BackgroundThe number of citations received is considered an index of study quality and impact. We aimed to examine the factors associated with the number of citations of published articles, focusing on the article length.MethodsOriginal human studies published in the first trimester of 2006 in 5 major General Medicine journals were analyzed with regard to the number of authors and of author-affiliated institutions, title and abstract word count, article length (number of print pages), number of bibliographic references, study design, and 2006 journal impact factor (JIF). A multiple linear regression model was employed to identify the variables independently associated with the number of article citations received through January 2012.ResultsOn univariate analysis the JIF, number of authors, article length, study design (interventional/observational and prospective/retrospective), title and abstract word count, number of author-affiliated institutions, and number of references were all associated with the number of citations received. On multivariate analysis with the logarithm of citations as the dependent variable, only article length [regression coefficient: 14.64 (95% confidence intervals: (5.76–23.50)] and JIF [3.37 (1.80–4.948)] independently predicted the number of citations. The variance of citations explained by these parameters was 51.2%.ConclusionIn a sample of articles published in major General Medicine journals, in addition to journal impact factors, article length and number of authors independently predicted the number of citations. This may reflect a higher complexity level and quality of longer and multi-authored studies.

ObjectiveTo investigate the microstructural and macrostructural white matter changes that accompany visual hallucinations and low visual performance in Parkinson disease, a risk factor for Parkinson dementia.MethodsWe performed fixel-based analysis, a novel technique that provides metrics of specific fiber-bundle populations within a voxel (or fixel). Diffusion MRI data were acquired from patients with Parkinson disease (n = 105, of whom 34 were low visual performers and 19 were hallucinators) and age-matched controls (n = 35). We used whole-brain fixel-based analysis to compare microstructural differences in fiber density (FD), macrostructural differences in fiber bundle cross section (FC), and the combined FD and FC (FDC) metric across all white matter fixels. We then performed a tract-of-interest analysis comparing the most sensitive FDC metric across 11 tracts within the visual system.ResultsPatients with Parkinson disease hallucinations exhibited macrostructural changes (reduced FC) within the splenium of the corpus callosum and the left posterior thalamic radiation compared to patients without hallucinations. While there were no significant changes in FD, we found large reductions in the combined FDC metric in Parkinson hallucinators within the splenium (>50% reduction compared to nonhallucinators). Patients with Parkinson disease and low visual performance showed widespread microstructural and macrostructural changes within the genu and splenium of the corpus callosum, bilateral posterior thalamic radiations, and left inferior fronto-occipital fasciculus.ConclusionsWe demonstrate specific white matter tract degeneration affecting posterior thalamic tracts in patients with Parkinson disease with hallucinations and low visual performance, providing direct mechanistic support for attentional models of visual hallucinations.

The mechanisms which are responsible for the selective vulnerability of specific neuronal populations in Parkinson’s disease are poorly understood. Oxidative stress secondary to brain iron accumulation is one postulated mechanism. We measured iron deposition in 180 cortical regions in 96 patients with Parkinson’s disease and 35 controls using quantitative susceptibility mapping. We estimated the expression of 15 745 genes in the same regions using transcriptomic data from the Allen Human Brain Atlas. Using partial least squares regression, we then identified the profile of gene transcription in the healthy brain that underlies increased cortical iron in patients with Parkinson’s disease relative to controls. With gene ontological tools, we investigated the biological processes and cell types associated with this transcriptomic profile. We identified the sets of genes whose spatial expression profiles in control brains correlated significantly with the spatial pattern of cortical iron deposition in Parkinson’s disease. Gene ontological analyses revealed that these genes were enriched for biological processes relating to heavy metal detoxification, synaptic function and nervous system development and were predominantly expressed in astrocytes and glutamatergic neurons. We also show that genes found to be differentially expressed in Parkinson’s disease play a role in explaining the pattern of cortical expression we identified. Our findings provide mechanistic insights into regional selective vulnerabilities in Parkinson’s disease, particularly into processes involving iron accumulation.

Dementia is one of the most debilitating aspects of Parkinson’s disease. There are no validated biomarkers that can track Parkinson’s disease progression, nor accurately identify patients who will develop dementia and when. Understanding the sequence of observable changes in Parkinson’s disease in people at elevated risk for developing dementia could provide an integrated biomarker for identifying and managing individuals who will develop Parkinson’s dementia. We aimed to estimate the sequence of clinical and neurodegeneration events, and variability in this sequence, using data-driven statistical modelling in two separate Parkinson’s cohorts, focusing on patients at elevated risk for dementia due to their age at symptom onset. We updated a novel version of an event-based model that has only recently been extended to cope naturally with clinical data, enabling its application in Parkinson’s disease for the first time. The observational cohorts included healthy control subjects and patients with Parkinson’s disease, of whom those diagnosed at age 65 or older were classified as having high risk of dementia. The model estimates that Parkinson’s progression in patients at elevated risk for dementia starts with classic prodromal features of Parkinson’s disease (olfaction, sleep), followed by early deficits in visual cognition and increased brain iron content, followed later by a less certain ordering of neurodegeneration in the substantia nigra and cortex, neuropsychological cognitive deficits, retinal thinning in dopamine layers, and further deficits in visual cognition. Importantly, we also characterize variation in the sequence. We found consistent, cross-validated results within cohorts, and agreement between cohorts on the subset of features available in both cohorts. Our sequencing results add powerful support to the increasing body of evidence suggesting that visual processing specifically is affected early in patients with Parkinson’s disease at elevated risk of dementia. This opens a route to earlier and more precise detection, as well as a more detailed understanding of the pathological mechanisms underpinning Parkinson’s dementia.

Parkinson’s dementia is characterised by changes in perception and thought, and preceded by visual dysfunction, making this a useful surrogate for dementia risk. Structural and functional connectivity changes are seen in humans with Parkinson’s disease, but the organisational principles are not known. We used resting-state fMRI and diffusion-weighted imaging to examine changes in structural-functional connectivity coupling in patients with Parkinson’s disease, and those at risk of dementia. We identified two organisational gradients to structural-functional connectivity decoupling: anterior-to-posterior and unimodal-to-transmodal, with stronger structural-functional connectivity coupling in anterior, unimodal areas and weakened towards posterior, transmodal regions. Next, we related spatial patterns of decoupling to expression of neurotransmitter receptors. We found that dopaminergic and serotonergic transmission relates to decoupling in Parkinson’s overall, but instead, serotonergic, cholinergic and noradrenergic transmission relates to decoupling in patients with visual dysfunction. Our findings provide a framework to explain the specific disorders of consciousness in Parkinson’s dementia, and the neurotransmitter systems that underlie these.