Ostrovska S. S., Liholetov E. О., PavlovaV. V., Derkach А. K., Shevchenko I. F., Adegova L. Y

LITERATURE REVIEWS

Scentific article

Abstract. Modern research in the field of Alzheimer’s disease (AD) is aimed at identifying biomarkers long before the threshold of clinical diagnosis of this disease is reached. It is expected that this area of research will benefit from the development of new conceptual models of AD, one of which is the study of the relationship between AD, cardiovascular disease (CVD) and cerebrovascular disease (CVD). Modern knowledge about the intersection of risk factors for the development of AD, CVD and CVD is used in order to find ways to delay or slow down the development of AD. Genetic markers that are simultaneously associated with the risk of developing AD, CVD or CVD have been identified. This is the allele ε4 APOE of the apolipoprotein E gene which increases the risk of AD and CVD, as well as mutations in the methylenetetrahydrofolate reductase (MTHFR) gene, which increase the risk of developing AD by 2.5 times and CVD by 3.7 times. Besides APOE and MTHFR there have been identified other genes that contribute to their development. Various aspects of the relationship between AD and vascular risk factors, such as chronic arterial hypertension, high cholesterol levels, hypertension / hypotension, coronary heart disease, diabetes mellitus, and white matter hyperintensity have been revealed. Features of general patient’s characteristics and pathophysiology for AD, CVD and CVD have been identified, which include: age range, decreased cerebral blood flow, genetic risk factor, chronic arterial hypertension, amyloid deposition (Aβ), morphological changes in the vasculature, violations of the blood-brain barrier permeability, high cholesterol, diabetes mellitus, cholinergic neurodegeneration, air pollution, pathogens (fungal, viral), depression, poor physical fitness, smoking and obesity. There is also evidence that the treatment of CVD and AD has much in common, which emphasizes the close relationship of these diseases. Thus, thiazide diuretics reduce blood pressure and the risk of developing asthma; an angiotensin receptor-1 blocker and an angiotensin-converting enzyme inhibitor reduce the risk of CVD and slow down the development of mild to moderate asthma; β-blockers prevent CVD in patients at increased risk of their development and prevent cognitive impairment in older people without dementia; non-steroidal anti-inflammatory drugs, such as statins, protect against CVD and AD; effective treatment of diabetes mellitus in the long term prevents the development of CVD, and intranasal insulin improves cognitive functions and modulates Aβ aggregation in the early stages of AD development. In addition, specific behavioral interventions such as aerobic exercise and physical training reliably protect against CVD and promote vascularization of the brain by improving cognitive function, therewith diets high in fat increase the risk of CVD and AD and carefully designed healthy diets prevent these diseases. Most of the research supports a model of synergistic interaction between vascular, cerebrovascular, and neurodegenerative processes in the early stages of AD pathogenesis. It has been suggested that later stages of the disease may demonstrate additive relationships. Thus, the data presented in the review indicate that interventions that improve vascular function weaken the pathology of AD; therefore, effective control of vascular risk factors is by far the most reliable way to delay this disease.

: Alzheimer’s disease, cardiovascular and cerebrovascular pathology, their relationship.

1. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:280-292.
2. Khachaturian Z, Lombardo J, Khachaturian A. New methods for the analysis of complex diseases. Alzheimers Dementia. 2011;6:475-4781.
3. Santos CY, Snyder PJ, Wu W, Zhang M, Echeverria A, Alber J, et al. Pathophysiologic relationship between Alzheimer’s disease, cerebrovascular disease, and cardiovascular risk: A review and synthesis. Alzheimers Dementia (Amst). 2017;7:69-87.
4. Bales KR, VErina T, Dodel RC, Du Y, Altstiel L, Bender M. Lack of apolipoprotein E dramatically reduces amyloid beta peptide deposition. Nature Genetics. 1997;17:263-264.
5. Mansoori N, Tripathi M, Luthra K, Alam R, Lakshmy R, Sharma S, et al. MTHFR (677 and 1298) and IL-6-174 G/C genes in pathogenesis of Alzheimer’s and vascular dementia and their epistatic interaction. Neurobiology of Aging. 2012;33:1003-8. 
6. Brainstorm C, Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, et al. Analysis of shared heritability in common disorders of the brain. Science. 2018;360(6395):8757.
7. Harrison SL, Ding J, Tang EY, Siervo M, Robinson L, Jagger C, et al. Cardiovascular disease risk models and longitudinal changes in cognition: a systematic review. PLoS One. 2014;9(12):e114431.
8. Dawber TR, Meadors GF, Moore FE. Epidemiological approaches to heart disease: the framingham study. American Journal of Public Health and the Nation’s Health.1951;41:279-281.
9. Viticchi G, Falsetti L, Buratti L, Boria C, Luzzi S, Bartolini M. Framingham risk score can predict cognitive decline progression in Alzheimer’s disease. Neurobiology of Aging. 2015;36:2940-2945.
10. Jung NY, Han JC. Ong YT, Cheung CY, Chen CP, Wong TY, et.al. Retinal microvasculature changes in amyloid-negative subcortical vascular cognitive impairment compared to amyloid-positive Alzheimer’s disease. Journal of the Neurological Sciences. 2019;396:94-101.
11. Feke GT, Hyman BT, Stern RA, Pasquale LR. Retinal blood flow in mild cognitive impairment and Alzheimer’s disease. Alzheimer’s Dementia. 2015;1:144-151.
12. Itzhaki RF. Corroboration of a Major Role for Herpes Simplex Vrus Type 1 in Alzheimer’s Disease. Frontiers in Aging Neuroscience. 2018;10:324.
13. Gelber RP, Ross GW, Petrovitch H, Masaki KH, Launer LJ, White LR. Antihypertensive medication use and risk of cognitive impairment: the Honolulu-Asia Aging Study. Neurology. 2013;81:888-895.
14. Isik AT, Kocyigit SE, Smith L, Aydin AE, Soysal PA. Сomparison of the prevalence of orthostatichypotensionbetween older patients with Alzheimer’s Disease, Lewy body dementia, and without dementia. Experiment Gerontology. 2019;124:110622.
15. Mouzat K, Chudinova A, Polge A, Kantar J,Camu W, Raoul C. et al. Regulation of Brain Cholesterol: What Role Do Liver X Receptors Play in Neurodegenerative Diseases. International Journal of Molecular Sciences. 2019;20(16):3858.
16. Ninomiya T. Epidemiological Evidence of the RelationshipBetween Diabetes and Dementia. Advances in Experim Med and Biology. 2019;1128:13-25.
17. Pisa D, Alonso R, Fernandez-Fernandez AM, Rabano A, Carrasco L. Polymicrobial Infections In Brain Tissue From Alzheimer’s Disease Patients. Scientific Reports. 2017;7:5559.
18. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B. The Alzheimer’s disease-associated Amyloid β-Protein is an Antimicrobial Peptide. PLoS One. 2010;5:9505.
19. Mordukhovich I, Coull B, Kloog I, Koutrakis P, Vokonas P, Schwartz J. Exposure to sub-chronic and long-term particulate air pollution and heart rate variability in an elderly cohort: the Normative Aging Study. Environmental Health. 2015;14:87-10.
20. Wu YC, Lin YC, Yu HL, Chen JH, Chen TF, Sun Y. Association between air pollutants and dementia risk in the elderly. Alzheimer Dementia. 2015;1:220-228.
21. Alber J, Alladi S, Bae HJ, Barton DA, Beckett LA, Bell JM, et al. White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities. Alzheimers Dementia (NY). 2019;5:107-117.
22. Sweeney MD, Montagne A, Sagare AP, Nation DA, Schneider LS, Chui HC. Vascular dysfunction-The disregarded partner of Alzheimer’s disease. Alzheimers Dementia. 2019;15:158-167.
23. Roseborough A, Ramirez J, Black SE, Edwards JD. Associations between amyloid beta and white matter hyperintensities: a systematic review. Alzheimers Dementia. 2017;13:1154-1167.
24. Smith EE. Cerebral amyloid angiopathy as a cause of neurodegeneration. Journal of Neurochemistry.2018;144:651-658.
25. Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dementia. 2018;14:535-562.
26. Vemuri P, Knopman DS. The role of cerebrovascular disease when there is concomitant Alzheimer disease. Biochim et Biophysica Acta. 2016;1862:952-956.
27. Dallaire-Theroux C, Callahan BL, Potvin O, Saikali S, Duchesne S. Radiological-Pathological Correlation in Alzheimer’s Disease: Systematic Review of Antemortem Magnetic Resonance Imaging Findings. Journal of Alzheimer’s Disease. 2017;57:575-601.
28. Kapasi A, DeCarli C, Schneider JA. Impact of multiple pathologies on the threshold for clinically overt dementia. Acta Neuropathologica. 2017;134:171-186.
29. Marnane M, Al-Jawadi OO, Mortazavi S, Pogorzelec KJ, Wang BW, Feldman HH. Periventricular hyperintensities are associated with elevated cerebral amyloid. Neurology. 2016;86:535-543.
30. Lee S, Viqar F, Zimmerman ME, Narkhede A, Tosto G, Benzinger TL. White matter hyperintensities are a core feature of Alzheimer’s disease: evidence from the dominantly inherited Alzheimer network. Annals of Neurology. 2016;79:929-939.
31. Arvanitains Z, Capuano AW, Leurgans SE, Bennet DA, Schneider JA. Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: a cross-sectional study. The Lancet Neurology. 2016;15:934-943.
32. Scarmeas N, Luchsinger JA, Schupf N, Brickman AM, Cosentino S, Tang MX. Physical Activity, Diet, and Risk of Alzheimer Disease. JAMA. 2009;302:627-637.
33. Singer J, Trollor JN, Baune BT, Sachdev PS, Smith E. Arterial stiffness, the brain and cognition: A systematic review. Ageing Resear Reviews. 2014;15:16-27.
34. Jung NY, Han JC. Ong YT, Cheung CY, Chen CP, Wong TY, et.al. Retinal microvasculature changes in amyloid-negative subcortical vascular cognitive impairment compared to amyloid-positiveAlzheimer’s disease. Journal of the Neurological Sciences. 2019;396:94-101.
35. Hartz AM, Bauer B, Soldner EL, Wolf A, Boy S, Backhaus R. Amyloid-beta contribuites to blood-brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy. Stroke. 2012;43:514-523.
36. Corbo RM, Scacchi R. Apolipoprotein E (APOE) allele distribution in the world. Is APOE-ε4 a ‘thrifty’ allele? Annalis of Human Genetics. 1999;63:301-310.
37. Kalaria RN, Akinyemi R, Ihara M. Does vascular pathology contribute to Alzheimer changes? Journal of the Neurological Sciences.2012;322:141-147.
38. Iadecola C. The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathologica. 2010;120:287-296.
39. Schneider JA, Wilson RS, Bienias JL, Evans DA, Bennett DA. Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology. Neurology. 2004;62:1148-1155.

«Bulletin of problems biology and medicine» Issue 1 (159), 2021 year, 302-307 pages, index UDK 616.894-053.8-02:616.1:616.83]-06

10.29254/2077-4214-2021-1-159-302-307