Combining biomarkers for prognostic modelling of Parkinson's disease.

Background: Patients with Parkinson's disease (PD) have variable rates of progression. More accurate prediction of progression could improve selection for clinical trials. Although some variance in clinical progression can be predicted by age at onset and phenotype, we hypothesise that this can be further improved by blood biomarkers.

Diagnosis Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome.

Importance: Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes but have not been prospectively studied.

Objective: To define the distinguishing features of PSP and CBS subtypes and to assess their usefulness in facilitating early diagnosis and separation from PD.

Automated Brainstem Segmentation Detects Differential Involvement in Atypical Parkinsonian Syndromes.

Objective: Brainstem segmentation has been useful in identifying potential imaging biomarkers for diagnosis and progression in atypical parkinsonian syndromes (APS). However, the majority of work has been performed using manual segmentation, which is time consuming for large cohorts.

Methods: We investigated brainstem involvement in APS using an automated method.

The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy.

Background: Studies on early-onset presentations of progressive supranuclear palsy (PSP) have been limited to those where a rare monogenic cause has been identified. Here, we have defined early-onset PSP (EOPSP) and investigated its genetic and clinico-pathological profile in comparison with late-onset PSP (LOPSP) and Parkinson's disease (PD).

Methods: We included subjects from the Queen Square Brain Bank, PROSPECT-UK study, and Tracking Parkinson's study.

Proximity extension assay testing reveals novel diagnostic biomarkers of atypical parkinsonian syndromes.

Objective: The high degree of clinical overlap between atypical parkinsonian syndromes (APS) and Parkinson's disease (PD) makes diagnosis challenging. We aimed to identify novel diagnostic protein biomarkers of APS using multiplex proximity extension assay (PEA) testing.

Methods: Cerebrospinal fluid (CSF) samples from two independent cohorts, each consisting of APS and PD cases, and controls, were analysed for neurofilament light chain (NF-L) and Olink Neurology and Inflammation PEA biomarker panels.

Variation at the TRIM11 locus modifies progressive supranuclear palsy phenotype.

Objective: The basis for clinical variation related to underlying progressive supranuclear palsy (PSP) pathology is unknown. We performed a genome-wide association study (GWAS) to identify genetic determinants of PSP phenotype.

Methods: Two independent pathological and clinically diagnosed PSP cohorts were genotyped and phenotyped to create Richardson syndrome (RS) and non-RS groups.

Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity.

Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduced maximal aerobic capacity (V̇O2 max ). Eleven healthy men were randomly assigned single-blind to an incremental semi-recumbent cycling test to determine V̇O2 max in both normoxia (21% O2) and hypoxia (12% O2) separated by a week.

Lifelong patterns of BMI and cardiovascular phenotype in individuals aged 60-64 years in the 1946 British birth cohort study: an epidemiological study.

Background: Excess body fat is associated with an increase in risk of type 2 diabetes and hypertension in adulthood and these risks can adversely affect progression of arterial disease. We aimed to assess the impact of lifelong patterns of adiposity on cardiovascular risk factors and carotid intima media thickness (cIMT) in later life in participants in the 1946 British birth cohort study.

Methods: The National Survey of Health and Development Study was a nationally representative sample of 5362 singleton births to married parents in England, Scotland, and Wales, stratified by social class, during 1 week in March 1946.

Body mass index and height from infancy to adulthood and carotid intima-media thickness at 60 to 64 years in the 1946 British Birth Cohort Study.

Objective: Atherosclerosis begins early in life and obesity is a key determinant. We investigated the role of body mass index (BMI) and height from infancy to adulthood in presenting with high adulthood carotid intima-media thickness.

Approach And Results: Odds ratios of BMI, and height Z scores at 2, 4, 6, 7, 11, 15, and 20 years, and changes between 2 and 4, 4 and 7, 7 and 15, and 15 and 20 years, for carotid intima-media thickness at 60 to 64 years in the upper quartile were estimated for 604 men and 669 women.

Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT): urinary screening and baseline biochemical and cardiovascular assessments.

Objective: We assessed the association between early increases in albumin excretion and cardiovascular (CV) and renal markers in a large cohort of young people with type 1 diabetes.

Research Design And Methods: As part of preliminary screening for a multicenter, randomized controlled trial of statins/ACE inhibitors, we measured albumin-creatinine ratio (ACR) in six early morning urine samples from 3,353 adolescents (10-16 years of age) and calculated tertiles based on an established algorithm. From those subjects deemed to be at higher risk (upper ACR tertile), we recruited 400 into the intervention study (trial cohort).