BackgroundIncreasing age is the biggest risk factor for dementia, of which Alzheimer’s disease is the commonest cause. The pathological changes underpinning Alzheimer’s disease are thought to develop at least a decade prior to the onset of symptoms. Molecular positron emission tomography and multi-modal magnetic resonance imaging allow key pathological processes underpinning cognitive impairment – including β-amyloid depostion, vascular disease, network breakdown and atrophy – to be assessed repeatedly and non-invasively. This enables potential determinants of dementia to be delineated earlier, and therefore opens a pre-symptomatic window where intervention may prevent the onset of cognitive symptoms.Methods/designThis paper outlines the clinical, cognitive and imaging protocol of “Insight 46”, a neuroscience sub-study of the MRC National Survey of Health and Development. This is one of the oldest British birth cohort studies and has followed 5362 individuals since their birth in England, Scotland and Wales during one week in March 1946. These individuals have been tracked in 24 waves of data collection incorporating a wide range of health and functional measures, including repeat measures of cognitive function. Now aged 71 years, a small fraction have overt dementia, but estimates suggest that ~1/3 of individuals in this age group may be in the preclinical stages of Alzheimer’s disease. Insight 46 is recruiting 500 study members selected at random from those who attended a clinical visit at 60–64 years and on whom relevant lifecourse data are available. We describe the sub-study design and protocol which involves a prospective two time-point (0, 24 month) data collection covering clinical, neuropsychological, β-amyloid positron emission tomography and magnetic resonance imaging, biomarker and genetic information. Data collection started in 2015 (age 69) and aims to be completed in 2019 (age 73).DiscussionThrough the integration of data on the socioeconomic environment and on physical, psychological and cognitive function from 0 to 69 years, coupled with genetics, structural and molecular imaging, and intensive cognitive and neurological phenotyping, Insight 46 aims to identify lifetime factors which influence brain health and cognitive ageing, with particular focus on Alzheimer’s disease and cerebrovascular disease. This will provide an evidence base for the rational design of disease-modifying trials.
Aim To describe the neuroradiological changes in patients with coronavirus disease 2019 (COVID-19). Materials and methods A retrospective review was undertaken of 3,403 patients who were confirmed positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and admitted to our institution between 1 March 2020 and 31 May 2020, and who underwent neuroimaging. Abnormal brain imaging was evaluated in detail and various imaging patterns on magnetic resonance imaging MRI were identified. Results Of the 3,403 patients with COVID-19, 167 (4.9%) had neurological signs or symptoms warranting neuroimaging. The most common indications were delirium (44/167, 26%), focal neurology (37/167, 22%), and altered consciousness (34/167, 20%). Neuroimaging showed abnormalities in 23% of patients, with MRI being abnormal in 20 patients and computed tomography (CT) in 18 patients. The most consistent neuroradiological finding was microhaemorrhage with a predilection for the splenium of the corpus callosum (12/20, 60%) followed by acute or subacute infarct (5/20, 25%), watershed white matter hyperintensities (4/20, 20%), and susceptibility changes on susceptibility-weighted imaging (SWI) in the superficial veins (3/20, 15%), acute haemorrhagic necrotising encephalopathy (2/20, 10%), large parenchymal haemorrhage (2/20, 10%), subarachnoid haemorrhage (1/20, 5%), hypoxic–ischaemic changes (1/20, 5%), and acute disseminated encephalomyelitis (ADEM)-like changes (1/20, 5%). Conclusion Various imaging patterns on MRI were observed including acute haemorrhagic necrotising encephalopathy, white matter hyperintensities, hypoxic-ischaemic changes, ADEM-like changes, and stroke. Microhaemorrhages were the most common findings. Prolonged hypoxaemia, consumption coagulopathy, and endothelial disruption are the likely pathological drivers and reflect disease severity in this patient cohort.
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