ObjectivesNeurodevelopmental impairment has become the most important comorbidity in infants with congenital heart disease (CHD). We aimed to (1) investigate the burden of brain lesions in infants with CHD prior to surgery and (2) explore clinical factors associated with injury.Study designProspective observational study.SettingSingle centre UK tertiary neonatal intensive care unit.Patients70 newborn infants with critical or serious CHD underwent brain MRI prior to surgery.Main outcome measuresPrevalence of cerebral injury including arterial ischaemic strokes (AIS), white matter injury (WMI) and intracranial haemorrhage.ResultsBrain lesions were observed in 39% of subjects (95% CI 28% to 50%). WMI was identified in 33% (95% CI 23% to 45%), subdural haemorrhage without mass effect in 33% (95% CI 23% to 45%), cerebellar haemorrhage in 9% (95% CI 4% to 18%) and AIS in 4% (95% CI 1.5% to 12%). WMI was distributed widely throughout the brain, particularly involving the frontal white matter, optic radiations and corona radiata. WMI exhibited restricted diffusion in 48% of cases. AIS was only observed in infants with transposition of the great arteries (TGA) who had previously undergone balloon atrial septostomy (BAS). AIS was identified in 23% (95% CI 8% to 50%) of infants with TGA who underwent BAS, compared with 0% (95% CI 0% to 20%) who did not.ConclusionsCerebral injury in newborns with CHD prior to surgery is common.

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Alzheimer's disease (AD) and cardiovascular disease (CVD) are strongly associated. Both are multifactorial disorders with long asymptomatic phases and similar risk factors. Indeed, CVD signatures such as cerebral microbleeds, micro‐infarcts, atherosclerosis, cerebral amyloid angiopathy and a procoagulant state are highly associated with AD. However, AD and CVD co‐development and the molecular mechanisms underlying such associations are not understood. Here, we review the evidence regarding the vascular component of AD and clinical studies using anticoagulants that specifically evaluated the development of AD and other dementias. Most studies reported a markedly decreased incidence of composite dementia in anticoagulated patients with atrial fibrillation, with the highest benefit for direct oral anticoagulants. However, sub‐analyses by differential dementia diagnosis were scarce and inconclusive. We finally discuss whether anticoagulation could be a plausible preventive/therapeutic approach for AD and, if so, which would be the best drug and strategy to maximize clinical benefit and minimize potential risks.

Background: Atherosclerosis has been linked to cognitive decline in late life; however, the impact of cardiovascular risk factors (CVRFs) and subclinical atherosclerosis on brain metabolism at earlier stages remains unexplored.Method: This study, aimed at determining the association between brain metabolism, subclinical atherosclerosis and CVRFs in midlife, included 547 asymptomatic middleaged participants (50±4 years, 82% men) from the Progression of Early Subclinical Atherosclerosis study with evidence of subclinical atherosclerosis. Participants underwent 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). Global brain FDG uptake and voxel-wise analyses were used to evaluate the associations of cerebral metabolism with CVRFs and atherosclerotic plaque burden in carotids and femorals assessed by 3D-vascular ultrasound.Result: Global FDG uptake showed an inverse correlation with 30-year Framingham Risk Score (30y-FRS) (β=-0.15, p<0.001). This association was mainly driven by the presence of hypertension (d=0.36, p<0.001). Carotid plaque burden was inversely associated with global brain FDG uptake (β=-0.16, p<0.001), even after adjusting for 30y-FRS. Voxel-wise approaches revealed that the brain areas most strongly affected by hypometabolism in association with 30y-FRS, hypertension, and carotid plaque burden were parietotemporal regions (angular, supramarginal, and inferior/middle temporal gyri) and the cingulate gyrus. Conclusion:In asymptomatic middle-aged individuals, cardiovascular risk is associated with brain hypometabolism, with hypertension being the modifiable CVRF showing the strongest association. Subclinical carotid plaque burden is also linked to reduced brain metabolism independently of CVRFs. Cerebral areas showing hypometabolism

Impaired brain glucose consumption is a possible trigger of Alzheimer&rsquo;s disease (AD). Previous work revealed affected brain structure and function by insulin resistance in terms of functional connectivity and white matter microstructure in a rat model of AD. Here, functional and structural metrics were further used to classify Alzheimer&rsquo;s from control rats using logistic regression. Our study highlights the MRI-derived biomarkers that best discriminate Alzheimer&rsquo;s vs control rats early in the course of the disease, with potential translation to human AD.

BackgroundApolipoprotein E (APOE) is the major genetic risk factor for late‐onset Alzheimer’s disease (AD) and is implicated in cardiovascular disease. TheAPOE‐ε4 allele is associated with brain hypometabolism in AD, mild cognitive impairment (MCI) (Mosconi et al. Neurology 2004) and in cognitively unimpaired middle‐aged individuals (Reiman et al. NEJM 1996). Greater longitudinal decreases in brain metabolism were reported in APOE‐ε4 carriers with MCI (Paranjpe et al. Neuroimage Clin 2019), but studies on brain metabolism longitudinal changes in unimpaired middle‐aged APOE‐ε4 carriers are scarce and with relatively small sample sizes (Reiman et al. PNAS 2001). The Progression of Early Subclinical Atherosclerosis (PESA) study is a longitudinal study following >4000 asymptomatic middle‐aged subjects deeply screened for cardiovascular risk factors (CVRFs) (Fernandez‐Ortiz et al. AHJ 2013). Individuals with the highest burden of atherosclerosis underwent FDG‐PET at baseline and CVRFs were associated with hypometabolism in AD regions (Cortés‐Canteli & Gispert et al. JACC 2021). Those individuals underwent a 6‐year follow‐up FDG‐PET. Here, we investigate the effect of APOE genotype on brain metabolism progression in middle‐aged asymptomatic individuals.Method365 cognitively unimpaired adults (mean age 50 years old) were genotyped for APOE and underwent two FDG‐PET studies (Table). Baseline and follow‐up images were spatially normalized to a group template in the MNI space. FDG‐uptake was normalized to the pons and images were subtracted, yielding a measure of brain metabolic change. An ANOVA model was carried out to compare brain metabolism change between APOE‐ResultAt the global level, we observed significantly greater decreases in FDG uptake in ε4 carriers compared to the reference ε3/ε3 genotype (p=0.024). Voxelwise analysis showed greater decreases between ε4 carriers and non‐ε4 carriers in the precuneus, supramarginal gyrus, hippocampus and anterior cingulate gyrus (Figure).ConclusionAsymptomatic middle‐aged APOE‐ε4 carriers have a greater decline in brain metabolism in regions known to display hypometabolism in AD, suggesting an increased vulnerability. Further analysis will reveal the extent to which AD pathology and/or other risk factors may mediate this association.