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Objective Posterior cortical atrophy (PCA) is a syndrome characterised by progressive disruption of visual processing and neurodegeneration in the parieto-occipital cortex. The most common underlying cause is Alzheimer’s pathology. Anterograde memory function and the medial temporal lobes (MTLs) are thought to be relatively preserved. Given that the typical pattern of atrophy in PCA overlaps with brain networks critical for the recollection of personal events, we hypothesised that patients would be impaired on a test of autobiographical memory. Method 14 PCA, 18 Alzheimer’s disease (AD) patients and 28 healthy controls completed the Autobiographical Interview. Results Both PCA and AD patients produced significantly less internal detail relevant to the chosen memories, compared with controls. However, the PCA group also produced a significantly greater amount of unrelated external detail compared with controls and AD. Across the lifespan, PCA and AD again showed similarly poor recall of relevant remote memory details compared with controls, with no temporal gradient evident in either group. Correlational analysis in PCA patients revealed a significant relationship between total external details and the Hayling test of inhibitory control, and a trend towards significance between internal details and visual imagery. Conclusion Our findings suggest that, despite relatively preserved MTL structures, PCA patients have significantly impaired remote memory. We propose that damage to posterior regions of the brain disrupts access to visual information integral to the autobiographical memory trace. Increased provision of external details may be a compensatory strategy due to lack of access to details relevant to episodic memories.

IntroductionResting-state functional magnetic resonance imaging (rs-fMRI) studies have previously shown significantly impaired connectivity in patients within the early motor phase of Parkinson's disease. Is it possible to detect the same imaging signature of Parkinson's in RBD subjects, before a clinical diagnosis of Parkinson's disease is established?MethodsTwenty-six patients with polysomnography-proven RBD and twenty-two age- and sex-matched healthy controls were recruited into the study. All subjects underwent a comprehensive structural and resting-state MRI protocol.ResultsVoxel-based morphometry analysis did not yield any significant grey matter differences between the two groups. Similarly, no significant differences of fractional anisotropy were found using white matter tract analysis. Rs-fMRI revealed decreased coactivation within the basal ganglia network (involving the caudate, putamen, globus pallidus bilaterally) and the sensorimotor network (precentral gyrus) of patients with RBD. A small area of increased coactivation was found in the default mode network of patients with RBD.ConclusionsOur findings support the presence of basal ganglia dysfunction in patients with RBD, likely representing the prodromal stages of Parkinson's disease. Clinical and neuroimaging follow up is necessary to assess the clinical utility of resting state fMRI to predict the onset of Parkinson's disease in RBD subjects.

Background Focality of onset and spread of pathology in MND are poorly understood. Biomarkers are needed to improve diagnosis and therapeutic monitoring, but must accurately reflect the inherent clinical and prognostic heterogeneity. Diffusion tensor imaging (DTI) is a sensitive MRI application for the noninvasive detection of white matter pathology. Methods High-field cerebral DTI was applied in an unbiased whole-brain analysis across a group of 24 unselected heterogeneous MND patients, and well-matched healthy controls. Patients were scored for clinical upper motor neurone (UMN) involvement, and disability (using the revised ALS Functional Rating Scale, ALSFRS-R). Results A consistent reduction in fractional anisotropy (FA) was demonstrated in the central corpus callosum (CC) of the MND patients, and correlated with disability. A separate whole-brain analysis in relation to UMN involvement highlighted the corticospinal tract (CST). Conclusions Corpus callosum FA is a promising biomarker for the heterogeneous syndrome of MND, and may provide a clue to the topographical spread of disease. FA reduction was related to disability, and did not simply reflect UMN involvement, which supports the inclusion of those subjects with apparently LMN/UMN-only phenotypes within one syndrome. The exquisite delineation of the CST in whole-brain analysis of FA in relation to clinical UMN involvement provided validation of both DTI and a “bedside score” as markers of UMN neuronal damage in MND.

The OPDC will focus on understanding the earliest pathological pathways in Parkinson9s disease (PD). Scientists with strengths in genetics and genomics, transgenic rodent PD models, in vivo neuroanatomy and neuropharmacology of the basal ganglia, magnetic resonance imaging (MRI), and analysis of protein biomarkers, will work closely with experts in clinical epidemiology and neurology of PD. We will identify causal genetic variants within pathways leading to PD from bioinformatics analyses of large-scale genomics projects. Variants will be characterised by resequencing genes in a clinical cohort of 2000 PD patients, 300 at-risk individuals and 300 age-matched controls. Induced pluripotent stem cells generated from individuals harbouring susceptibility variants will be differentiated into dopaminergic neurones. Genetic variant effects on genome-wide transcription/cellular dopamine homeostasis will identify best candidates to use in improved rodent models. BAC transgenesis will be used to express causal variants at physiologically-relevant levels preserving temporal and spatial expression. New models will be analysed for earliest changes of dopamine neuropharmacology compared to midbrain MRI. Biomarker studies on microRNAs/proteins will correlate blood/CSF findings with neuroanatomical alterations. This will lead to improved methods of earlier diagnosis of PD, identify new molecular targets for therapy, and generate improved models for testing neuroprotective treatments.