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1. Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective

Author

Elahi, Fanny M, Alladi, Suvarna, Black, Sandra E, Claassen, Jurgen AHR, DeCarli, Charles, Hughes, Timothy M, Moonen, Justine, Pajewski, Nicholas M, Price, Brittani R, Satizabal, Claudia, Shaaban, C Elizabeth, Silva, Nárlon CBS, Snyder, Heather M, Sveikata, Lukas, Williamson, Jeff D, Wolters, Frank J, and Hainsworth, Atticus H

Subjects
Biomedical and Clinical Sciences, Brain Disorders, Aging, Clinical Trials and Supportive Activities, Cardiovascular, Clinical Research, Acquired Cognitive Impairment, Neurodegenerative, Behavioral and Social Science, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Hypertension, Prevention, Dementia, Women's Health, 6.1 Pharmaceuticals, Humans, Aged, Aged, 80 and over, Cognitive Dysfunction, Antihypertensive Agents, Internationality, aging, blood pressure, clinical trials, cognitive impairment, dementia, hypertension, prevention, vascular disease, Biomedical and clinical sciences
Abstract

A large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP  80 years), will maximize external validity and global implementation of trial findings. New biomarkers will improve phenotyping to stratify patients to optimal treatments. Currently no antihypertensive drug class stands out for dementia risk reduction. Multi-domain interventions, incorporating lifestyle change (exercise, diet) alongside medications, may maximize global impact. Given the low cost and wide availability of antihypertensive drugs, intensive BP reduction may be a cost-effective means to reduce dementia risk in diverse, aging populations worldwide.

Published
2023

2. Collagen IV deficiency causes hypertrophic remodeling and endothelium-dependent hyperpolarization in small vessel disease with intracerebral hemorrhage

Author

McNeilly, Sarah, Thomson, Cameron R., Gonzalez-Trueba, Laura, Sin, Yuan Yan, Granata, Alessandra, Hamilton, Graham, Lee, Michelle, Boland, Erin, McClure, John D., Lumbreras-Perales, Cristina, Aman, Alisha, Kumar, Apoorva A., Cantini, Marco, Gök, Caglar, Graham, Delyth, Tomono, Yasuko, Anderson, Christopher D., Lu, Yinhui, Smith, Colin, Markus, Hugh S., Abramowicz, Marc, Vilain, Catheline, Al-Shahi Salman, Rustam, Salmeron-Sanchez, Manuel, Hainsworth, Atticus H., Fuller, William, Kadler, Karl E., Bulleid, Neil J., and Van Agtmael, Tom

Published
2024
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7. A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia

Author

Sri, Sarmi, Greenstein, Adam, Granata, Alessandra, Collcutt, Alex, Jochems, Angela C C, McColl, Barry W, Castro, Blanca Díaz, Webber, Caleb, Reyes, Carmen Arteaga, Hall, Catherine, Lawrence, Catherine B, Hawkes, Cheryl, Pegasiou-Davies, Chrysia-Maria, Gibson, Claire, Crawford, Colin L, Smith, Colin, Vivien, Denis, McLean, Fiona H, Wiseman, Frances, Brezzo, Gaia, Lalli, Giovanna, Pritchard, Harry A T, Markus, Hugh S, Bravo-Ferrer, Isabel, Taylor, Jade, Leiper, James, Berwick, Jason, Gan, Jian, Gallacher, John, Moss, Jonathan, Goense, Jozien, McMullan, Letitia, Work, Lorraine, Evans, Lowri, Stringer, Michael S, Ashford, MLJ, Abulfadl, Mohamed, Conlon, Nina, Malhotra, Paresh, Bath, Philip, Canter, Rebecca, Brown, Rosalind, Ince, Selvi, Anderle, Silvia, Young, Simon, Quick, Sophie, Szymkowiak, Stefan, Hill, Steve, Allan, Stuart, Wang, Tao, Quinn, Terry, Procter, Tessa, Farr, Tracy D, Zhao, Xiangjun, Yang, Zhiyuan, Hainsworth, Atticus H, and Wardlaw, Joanna M

Published
2023
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8. Testing the cognitive effects of tadalafil. Neuropsychological secondary outcomes from the PASTIS trial

Author

Pauls, Mathilde MH, Fish, Jessica, Binnie, Lauren R, Benjamin, Philip, Betteridge, Shai, Clarke, Brian, Dhillon, Mohani-Preet K, Ghatala, Rita, Hainsworth, Fearghal AH, Howe, Franklyn A, Khan, Usman, Kruuse, Christina, Madigan, Jeremy B, Moynihan, Barry, Patel, Bhavini, Pereira, Anthony C, Rostrup, Egill, Shtaya, Anan BY, Spilling, Catherine A, Trippier, Sarah, Williams, Rebecca, Young, Robin, Barrick, Thomas R, Isaacs, Jeremy D, and Hainsworth, Atticus H

Published
2023
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9. Test–retest reliability of arterial spin labelling for cerebral blood flow in older adults with small vessel disease

Author

Binnie, Lauren R., Pauls, Mathilde M. H., Benjamin, Philip, Dhillon, Mohani-Preet K., Betteridge, Shai, Clarke, Brian, Ghatala, Rita, Hainsworth, Fearghal A. H., Howe, Franklyn A., Khan, Usman, Kruuse, Christina, Madigan, Jeremy B., Moynihan, Barry, Patel, Bhavini, Pereira, Anthony C., Rostrup, Egill, Shtaya, Anan B. Y., Spilling, Catherine A., Trippier, Sarah, Williams, Rebecca, Isaacs, Jeremy D., Barrick, Thomas R., and Hainsworth, Atticus H.

Published
2022
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11. Translational models for vascular cognitive impairment: a review including larger species

Author

Hainsworth, Atticus H, Allan, Stuart M, Boltze, Johannes, Cunningham, Catriona, Farris, Chad, Head, Elizabeth, Ihara, Masafumi, Isaacs, Jeremy D, Kalaria, Raj N, Lesnik Oberstein, Saskia AMJ, Moss, Mark B, Nitzsche, Björn, Rosenberg, Gary A, Rutten, Julie W, Salkovic-Petrisic, Melita, and Troen, Aron M

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Vascular Cognitive Impairment/Dementia, Dementia, Acquired Cognitive Impairment, Nutrition, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease Related Dementias (ADRD), Aging, Brain Disorders, Alzheimer's Disease, Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, Neurological, Cardiovascular, Animals, Brain, Dementia, Vascular, Disease Models, Animal, Risk Factors, Experimental models, In vivo models, Translational models, VCID, Vascular cognitive impairment, Vascular dementia, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundDisease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited.MethodsWe included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations).ConclusionsWe concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required.

Published
2017

13. Post-mortem assessment in vascular dementia: advances and aspirations

Author

McAleese, Kirsty E, Alafuzoff, Irina, Charidimou, Andreas, De Reuck, Jacques, Grinberg, Lea T, Hainsworth, Atticus H, Hortobagyi, Tibor, Ince, Paul, Jellinger, Kurt, Gao, Jing, Kalaria, Raj N, Kovacs, Gabor G, Kövari, Enikö, Love, Seth, Popovic, Mara, Skrobot, Olivia, Taipa, Ricardo, Thal, Dietmar R, Werring, David, Wharton, Stephen B, and Attems, Johannes

Subjects
Health Services and Systems, Health Sciences, Vascular Cognitive Impairment/Dementia, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Dementia, Biomedical Imaging, Brain Disorders, Alzheimer's Disease Related Dementias (ADRD), Neurosciences, Acquired Cognitive Impairment, Cerebrovascular, Alzheimer's Disease, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Cardiovascular, Neurological, Aged, Alzheimer Disease, Autopsy, Brain, Cerebrovascular Disorders, Comorbidity, Dementia, Vascular, Humans, Prevalence, Vascular dementia, Vascular cognitive impairment, Cerebrovascular disease, Cerebrovascular lesions, Neuropathology, Magnetic resonance imaging, Post-mortem MRI, Mixed dementia, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundCerebrovascular lesions are a frequent finding in the elderly population. However, the impact of these lesions on cognitive performance, the prevalence of vascular dementia, and the pathophysiology behind characteristic in vivo imaging findings are subject to controversy. Moreover, there are no standardised criteria for the neuropathological assessment of cerebrovascular disease or its related lesions in human post-mortem brains, and conventional histological techniques may indeed be insufficient to fully reflect the consequences of cerebrovascular disease.DiscussionHere, we review and discuss both the neuropathological and in vivo imaging characteristics of cerebrovascular disease, prevalence rates of vascular dementia, and clinico-pathological correlations. We also discuss the frequent comorbidity of cerebrovascular pathology and Alzheimer's disease pathology, as well as the difficult and controversial issue of clinically differentiating between Alzheimer's disease, vascular dementia and mixed Alzheimer's disease/vascular dementia. Finally, we consider additional novel approaches to complement and enhance current post-mortem assessment of cerebral human tissue.ConclusionElucidation of the pathophysiology of cerebrovascular disease, clarification of characteristic findings of in vivo imaging and knowledge about the impact of combined pathologies are needed to improve the diagnostic accuracy of clinical diagnoses.

Published
2016

16. White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities

Author

Alber, Jessica, Alladi, Suvarna, Bae, Hee-Joon, Barton, David A., Beckett, Laurel A., Bell, Joanne M., Berman, Sara E., Biessels, Geert Jan, Black, Sandra E., Bos, Isabelle, Bowman, Gene L., Brai, Emanuele, Brickman, Adam M., Callahan, Brandy L., Corriveau, Roderick A., Fossati, Silvia, Gottesman, Rebecca F., Gustafson, Deborah R., Hachinski, Vladimir, Hayden, Kathleen M., Helman, Alex M., Hughes, Timothy M., Isaacs, Jeremy D., Jefferson, Angela L., Johnson, Sterling C., Kapasi, Alifiya, Kern, Silke, Kwon, Jay C., Kukolja, Juraj, Lee, Athene, Lockhart, Samuel N., Murray, Anne, Osborn, Katie E., Power, Melinda C., Price, Brittani R., Rhodius-Meester, Hanneke F.M., Rondeau, Jacqueline A., Rosen, Allyson C., Rosene, Douglas L., Schneider, Julie A., Scholtzova, Henrieta, Shaaban, C. Elizabeth, Silva, Narlon C.B.S., Snyder, Heather M., Swardfager, Walter, Troen, Aron M., van Veluw, Susanne J., Vemuri, Prashanthi, Wallin, Anders, Wellington, Cheryl, Wilcock, Donna M., Xie, Sharon Xiangwen, and Hainsworth, Atticus H.

Published
2019
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22. UK consensus on pre-clinical vascular cognitive impairment functional outcomes assessment: Questionnaire and workshop proceedings

Author

McFall, Aisling, Hietamies, Tuuli M, Bernard, Ashton, Aimable, Margaux, Allan, Stuart M, Bath, Philip M, Brezzo, Gaia, Carare, Roxana O, Carswell, Hilary V, Clarkson, Andrew N, Currie, Gillian, Farr, Tracy D, Fowler, Jill H, Good, Mark, Hainsworth, Atticus H, Hall, Catherine, Horsburgh, Karen, Kalaria, Rajesh, Kehoe, Patrick, Lawrence, Catherine, Macleod, Malcolm, McColl, Barry W, McNeilly, Alison, Miller, Alyson A, Miners, Scott, Mok, Vincent, O’Sullivan, Michael, Platt, Bettina, Sena, Emily S, Sharp, Matthew, Strangward, Patrick, Szymkowiak, Stefan, Touyz, Rhian M, Trueman, Rebecca C, White, Claire, McCabe, Chris, Work, Lorraine M, and Quinn, Terence J

Published
2020
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29. Clinical trials in vascular cognitive impairment following SPRINT-MIND:An international perspective

Author

Elahi, Fanny M., Alladi, Suvarna, Black, Sandra E., Claassen, Jurgen A.H.R., DeCarli, Charles, Hughes, Timothy M., Moonen, Justine, Pajewski, Nicholas M., Price, Brittani R., Satizabal, Claudia, Shaaban, C. Elizabeth, Silva, Nárlon C.B.S., Snyder, Heather M., Sveikata, Lukas, Williamson, Jeff D., Wolters, Frank J., Hainsworth, Atticus H., Elahi, Fanny M., Alladi, Suvarna, Black, Sandra E., Claassen, Jurgen A.H.R., DeCarli, Charles, Hughes, Timothy M., Moonen, Justine, Pajewski, Nicholas M., Price, Brittani R., Satizabal, Claudia, Shaaban, C. Elizabeth, Silva, Nárlon C.B.S., Snyder, Heather M., Sveikata, Lukas, Williamson, Jeff D., Wolters, Frank J., and Hainsworth, Atticus H.

Abstract

A large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP < 120 vs. <140 mm Hg). In this perspective, we discuss key questions and make recommendations for clinical practice and for clinical trials, following SPRINT-MIND. Future trials should embody cognitive endpoints appropriate to the participant group, ideally with adaptive designs that ensure robust answers for cognitive and cardiovascular endpoints. Reliable data from diverse populations, including the oldest-old (age > 80 years), will maximize external validity and global implementation of trial findings. New biomarkers will improve phenotyping to stratify patients to optimal treatments. Currently no antihypertensive drug class stands out for dementia risk reduction. Multi-domain interventions, incorporating lifestyle change (exercise, diet) alongside medications, may maximize global impact. Given the low cost and wide availability of antihypertensive drugs, intensive BP reduction may be a cost-effective means to reduce dementia risk in diverse, aging populations worldwide.

Published
2023

30. Cerebral Small Vessel Disease, Hypertension, and Vascular Contributions to Cognitive Impairment and Dementia.

Author

Hainsworth, Atticus H., Markus, Hugh S., and Schneider, Julie A.

Abstract

Hypertension-associated cerebral small vessel disease is a common finding in older people. Strongly associated with age and hypertension, small vessel disease is found at autopsy in over 50% of people aged ≥65 years, with a spectrum of clinical manifestations. It is the main cause of lacunar stroke and a major source of vascular contributions to cognitive impairment and dementia. The brain areas affected are subcortical and periventricular white matter and deep gray nuclei. Neuropathological sequelae are diffuse white matter lesions (seen as white matter hyperintensities on T2-weighted magnetic resonance imaging), small ischemic foci (lacunes or microinfarcts), and less commonly, subcortical microhemorrhages. The most common form of cerebral small vessel disease is concentric, fibrotic thickening of small penetrating arteries (up to 300 microns outer diameter) termed arteriolosclerosis. Less common forms are small artery atheroma and lipohyalinosis (the lesions described by C. Miller Fisher adjacent to lacunes). Other microvascular lesions that are not reviewed here include cerebral amyloid angiopathy and venous collagenosis. Here, we review the epidemiology, neuropathology, clinical management, genetics, preclinical models, and pathogenesis of hypertensive small vessel disease. Knowledge gaps include initiating factors, molecular pathogenesis, relationships between arterial pathology and tissue damage, possible reversibility, pharmacological targets, and molecular biomarkers. Progress is anticipated from multicell transcriptomic and proteomic profiling, novel experimental models and further target-finding and interventional clinical studies. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Vascular Collagen Type-IV in Hypertension and Cerebral Small Vessel Disease.

Author

Kumar, Apoorva A., Yeo, Natalie, Whittaker, Max, Attra, Priya, Barrick, Thomas R., Bridges, Leslie R., Dickson, Dennis W., Esiri, Margaret M., Farris, Chad W., Graham, Delyth, Lin, Wen Lang, Meijles, Daniel N., Pereira, Anthony C., Perry, Gregory, Rosene, Douglas L., Shtaya, Anan B., Van Agtmael, Tom, Zamboni, Giovanna, and Hainsworth, Atticus H.

Published
2023
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32. Transgenic Domestic Pigs for research in Vascular Contributions to Cognitive Impairment and Dementia.

Author

Hainsworth, Atticus H, Onwuzuruike, Love, Ramesh, Misha, Ascione, Raimondo, Berry, Colin, Bridges, Leslie, Cash, Diana, Clutton, Eddie, Daniel, Carola, Gao, Betty, Isaacs, Jeremy D, Lillico, Simon, Madigan, Jeremy, Meijles, Daniel, Nixon, James, Osei, Stephanie, Ritchie, Adrian, Romanowska, Monika, Tennant, Peter, and Warren, Claire

Abstract

Background: Cardiovascular disease causes vascular dementia and contributes to most clinical dementia. This is embodied in the concept of vascular contributions to cognitive impairment and dementia (VCID). The potent endogenous peptide endothelin‐1 (ET1) causes small artery vasoconstriction and fibrosis. ET1 is implicated in microvascular disease and in VCID. There are few experimental animal models relevant to VCID [Hainsworth et al. 2017]. Pigs are higher mammals with a gyrencephalic brain and extensive subcortical white matter. Method: We engineered domestic pigs carrying additional copies of the ET1‐encoding gene EDN1 under a Tet‐ON promotor, by lentiviral injection into blastocysts. We induced transgene expression for up to 8 days using oral doxycycline in young adults. Result: We studied ET1‐overexpressing (n = 6, 3F/3M, mean±SD age 184±61 days) and control animals (n = 5, 3F/2M, 149±41 days). Following doxycycline treatment we observed a wide range of transgene expression at mRNA level. Antibody labelling indicated a spectrum of ET1 abundance in brain and heart tissue. Heart weight was 460±106 g in ET1‐overexpressing pigs and 394±25 g in controls. Brain weight: 104±14.4 g in ET1‐overexpressing, 101±9.0 in controls. We will report phenotypes relevant to inflammation and blood vessel fibrosis. Conclusion: Adult‐onset EDN1 induction in domestic pigs produces ET1 overexpression that is well‐tolerated to 8 days. Reference: Hainsworth AH, et al. (2017) BMC Med.15(1):16. Translational models for vascular cognitive impairment: a review including larger species. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Does tadalafil increase brain blood flow? The PASTIS trial

Author

Hainsworth, Atticus H, primary, Pauls, Mathilde, additional, Binnie, Lauren, additional, Benjamin, Philip, additional, Betteridge, Shai, additional, Clarke, Brian, additional, Dhillon, Mohani‐Preet, additional, Ghatala, Rita, additional, Hainsworth, Fearghal, additional, Howe, Franklyn, additional, Khan, Usman, additional, Kruuse, Christina, additional, Madigan, Jeremy, additional, Moynihan, Barry, additional, Patel, Bhavini, additional, Pereira, Anthony, additional, Rostrup, Egill, additional, Shtaya, Anan, additional, Spilling, Catherine A, additional, Trippier, Sarah, additional, Williams, Rebecca, additional, Young, Robin, additional, Barrick, Thomas R, additional, and Isaacs, Jeremy D, additional

Published
2022
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34. Vascular Collagen Type-IV in Hypertension and Cerebral Small Vessel Disease

Author

Kumar, Apoorva A., primary, Yeo, Natalie, additional, Whittaker, Max, additional, Attra, Priya, additional, Barrick, Thomas R., additional, Bridges, Leslie R., additional, Dickson, Dennis W., additional, Esiri, Margaret M., additional, Farris, Chad W., additional, Graham, Delyth, additional, Lin, Wen Lang, additional, Meijles, Daniel N., additional, Pereira, Anthony C., additional, Perry, Gregory, additional, Rosene, Douglas L., additional, Shtaya, Anan B., additional, Van Agtmael, Tom, additional, Zamboni, Giovanna, additional, and Hainsworth, Atticus H., additional

Published
2022
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39. What does aducanumab treatment of Alzheimer's disease mean for research on vascular cognitive disorders?

Author

Wallin, Anders, Alladi, Suvarna, Black, Sandra E, Chen, Christopher, Greenberg, Steven M, Gustafson , Deborah, Isaacs, Jeremy D, Jokinen, Hanna, Kalaria, Raj, Mok, Vincent, Pantoni, Leonardo, Pasquier , Florence, Roman, Gustavo C, Rosenberg, Gary A, Schmidt, Reinhold, Smith, Eric E, Hainsworth, Atticus H, Department of Psychology and Logopedics, and HUS Neurocenter

Subjects
515 Psychology, education, 3124 Neurology and psychiatry
Abstract

Non

Published
2022

40. The PASTIS trial:Testing tadalafil for possible use in vascular cognitive impairment

Author

Pauls, Mathilde M. H., Binnie, Lauren R., Benjamin, Philip, Betteridge, Shai, Clarke, Brian, Dhillon, Mohani-Preet K., Ghatala, Rita, Hainsworth, Fearghal A. H., Howe, Franklyn A., Khan, Usman, Kruuse, Christina, Madigan, Jeremy B., Moynihan, Barry, Patel, Bhavini, Pereira, Anthony C., Rostrup, Egill, Shtaya, Anan B. Y., Spilling, Catherine A., Trippier, Sarah, Williams, Rebecca, Young, Robin, Barrick, Thomas R., Isaacs, Jeremy D., Hainsworth, Atticus H., Pauls, Mathilde M. H., Binnie, Lauren R., Benjamin, Philip, Betteridge, Shai, Clarke, Brian, Dhillon, Mohani-Preet K., Ghatala, Rita, Hainsworth, Fearghal A. H., Howe, Franklyn A., Khan, Usman, Kruuse, Christina, Madigan, Jeremy B., Moynihan, Barry, Patel, Bhavini, Pereira, Anthony C., Rostrup, Egill, Shtaya, Anan B. Y., Spilling, Catherine A., Trippier, Sarah, Williams, Rebecca, Young, Robin, Barrick, Thomas R., Isaacs, Jeremy D., and Hainsworth, Atticus H.

Abstract

Introduction: There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI. Methods: In a double-blind, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling. Results: Tadalafil increased CBF non-significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P =.0960). There were incidental treatment effects on systolic and diastolic blood pressure (–7.8, –4.9 mmHg; P <.001). No serious adverse events were observed. Discussion: This trial did not identify a significant treatment effect of single-administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.

Published
2022

41. The PASTIS trial: Testing tadalafil for possible use in vascular cognitive impairment

Author

Pauls, Mathilde M.H., primary, Binnie, Lauren R., additional, Benjamin, Philip, additional, Betteridge, Shai, additional, Clarke, Brian, additional, Dhillon, Mohani‐Preet K., additional, Ghatala, Rita, additional, Hainsworth, Fearghal A.H., additional, Howe, Franklyn A., additional, Khan, Usman, additional, Kruuse, Christina, additional, Madigan, Jeremy B., additional, Moynihan, Barry, additional, Patel, Bhavini, additional, Pereira, Anthony C., additional, Rostrup, Egill, additional, Shtaya, Anan B.Y., additional, Spilling, Catherine A., additional, Trippier, Sarah, additional, Williams, Rebecca, additional, Young, Robin, additional, Barrick, Thomas R., additional, Isaacs, Jeremy D., additional, and Hainsworth, Atticus H., additional

Published
2022
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44. Vasculocentric Axonal NfH in Small Vessel Disease

Author

Anad, Adam, primary, Barker, Miriam K, additional, Katanga, Jessica A, additional, Arfanakis, Konstantinos, additional, Bridges, Leslie R, additional, Esiri, Margaret M, additional, Isaacs, Jeremy D, additional, Prpar Mihevc, Sonja, additional, Pereira, Anthony C, additional, Schneider, Julie A, additional, and Hainsworth, Atticus H, additional

Published
2022
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45. What does aducanumab treatment of Alzheimer's disease mean for research on vascular cognitive disorders?

Author

Wallin, Anders, primary, Alladi, Suvarna, additional, Black, Sandra E, additional, Chen, Christopher, additional, Greenberg, Steven M, additional, Gustafson, Deborah, additional, Isaacs, Jeremy D, additional, Jokinen, Hanna, additional, Kalaria, Raj, additional, Mok, Vincent, additional, Pantoni, Leonardo, additional, Pasquier, Florence, additional, Roman, Gustavo C, additional, Rosenberg, Gary A., additional, Schmidt, Reinhold, additional, Smith, Eric E, additional, and Hainsworth, Atticus H, additional

Published
2022
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48. The epidemiology is promising, but the trial evidence is weak. Why pharmacological dementia risk reduction trials haven't lived up to expectations, and where do we go from here?

Author

Peters, Ruth, primary, Dodge, Hiroko H., additional, James, Sarah, additional, Jicha, Gregory A., additional, Meyer, Pierre‐Francois, additional, Richards, Marcus, additional, Smith, A. David, additional, Yassine, Hussein N., additional, Abner, Erin, additional, Hainsworth, Atticus H., additional, Kehoe, Patrick G., additional, Beckett, Nigel, additional, Anderson, Craig S., additional, and Anstey, Kaarin J., additional

Published
2021
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