Neuroimaging and Clinical Findings in Healthy Middle-Aged Adults With Mild Traumatic Brain Injury in the PREVENT Dementia Study.

Importance: Traumatic brain injuries (TBI) represent an important, potentially modifiable risk factor for dementia. Despite frequently observed vascular imaging changes in individuals with TBI, the relationships between TBI-associated changes in brain imaging and clinical outcomes have largely been overlooked in community cases of TBI.

Objective: To assess whether TBI are associated with and interact with midlife changes in neuroimaging and clinical features in otherwise healthy individuals.

Efficient and effective assessment of deficits and their neural bases in stroke aphasia.

Objective: Multi-assessment batteries are necessary for diagnosing and quantifying the multifaceted deficits observed post-stroke. Extensive batteries are thorough but impractically long for clinical settings or large-scale research studies. Clinically-targeted "shallow" batteries superficially cover a wide range of language skills relatively quickly but can struggle to identify mild deficits or quantify the impairment level.

The multidimensional nature of aphasia recovery post-stroke.

Language is not a single function, but instead results from interactions between neural representations and computations that can be damaged independently of each other. Although there is now clear evidence that the language profile in post-stroke aphasia reflects graded variations along multiple underlying dimensions ('components'), it is still entirely unknown if these distinct language components have different recovery trajectories and rely on the same, or different, neural regions during aphasia recovery. Accordingly, this study examined whether language components in the subacute stage: (i) mirror those observed in the chronic stage; (ii) recover together in a homogeneous manner; and (iii) have recovery trajectories that relate to changing activation in distinct or overlapping underlying brain regions.

CAIDE dementia risk score relates to severity and progression of cerebral small vessel disease in healthy midlife adults: the PREVENT-Dementia study.

Background: Markers of cerebrovascular disease are common in dementia, and may be present before dementia onset. However, their clinical relevance in midlife adults at risk of future dementia remains unclear. We investigated whether the Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score was associated with markers of cerebral small vessel disease (SVD), and if it predicted future progression of SVD.

Language networks in aphasia and health: A 1000 participant activation likelihood estimation meta-analysis.

Aphasia recovery post-stroke is classically and most commonly hypothesised to rely on regions that were not involved in language premorbidly, through 'neurocomputational invasion' or engagement of 'quiescent homologues'. Contemporary accounts have suggested, instead, that recovery might be supported by under-utilised areas of the premorbid language network, which are downregulated in health to save neural resources ('variable neurodisplacement'). Despite the importance of understanding the neural bases of language recovery clinically and theoretically, there is no consensus as to which specific regions are more likely to be activated in post-stroke aphasia (PSA) than healthy individuals.

Auditory beat perception is related to speech output fluency in post-stroke aphasia.

Aphasia affects at least one third of stroke survivors, and there is increasing awareness that more fundamental deficits in auditory processing might contribute to impaired language performance in such individuals. We performed a comprehensive battery of psychoacoustic tasks assessing the perception of tone pairs and sequences across the domains of pitch, rhythm and timbre in 17 individuals with post-stroke aphasia and 17 controls. At the level of individual differences we demonstrated a correlation between metrical pattern (beat) perception and speech output fluency with strong effect (Spearman's rho = 0.

Inherited risk of dementia and the progression of cerebral small vessel disease and inflammatory markers in cognitively healthy midlife adults: the PREVENT-Dementia study.

Cerebral small vessel disease (SVD) and inflammation are increasingly recognized as key contributors to Alzheimer's disease (AD), although the timing, trajectory, and relation between them early in the disease process is unclear. Therefore, to investigate very early-stage changes, we compared 158 healthy midlife adults with and without inherited AD predisposition (APOE4 carriership (38% positive), parental family history (FH) of dementia (54% positive)) on markers of SVD (white matter hyperintensities (WMH), cerebral microbleeds), and inflammation (C-reactive protein (CRP), fibrinogen), cross-sectionally and longitudinally over two years. While WMH severity was comparable between groups at baseline, longitudinal progression of WMH was greater in at-risk groups (APOE4+ and FH+).

In vivo neuroinflammation and cerebral small vessel disease in mild cognitive impairment and Alzheimer's disease.

Introduction: Associations between cerebral small vessel disease (SVD) and inflammation have been largely examined using peripheral blood markers of inflammation, with few studies measuring inflammation within the brain. We investigated the cross-sectional relationship between SVD and in vivo neuroinflammation using [C]PK11195 positron emission tomography (PET) imaging.

Methods: Forty-two participants were recruited (according to NIA-AA guidelines, 14 healthy controls, 14 mild Alzheimer's disease, 14 amyloid-positive mild cognitive impairment).

Peak Width of Skeletonized Mean Diffusivity as a Marker of Diffuse Cerebrovascular Damage.

Background: The peak width of skeletonized mean diffusivity (PSMD) has been proposed as a fully automated imaging marker of relevance to cerebral small vessel disease (SVD). We assessed PSMD in relation to conventional SVD markers, global measures of neurodegeneration, and cognition.

Methods: 145 participants underwent 3T brain MRI and cognitive assessment.

The neural and neurocomputational bases of recovery from post-stroke aphasia.

Language impairment, or aphasia, is a disabling symptom that affects at least one third of individuals after stroke. Some affected individuals will spontaneously recover partial language function. However, despite a growing number of investigations, our understanding of how and why this recovery occurs is very limited.

Enzyme replacement therapy and white matter hyperintensity progression in Fabry disease.

Objective: To explore the association between enzyme replacement therapy (ERT), clinical characteristics, and the rate of progression of white matter hyperintensities (WMH) in patients with Fabry disease (FD).

Methods: Patients with a confirmed diagnosis of FD, aged 18 years or older, participating in an existing FD observational study (NCT00196742), with at least 2 serial MRI brain scans at least 2 years apart for the period between December 2006 and August 2016 were included in this cohort study. Total WMH volume was estimated for each image using a semiautomated procedure.

Cerebral small vessel disease in middle age and genetic predisposition to late-onset Alzheimer's disease.

Introduction: Cerebral small vessel disease (CSVD) is associated with late-onset Alzheimer's disease (LOAD) and might contribute to the relationship between apolipoprotein E ε4 (APOE ε4) and LOAD, in older people. However, it is unclear whether CSVD begins in middle age in individuals genetically predisposed to LOAD.

Methods: We assessed the relationship between radiological markers of CSVD, white matter hyperintensities and microbleeds, and genetic predisposition to LOAD in a cross-sectional analysis of cognitively normal subjects aged 40-59 years recruited from the PREVENT Dementia study.

Discontinuation and non-publication of clinical trials in cardiovascular medicine.

Background: Appropriate dissemination of clinical data is crucial for minimising bias. Despite this, high rates of study discontinuation and non-publication have been reported among clinical trials. Cardiovascular medicine receives a substantial proportion of academic funding; however, predictors of non-publication among cardiovascular trials are not well-established.