Peripheral Immune Dysregulation and Blood Biomarkers in Vascular Cognitive Impairment and Vascular Dementia
Peripheral Immune Dysregulation and Serum Biomarkers in Vascular Dementia
Abstract
Vascular cognitive impairment (VCI) and vascular dementia (VaD) are major clinical consequences of cerebrovascular injury, with cerebral small vessel disease (CSVD) serving as their most common structural substrate. Although neuroimaging and cognitive assessment remain central to diagnosis and follow-up, accessible blood-based tools for early risk identification and progression monitoring are still limited.
Emerging evidence suggests that peripheral immune dysregulation contributes to CSVD progression through chronic inflammatory imbalance, endothelial dysfunction, blood-brain barrier vulnerability, and inflammation-coagulation coupling. Blood biomarkers have therefore attracted increasing interest, ranging from routine inflammatory proteins and blood cell–derived indices to markers related to endothelial activation, barrier injury, extracellular matrix remodeling, and neural injury. Current evidence indicates that most single biomarkers have limited specificity and variable reproducibility, whereas panel-based approaches may offer better translational potential. In this review, we summarize the biological rationale and clinical evidence for peripheral immune and blood biomarkers in VCI/CSVD, and propose a time-layer and panel-oriented framework to distinguish background risk markers, pathway-activity markers, and downstream injury markers. We further discuss key methodological issues, including disease heterogeneity, sampling windows, repeated measurements, medication effects, external validation, and model transportability. Overall, near-term clinical progress is more likely to come from parsimonious multimarker panels integrated with imaging progression and cognitive trajectories than from any single biomarker. Future studies should prioritize standardized sampling, longitudinal design, and multicenter validation to support risk stratification and biomarker-guided intervention research.
1. Markus HS, Joutel A. The pathogenesis of cerebral small vessel disease and vascular cognitive impairment. Physiol Rev. 2025;105(3):1075-171.
2. Lee AY. Vascular dementia. Chonnam Medical Journal. 2011;47(2):66-71.
3. Hannawi Y. Cerebral small vessel disease: a review of the pathophysiological mechanisms. Transl Stroke Res. 2024;15(6):1050-69.
4. Chojdak-Łukasiewicz J, Dziadkowiak E, Zimny A, Paradowski B. Cerebral small vessel disease: a review. Adv Clin Exp Med. 2021;30(3):349-56.
5. Li Q, Yang Y, Reis C, Tao T, Li W, Li X, et al. Cerebral small vessel disease. Cell Transplant. 2018;27(12):1711-22.
6. Jochems ACC, Muñoz Maniega S, Clancy U, Arteaga-Reyes C, Jaime Garcia D, Chappell FM, et al. Longitudinal cognitive changes in cerebral small vessel disease: the effect of white matter hyperintensity regression and progression. Neurology. 2025;104(4):e213323.
7. Martins-Filho RK, Zotin MC, Rodrigues G, Pontes-Neto O. Biomarkers related to endothelial dysfunction and vascular cognitive impairment: a systematic review. Dement Geriatr Cogn. 2020;49(4):365-74.
8. Osman A, Kanaan A, Azeroual S, Abubakr M, Jwayyed J, Bhutta R. Hypertension and cerebral small vessel disease: a review of the pathophysiology, progression, and prevention. Cureus J Med Science. 2025;17(9):e92760.
9. Hostettler IC, Schwarz G, Ambler G, Wilson D, Banerjee G, Seiffge DJ, et al. Cerebral small vessel disease and functional outcome prediction after intracerebral hemorrhage. Neurology. 2021;96(15):e1954-65.
10. Wu L, Chai YL, Cheah IK, Chia RSL, Hilal S, Arumugam TV, et al. Blood-based biomarkers of cerebral small vessel disease. Ageing Res Rev. 2024;95:102247.
11. Cui M, Jin Z, Wang Y, Jiang J, Peng S, Wei Q, et al. Imaging, biomarkers, and vascular cognitive impairment in China: rationale and design for the VICA study. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 2024;20(12):8898-909.
12. Chang Wong E, Chang Chui H. Vascular cognitive impairment and dementia. Continuum (Minneapolis, Minn.). 2022;28(3):750-80.
13. Song J, Zhou D, Jia L, Wang M, Lan D, Li J, et al. The possible causal relationship between COVID-19 and imaging markers of cerebral small vessel disease: a Mendelian randomization study. Neurol Res. 2024;46(8):735-42.
14. Rost NS, Brodtmann A, Pase MP, van Veluw SJ, Biffi A, Duering M, et al. Post-stroke cognitive impairment and dementia. Circ Res. 2022;130(8):1252-71.
15. Pinter D, Enzinger C, Fazekas F. Cerebral small vessel disease, cognitive reserve and cognitive dysfunction. J Neurol. 2015;262(11):2411-9.
16. Noz MP, Ter Telgte A, Wiegertjes K, Tuladhar AM, Kaffa C, Kersten S, et al. Proinflammatory monocyte phenotype during acute progression of cerebral small vessel disease. Front Cardiovasc Med. 2021;8:639361.
17. Akif A, My Nguyen TT, Liu L, Xu X, Kulkarni A, Jiang J, et al. Targeting NLRP3 signaling with a novel sulfonylurea compound for the treatment of vascular cognitive impairment and dementia. Research Square. 2024:3-5611378.
18. Hosoki S, Hansra GK, Jayasena T, Poljak A, Mather KA, Catts VS, et al. Molecular biomarkers for vascular cognitive impairment and dementia. Nature Reviews. Neurology. 2023;19(12):737-53.
19. Li T, Huang Y, Cai W, Chen X, Men X, Lu T, et al. Age-related cerebral small vessel disease and inflammaging. Cell Death Dis. 2020;11(10):932.
20. Singh MV, Uddin MN, Covacevich Vidalle M, Sutton KR, Boodoo ZD, Peterson AN, et al. Non-classical monocyte levels correlate negatively with HIV-associated cerebral small vessel disease and cognitive performance. Front Cell Infect Mi. 2024;14:1405431.
21. Shi Y, Mao H, Miao W, Deng J, Gao Q, Zeng S, et al. Potential association of neutrophil extracellular traps with cognitive impairment in cerebral small vessel disease. The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences. 2023;78(11):1999-2006.
22. Levi M, van der Poll T. Coagulation and sepsis. Thromb Res. 2017;149:38-44.
23. Markus HS, de Leeuw FE. Cerebral small vessel disease: recent advances and future directions. International Journal of Stroke : Official Journal of the International Stroke Society. 2023;18(1):4-14.
24. Wang Y, Meng R, Song H, Liu G, Hua Y, Cui D, et al. Remote ischemic conditioning may improve outcomes of patients with cerebral small-vessel disease. Stroke. 2017;48(11):3064-72.
25. Csiszar A, Sosnowska D, Wang M, Lakatta EG, Sonntag WE, Ungvari Z. Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment. The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences. 2012;67(8):811-20.
26. Jenkins TA. Metabolic syndrome and vascular-associated cognitive impairment: a focus on preclinical investigations. Curr Diabetes Rep. 2022;22(8):333-40.
27. Low A, Mak E, Rowe JB, Markus HS, O'Brien JT. Inflammation and cerebral small vessel disease: a systematic review. Ageing Res Rev. 2019;53:100916.
28. Tian Z, Ji X, Liu J. Neuroinflammation in vascular cognitive impairment and dementia: current evidence, advances, and prospects. International Journal of Molecular Sciences. 2022;23(11):6224.
29. Sun Z, Harshfield EL, de Leeuw F, Burgess S, Butterworth AS, Riksen NP, et al. Proteins involved in endothelial function and inflammation are implicated in cerebral small vessel disease. Stroke. 2025;56(3):692-704.
30. Hong H, Hong L, Luo X, Zeng Q, Li K, Wang S, et al. The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer's disease continuum participants. Alzheimers Res Ther. 2024;16(1):43.
31. Mustapha M, Nassir CMNC, Aminuddin N, Safri AA, Ghazali MM. Cerebral small vessel disease (CSVD) - lessons from the animal models. Front Physiol. 2019;10:1317.
32. Vickers AJ, Holland F. Decision curve analysis to evaluate the clinical benefit of prediction models. The Spine Journal: Official Journal of the North American Spine Society. 2021;21(10):1643-8.
33. Liao L, Huang W, Ma R, He X, Su M, Sha D. Potential biomarkers for cerebral small vessel disease with cognitive impairment: a systematic review and meta-analysis. Front Aging Neurosci. 2025;16:1475571.
34. Xia Z, Jiang L, Cai X, Jing J, Li S, Wang M, et al. Associations between endothelial inflammatory markers and cerebral small vessel disease in a community-based population. International Journal of Stroke: Official Journal of the International Stroke Society. 2025:17474930251380170.
35. Wang Y, Ma L, Zhang M, Wei J, Li X, Pan X, et al. Blood neutrophil-to-lymphocyte ratio as a predictor of cerebral small-vessel disease. Med Sci Monitor. 2022;28:e935516.
36. Martirosian RA, Wiedner CD, Sanchez J, Mun KT, Marla K, Teran C, et al. Association of incident stroke risk with an IL-18-centered inflammatory network biomarker composite. Stroke. 2024;55(6):1601-8.
37. Hong H, Tozer DJ, Chen Y, Brown RB, Low A, Markus HS. Perivascular space dysfunction in cerebral small vessel disease is related to neuroinflammation. Brain: A Journal of Neurology. 2025;148(5):1540-50.
38. Zanon Zotin MC, Sveikata L, Viswanathan A, Yilmaz P. Cerebral small vessel disease and vascular cognitive impairment: from diagnosis to management. Curr Opin Neurol. 2021;34(2):246-57.
39. Gomez GT, Shi L, Fohner AE, Chen J, Yang Y, Fornage M, et al. Plasma proteome-wide analysis of cerebral small vessel disease identifies novel biomarkers and disease pathways. Medrxiv: The Preprint Server for Health Sciences. 2024:2010-24.
40. Xi L, Junjian Z, Yumin L, Yunwen L, Hongbin W. Serum biomarkers of vascular cognitive impairment evaluated by bead-based proteomic technology. Neurosci Lett. 2009;463(1):6-11.
41. Deshpande T, Hannocks M, Kapupara K, Samawar SKR, Wachsmuth L, Faber C, et al. Microglial activation without peripheral immune cell infiltration characterises mouse and human cerebral small vessel disease. Neuropath Appl Neuro. 2024;50(6):e13015.
42. Liu C, Liu R, Tian N, Fa W, Liu K, Wang N, et al. Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: the MIND-China study. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 2024;20(9):6133-45.
43. Cao Y, Deng H, Liu S, Zeng X, Gou Y, Zhang W, et al. Development and validation of a machine learning-based risk prediction model for stroke-associated pneumonia in older adult hemorrhagic stroke. Front Neurol. 2025;16:1591570.
44. Zhang Z, Rousson V, Lee W, Ferdynus C, Chen M, Qian X, et al. Decision curve analysis: a technical note. Ann Transl Med. 2018;6(15):308.
45. Alborelli I, Jermann PM. Preanalytical variables and sample quality control for clinical variant analysis. Methods in Molecular Biology (Clifton, N.J.). 2022;2493:331-51.
46. Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49(12):1373-9.
47. Dark P, Hossain A, McAuley DF, Brealey D, Carlson G, Clayton JC, et al. Biomarker-guided antibiotic duration for hospitalized patients with suspected sepsis: the ADAPT-Sepsis randomized clinical trial. Jama-J Am Med Assoc. 2025;333(8):682-93.
48. Li Y, Liu D, Yang Y, Cai X, Sun J, Pan Y, et al. Heterogeneity of cerebral small vessel disease based on imaging markers in a community-based population. Stroke Vasc Neurol. 2026:2025-4504.
49. Fan Y, Xiao B, Zhang M. Potential intersections between lncRNA, vascular cognitive impairment, and immunization strategies: insights and future directions. Vaccines-Basel. 2024;12(3):251.
50. Li W, Zhang Y, Li C, Jiang M, Wang D, Chao L, et al. Multi-omics exploration of chaperone-mediated immune-proteostasis crosstalk in vascular dementia and identification of diagnostic biomarkers. Front Immunol. 2025;16:1615540.
51. Santisteban MM, Iadecola C, Carnevale D. Hypertension, neurovascular dysfunction, and cognitive impairment. Hypertension (Dallas, Tex.: 1979). 2023;80(1):22-34.
52. Wessels AM, Lane KA, Gao S, Hall KS, Unverzagt FW, Hendrie HC. Diabetes and cognitive decline in elderly African Americans: a 15-year follow-up study. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 2011;7(4):418-24.
53. Meguro K, Dodge HH. Vascular mild cognitive impairment: identifying disease in community-dwelling older adults, reducing risk factors, and providing support. The Osaki-Tajiri and Kurihara projects. Journal of Alzheimer's Disease: JAD. 2019;70(s1):S293-302.
54. Sachdev PS, Bentvelzen AC, Gustafson D, Hansra GK, Hosoki S, Jiang J, et al. Vascular cognitive impairment and dementia: clinical features, neuropathology, and biomarkers. J Am Coll Cardiol. 2026;87(1):52-76.
55. Abdelnour C, Gibson LL, Batzu L, Aarsland D. How to advance the pharmacological management of cognitive impairment in Parkinson's disease. Journal of Parkinson's Disease. 2025:1877718X251315645.
56. Ferrando-Vivas P, Shankar-Hari M, Thomas K, Doidge JC, Caskey FJ, Forni L, et al. Improving risk prediction model quality in the critically ill: data linkage study. Southampton (UK), National Institute for Health and Care Research, 2022.
57. Gray E, Oeckl P, Amador MDM, Andreasson U, An J, Blennow K, et al. A multi-center study of neurofilament assay reliability and inter-laboratory variability. Amyotroph Lat Scl Fr. 2020;21(5-6):452-8.
58. Ma Y, Tully PJ, Hofman A, Tzourio C. Blood pressure variability and dementia: a state-of-the-art review. Am J Hypertens. 2020;33(12):1059-66.
59. Clancy U, Arteaga-Reyes C, Jaime Garcia D, Hewins W, Locherty R, Valdés Hernández MDC, et al. Incident infarcts in patients with stroke and cerebral small vessel disease: frequency and relation to clinical outcomes. Neurology. 2024;103(5):e209750.
60. DuBois KN, Pal S, Maher AC, Heidebrink J, Persad C, Giordani BM, et al. Dementia etiology classification using NULISA plasma biomarkers and machine learning. Medrxiv: The Preprint Server for Health Sciences. 2025:2012-25.
2. Lee AY. Vascular dementia. Chonnam Medical Journal. 2011;47(2):66-71.
3. Hannawi Y. Cerebral small vessel disease: a review of the pathophysiological mechanisms. Transl Stroke Res. 2024;15(6):1050-69.
4. Chojdak-Łukasiewicz J, Dziadkowiak E, Zimny A, Paradowski B. Cerebral small vessel disease: a review. Adv Clin Exp Med. 2021;30(3):349-56.
5. Li Q, Yang Y, Reis C, Tao T, Li W, Li X, et al. Cerebral small vessel disease. Cell Transplant. 2018;27(12):1711-22.
6. Jochems ACC, Muñoz Maniega S, Clancy U, Arteaga-Reyes C, Jaime Garcia D, Chappell FM, et al. Longitudinal cognitive changes in cerebral small vessel disease: the effect of white matter hyperintensity regression and progression. Neurology. 2025;104(4):e213323.
7. Martins-Filho RK, Zotin MC, Rodrigues G, Pontes-Neto O. Biomarkers related to endothelial dysfunction and vascular cognitive impairment: a systematic review. Dement Geriatr Cogn. 2020;49(4):365-74.
8. Osman A, Kanaan A, Azeroual S, Abubakr M, Jwayyed J, Bhutta R. Hypertension and cerebral small vessel disease: a review of the pathophysiology, progression, and prevention. Cureus J Med Science. 2025;17(9):e92760.
9. Hostettler IC, Schwarz G, Ambler G, Wilson D, Banerjee G, Seiffge DJ, et al. Cerebral small vessel disease and functional outcome prediction after intracerebral hemorrhage. Neurology. 2021;96(15):e1954-65.
10. Wu L, Chai YL, Cheah IK, Chia RSL, Hilal S, Arumugam TV, et al. Blood-based biomarkers of cerebral small vessel disease. Ageing Res Rev. 2024;95:102247.
11. Cui M, Jin Z, Wang Y, Jiang J, Peng S, Wei Q, et al. Imaging, biomarkers, and vascular cognitive impairment in China: rationale and design for the VICA study. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 2024;20(12):8898-909.
12. Chang Wong E, Chang Chui H. Vascular cognitive impairment and dementia. Continuum (Minneapolis, Minn.). 2022;28(3):750-80.
13. Song J, Zhou D, Jia L, Wang M, Lan D, Li J, et al. The possible causal relationship between COVID-19 and imaging markers of cerebral small vessel disease: a Mendelian randomization study. Neurol Res. 2024;46(8):735-42.
14. Rost NS, Brodtmann A, Pase MP, van Veluw SJ, Biffi A, Duering M, et al. Post-stroke cognitive impairment and dementia. Circ Res. 2022;130(8):1252-71.
15. Pinter D, Enzinger C, Fazekas F. Cerebral small vessel disease, cognitive reserve and cognitive dysfunction. J Neurol. 2015;262(11):2411-9.
16. Noz MP, Ter Telgte A, Wiegertjes K, Tuladhar AM, Kaffa C, Kersten S, et al. Proinflammatory monocyte phenotype during acute progression of cerebral small vessel disease. Front Cardiovasc Med. 2021;8:639361.
17. Akif A, My Nguyen TT, Liu L, Xu X, Kulkarni A, Jiang J, et al. Targeting NLRP3 signaling with a novel sulfonylurea compound for the treatment of vascular cognitive impairment and dementia. Research Square. 2024:3-5611378.
18. Hosoki S, Hansra GK, Jayasena T, Poljak A, Mather KA, Catts VS, et al. Molecular biomarkers for vascular cognitive impairment and dementia. Nature Reviews. Neurology. 2023;19(12):737-53.
19. Li T, Huang Y, Cai W, Chen X, Men X, Lu T, et al. Age-related cerebral small vessel disease and inflammaging. Cell Death Dis. 2020;11(10):932.
20. Singh MV, Uddin MN, Covacevich Vidalle M, Sutton KR, Boodoo ZD, Peterson AN, et al. Non-classical monocyte levels correlate negatively with HIV-associated cerebral small vessel disease and cognitive performance. Front Cell Infect Mi. 2024;14:1405431.
21. Shi Y, Mao H, Miao W, Deng J, Gao Q, Zeng S, et al. Potential association of neutrophil extracellular traps with cognitive impairment in cerebral small vessel disease. The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences. 2023;78(11):1999-2006.
22. Levi M, van der Poll T. Coagulation and sepsis. Thromb Res. 2017;149:38-44.
23. Markus HS, de Leeuw FE. Cerebral small vessel disease: recent advances and future directions. International Journal of Stroke : Official Journal of the International Stroke Society. 2023;18(1):4-14.
24. Wang Y, Meng R, Song H, Liu G, Hua Y, Cui D, et al. Remote ischemic conditioning may improve outcomes of patients with cerebral small-vessel disease. Stroke. 2017;48(11):3064-72.
25. Csiszar A, Sosnowska D, Wang M, Lakatta EG, Sonntag WE, Ungvari Z. Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment. The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences. 2012;67(8):811-20.
26. Jenkins TA. Metabolic syndrome and vascular-associated cognitive impairment: a focus on preclinical investigations. Curr Diabetes Rep. 2022;22(8):333-40.
27. Low A, Mak E, Rowe JB, Markus HS, O'Brien JT. Inflammation and cerebral small vessel disease: a systematic review. Ageing Res Rev. 2019;53:100916.
28. Tian Z, Ji X, Liu J. Neuroinflammation in vascular cognitive impairment and dementia: current evidence, advances, and prospects. International Journal of Molecular Sciences. 2022;23(11):6224.
29. Sun Z, Harshfield EL, de Leeuw F, Burgess S, Butterworth AS, Riksen NP, et al. Proteins involved in endothelial function and inflammation are implicated in cerebral small vessel disease. Stroke. 2025;56(3):692-704.
30. Hong H, Hong L, Luo X, Zeng Q, Li K, Wang S, et al. The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer's disease continuum participants. Alzheimers Res Ther. 2024;16(1):43.
31. Mustapha M, Nassir CMNC, Aminuddin N, Safri AA, Ghazali MM. Cerebral small vessel disease (CSVD) - lessons from the animal models. Front Physiol. 2019;10:1317.
32. Vickers AJ, Holland F. Decision curve analysis to evaluate the clinical benefit of prediction models. The Spine Journal: Official Journal of the North American Spine Society. 2021;21(10):1643-8.
33. Liao L, Huang W, Ma R, He X, Su M, Sha D. Potential biomarkers for cerebral small vessel disease with cognitive impairment: a systematic review and meta-analysis. Front Aging Neurosci. 2025;16:1475571.
34. Xia Z, Jiang L, Cai X, Jing J, Li S, Wang M, et al. Associations between endothelial inflammatory markers and cerebral small vessel disease in a community-based population. International Journal of Stroke: Official Journal of the International Stroke Society. 2025:17474930251380170.
35. Wang Y, Ma L, Zhang M, Wei J, Li X, Pan X, et al. Blood neutrophil-to-lymphocyte ratio as a predictor of cerebral small-vessel disease. Med Sci Monitor. 2022;28:e935516.
36. Martirosian RA, Wiedner CD, Sanchez J, Mun KT, Marla K, Teran C, et al. Association of incident stroke risk with an IL-18-centered inflammatory network biomarker composite. Stroke. 2024;55(6):1601-8.
37. Hong H, Tozer DJ, Chen Y, Brown RB, Low A, Markus HS. Perivascular space dysfunction in cerebral small vessel disease is related to neuroinflammation. Brain: A Journal of Neurology. 2025;148(5):1540-50.
38. Zanon Zotin MC, Sveikata L, Viswanathan A, Yilmaz P. Cerebral small vessel disease and vascular cognitive impairment: from diagnosis to management. Curr Opin Neurol. 2021;34(2):246-57.
39. Gomez GT, Shi L, Fohner AE, Chen J, Yang Y, Fornage M, et al. Plasma proteome-wide analysis of cerebral small vessel disease identifies novel biomarkers and disease pathways. Medrxiv: The Preprint Server for Health Sciences. 2024:2010-24.
40. Xi L, Junjian Z, Yumin L, Yunwen L, Hongbin W. Serum biomarkers of vascular cognitive impairment evaluated by bead-based proteomic technology. Neurosci Lett. 2009;463(1):6-11.
41. Deshpande T, Hannocks M, Kapupara K, Samawar SKR, Wachsmuth L, Faber C, et al. Microglial activation without peripheral immune cell infiltration characterises mouse and human cerebral small vessel disease. Neuropath Appl Neuro. 2024;50(6):e13015.
42. Liu C, Liu R, Tian N, Fa W, Liu K, Wang N, et al. Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: the MIND-China study. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 2024;20(9):6133-45.
43. Cao Y, Deng H, Liu S, Zeng X, Gou Y, Zhang W, et al. Development and validation of a machine learning-based risk prediction model for stroke-associated pneumonia in older adult hemorrhagic stroke. Front Neurol. 2025;16:1591570.
44. Zhang Z, Rousson V, Lee W, Ferdynus C, Chen M, Qian X, et al. Decision curve analysis: a technical note. Ann Transl Med. 2018;6(15):308.
45. Alborelli I, Jermann PM. Preanalytical variables and sample quality control for clinical variant analysis. Methods in Molecular Biology (Clifton, N.J.). 2022;2493:331-51.
46. Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49(12):1373-9.
47. Dark P, Hossain A, McAuley DF, Brealey D, Carlson G, Clayton JC, et al. Biomarker-guided antibiotic duration for hospitalized patients with suspected sepsis: the ADAPT-Sepsis randomized clinical trial. Jama-J Am Med Assoc. 2025;333(8):682-93.
48. Li Y, Liu D, Yang Y, Cai X, Sun J, Pan Y, et al. Heterogeneity of cerebral small vessel disease based on imaging markers in a community-based population. Stroke Vasc Neurol. 2026:2025-4504.
49. Fan Y, Xiao B, Zhang M. Potential intersections between lncRNA, vascular cognitive impairment, and immunization strategies: insights and future directions. Vaccines-Basel. 2024;12(3):251.
50. Li W, Zhang Y, Li C, Jiang M, Wang D, Chao L, et al. Multi-omics exploration of chaperone-mediated immune-proteostasis crosstalk in vascular dementia and identification of diagnostic biomarkers. Front Immunol. 2025;16:1615540.
51. Santisteban MM, Iadecola C, Carnevale D. Hypertension, neurovascular dysfunction, and cognitive impairment. Hypertension (Dallas, Tex.: 1979). 2023;80(1):22-34.
52. Wessels AM, Lane KA, Gao S, Hall KS, Unverzagt FW, Hendrie HC. Diabetes and cognitive decline in elderly African Americans: a 15-year follow-up study. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 2011;7(4):418-24.
53. Meguro K, Dodge HH. Vascular mild cognitive impairment: identifying disease in community-dwelling older adults, reducing risk factors, and providing support. The Osaki-Tajiri and Kurihara projects. Journal of Alzheimer's Disease: JAD. 2019;70(s1):S293-302.
54. Sachdev PS, Bentvelzen AC, Gustafson D, Hansra GK, Hosoki S, Jiang J, et al. Vascular cognitive impairment and dementia: clinical features, neuropathology, and biomarkers. J Am Coll Cardiol. 2026;87(1):52-76.
55. Abdelnour C, Gibson LL, Batzu L, Aarsland D. How to advance the pharmacological management of cognitive impairment in Parkinson's disease. Journal of Parkinson's Disease. 2025:1877718X251315645.
56. Ferrando-Vivas P, Shankar-Hari M, Thomas K, Doidge JC, Caskey FJ, Forni L, et al. Improving risk prediction model quality in the critically ill: data linkage study. Southampton (UK), National Institute for Health and Care Research, 2022.
57. Gray E, Oeckl P, Amador MDM, Andreasson U, An J, Blennow K, et al. A multi-center study of neurofilament assay reliability and inter-laboratory variability. Amyotroph Lat Scl Fr. 2020;21(5-6):452-8.
58. Ma Y, Tully PJ, Hofman A, Tzourio C. Blood pressure variability and dementia: a state-of-the-art review. Am J Hypertens. 2020;33(12):1059-66.
59. Clancy U, Arteaga-Reyes C, Jaime Garcia D, Hewins W, Locherty R, Valdés Hernández MDC, et al. Incident infarcts in patients with stroke and cerebral small vessel disease: frequency and relation to clinical outcomes. Neurology. 2024;103(5):e209750.
60. DuBois KN, Pal S, Maher AC, Heidebrink J, Persad C, Giordani BM, et al. Dementia etiology classification using NULISA plasma biomarkers and machine learning. Medrxiv: The Preprint Server for Health Sciences. 2025:2012-25.
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| Issue | Articles in Press | |
| Section | Review Article(s) | |
| Keywords | ||
| Blood-brain barrier Cerebral small vessel disease Endothelial function Peripheral immune homeostasis Serum biomarkers Vascular cognitive impairment | ||
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How to Cite
1.
Qi S, Zhang X. Peripheral Immune Dysregulation and Blood Biomarkers in Vascular Cognitive Impairment and Vascular Dementia. Iran J Allergy Asthma Immunol. 2026;:1-19.
