Reliable biomarkers of frontotemporal dementia (FTD) are currently lacking. FTD may be associated with chronic immune dysfunction, microglial activation and raised inflammatory markers, particularly in progranulin (GRN) mutation carriers. Levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) are elevated in Alzheimer's disease (AD), but they have not been fully explored in FTD.

Background Cardiovascular risk factors vary between ethnicities but little is known about their differential effects on white matter hyperintensities ( WMH ), an indicator of brain aging and burden of cerebrovascular disease. Methods and Results Brain magnetic resonance imaging scans from 213 people of South Asian and 256 of European ethnicity (total=469) were analyzed for global and regional WMH load. Associations with cardiovascular risk factors and a composite cardiovascular risk score (National Cholesterol Education Programme Adult Treatment Panel III) were compared by ethnicity, diabetes mellitus, smoking, and hypertension status. Distributional patterns of WMH were similar by ethnicity but the vulnerability to specific risk factors differed. Associations between WMH and age or National Cholesterol Education Programme Adult Treatment Panel III scores were stronger in South Asians compared with Europeans. For instance, a year of age led to an excess of 3.8% (confidence interval=[0.2, 7.6]; P=0.04) of WMH load in frontal regions in South Asians compared with Europeans. In the diabetic subgroup, South Asians had more WMH than Europeans (+63.3%, confidence interval=[14.1, 133.9]; P=0.007), particularly in the deeper regions (+102% confidence interval=[24, 329]; P=0.004). In the population as a whole, diabetes mellitus was not, or only weakly, related to an increase in WMH volume (12.4%, confidence interval=[-10.7, 41.3]; P=0.32), and diabetes mellitus duration was a positive predictor of frontal periventricular WMH load in Europeans but not in South Asians. In turn, diastolic blood pressure was positively associated with WMH volumes in South Asians but not in Europeans. Hypertension was not associated with WMH load ( P=0.9). Conclusions Distribution patterns of WMH are similar in South Asians and Europeans but older age and higher cardiovascular risk are associated with more WMH in South Asians.

Increased CSF levels of a number of synaptic markers have been reported in Alzheimer's disease (AD), but little is known about their concentrations in frontotemporal dementia (FTD). We investigated this in three synaptic proteins, neurogranin, SNAP-25, and synaptotagmin-1.

To explore the value of olfactory identification deficits as a predictor of cerebral β-amyloid status and other markers of brain health in cognitively normal adults aged ~ 70 years.

Better understanding is needed of the degree to which individuals tolerate Alzheimer disease (AD)-like pathological tau with respect to brain structure (brain resilience) and cognition (cognitive resilience).

As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention.

Mental health issues have been reported after SARS-CoV-2 infection. However, comparison to prevalence in uninfected individuals and contribution from common risk factors (eg, obesity and comorbidities) have not been examined. We identified how COVID-19 relates to mental health in the large community-based COVID Symptom Study.

Worldwide, racial and ethnic minorities have been disproportionately impacted by COVID-19 with increased risk of infection, its related complications, and death. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy may result in differences in uptake. We performed a cohort study among U.S. and U.K. participants who volunteered to take part in the smartphone-based COVID Symptom Study (March 2020-February 2021) and used logistic regression to estimate odds ratios of vaccine hesitancy and uptake. In the U.S. (n = 87,388), compared to white participants, vaccine hesitancy was greater for Black and Hispanic participants and those reporting more than one or other race. In the U.K. (n = 1,254,294), racial and ethnic minority participants showed similar levels of vaccine hesitancy to the U.S. However, associations between participant race and ethnicity and levels of vaccine uptake were observed to be different in the U.S. and the U.K. studies. Among U.S. participants, vaccine uptake was significantly lower among Black participants, which persisted among participants that self-reported being vaccine-willing. In contrast, statistically significant racial and ethnic disparities in vaccine uptake were not observed in the U.K sample. In this study of self-reported vaccine hesitancy and uptake, lower levels of vaccine uptake in Black participants in the U.S. during the initial vaccine rollout may be attributable to both hesitancy and disparities in access.

To test whether pregnant and non-pregnant women differ in COVID-19 symptom profile and severity. To extend previous investigations on hospitalized pregnant women to those who did not require hospitalization.

Brain tissue segmentation from multimodal MRI is a key building block of many neuroimaging analysis pipelines. Established tissue segmentation approaches have, however, not been developed to cope with large anatomical changes resulting from pathology, such as white matter lesions or tumours, and often fail in these cases. In the meantime, with the advent of deep neural networks (DNNs), segmentation of brain lesions has matured significantly. However, few existing approaches allow for the joint segmentation of normal tissue and brain lesions. Developing a DNN for such a joint task is currently hampered by the fact that annotated datasets typically address only one specific task and rely on task-specific imaging protocols including a task-specific set of imaging modalities. In this work, we propose a novel approach to build a joint tissue and lesion segmentation model from aggregated task-specific hetero-modal domain-shifted and partially-annotated datasets. Starting from a variational formulation of the joint problem, we show how the expected risk can be decomposed and optimised empirically. We exploit an upper bound of the risk to deal with heterogeneous imaging modalities across datasets. To deal with potential domain shift, we integrated and tested three conventional techniques based on data augmentation, adversarial learning and pseudo-healthy generation. For each individual task, our joint approach reaches comparable performance to task-specific and fully-supervised models. The proposed framework is assessed on two different types of brain lesions: White matter lesions and gliomas. In the latter case, lacking a joint ground-truth for quantitative assessment purposes, we propose and use a novel clinically-relevant qualitative assessment methodology.

Late onset depression (LOD) may precede the diagnosis of Parkinson's disease (PD) or dementia with Lewy bodies (DLB). We aimed to determine the rate of clinical and imaging features associated with prodromal PD/DLB in patients with LOD.

Human prion diseases are remarkable for long incubation times followed typically by rapid clinical decline. Seed amplification assays and neurodegeneration biofluid biomarkers are remarkably useful in the clinical phase, but their potential to predict clinical onset in healthy people remains unclear. This is relevant not only to the design of preventive strategies in those at-risk of prion diseases, but more broadly, because prion-like mechanisms are thought to underpin many neurodegenerative disorders. Here, we report the accrual of a longitudinal biofluid resource in patients, controls and healthy people at risk of prion diseases, to which ultrasensitive techniques such as real-time quaking-induced conversion (RT-QuIC) and single molecule array (Simoa) digital immunoassays were applied for preclinical biomarker discovery. We studied 648 CSF and plasma samples, including 16 people who had samples taken when healthy but later developed inherited prion disease (IPD) ('converters'; range from 9.9 prior to, and 7.4 years after onset). Symptomatic IPD CSF samples were screened by RT-QuIC assay variations, before testing the entire collection of at-risk samples using the most sensitive assay. Glial fibrillary acidic protein (GFAP), neurofilament light (NfL), tau and UCH-L1 levels were measured in plasma and CSF. Second generation (IQ-CSF) RT-QuIC proved 100% sensitive and specific for sporadic Creutzfeldt-Jakob disease (CJD), iatrogenic and familial CJD phenotypes, and subsequently detected seeding activity in four presymptomatic CSF samples from three E200K carriers; one converted in under 2 months while two remain asymptomatic after at least 3 years' follow-up. A bespoke HuPrP P102L RT-QuIC showed partial sensitivity for P102L disease. No compatible RT-QuIC assay was discovered for classical 6-OPRI, A117V and D178N, and these at-risk samples tested negative with bank vole RT-QuIC. Plasma GFAP and NfL, and CSF NfL levels emerged as proximity markers of neurodegeneration in the typically slow IPDs (e.g. P102L), with significant differences in mean values segregating healthy control from IPD carriers (within 2 years to onset) and symptomatic IPD cohorts; plasma GFAP appears to change before NfL, and before clinical conversion. In conclusion, we show distinct biomarker trajectories in fast and slow IPDs. Specifically, we identify several years of presymptomatic seeding positivity in E200K, a new proximity marker (plasma GFAP) and sequential neurodegenerative marker evolution (plasma GFAP followed by NfL) in slow IPDs. We suggest a new preclinical staging system featuring clinical, seeding and neurodegeneration aspects, for validation with larger prion at-risk cohorts, and with potential application to other neurodegenerative proteopathies.

Cerebral blood flow (CBF) estimates from arterial spin labelling (ASL) show unexplained variability in older populations. We studied the impact of variation of haematocrit (Hct) on CBF estimates in a tri-ethnic elderly population.

White matter hyperintensities (WMH) are commonly detected in the brain of elderly individuals and have been associated with a negative impact on multiple cognitive domains. We aim to investigate the impact of global and regional distribution of WMH on episodic memory and executive function in middle-aged cognitively unimpaired participants [N = 561 (45-75 years)] enriched for Alzheimer's disease risk factors. WMH were automatically segmented from FLAIR, T1 and FSE MR images. WMH load was calculated both globally and regionally. At each cerebral lobe, regional WMH load was measured at four equidistant layers extending from the lateral ventricles to juxtacortical areas. Cognition was measured by The Memory Binding Test (MBT) and WAIS-IV subtests. Global composite z-scores were calculated for the two cognitive domains. Association between global and regional WMH measurements were sought against cognitive measures, both in global composite scores and in individual subtests. We adjusted cognition and WMH burden for the main sociodemographic (age, sex and education) and genetic factors (APOE-ε4). Memory and executive function were significantly associated with global WMH load. Regionally, lower executive performance was mainly associated with higher deep WMH load in frontal areas and, to a lower degree, in occipital, parietal and temporal regions. Lower episodic memory performance was correlated with higher WMH burden in deep frontal and occipital areas. Our novel methodological approach of regional analysis allowed us to reveal the association between cognition and WMH in strategic brain locations. Our results suggest that, even a small WMH load can impact cognition in cognitively unimpaired middle-aged subjects.

Frontotemporal dementia (FTD) is a pathologically heterogeneous neurodegenerative disorder associated usually with tau or TDP-43 pathology, although some phenotypes such as logopenic variant primary progressive aphasia are more commonly associated with Alzheimer's disease pathology. Currently, there are no biomarkers able to diagnose the underlying pathology during life. In this study, we aimed to investigate the potential of novel tau species within cerebrospinal fluid (CSF) as biomarkers for tau pathology in FTD.

White matter hyperintensities (WMH) of presumed vascular origin have been associated with an increased risk of Alzheimer's disease (AD). This study aims to describe the patterns of WMH associated with dementia risk estimates and individual risk factors in a cohort of middle-aged/late middle-aged individuals (mean 58 (interquartile range 51-64) years old).

Increasing 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.

There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA).

Data for front-line health-care workers and risk of COVID-19 are limited. We sought to assess risk of COVID-19 among front-line health-care workers compared with the general community and the effect of personal protective equipment (PPE) on risk.

Neurofilament light (NFL) is an emerging marker of axonal degeneration. This study investigated the relationship between white matter hyperintensities (WMHs) and plasma NFL in a large elderly cohort with, and without, cognitive impairment. We used the Alzheimer's Disease Neuroimaging Initiative and included 163 controls, 103 participants with a significant memory concern, 279 with early mild cognitive impairment (EMCI), 152 with late mild cognitive impairment (LMCI), and 130 with Alzheimer's disease, with 3T MRI and plasma NFL data. Multiple linear regression models examined the relationship between WMHs and NFL, with and without age adjustment. We used smoking status, history of hypertension, history of diabetes, and BMI as additional covariates to examine the effect of vascular risk. We found increases of between 20% and 41% in WMH volume per 1SD increase in NFL in significant memory concern, early mild cognitive impairment, late mild cognitive impairment, and Alzheimer's disease groups (p < 0.02). Marked attenuation of the positive associations between WMHs and NFL were seen after age adjustment, suggesting that a significant proportion of the association between NFL and WMHs is age-related. No effect of vascular risk was observed. These results are supportive of a link between WMH and axonal degeneration in early to late disease stages, in an age-dependent, but vascular risk-independent manner.