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2. 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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3. 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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5. 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

6. Estimating demand for potential disease-modifying therapies for Alzheimer's disease in the UK

Author

Laurell, Axel A. S., primary, Venkataraman, Ashwin V., additional, Schmidt, Tatjana, additional, Montagnese, Marcella, additional, Mueller, Christoph, additional, Stewart, Robert, additional, Lewis, Jonathan, additional, Mundell, Clare, additional, Isaacs, Jeremy D., additional, Krishnan, Mani S., additional, Barber, Robert, additional, Rittman, Timothy, additional, and Underwood, Benjamin R., additional

Published
2024
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9. Estimating Demand for Potential Disease modifying Therapies for Alzheimer’s Disease in the UK

Author

Laurell, Axel AS, primary, Venkataraman, Ashwin V, additional, Schmidt, Tatjana, additional, Montagnese, Marcella, additional, Mueller, Christoph, additional, Stewart, Robert, additional, Lewis, Jonathan, additional, Mundell, Clare, additional, Isaacs, Jeremy D, additional, Krishnan, Mani S, additional, Barber, Robert, additional, Rittman, Timothy, additional, and Underwood, Benjamin R, additional

Published
2023
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11. 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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15. 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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19. Functional cognitive disorder affects reaction time, subjective mental effort and global metacognition.

Author

Teodoro, Tiago, Koreki, Akihiro, Chen, Jiaying, Coebergh, Jan, Poole, Norman, Ferreira, Joaquim J, Edwards, Mark J, and Isaacs, Jeremy D

Subjects
STROOP effect, METACOGNITION, SLEEP interruptions, ACTIVE listening, AFFECTIVE disorders, AUDITORY perception
Abstract

We previously hypothesized that functional cognitive disorder is characterized by heightened subjective mental effort, exhausted attentional reserve and metacognitive failure. To test this hypothesis, we administered a Stroop colour-word task in which attentional demand was varied by task difficulty (congruent versus incongruent cues) and the presence of a secondary auditory stimulus (passive or active listening to an oddball-type paradigm). We measured subjective mental effort, objective performance (reaction times and accuracy), metacognition and EEG-based biomarkers of mental workload. We tested 19 functional cognitive disorder patients and 23 healthy controls. Patients reported higher levels of depression, anxiety, fatigue, pain, sleep disruption, dissociation and obsessiveness. They rated their memory as significantly poorer than healthy controls; however, accuracy did not differ between groups in any condition. In contrast to healthy controls, patients rated their performance as poorer on the congruent Stroop task with background noise compared to silent conditions. Functional cognitive disorder was consistently associated with slower reaction times but this was not exacerbated by increased attentional demand. Patients but not healthy controls reported greater mental workload in noisy conditions but EEG biomarkers were similar between groups, regardless of task difficulty. Functional cognitive disorder has significant syndromic overlap with mood disorders and chronic fatigue and pain. It is associated with global metacognitive failure whereas local (task-specific) metacognition is only selectively impaired. Patients were slower than healthy controls, which might contribute to the 'brain fog' reported in this condition. Although subjective mental effort was increased in noisy conditions, we found no evidence of attentional exhaustion in functional cognitive disorder. Our results indicate that functional cognitive disorder is a multisystem condition affecting reaction time, subjective mental effort and global metacognition. [ABSTRACT FROM AUTHOR]

Published
2023
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22. 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

23. 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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24. 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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25. 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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29. Differences in care between younger and older patients in the 2019 English national memory service audit.

Author

Cook, Laura D., Souris, Helen, and Isaacs, Jeremy D.

Subjects
DEMENTIA, OUTPATIENT medical care, CLINICAL trials
Abstract

Aims and method This paper analyses how practice varied between patients aged <65 and =65 years in the 2019 UK national memory service audit. Results Data on 3959 patients were analysed. Those aged <65 (7% of the sample) were less likely than those aged =65 to be diagnosed with dementia (23 v. 67%) and more likely to receive a functional, psychiatric or no diagnosis. Younger patients were more likely to have magnetic resonance imaging; use of dementia biomarkers was low in both groups. Frontotemporal dementia and functional cognitive disorder were diagnosed infrequently. Use of dementia navigators/advisors and carer psychoeducation was similar between groups; younger patients were less likely to be offered but more likely to accept cognitive stimulation therapy. Clinical implications Memory services seeing younger people need expertise in functional cognitive disorder, alongside clinical skills and technologies to diagnose rarer forms of dementia. Further work is needed to understand why cognitive stimulation therapy is less frequently offered to younger people. [ABSTRACT FROM AUTHOR]

Published
2022
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30. Reply: Functional cognitive disorder: dementia’s blind spot

Author

Ball, Harriet A, primary, McWhirter, Laura, additional, Ballard, Clive, additional, Bhome, Rohan, additional, Blackburn, Daniel J, additional, Edwards, Mark J, additional, Fox, Nick C, additional, Howard, Robert, additional, Huntley, Jonathan, additional, Isaacs, Jeremy D, additional, Larner, A J, additional, Nicholson, Timothy R, additional, Pennington, Catherine M, additional, Poole, Norman, additional, Price, Gary, additional, Price, J P, additional, Reuber, Markus, additional, Ritchie, Craig, additional, Rossor, Martin N, additional, Schott, Jonathan M, additional, Venneri, Annalena, additional, Stone, Jon, additional, and Carson, Alan J, additional

Published
2021
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32. Mild Cognitive Impairment: the Manchester consensus

Author

Dunne, Ross A, primary, Aarsland, Dag, additional, O’Brien, John T, additional, Ballard, Clive, additional, Banerjee, Sube, additional, Fox, Nick C, additional, Isaacs, Jeremy D, additional, Underwood, Benjamin R, additional, Perry, Richard J, additional, Chan, Dennis, additional, Dening, Tom, additional, Thomas, Alan J, additional, Schryer, Jeffrey, additional, Jones, Anne-Marie, additional, Evans, Alison R, additional, Alessi, Charles, additional, Coulthard, Elizabeth J, additional, Pickett, James, additional, Elton, Peter, additional, Jones, Roy W, additional, Mitchell, Susan, additional, Hooper, Nigel, additional, Kalafatis, Chris, additional, Rasmussen, Jill G C, additional, Martin, Helen, additional, Schott, Jonathan M, additional, and Burns, Alistair, additional

Published
2020
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35. Functional cognitive disorder: dementia’s blind spot

Author

Ball, Harriet A, primary, McWhirter, Laura, additional, Ballard, Clive, additional, Bhome, Rohan, additional, Blackburn, Daniel J, additional, Edwards, Mark J, additional, Fleming, Stephen M, additional, Fox, Nick C, additional, Howard, Robert, additional, Huntley, Jonathan, additional, Isaacs, Jeremy D, additional, Larner, Andrew J, additional, Nicholson, Timothy R, additional, Pennington, Catherine M, additional, Poole, Norman, additional, Price, Gary, additional, Price, Jason P, additional, Reuber, Markus, additional, Ritchie, Craig, additional, Rossor, Martin N, additional, Schott, Jonathan M, additional, Teodoro, Tiago, additional, Venneri, Annalena, additional, Stone, Jon, additional, and Carson, Alan J, additional

Published
2020
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42. Mild Cognitive Impairment: the Manchester consensus.

Author

Dunne, Ross A, Aarsland, Dag, O'Brien, John T, Ballard, Clive, Banerjee, Sube, Fox, Nick C, Isaacs, Jeremy D, Underwood, Benjamin R, Perry, Richard J, Chan, Dennis, Dening, Tom, Thomas, Alan J, Schryer, Jeffrey, Jones, Anne-Marie, Evans, Alison R, Alessi, Charles, Coulthard, Elizabeth J, Pickett, James, Elton, Peter, and Jones, Roy W

Subjects
AMYLOID beta-protein precursor, BIOMARKERS, CEREBRAL circulation, CONSENSUS (Social sciences), NEURORADIOLOGY, MILD cognitive impairment
Abstract

Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5–15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer's disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI. [ABSTRACT FROM AUTHOR]

Published
2021
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43. Perfusion by Arterial Spin Labelling following Single dose Tadalafil in Small vessel\ud disease (PASTIS): study protocol for a randomized controlled trial

Author

Pauls, Mathilde, Clarke, Natasha, Trippier, Sarah, Betteridge, Shai, Howe, Franklyn, Khan, Usman, Kruuse, Christina, Madigan, Jeremy, Moynihan, Barry, Pereira, Anthony, Rolfe, Debbie, Rostrup, Egill, Haig, Caroline, Barrick, Thomas, Isaacs, Jeremy D., and Hainsworth, Atticus H.

Abstract

Background: \ud Cerebral small vessel disease is a common cause of vascular cognitive impairment in older people, with no licensed treatment. Cerebral blood flow is reduced in small vessel disease. Tadalafil is a widely prescribed phosphodiesterase-5 inhibitor that increases blood flow in other vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease.\ud \ud Methods/design: \ud Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. Sample size: 54 participants are required to detect a 15% increase in cerebral blood flow in subcortical white matter (p

Published
2017

44. 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 A.M.J., Moss, Mark B., Nitzsche, Björn, Rosenberg, Gary A, Rutten, Julie W., Salkovic- Petrisic, Melita, Troen, and Aron M

Subjects
Experimental models, In vivo models, Translational models, VCID, Vascular cognitive impairment, Vascular dementia
Abstract

BACKGROUND: Disease 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. METHODS: We 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). CONCLUSIONS: We 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

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