factors are implicated in the MCI pathogenesis.

Methods

This is a cross-sectional study performed on 34 subjects with clinical diagnosis of MCI and 37 controls, older than 60 years. Patients were enrolled from a geriatric outpatient clinic. All the recognized cardiovascular risk factors and an objective state of cognitive impairment were used as exclusion criteria. Cognitive function was evaluated using a scientific-validated neuropsychological battery, whereas MCI was recognized according to the Petersen criteria. Endothelial function was evaluated according to FMD from the brachial artery. The association between FMD and MCI was evaluated both by using a multivariate analysis and a correlation test. Finally, using the ANOVA analysis of variance, we tested the differences in flow-mediated dilation among MCI subgroups.

Results

Brachial FMD was significantly associated with MCI (p < 0.01). The multivariate analysis showed that age, years of education and MMSE independently predicted the FMD variation (r 2 = 0.73; p < 0.0001). In addition, MCI patients with prevalent amnestic multiple domain impairment showed the worst brachial FMD.

Conclusions

This finding suggests that vascular dysfunction may play a role in the pathogenesis of cognitive impairment and underlines the lack of therapeutic strategies targeted to such dysfunctions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC (2004) Mild cognitive impairment-beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256:240–246

    Article  PubMed  CAS  Google Scholar 

  2. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56:303–308

    Article  PubMed  CAS  Google Scholar 

  3. Petersen RC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med 256:183–194

    Article  PubMed  CAS  Google Scholar 

  4. Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, Belleville S, Brodaty H, Bennett D, Chertkow H, Cummings JL, de Leon M, Feldman H, Ganguli M, Hampel H, Scheltens P, Tierney MC, Whitehouse P, Winblad B (2006) Mild cognitive impairment. Lancet 367:1262–1270

    Article  PubMed  Google Scholar 

  5. Trittschuh EH, Crane PK, Larson EB, Cholerton B, McCormick WC, McCurry SM, Bowen JD, Baker LD, Craft S (2011) Effects of varying diagnostic criteria on prevalence of mild cognitive impairment in a community based sample. J Alzheimers Dis 25(1):163–173

    Google Scholar 

  6. Schinka JA, Loewenstein DA, Raj A, Schoenberg MR, Banko JL, Potter H, Duara R (2010) Defining mild cognitive impairment: impact of varying decision criteria on neuropsychological diagnostic frequencies and correlates. Am J Geriatr Psychiatry 18:684–691

    Article  PubMed  Google Scholar 

  7. Petersen RC, Waring SC, Smith GE, Tangalos EG, Thibodeau SN (1996) Predictive value of APOE genotyping in incipient Alzheimer’s disease. Ann N Y Acad Sci 802:58–69

    Article  PubMed  CAS  Google Scholar 

  8. Ritchie K, Artero S, Touchon J (2001) Classification criteria for mild cognitive impairment: a population-based validation study. Neurology 56:37–42

    Article  PubMed  CAS  Google Scholar 

  9. Ritchie K, Touchon J (2000) Mild cognitive impairment: conceptual basis and current nosological status. Lancet 355:225–228

    Article  PubMed  CAS  Google Scholar 

  10. Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R (2005) Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology 65:545–551

    Article  PubMed  CAS  Google Scholar 

  11. Luchsinger JA, Brickman AM, Reitz C, Cho SJ, Schupf N, Manly JJ, Tang MX, Small SA, Mayeux R, DeCarli C, Brown TR (2009) Subclinical cerebrovascular disease in mild cognitive impairment. Neurology 73:450–456

    Article  PubMed  CAS  Google Scholar 

  12. de la Torre JC (2010) Vascular risk factor detection and control may prevent Alzheimer’s disease. Ageing Res Rev 9:218–225

    Article  PubMed  Google Scholar 

  13. Dede DS, Yavuz B, Yavuz BB, Cankurtaran M, Halil M, Ulger Z, Cankurtaran ES, Aytemir K, Kabakci G, Ariogul S (2007) Assessment of endothelial function in Alzheimer’s disease: is Alzheimer’s disease a vascular disease? J Am Geriatr Soc 55:1613–1617

    Article  PubMed  Google Scholar 

  14. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39:257–265

    Article  PubMed  Google Scholar 

  15. de Matthaeis A, Greco A, Serviddio G, Stramaglia G, Vendemiale G (2010) Endothelial dysfunction evaluated by flow mediated dilation is strongly associated to metabolic syndrome in the elderly. Aging Clin Exp Res 22(4):303–307

    Google Scholar 

  16. Rickham PP (1964) Human experimentation code of ethics of the World Medical Association. Declaration of Helsinki. Br Med J2:177–177

  17. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  PubMed  CAS  Google Scholar 

  18. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL (1982) A new clinical scale for the staging of dementia. Br J Psychiatry 140:566–572

    Article  PubMed  CAS  Google Scholar 

  19. Carlesimo GA, Caltagirone C, Gainotti G (1996) The Mental Deterioration Battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. The Group for the Standardization of the Mental Deterioration Battery. Eur Neurol 36:378–384

    Article  PubMed  CAS  Google Scholar 

  20. Spoletini I, Marra C, Di IF, Gianni W, Sancesario G, Giubilei F, Trequattrini A, Bria P, Caltagirone C, Spalletta G (2008) Facial emotion recognition deficit in amnestic mild cognitive impairment and Alzheimer disease. Am J Geriatr Psychiatry 16:389–398

    Article  PubMed  Google Scholar 

  21. Katz S, Akpom CA (1976) A measure of primary sociobiological functions. Int J Health Serv 6:493–508

    Article  PubMed  CAS  Google Scholar 

  22. Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186

    Article  PubMed  CAS  Google Scholar 

  23. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340:1111–1115

    Article  PubMed  CAS  Google Scholar 

  24. Juonala M, Kahonen M, Laitinen T, Hutri-Kahonen N, Jokinen E, Taittonen L, Pietikainen M, Helenius H, Viikari JS, Raitakari OT (2008) Effect of age and sex on carotid intima-media thickness, elasticity and brachial endothelial function in healthy adults: the cardiovascular risk in Young Finns Study. Eur Heart J29:1198–1206

    Article  Google Scholar 

  25. Tsuchiya K, Nakayama C, Iwashima F, Sakai H, Izumiyama H, Doi M, Hirata Y (2007) Advanced endothelial dysfunction in diabetic patients with multiple risk factors; importance of insulin resistance. J Atheroscler Thromb 14:303–309

    Article  PubMed  CAS  Google Scholar 

  26. Taddei S, Virdis A, Mattei P, Ghiadoni L, Fasolo CB, Sudano I, Salvetti A (1997) Hypertension causes premature aging of endothelial function in humans. Hypertension 29:736–743

    Article  PubMed  CAS  Google Scholar 

  27. Lind L (2006) Impact of ageing on the measurement of endothelium-dependent vasodilation. Pharmacol Rep 58(Suppl):41–46

    Google Scholar 

  28. Yavuz BB, Yavuz B, Sener DD, Cankurtaran M, Halil M, Ulger Z, Nazli N, Kabakci G, Aytemir K, Tokgozoglu L, Oto A, Ariogul S (2008) Advanced age is associated with endothelial dysfunction in healthy elderly subjects. Gerontology 54:153–156

    Article  PubMed  CAS  Google Scholar 

  29. Kimura Y, Matsumoto M, Den YB, Iwai K, Munehira J, Hattori H, Hoshino T, Yamada K, Kawanishi K, Tsuchiya H (1999) Impaired endothelial function in hypertensive elderly patients evaluated by high resolution ultrasonography. Can J Cardiol 15:563–568

    PubMed  CAS  Google Scholar 

  30. Yeboah J, Burke GL, Crouse JR, Herrington DM (2008) Relationship between brachial flow-mediated dilation and carotid intima-media thickness in an elderly cohort: the Cardiovascular Health Study. Atherosclerosis 197:840–845

    Article  PubMed  CAS  Google Scholar 

  31. Luis CA, Barker WW, Loewenstein DA, Crum TA, Rogaeva E, Kawarai T, St George-Hyslop P, Duara R (2004) Conversion to dementia among two groups with cognitive impairment. A preliminary report. Dement Geriatr Cogn Disord 18:307–313

    Article  PubMed  Google Scholar 

  32. Elias-Sonnenschein LS, Viechtbauer W, Ramakers IH, Verhey FR, Visser PJ (2011) Predictive value of APOE-epsilon4 allele for progression from MCI to AD-type dementia: a meta-analysis. J Neurol Neurosurg Psychiatry 82:1149–1156

    Article  PubMed  Google Scholar 

  33. Yip AG, McKee AC, Green RC, Wells J, Young H, Cupples LA, Farrer LA (2005) APOE, vascular pathology, and the AD brain. Neurology 65:259–265

    Article  PubMed  CAS  Google Scholar 

  34. Hamalainen A, Grau-Olivares M, Tervo S, Niskanen E, Pennanen C, Huuskonen J, Kivipelto M, Hanninen T, Tapiola M, Vanhanen M, Hallikainen M, Helkala EL, Nissinen A, Vanninen RL, Soininen H (2008) Apolipoprotein E epsilon 4 allele is associated with increased atrophy in progressive mild cognitive impairment: a voxel-based morphometric study. Neurodegener Dis 5:186–189

    Article  PubMed  CAS  Google Scholar 

  35. Guangda X, Yuhua W (2003) Apolipoprotein e4 allele and endothelium-dependent arterial dilation in Type 2 diabetes mellitus without angiopathy. Diabetologia 46:514–519

    PubMed  CAS  Google Scholar 

  36. Guang-da X, You-ying L, Zhi-song C, Yu-sheng H, Xiang-jiu Y (2004) Apolipoprotein e4 allele is predictor of coronary artery disease death in elderly patients with type 2 diabetes mellitus. Atherosclerosis 175:77–81

    Article  PubMed  Google Scholar 

  37. Helzner EP, Luchsinger JA, Scarmeas N, Cosentino S, Brickman AM, Glymour MM, Stern Y (2009) Contribution of vascular risk factors to the progression in Alzheimer disease. Arch Neurol 66:343–348

    Article  PubMed  Google Scholar 

  38. de la Torre JC (2010) The vascular hypothesis of Alzheimer’s disease: bench to bedside and beyond. Neurodegener Dis 7:116–121

    Article  PubMed  Google Scholar 

  39. Grammas P (2011) Neurovascular dysfunction, inflammation and endothelial activation: implications for the pathogenesis of Alzheimer’s disease. J Neuroinflammation 8:26

    Article  PubMed  CAS  Google Scholar 

  40. Serviddio G, Romano AD, Cassano T, Bellanti F, Altomare E, Vendemiale G (2011) Principles and therapeutic relevance for targeting mitochondria in aging and neurodegenerative diseases. Curr Pharm Des 17:2036–2055

    Article  PubMed  CAS  Google Scholar 

  41. DeCarli C (2003) Mild cognitive impairment: prevalence, prognosis, aetiology, and treatment. Lancet Neurol 2:15–21

    Article  PubMed  Google Scholar 

  42. Avorn J (1983) Biomedical and social determinants of cognitive impairment in the elderly. J Am Geriatr Soc 31:137–143

    PubMed  CAS  Google Scholar 

  43. Ojala-Oksala J, Jokinen H, Kopsi V, Lehtonen K, Luukkonen L, Paukkunen A, Seeck L, Melkas S, Pohjasvaara T, Karhunen P, Hietanen M, Erkinjuntti T, Oksala N (2012) Educational history is an independent predictor of cognitive deficits and long-term survival in postacute patients with mild to moderate ischemic stroke. Stroke 43(11):2931–2935

    Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gianluigi Vendemiale.

Additional information

G. Vendemiale and A. D. Romano contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vendemiale, G., Romano, A.D., Dagostino, M. et al. Endothelial dysfunction associated with mild cognitive impairment in elderly population. Aging Clin Exp Res 25, 247–255 (2013). https://doi.org/10.1007/s40520-013-0043-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40520-013-0043-8

Keywords

Navigation