المؤلفون: 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., Hainsworth, Atticus H.

المصدر: Binnie , L R , Pauls , M M H , Benjamin , P , Dhillon , M P K , Betteridge , S , Clarke , B , Ghatala , R , Hainsworth , F A H , Howe , F A , Khan , U , Kruuse , C , Madigan , J B , Moynihan , B , Patel , B , Pereira , A C , Rostrup , E , Shtaya , A B Y , Spilling , C A , Trippier , S , Williams , R , Isaacs , J D , Barrick ....

مصطلحات موضوعية: Arterial spin labelling, Cerebral blood flow, Small vessel disease, Vascular aging, White matter lesions

الوصف: Cerebral small vessel disease (SVD) is common in older people and is associated with lacunar stroke, white matter hyperintensities (WMH) and vascular cognitive impairment. Cerebral blood flow (CBF) is reduced in SVD, particularly within white matter. Here we quantified test–retest reliability in CBF measurements using pseudo-continuous arterial spin labelling (pCASL) in older adults with clinical and radiological evidence of SVD (N=54, mean (SD): 66.9 (8.7) years, 15 females/39 males). We generated whole-brain CBF maps on two visits at least 7 days apart (mean (SD): 20 (19), range 7-117 days). Test–retest reliability for CBF was high in all tissue types, with intra-class correlation coefficient [95%CI]: 0.758 [0.616, 0.852] for whole brain, 0.842 [0.743, 0.905] for total grey matter, 0.771 [0.636, 0.861] for deep grey matter (caudate-putamen and thalamus), 0.872 [0.790, 0.923] for normal-appearing white matter (NAWM) and 0.780 [0.650, 0.866] for WMH (all p<0.001). ANCOVA models indicated significant decline in CBF in total grey matter, deep grey matter and NAWM with increasing age and diastolic blood pressure (all p<0.001). CBF was lower in males relative to females (p=0.013 for total grey matter, p=0.004 for NAWM). We conclude that pCASL has high test–retest reliability as a quantitative measure of CBF in older adults with SVD. These findings support the use of pCASL in routine clinical imaging and as a clinical trial endpoint. All data come from the PASTIS trial, prospectively registered at: https://eudract.ema.europa.euTest (2015-001235-20, registered 13/05/2015), http://www.clinicaltrials.govTest (NCT02450253, registered 21/05/2015).

وصف الملف: application/pdf

الإتاحة: https://doi.org/10.1007/s12975-021-00983-5Test
https://curis.ku.dk/portal/da/publications/testretest-reliability-of-arterial-spin-labelling-for-cerebral-blood-flow-in-older-adults-with-small-vessel-diseaseTest(4c91983f-c155-47f3-b0c2-f6518322c612).html
https://curis.ku.dk/ws/files/314965656/Binnie2022_Article_TestRetestReliabilityOfArteria.pdfTest

المؤلفون: 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.

المصدر: Pauls , M M H , Binnie , L R , Benjamin , P , Betteridge , S , Clarke , B , Dhillon , M-P K , Ghatala , R , Hainsworth , F A H , Howe , F A , Khan , U , Kruuse , C , Madigan , J B , Moynihan , B , Patel , B , Pereira , A C , Rostrup , E , Shtaya , A B Y , Spilling , C A , Trippier , S , Williams , R , Young , R , Barrick , T ....

مصطلحات موضوعية: cerebral blood flow, clinical trials, PDE5, small vessel disease, tadalafil, vascular cognitive impairment, vascular cognitive impairment and dementia

الوصف: 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.

وصف الملف: application/pdf

الإتاحة: https://doi.org/10.1002/alz.12559Test
https://curis.ku.dk/portal/da/publications/the-pastis-trialTest(71dcb1bc-e2b5-44ec-a370-1aabdb9a7cf8).html
https://curis.ku.dk/ws/files/333625062/Alzheimer_s_Dementia_2022_Pauls_The_PASTIS_trial_Testing_tadalafil_for_possible_use_in_vascular_cognitive.pdfTest

المؤلفون: 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

المصدر: Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2022, Vol. 18 Issue 12, p2393-2402, 10p

مستخلص: 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. [ABSTRACT FROM AUTHOR]

: Copyright of Alzheimer's & Dementia: The Journal of the Alzheimer's Association is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Pauls, Mathilde Mh, Moynihan, Barry, Barrick, Thomas R, Kruuse, Christina, Madigan, Jeremy B, Hainsworth, Atticus H, Isaacs, Jeremy D

المصدر: J Cereb Blood Flow Metab ; ISSN:1559-7016 ; Volume:38 ; Issue:2

مصطلحات موضوعية: Cerebral blood flow, dementia, phosphodiesterase-5 inhibitors, small vessel disease, vascular cognitive impairment

الوصف: Agents that augment cerebral blood flow (CBF) could be potential treatments for vascular cognitive impairment. Phosphodiesterase-5 inhibitors are vasodilating drugs established in the treatment of erectile dysfunction (ED) and pulmonary hypertension. We reviewed published data on the effects of phosphodiesterase-5 inhibitors on CBF in adult humans. A systematic review according to PRISMA guidelines was performed. Embase, Medline and Cochrane Library Trials databases were searched. Sixteen studies with 353 participants in total were retrieved. Studies included healthy volunteers and patients with migraine, ED, type 2 diabetes, stroke, pulmonary hypertension, Becker muscular dystrophy and subarachnoid haemorrhage. Most studies used middle cerebral artery flow velocity to estimate CBF. Few studies employed direct measurements of tissue perfusion. Resting CBF velocity was unaffected by phosphodiesterase-5 inhibitors, but cerebrovascular regulation was improved in ED, pulmonary hypertension, diabetes, Becker's and a group of healthy volunteers. This evidence suggests that phosphodiesterase-5 inhibitors improve responsiveness of the cerebral vasculature, particularly in disease states associated with an impaired endothelial dilatory response. This supports the potential therapeutic use of phosphodiesterase-5 inhibitors in vascular cognitive impairment where CBF is reduced. Further studies with better resolution of deep CBF are warranted. The review is registered on the PROSPERO database (registration number CRD42016029668).

العلاقة: https://doi.org/10.1177/0271678X17747177Test; https://pubmed.ncbi.nlm.nih.gov/29256324Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951021Test/

الإتاحة: https://doi.org/10.1177/0271678X17747177Test
https://pubmed.ncbi.nlm.nih.gov/29256324Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951021Test/