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

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; Hainsworth, Atticus H

doi:10.1016/j.cccb.2023.100187

Cited by 1 publication

(1 citation statement)

References 42 publications

(64 reference statements)

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“…Cerebral outcomes in diabetes might be improved following treatments targeting the pathways through which diabetes damages the microcirculation [53]. Indeed, recent evidence suggests that selective inhibitors of the cytoplasmic enzyme phosphodiesterase-5 (PDE5i), such as sildenafil, vardenafil, and tadalafil, which are vasodilator medications, improve cognitive outcomes before chronic use [54], [55], reinforcing the idea that an increase in cerebral peripheral resistance in the context of microvascular damage could play a role in age-related cognitive decline. Further, MRI FLAIR and susceptibility-weighted imaging (SWI) sequences are useful for detecting changes in white matter hyperintensities in patients with prodromal dementia [56].…”

Section: Discussionmentioning

confidence: 99%

Impact of cardiometabolic factors and blood beta-amyloid on the volume of white matter hyperintensities in dementia-free subjects with cognitive complaints

Riquelme-Contreras,

Hornberger,

Khondoker

et al. 2024

Preprint

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IntroductionWhite matter hyperintensities (WMH) in Alzheimer’s disease (AD) have traditionally been associated with cerebrovascular diseases. Amyloid β (Aβ) deposition reportedly contributes to WMHs; however, this relationship remains unclear in dementia-free subjects with cognitive complaints (CC). Here, we explored the relationship between WMHs and cardiometabolic and Aβ blood biomarkers in a community-based cohort of Latin American CC participants.MethodsWe recruited 112 individuals with CC (69 – 92 YO, 90 females) with available plasma Aβ biomarkers and cardiometabolic markers (systolic – diastolic blood pressure and glycaemia). WMHs were quantified using a lesion segmentation tool based on SPM12 and segmented using the John Hopkins University (JHU) Atlas and ALVIN segmentation for periventricular and subcortical white matter. Linear multiple regression models were fitted to assess total WMH lesions and the segmented tract, using demographics, cardiometabolic, and Aβ blood biomarker measures as independent variables.ResultsAfter multiple comparison corrections, diastolic blood pressure was associated with WMHs, specifically in the right anterior thalamic radiation, left cingulum, minor forceps, and subcortical ALVIN segmentation. Glycaemia was associated with WMH volume in forceps major, forceps minor, and right fronto-occipital fasciculi. Conversely, Aβ blood biomarkers and systolic blood pressure showed no association with WMH overall or in specific tracts.ConclusionOur findings suggest that, in dementia-free CC individuals, WMH volume was more related to cardiometabolic factors, whereas Aβ blood biomarkers might be of less relevance. Dementia prevention strategies in individuals might be a useful focus for managing high peripheral vessel resistance and endothelial damage due to hypertension and hyperglycaemia.

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