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Abstract
Cognitive impairment and dementia are significant health burdens worldwide. Aging, hypertension, and diabetes are the primary risk factors for Alzheimer’s disease and Alzheimer’s disease and related dementias (AD/ADRD). There are no effective treatments for AD/ADRD to date. An emerging body of evidence indicates that cerebral vascular dysfunction and hypoperfusion precedes the development of other AD pathological phenotypes and cognitive impairment. However, vascular contribution to dementia is not currently well understood. This commentary highlights the emerging concepts and mechanisms underlying the microvascular contribution to AD/ADRD, including hypotheses targeting the anterograde and retrograde cerebral vascular pathways, as well as the cerebral capillaries and the venous system. We also briefly discuss vascular endothelial dysfunction, oxidative stress, inflammation, and cellular senescence that may contribute to impaired cerebral blood flow autoregulation, neurovascular uncoupling, and dysfunction of cerebral capillaries and the venous system.
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1.
Alzheimer’s disease facts and figures. Alzheimers Dement 2021; 17(3): 327–406.
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2.
Wang S , Roman RJ , Fan F . Duration and magnitude of bidirectional fluctuation in blood pressure: the link between cerebrovascular dysfunction and cognitive impairment following spinal cord injury. J Neurobiol Physiol 2020; 2(1): 15–18.
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3.
Csipo T , Lipecz A , Owens C , Mukli P , Perry JW , Tarantini S , et al. Sleep deprivation impairs cognitive performance, alters task-associated cerebral blood flow and decreases cortical neurovascular coupling-related hemodynamic responses. Sci Rep 2021; 11(1): 20994.
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4.
Fang X , Zhang H , Wang S , Liu Y , Gao W , Roman RJ , et al. Abstract P076: cerebral vascular dysfunction precedes cognitive impairment in Alzheimer’s disease. Hypertension 2020; 76(Suppl_1): AP076–AP076.
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5.
Huang LK , Chao SP , Hu CJ . Clinical trials of new drugs for Alzheimer disease. J Biomed Sci 2020; 27(1): 18.
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6.
Fan F , Roman RJ . Reversal of cerebral hypoperfusion: a novel therapeutic target for the treatment of AD/ADRD? Geroscience 2021; 43(2): 1065–1067.
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7.
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Guo Y , Wang S , Liu Y , Fan L , Booz GW , Roman RJ , et al. Accelerated cerebral vascular injury in diabetes is associated with vascular smooth muscle cell dysfunction. Geroscience 2020; 42(2): 547–561.
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14.
Liu Y , Zhang H , Wang S , Guo Y , Fang X , Zheng B , et al. Reduced pericyte and tight junction coverage in old diabetic rats are associated with hyperglycemia-induced cerebrovascular pericyte dysfunction. Am J Physiol Heart Circ Physiol 2021; 320(2): H549–H562.
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19.
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20.
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Zhang H , Roman R , Fan F . Hippocampus is more susceptible to hypoxic injury: has the Rosetta Stone of regional variation in neurovascular coupling been deciphered? Geroscience 2022; 44(1): 127–130.
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24.
Tarantini S , Tran CHT , Gordon GR , Ungvari Z , Csiszar A . Impaired neurovascular coupling in aging and Alzheimer’s disease: contribution of astrocyte dysfunction and endothelial impairment to cognitive decline. Exp Gerontol 2017; 94: 52–58.
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26.
Crumpler R , Roman RJ , Fan F . Capillary stalling: a mechanism of decreased cerebral blood flow in AD/ADRD. J Exp Neurol 2021; 2(4): 149–153.
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27.
Cruz Hernández JC , Bracko O , Kersbergen CJ , Muse V , Haft-Javaherian M , Berg M , et al. Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models. Nat Neurosci 2019; 22(3): 413–420.
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28.
Fulop GA , Tarantini S , Yabluchanskiy A , Molnar A , Prodan CI , Kiss T , et al. Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment. Am J Physiol Heart Circ Physiol 2019; 316(5): H1124–H1140.
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Yabluchanskiy A , Nyul-Toth A , Csiszar A , Gulej R , Saunders D , Towner R , et al. Age-related alterations in the cerebrovasculature affect neurovascular coupling and BOLD fMRI responses: insights from animal models of aging. Psychophysiology 2021; 58(7): e13718.
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32.
Lipecz A , Csipo T , Tarantini S , Hand RA , Ngo BN , Conley S , et al. Age-related impairment of neurovascular coupling responses: a dynamic vessel analysis (DVA)-based approach to measure decreased flicker light stimulus-induced retinal arteriolar dilation in healthy older adults. Geroscience 2019; 41(3): 341–349.
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Editor-in-Chief
László ROSIVALL (Semmelweis University, Budapest, Hungary)
Managing Editor
Anna BERHIDI (Semmelweis University, Budapest, Hungary)
Co-Editors
- Gábor SZÉNÁSI (Semmelweis University, Budapest, Hungary)
- Ákos KOLLER (Semmelweis University, Budapest, Hungary)
- Zsolt RADÁK (University of Physical Education, Budapest, Hungary)
- László LÉNÁRD (University of Pécs, Hungary)
- Zoltán UNGVÁRI (Semmelweis University, Budapest, Hungary)
Assistant Editors
- Gabriella DÖRNYEI (Semmelweis University, Budapest, Hungary)
- Zsuzsanna MIKLÓS (Semmelweis University, Budapest, Hungary)
- György NÁDASY (Semmelweis University, Budapest, Hungary)
Hungarian Editorial Board
- György BENEDEK (University of Szeged, Hungary)
- Zoltán BENYÓ (Semmelweis University, Budapest, Hungary)
- Mihály BOROS (University of Szeged, Hungary)
- László CSERNOCH (University of Debrecen, Hungary)
- Magdolna DANK (Semmelweis University, Budapest, Hungary)
- László DÉTÁRI (Eötvös Loránd University, Budapest, Hungary)
- Zoltán GIRICZ (Semmelweis University, Budapest, Hungary and Pharmahungary Group, Szeged, Hungary)
- Zoltán HANTOS (Semmelweis University, Budapest and University of Szeged, Hungary)
- Zoltán HEROLD (Semmelweis University, Budapest, Hungary)
- László HUNYADI (Semmelweis University, Budapest, Hungary)
- Gábor JANCSÓ (University of Pécs, Hungary)
- Zoltán KARÁDI (University of Pecs, Hungary)
- Miklós PALKOVITS (Semmelweis University, Budapest, Hungary)
- Gyula PAPP (University of Szeged, Hungary)
- Gábor PAVLIK (University of Physical Education, Budapest, Hungary)
- András SPÄT (Semmelweis University, Budapest, Hungary)
- Gyula SZABÓ (University of Szeged, Hungary)
- Zoltán SZELÉNYI (University of Pécs, Hungary)
- Lajos SZOLLÁR (Semmelweis University, Budapest, Hungary)
- Gyula TELEGDY (MTA-SZTE, Neuroscience Research Group and University of Szeged, Hungary)
- József TOLDI (MTA-SZTE Neuroscience Research Group and University of Szeged, Hungary)
- Árpád TÓSAKI (University of Debrecen, Hungary)
International Editorial Board
- Dragan DJURIC (University of Belgrade, Serbia)
- Christopher H. FRY (University of Bristol, UK)
- Stephen E. GREENWALD (Blizard Institute, Barts and Queen Mary University of London, UK)
- Osmo Otto Päiviö HÄNNINEN (Finnish Institute for Health and Welfare, Kuopio, Finland)
- Helmut G. HINGHOFER-SZALKAY (Medical University of Graz, Austria)
- Tibor HORTOBÁGYI (University of Groningen, Netherlands)
- George KUNOS (National Institutes of Health, Bethesda, USA)
- Massoud MAHMOUDIAN (Iran University of Medical Sciences, Tehran, Iran)
- Tadaaki MANO (Gifu University of Medical Science, Japan)
- Luis Gabriel NAVAR (Tulane University School of Medicine, New Orleans, USA)
- Hitoo NISHINO (Nagoya City University, Japan)
- Ole H. PETERSEN (Cardiff University, UK)
- Ulrich POHL (German Centre for Cardiovascular Research and Ludwig-Maximilians-University, Planegg, Germany)
- Andrej A. ROMANOVSKY (University of Arizona, USA)
- Anwar Ali SIDDIQUI (Aga Khan University, Karachi, Pakistan)
- Csaba SZABÓ (University of Fribourg, Switzerland)
- Eric VICAUT (Université de Paris, UMRS 942 INSERM, France)
- Nico WESTERHOF (Vrije Universiteit Amsterdam, The Netherlands)
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Physiology International
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- SCOPUS
- WoS - Science Citation Index Expanded
| 2022 | |
|---|---|
| Web of Science | |
| Total Cites WoS |
335 |
| Journal Impact Factor | 1.4 |
| Rank by Impact Factor |
Physiology (Q4) |
| Impact Factor without Journal Self Cites |
1.4 |
| 5 Year Impact Factor |
1.6 |
| Journal Citation Indicator | 0.42 |
| Rank by Journal Citation Indicator |
Physiology (Q4) |
| Scimago | |
| Scimago H-index |
33 |
| Scimago Journal Rank |
0.362 |
| Scimago Quartile Score |
Physiology (medical) (Q3) |
| Scopus | |
| Scopus Cite Score |
2.8 |
| Scopus CIte Score Rank |
Physiology 68/102 (33rd PCTL) |
| Scopus SNIP |
0.508 |
| 2021 | |
|---|---|
| Web of Science | |
| Total Cites WoS |
330 |
| Journal Impact Factor | 1,697 |
| Rank by Impact Factor |
Physiology 73/81 |
| Impact Factor without Journal Self Cites |
1,697 |
| 5 Year Impact Factor |
1,806 |
| Journal Citation Indicator | 0,47 |
| Rank by Journal Citation Indicator |
Physiology 69/86 |
| Scimago | |
| Scimago H-index |
31 |
| Scimago Journal Rank |
0,32 |
| Scimago Quartile Score | Medicine (miscellaneous) (Q3) Physiology (medical) (Q3) |
| Scopus | |
| Scopus Cite Score |
2,7 |
| Scopus CIte Score Rank |
Physiology (medical) 69/101 (Q3) |
| Scopus SNIP |
0,591 |
| 2020 | |
| Total Cites | 245 |
| WoS | |
| Journal Impact Factor |
2,090 |
| Rank by | Physiology 62/81 (Q4) |
| Impact Factor | |
| Impact Factor | 1,866 |
| without | |
| Journal Self Cites | |
| 5 Year | 1,703 |
| Impact Factor | |
| Journal | 0,51 |
| Citation Indicator | |
| Rank by Journal | Physiology 67/84 (Q4) |
| Citation Indicator | |
| Citable | 42 |
| Items | |
| Total | 42 |
| Articles | |
| Total | 0 |
| Reviews | |
| Scimago | 29 |
| H-index | |
| Scimago | 0,417 |
| Journal Rank | |
| Scimago | Physiology (medical) Q3 |
| Quartile Score | |
| Scopus | 270/1140=1,9 |
| Scite Score | |
| Scopus | Physiology (medical) 71/98 (Q3) |
| Scite Score Rank | |
| Scopus | 0,528 |
| SNIP | |
| Days from | 172 |
| submission | |
| to acceptance | |
| Days from | 106 |
| acceptance | |
| to publication |
| 2019 | |
|---|---|
| Total Cites WoS |
137 |
| Impact Factor | 1,410 |
| Impact Factor without Journal Self Cites |
1,361 |
| 5 Year Impact Factor |
1,221 |
| Immediacy Index |
0,294 |
| Citable Items |
34 |
| Total Articles |
33 |
| Total Reviews |
1 |
| Cited Half-Life |
2,1 |
| Citing Half-Life |
9,3 |
| Eigenfactor Score |
0,00028 |
| Article Influence Score |
0,215 |
| % Articles in Citable Items |
97,06 |
| Normalized Eigenfactor |
0,03445 |
| Average IF Percentile |
12,963 |
| Scimago H-index |
27 |
| Scimago Journal Rank |
0,267 |
| Scopus Scite Score |
235/157=1,5 |
| Scopus Scite Score Rank |
Physiology (medical) 73/99 (Q3) |
| Scopus SNIP |
0,38 |
| Physiology International | |
|---|---|
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| Physiology International | |
|---|---|
| Language | English |
| Size | B5 |
| Year of Foundation |
2006 (1950) |
| Volumes per Year |
1 |
| Issues per Year |
4 |
| Founder | Magyar Tudományos Akadémia |
| Founder's Address |
H-1051 Budapest, Hungary, Széchenyi István tér 9. |
| Publisher | Akadémiai Kiadó |
| Publisher's Address |
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245. |
| Responsible Publisher |
Chief Executive Officer, Akadémiai Kiadó |
| ISSN | 2498-602X (Print) |
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