AIM: To determine rates of cerebral atrophy in individuals with symptoms of memory loss but no objective cognitive impairment (SNCI) and their association with future cognitive decline. METHODS: Thirty-two SNCI subjects, 16 with mild cognitive impairment (MCI) and 27 control subjects had clinical assessment and magnetic resonance imaging at baseline and 1 year later. Rates of whole brain atrophy (WBA), hippocampal atrophy (HA) and ventricular enlargement (VE) were measured. Our outcome was clinical diagnosis at 2 years after entry into the study. RESULTS: The MCI group had greater rates of WBA, HA and VE than both controls and SNCI subjects. As a group SNCI subjects did not have significantly greater rates of atrophy than the controls. However, SNCI subjects who progressed to MCI or dementia had increased rates of atrophy compared with those who remained stable. DISCUSSION: Individuals with memory complaints but no objective memory deficits, who progress to MCI or dementia, have increased rates of cerebral atrophy. Copyright (c) 2010 John Wiley & Sons, Ltd.

OBJECTIVE: To investigate whether global and regional beta-amyloid (Abeta) burden as measured with 11C Pittsburgh compound B (PIB) PET is associated with hippocampal atrophy characterized using MRI in healthy controls and patients with amnestic mild cognitive impairment (aMCI) or Alzheimer disease (AD). METHODS: Ninety-two elderly healthy controls, 32 subjects with aMCI, and 35 patients with AD were imaged using 11C-PIB PET and MRI. Hippocampal volume was measured and PIB standardized uptake value ratio was extracted after partial volume correction within 41 regions of interest. Global, regional, and voxel-based correlations between PIB and hippocampal volume were computed for each group. RESULTS: In healthy control participants with elevated neocortex PIB retention, significant correlation was found between PIB retention in the inferior temporal region and hippocampal volume using both region-based and voxel-based approaches. No correlation was found in any other group. CONCLUSIONS: The strong correlation between hippocampal atrophy and beta-amyloid (Abeta) burden in the Pittsburgh compound B-positive healthy control group suggests that Abeta deposition in the inferior temporal neocortex is related to hippocampal synaptic and neuronal degeneration.

Neural network breakdown is a key issue in neurodegenerative disease, but the mechanisms are poorly understood. Here we investigated patterns of brain atrophy produced by defined molecular lesions in the two common forms of genetically mediated frontotemporal lobar degeneration (FTLD). Nine patients with progranulin (GRN) mutations and eleven patients with microtubule-associated protein tau (MAPT) mutations had T1 MR brain imaging. Brain volumetry and grey and white matter voxel-based morphometry (VBM) were used to assess patterns of cross-sectional atrophy in the two groups. In a subset of patients with longitudinal MRI rates of whole brain atrophy were derived using the brain-boundary-shift integral and a VBM-like analysis of voxel-wise longitudinal volume change was performed. The GRN mutation group showed asymmetrical atrophy whereas the MAPT group showed symmetrical atrophy. Brain volumes were smaller in the GRN group with a faster rate of whole brain atrophy. VBM delineated a common anterior cingulate-prefrontal-insular pattern of atrophy in both disease groups. Additional disease-specific profiles of grey and white matter loss were identified on both cross-sectional and longitudinal imaging: GRN mutations were associated with asymmetrical inferior frontal, temporal and inferior parietal lobe grey matter atrophy and involvement of long intrahemispheric association white matter tracts, whereas MAPT mutations were associated with symmetrical anteromedial temporal lobe and orbitofrontal grey matter atrophy and fornix involvement. The findings suggest that the effects of GRN and MAPT mutations are expressed in partly overlapping but distinct anatomical networks that link specific molecular dysfunction with clinical phenotype.

We describe an improved method of measuring brain atrophy rates from serial MRI for multi-site imaging studies of Alzheimer's disease (AD). The method (referred to as KN-BSI) improves an existing brain atrophy measurement technique - the boundary shift integral (classic-BSI), by performing tissue-specific intensity normalisation and parameter selection. We applied KN-BSI to measure brain atrophy rates of 200 normal and 141 AD subjects using baseline and 1-yearMRI scans downloaded fromthe Alzheimer's Disease Neuroimaging Initiative database. Baseline and repeat images were reviewed as pairs by expert raters and given quality scores. Including all image pairs, regardless of quality score, mean KN-BSI atrophy rates were 0.09% higher (95% CI 0.03% to 0.16%, p= 0.007) than classic-BSI rates in controls and 0.07% higher (-0.01% to 0.16%, p=0.07) higher in ADs. The SD of the KN-BSI rates was 22% lower (15% to 29%, p< 0.001) in controls and 13% lower (6% to 20%, p= 0.001) in ADs, compared to classic-BSI. Using these results, the estimated sample size (needed per treatment arm) for a hypothetical trial of a treatment for AD (80% power, 5% significance to detect a 25% reduction in atrophy rate) would be reduced from 120 to 81 (a 32% reduction, 95% CI= 18% to 45%, p< 0.001) when using KN-BSI instead of classic-BSI. Weconcluded that KN-BSI offers more robust brain atrophy measurement than classic-BSI and substantially reduces sample sizes needed in clinical trials.

Background: Possession of one or more apolipoprotein E (APOE) epsilon4 alleles may influence the distribution of atrophy and clinical phenotype. We aimed to assess the influence of APOE genotype on cortical thickness and regional brain volumes in AD (Alzheimer's disease). Methods: We included 38 patients (9 epsilon4 non-carriers, 23 epsilon4 heterozygotes, 6 epsilon4 homozygotes) and 23 controls. Each subject had 2 magnetic resonance imaging (MRI) scans and a neuropsychological battery. Cortical thickness and isthmus cingulate volume were measured using FreeSurfer; the volumes of the hippocampus, whole brain, and lateral ventricles were calculated using manual and semi-automated volumetry. Results: Compared with controls, cortical thickness was significantly lower: in the bilateral temporal, posterior parietal and occipital regions in non-carriers, in the medial temporal and left parietal regions in heterozygotes, and in the medial temporal lobe in homozygotes. Comparisons between AD subgroups did not show significant differences. A trend for larger brain and isthmus cingulate volumes and smaller hippocampal and ventricular volumes with increasing epsilon4 dose were seen. These differences were supported by neuropsychological profiles. Conclusion: These results suggest that APOE genotype may influence the topography of regional atrophy and cortical thinning in AD.

Alzheimer's disease (AD) and semantic dementia (SD) are characterized by different patterns of global and temporal lobe atrophy which can be studied using magnetic resonance imaging (MRI). Manual delineation of regions of interest is time-consuming. FreeSurfer is a freely-available automated technique which has a facility to label cortical and subcortical brain regions automatically. As with all automated techniques comparison with existing methods is important. Eight temporal lobe structures in each hemisphere were delineated using FreeSurfer and compared with manual segmentations in 10 control, 10 AD, and 10 SD subjects. The reproducibility errors for the manual segmentations ranged from 3%-6%. Differences in protocols between the two methods led to differences in absolute volumes with the greatest differences between methods found bilaterally in the hippocampus, entorhinal cortex and fusiform gyrus (p<0.005). However, good correlations between the methods were found for most regions, with the highest correlations shown for the ventricles, whole brain and left medial-inferior temporal gyrus (r>0.9), followed by the bilateral amygdala and hippocampus, left superior temporal gyrus, right medial-inferior temporal gyrus and left temporal lobe (r>0.8). Overlap ratios differed between methods bilaterally in the amygdala, superior temporal gyrus, temporal lobe, left fusiform gyrus and right parahippocampal gyrus (p<0.01). Despite differences in protocol and volumes, both methods showed similar atrophy patterns in the patient groups compared with controls, and similar right-left differences, suggesting that both methods accurately distinguish between the three groups.

A large number of algorithms have been developed to perform non-rigid registration and it is a tool commonly used in medical image analysis. The free-form deformation algorithm is a well-established technique, but is extremely time consuming. In this paper we present a parallel-friendly formulation of the algorithm suitable for graphics processing unit execution. Using our approach we perform registration of T1-weighted MR images in less than 1min and show the same level of accuracy as a classical serial implementation when performing segmentation propagation. This technology could be of significant utility in time-critical applications such as image-guided interventions, or in the processing of large data sets.

OBJECTIVE: To assess the relationship between MRI-derived changes in whole-brain and ventricular volume with change in cognitive scores in Alzheimer's disease (AD), mild cognitive impairment (MCI) and control subjects. MATERIAL AND METHODS: In total 131 control, 231 MCI and 99 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort with T1-weighted volumetric MRIs from baseline and 12-month follow-up were used to derive volume changes. Mini mental state examination (MMSE), Alzheimer's disease assessment scale (ADAS)-cog and trails test changes were calculated over the same period. RESULTS: Brain atrophy rates and ventricular enlargement differed between subject groups (p < 0.0005) and in MCI and AD were associated with MMSE changes. Both measures were additionally associated with ADAS-cog and trails-B in MCI patients, and ventricular expansion was associated with ADAS-cog in AD patients. Brain atrophy (p < 0.0005) and ventricular expansion rates (p = 0.001) were higher in MCI subjects who progressed to AD within 12 months of follow-up compared with MCI subjects who remained stable. MCI subjects who progressed to AD within 12 months had similar atrophy rates to AD subjects. CONCLUSION: Whole-brain atrophy rates and ventricular enlargement differed between patient groups and healthy controls, and tracked disease progression and psychological decline, demonstrating their relevance as biomarkers.

As encoding spatial information into mutual information (MI) can improve the nonrigid registration against bias fields where the conventional MI is challenged, we propose to unify this encoding into the computation of the joint probability distribution function (PDF). The PDF is computed based on local volumes while the global intensity information is also incorporated to maintain the global intensity class linkage. We demonstrate this computation method can unify the PDF computation in regional MI, conditional MI, and the conventional MI. We then derive two categories of methods and apply them to different registration tasks. The experimental results demonstrate that both categories can significantly improve the registration.

The primary progressive aphasias (PPA) are paradigmatic disorders of language network breakdown associated with focal degeneration of the left cerebral hemisphere. Here we addressed brain correlates of PPA in a detailed neuroanatomical analysis of the third canonical syndrome of PPA, logopenic/phonological aphasia (LPA), in relation to the more widely studied clinico-anatomical syndromes of semantic dementia (SD) and progressive nonfluent aphasia (PNFA). 32 PPA patients (9 SD, 14 PNFA, 9 LPA) and 18 cognitively-normal controls had volumetric brain MRI with regional volumetry, cortical thickness, grey and white matter voxel-based morphometry analyses. 5/9 patients with LPA had cerebrospinal fluid biomarkers consistent with Alzheimer (AD) pathology (AD-PPA) and 2/9 patients had progranulin (GRN) mutations (GRN-PPA). The LPA group had tissue loss in a widespread left hemisphere network. Compared with PNFA and SD, the LPA group had more extensive involvement of grey matter in posterior temporal and parietal cortices and and long association white matter tracts. Overlapping but distinct networks were involved in the AD-PPA and GRN-PPA subgroups, with more anterior temporal lobe involvement in GRN-PPA. The importance of these findings are threefold: firstly, the clinico-anatomical entity of LPA has a profile of brain damage that is complementary to the network-based disorders of SD and PNFA; secondly, the core phonological processing deficit in LPA is likely to arise from temporo-parietal junction damage but disease spread occurs through the dorsal language network (and in GRN-PPA, also the ventral language network); and finally, GRN mutations provide a specific molecular substrate for language network dysfunction.