Association between MPV and Cerebral Vascular Ischemic Burden in Mild to Moderate Alzheimers’s Disease

Abstract

Objective: Vascular pathologies and chronic neuroinflammation play an important role in Alzheimer's Disease (AD). Increased platelet activity, which underlies the pathophysiology of atherosclerosis and systemic inflammation, has been reported several times of AD. However, the relationship between this increase and neuroimaging correlates has not been studied yet. This study aims to evaluate the relationship between mean platelet volume (MPV), as a reliable indicator of platelet activity, and vascular ischemic burden in neuroimaging of AD. Materials and Methods: Medical records of mild-moderate AD cases diagnosed in our dementia outpatient clinic between 2021-2022 were retrospectively reviewed. Patients were classified as having "mild" or "severe" vascular ischemic burden on MRI. Clinical findings and platelet markers (Platelet-PLT, Platelet Distribution Width-PDW, Mean Platelet Volume-MPV) were compared between the groups. Multivariate regression was applied for potential confounders regarding vascular ischemic burden. Results: Out of 59 patients, 36 had ‘mild' and 23 had 'severe' ischemic burden. Demographic and clinical features were similar; however, MPV was significantly higher in the group with severe ischemia (p:0.013). Multivariate analysis revealed an independent association between MPV and ischemic burden. An MPV value of ≥8.7 fL had a sensitivity of 69.6% and a specificity of 61% for severe burden. Conclusion: Our results highlight the role of platelet activation in the vascular pathogenesis of AD. During the early evaluation of AD, increased MPV can serve as a marker to determine the high-risk group in terms of cerebral ischemic burden. This might enable close monitoring and timely management of high-risk patients regarding the development of vascular morbidities.

Keywords

• Alzheimer
• mean platelet volume
• MPV
• vascular ischemic burden
• inflammation

Hafif-Orta Evre Alzheimer Hastalığında MPV’nin Serebral Vasküler İskemik Yükle İlişkisi

Abstract

Amaç: Alzheimer Hastalığı’nın (AH) temelinde, vasküler patolojiler ve kronik nöroinflamasyon önemli yer tutmaktadır. Ateroskleroz ve sistemik inflamasyon patofizyolojisinde kritik rol oynayan trombosit aktivitesinin de, AH’de arttığı çok kez bildirilmiştir. Ancak bu artışın, hastalıktaki nörogörüntüleme korelatlarıyla ilişkisi henüz incelenmemiştir. Bu çalışmada amaç, trombosit aktivitesinin göstergesi olan ortalama trombosit hacminin (MPV), AH nörogörüntülemesindeki vasküler iskemik yükle ilişkisini değerlendirmektir. Gereç ve Yöntem: 2021-2022 yılları arasında demans polikliniğimizde tanı alan hafif-orta evre AH olgularının kayıtları retrospektif incelendi. Hastalar MRG’deki iskemik yüke göre “ağır” veya “hafif” olarak sınıflandırıldı ve klinik bulgular ile platelet belirteçleri (Platelet-PLT, Platelet Dağılım Genişliği-PDW, Ortalama Trombosit Hacmi-MPV) gruplar arasında karşılaştırıldı. Vasküler yükle ilişkili potansiyel değişkenlere yönelik çoklu regresyon analizi uygulandı. Bulgular: İncelenen 59 hastanın 36’sı MRG’de ‘hafif’, 23’ü ‘ağır’ vasküler iskemik yüke sahipti. Gruplar demografik ve klinik yönden benzerken; MPV ağır iskemik yükü olan grupta anlamlı yüksekti (p:0.013). Çoklu regresyonda, MPV ve iskemik yük arasında bağımsız ilişki gözlendi. ≥8.7 fL MPV değerinin ağır serebral iskemik yük varlığı açısından %69,6 duyarlılığa ve %61 özgüllüğe sahip olduğu görüldü. Sonuç: Bulgularımız AH vasküler patogenezinde trombosit aktivasyonunun rolünü vurgulamaktadır. Artmış MPV AH’nın erken dönem değerlendirmesinde, serebral iskemik yük açısından yüksek riskli grubun belirlenmesinde bir belirteç olarak kullanılabilir. Bu erken tespit; vasküler morbiditeler açısından yakın takibe ve korunma/tedavi stratejilerini zamanında planlamaya olanak sağlayacaktır.

Keywords

• Anahtar Kelimeler: Alzheimer Hastalığı
• ortalama trombosit hacmi
• MPV
• vasküler iskemik yük
• inflamasyon

References

1. Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al. (2018). American heart association council on epidemiology and prevention statistics committee and stroke statistics subcommittee. heart disease and stroke statistics-2018 update: a report from the american heart association. Circulation, 137(12), e67-e492. https://doi.org/10.1161/CIR.0000000000000558
2. Bermejo P, Martin-Aragon S, Benedi J, Susin C, Felici E, Gil P, et al. (2008). Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer’s disease. Immunol Lett., 117, 198–202. https://doi.org/10.1016/j.imlet.2008.02.002.
3. Casoli T, Di Stefano G, Balietti M, Solazzi M, Giorgetti B, Fattoretti P. (2010). Peripheral inflammatory biomarkers of alzheimer's disease: The role of platelets. Biogerontology, 11(5), 627-633. https://doi.org/10.1007/s10522-010-9281-8
4. Chen SH, Bu XL, Jin WS, Shen LL, Wang J, Zhuang ZQ, et al. (2017). Altered peripheral profile of blood cells in alzheimer disease: A hospital-based case-control study. Medicine (Baltimore), 96(21), e6843. https://doi.org/10.1097/MD.0000000000006843
5. Choi DH, Kang SH, Song H. (2016). Mean platelet volume: A potential biomarker of the risk and prognosis of heart disease. Korean J Intern Med., 31(6), 1009-1017. https://doi.org/10.3904/kjim.2016.078
6. Custodio N, Montesinos R, Lira D, Herrera-Pérez E, Bardales Y, Valeriano-Lorenzo L. (2017). Mixed dementia: A review of the evidence. Dement Neuropsychol., 11(4), 364-370. https://doi.org/10.1590/1980-57642016dn11-040005.
7. De la Torre JC. (2010). Vascular risk factor detection and control may prevent alzheimer's disease. Ageing Res Rev., 9(3), 218-225. https://doi.org/10.1016/j.arr.2010.04.002 Dong X, Nao J, Shi J, Zheng D. (2019). Predictive value of routine peripheral blood biomarkers in alzheimer's disease. Front Aging Neurosci., 11, 332. https://doi.org/10.3389/fnagi.2019.00332
8. Elman-Shina K, Efrati S. (2022). Ischemia as a common trigger for alzheimer's disease. Front Aging Neurosci, 14, 1012779. https://doi.org/10.3389/fnagi.2022.1012779

9. Fazekas F, Chawluk JW, Alavi A, Hurtig HI, Zimmerman RA. (1987). MR Signal Abnormalities at 1.5 T in Alzheimer's Dementia and Normal Aging. AJNR Am J Neuroradiol., 8(3), 421-6. https://doi.org/10.2214/ajr.149.2.351.
10. Greisenegger S, Endler G, Hsieh K, Tentschert S, Mannhalter C, Lalouschek W. (2004). Is elevated mean platelet volume associated with a worse outcome in patients with acute ischemic cerebrovascular events? Stroke; 35(7), 1688-1691. https://doi.org/10.1161/01.STR.0000130512.81212.a2.
11. Guzel S, Unal A, Yıldız O, Oguz K, Kucukyalcin V, Celik Guzel E, et al. (2013). Alzheimer Hastalığında Ortalama Trombosit Hacmi Düzeyleri Vasküler Risk Göstergesi Olabilir mi? International Anatolia Academic Online Journal Health Sciences, 1(2), 3-10.
12. Huang LT, Zhang CP, Wang YB, Wang JH. (2022). Association of peripheral blood cell profile with alzheimer's disease: A meta-analysis. Front Aging Neurosci., 14, 888946. https://doi.org/10.3389/fnagi.2022.888946 Korniluk A, Koper-Lenkiewicz OM, Kaminska J, Kemona H, Dymicka-Piekarska V. (2019). Mean platelet volume (mpv): New perspectives for an old marker in the course and prognosis of inflammatory conditions. Mediators Inflamm., 2019, 9213074. https://doi.org/10.1155/2019/9213074.
13. Krzystanek E, Krzystanek M, Opala G, Trzeciak HI, Siuda J, Małecki A. (2007). Platelet phospholipase A2 activity in patients with Alzheimer’s disease, vascular dementia and ischemic stroke. J Neural Transm., 114, 1033–1039. https://doi.org/10.1007/s00702-007-0669-9
14. Lance MD, Sloep M, Henskens YM, Marcus MA. (2012). Mean platelet volume as a diagnostic marker for cardiovascular disease: Drawbacks of preanalytical conditions and measuring techniques. Clin Appl Thromb Hemost., 18(6), 561-568. https://doi.org/10.1177/1076029612458147
15. Liang QC, Jin D, Li Y, Wang RT. (2014). Mean platelet volume and platelet distribution width in vascular dementia and alzheimer's disease. Platelets, 25(6), 433-438. https://doi.org/10.3109/09537104.2013.831064
16. Prodan CI, Ross ED, Stoner JA, Cowan LD, Vincent AS, Dale GL. (2011). Coated-platelet levels and progression from mild cognitive impairment to Alzheimer disease. Neurology, 76(3), 247-52. https://doi.org/10.1212/WNL.0b013e3182074bd2
17. Sevush S, Jy W, Horstman LL, Mao WW, Kolodny L, Ahn YS. (1998). Platelet Activation in Alzheimer Disease. Arch Neurol., 55(4), 530–536. https://doi.org/10.1001/archneur.55.4.530
18. Slavka G, Perkmann T, Haslacher H, Greisenegger S, Marsik C, Wagner OF, et al. (2011). Mean platelet volume may represent a predictive parameter for overall vascular mortality and ischemic heart disease. Arterioscler Thromb Vasc Biol., 31(5), 1215-1218. https://doi.org/10.1161/ATVBAHA.110.221788.
19. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR (1997). Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA, 277(10), 813-7. PMID: 9052711.
20. Tohgi H, Suzuki H, Tamura K, Kimura B. (1991). Platelet volume, aggregation, and adenosine triphosphate release in cerebral thrombosis. Stroke, 22, 17–21. https://doi.org/10.1161/01.str.22.1.17
21. Talib LL, Joaquim HP, Forlenza OV. (2012). Platelet biomarkers in alzheimer's disease. World J Psychiatry, 2(6), 95-101. https://doi.org/10.5498/wjp.v2.i6.95.
22. Wang RT, Jin D, Li Y, Liang QC. (2013). Decreased mean platelet volume and platelet distribution width are associated with mild cognitive impairment and alzheimer's disease. J Psychiatr Res., 47(5), 644-649. https://doi.org/10.1016/j.jpsychires.2013.01.014
23. Yesil Y, Kuyumcu ME, Cankurtaran M, Uz B, Kara A, Kilic MK, et al. (2012). Increased mean platelet volume (mpv) indicating the vascular risk in alzheimer's disease (ad). Arch Gerontol Geriatr., 55(2), 257-260. https://doi.org/10.1016/j.archger.2011.09.016