C. Loane

Aberrant nigral diffusion in Parkinson's disease: A longitudinal diffusion tensor imaging study.

Measuring microstructure alterations with diffusion tensor imaging in PD is potentially a valuable tool to use as a biomarker for early diagnosis and to track disease progression. Previous studies have reported a specific decrease of nigral fractional anisotropy in PD. However, to date the effect of disease progression on nigral or striatal diffusion indices has not been fully explored.

Motor associations of iron accumulation in deep grey matter nuclei in Parkinson's disease: a cross-sectional study of iron-related magnetic resonance imaging susceptibility

To determine whether iron deposition in deep brain nuclei assessed using high‐pass filtered phase imaging plays a role in motor disease severity in Parkinsons disease (PD).

11C-PE2I and 18F-Dopa PET for assessing progression rate in Parkinson's : A longitudinal study

18F‐dopa PET measuring aromatic l‐amino acid decarboxylase activity is regarded as the gold standard for evaluating dopaminergic function in Parkinsons disease. Radioligands for dopamine transporters are also used in clinical trials and for confirming PD diagnosis. Currently, it is not clear which imaging marker is more reliable for assessing clinical severity and rate of progression. The objective of this study was to directly compare 18F‐dopa with the highly selective dopamine transporter radioligand 11C‐PE2I for the assessment of motor severity and rate of progression in PD.

Association between precuneus volume and autobiographical memory impairment in posterior cortical atrophy: Beyond the visual syndrome.

Posterior cortical atrophy is a neurodegenerative syndrome characterised by progressive disruption of visual and perceptual processing, associated with atrophy in the parieto-occipital cortex. Current diagnostic criteria describe relative sparing of episodic memory function, but recent findings suggest that anterograde memory is often impaired. Whether these deficits extend to remote memory has not been addressed. A large body of evidence suggests that the recollection of an autobiographical event from the remote past coincides with the successful retrieval of visual images. We hypothesised that the profound visual processing deficits in posterior cortical atrophy would result in impaired autobiographical memory retrieval. Fourteen posterior cortical atrophy patients, eighteen typical Alzheimers disease patients and twenty-eight healthy controls completed the Autobiographical Interview. Autobiographical memory in posterior cortical atrophy was characterised by a striking loss of internal, episodic detail relative to controls and to same extent as typical Alzheimers disease patients, in conjunction with an increase in external details tangential to the memory described. The memory narratives of posterior cortical atrophy patients showed a specific reduction in spatiotemporal and perceptual detail. Voxel-based morphometry analysis revealed atrophy of the parieto-occipital cortices in posterior cortical atrophy but relatively spared hippocampi bilaterally, compared with characteristic atrophy of the medial temporal lobes in typical Alzheimers disease. Analysis of brain regions showing posterior cortical atrophy-specific atrophy revealed a correlation between perceptual details in autobiographical memory and grey matter density in the right precuneus. This study demonstrates remote memory impairment in posterior cortical atrophy despite relatively preserved medial temporal lobe structures. The results demonstrate, for the first time, profound autobiographical memory impairment in PCA and suggest that this is driven by the well-recognised deficits in higher-order visual processing. The findings are discussed in the context of posterior parietal contributions to imagery and memory, and the clinical implications of autobiographical memory impairment for diagnostic and management protocols in posterior cortical atrophy.

Lateral parietal contributions to memory impairment in posterior cortical atrophy

Objective Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterised by progressive impairment in visuospatial and perceptual function. Recent findings show that memory functioning can also be compromised early in the course of disease. In this study, we investigated the neural basis of memory impairment in PCA, and hypothesised that correlations would be observed with parietal cortex rather than classic medial temporal memory structures. Methods Eighteen PCA patients, 15 typical Alzheimers disease (tAD) patients and 21 healthy controls underwent memory testing with the Rey Auditory Verbal Learning Test (RAVLT) word list and MRI. Voxel-based morphometry (VBM) was used to identify regions in the parietal and medial temporal lobes that correlated with memory performance. Results Compared with controls, PCA patients were impaired at learning, immediate and delayed recall and recognition of the RAVLT. Learning rate and immediate recall was significantly better in PCA compared to tAD, whereas there was no difference in delayed recall. Recognition memory also was not statistically different between patient groups, but PCA patients made significantly more false positive errors than tAD patients. VBM analysis in the PCA patients revealed a significant correlation between total learning and grey matter density in the right supramarginal gyrus, right angular gyrus and left postcentral gyrus. The left post central gyrus also significantly correlated with immediate and delayed recall and with recognition memory. No correlations were detected in the medial temporal lobe. Conclusions The findings provide novel evidence that early verbal memory impairment is frequently observed in PCA, and is associated with damage to lateral parietal structures. The results have implications for the diagnosis and management of PCA.

14 Neurobehavioural characteristics of limbic encephalitis associated with voltage-gated potassium channel complex antibodies

Objective Limbic encephalitis associated with antibodies to the voltage-gated potassium channel complex (VGKC-LE) often results in memory impairment with accompanying hippocampal damage thus potentially providing a robust human model of hippocampal amnesia. However, comprehensive characterisation of the neurobehavioural profile of VGKC-LE patients is currently lacking. We aim to provide a detailed description of the clinical outcome of these patients as well as determine whether they are indeed a useful model for hippocampal amnesia studies. Method A group of VGKC-LE patients (n=17) and matched controls underwent clinical interview and extensive neuropsychology testing covering multiple cognitive domains. Structural magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) was acquired in all subjects. Investigation of atrophy profiles was completed via manual delineation of medial temporal lobes (MTL) structures and FreeSurfer cortical parcellation using non-parametric permutation testing. Rs-fMRI data were analysed using both independent component analysis (ICA) and seed-based connectivity analysis (SBCA) to investigate aberrant functional connectivity of the default mode network (DMN) and anterior and posterior memory networks. Associations between memory performance and structure and functional measures were investigated. Results The neuropsychological profile indicates memory function is preferentially affected whereas non-memory function is spared. Moreover, recall memory (recall composite; p<0.01) appears to be more affected than recognition memory (faces, p=0.24; words, p=0.1; scenes, p<0.01). Structural MRI analyses confirms focal hippocampal atrophy with no evidence for a consistent reduction of other sub-cortical or cortical regions. No significant association between hippocampal atrophy and memory performance was detected. ICA analysis failed to detect significant DMN differences in patients vs. controls both at the whole DMN network and within DMN network level. SBCA demonstrated reduced functional connectivity evident from anterior hippocampi to each contralateral temporal pole. Functional connectivity between left anterior hippocampus and right temporal pole was significantly correlated with WMS-IV Word List delayed recall scores (r=−0.584; p=0.05) in patients. Conclusions We have demonstrated that VGKC-LE patients present with persistent memory impairment in line with a previous retrospective study (Butler et al., 2014; JNNP). We also demonstrate that VGKC-LE patients have focal hippocampal atrophy supporting the use of patients with limbic encephalitis as a human model of hippocampal amnesia. However, the presence of hippocampal atrophy alone does not clearly explain the memory deficits. Instead, our data strongly suggest that a functional disturbance at rest is a contributory factor and could explain inconsistencies currently existing in the hippocampal amnesia literature.