American journal of Alzheimer's disease and other dementias, Jan 14, 2016
Spatial navigation is one of the cognitive functions known to decline in both normal and patholog... more Spatial navigation is one of the cognitive functions known to decline in both normal and pathological aging. In the present study, we aimed to assess the neural correlates of the decline of topographical memory in patients with amnestic mild cognitive impairment (aMCI). Patients with aMCI and age-matched controls were engaged in an intensive learning paradigm, lasting for 5 days, during which they had to encode 1 path from an egocentric perspective and 1 path from an allocentric perspective. After the learning period, they were asked to retrieve each of these paths using an allocentric or egocentric frame of reference while undergoing a functional magnetic resonance imaging scan. We found that patients with aMCI showed a specific deficit in storing new topographical memories from an allocentric perspective and retrieving stored information to perform the egocentric task. Imaging data suggest that this general decline is correlated with hypoactivation of the brain areas generally inv...
Hybrid PET-MRI is an emerging technique that allows multimodal evaluation of brain structure and ... more Hybrid PET-MRI is an emerging technique that allows multimodal evaluation of brain structure and function. This study evaluates longitudinal PET-MRI in one patient with stage-2 joHD, to assess changes related to disease progression. This approach might be useful to test the efficacy of disease-modifying drugs.
Background Juvenile-onset Huntington’s disease (joHD, neurological onset ≤20 years) is a rare HD ... more Background Juvenile-onset Huntington’s disease (joHD, neurological onset ≤20 years) is a rare HD variant associated with large CAG repeat-size alleles (>60), showing different clinical features from adulthood HD. Aims The aim of this study is twofold: i) To evaluate multimodal hybrid PET-MRI data fusion for characterizing joHD longitudinal brain changes; ii) to identify potential markers of disease progression, which might be useful in future trials to test disease-modifying drugs. Methods A 20-year-old female with stage-2 joHD, 62 CAG repeats and onset at 16 years, underwent 3T [18F]fluorodeoxyglucose (FDG) PET-MRI at two timepoints (Oct 2019, UHDRS-motor score=45 units and Feb 2021, UHDRS-motor score=53 units). The protocol included the simultaneous acquisition of FDG-PET, T1-weighted and resting-state functional MRI (rs-fMRI). Voxel-wise percentage changes at follow-up relative to baseline status were calculated on (i) grey matter (GM) density, (ii) FDG-PET uptake, (iii) rs-fMRI regional homogeneity (ReHo), and (iv) rs-fMRI amplitude of low frequency fluctuation (fALFF). Results Whole-brain GM density decreased by 31.9±21.1%. FDG uptake increased in the frontoparietal network (approx. 20%), while decreasing in the remaining regions, including the thalamus. ReHo and fALFF followed the pattern of PET changes, also highlighting increased functional connectivity in the frontal cortex opposed to decreased connectivity in posterior regions. Conclusion Hybrid PET/MRI is an emerging technique that allows individually-tailored evaluation of brain changes. Preliminary results are promising and showed rapid structural and metabolic changes in an adult patient with stage 2 joHD, resembling the trajectories reported in the literature in advanced adult HD patients, and involving specific regions thought to be key hubs affected by this disease.
The “Spazio Huntington—A Place for Children” program was launched in 2019. The aim was to contact... more The “Spazio Huntington—A Place for Children” program was launched in 2019. The aim was to contact at risk kids within Huntington disease (HD) families, to provide counseling to their parents and to start a prospective follow-up of kids suspicious to manifest pediatric HD (PHD). We met 25 at risk kids in two years, four of whom with PHD and highly expanded (HE) mutations beyond 80 CAG repeats. We rated motor, neuropsychological and behavioral changes in all PHD kids by the Unified HD Rating Scale (UHDRS)-total motor score (TMS) and additional measures of (1) cognitive level (Leiter International Performance Scale), (2) adaptive functioning (Adaptive Behavior Assessment Systems), (3) receptive language (Peabody Picture Vocabulary Test) and (4) behavioral abnormalities (Child Behavior Check List and Children’s Yale–Brown Obsessive Compulsive Scale). All PHD kids showed a severe progression of neurological and psychiatric manifestations including motor, cognitive and behavioral changes....
Cortical hubs play a fundamental role in the functional architecture of brain connectivity at res... more Cortical hubs play a fundamental role in the functional architecture of brain connectivity at rest. However, the anatomical scaffold underlying their centrality is still under debate. Certainly, the brain function and anatomy are significantly entwined through synaptogenesis and pruning mechanisms that continuously reshape structural and functional connections. Thus, if hubs are expected to exhibit a large number of direct anatomical connections with the rest of the brain, such a dense wiring is extremely inefficient in energetic terms. In this work, we investigate these aspects on fMRI and DTI data from a set of know resting‐state networks, starting from the hypothesis that to promote integration, functional, and anatomical connections link different areas at different scales or hierarchies. Thus, we focused on the role of functional hubs in this hierarchical organization of functional and anatomical architectures. We found that these regions, from a structural point of view, are f...
Journal of Neurology, Neurosurgery & Psychiatry, 2014
Background Higher iron concentration in subcortical grey matter structures is documented in Hunti... more Background Higher iron concentration in subcortical grey matter structures is documented in Huntington’s disease (HD) but the disease effects on white matter (WM) is less well documented. We have previously reported macro and microstructural alterations in the corpus callosum (CC) in HD. Aims To investigate the regional iron content in the CC using the Transverse Relations Rate (T2*) and DTI tractography. We examined the CC in its entirety and segmented into its seven anatomical sub regions: the orbital frontal (OF), anterior frontal (AF), superior frontal (SF), superior parietal (SP), posterior parietal (PP), temporal (Temp), and occipital (Occ). Methods Subjects groups included 25 HD patients, 25 presymptomatic HD (PreHD) subjects, 40 healthy controls. Six consecutive T2*-weighted gradient echo-planar whole-brain volumes were acquired at different time of echo. Tractography was performed for each region of the CC by manually drawing two regions of interest on each individuals fractional anisotropy colour map. To test for callosal differences, a Mancova was applied covering for gender and age. Results We found reduced iron content in HD patients across the CC as a whole. Regional results revealed increased iron in the Occ, SP, and OF tracts of Pre-HD subjects when compared with HD patients and decreased iron in the Occ tract of HD patients when compared with controls as well as increased iron in the OF of Pre-HD subjects compared to controls. Conclusion An increase of iron content has been suggested to be associated with remyelination process in attempting to repair myelin damage. Our results are in agreement with this hypothesis and suggest an attemp to repair myelin in the posterior callosal fibre (the Occ) and motor fibres (SP) in presymptomatic stage of HD (higher iron content). This process eventually fails, with the pathology progression, as indicate by lower content of iron in HD. Abstract E09 Figure 1
American journal of Alzheimer's disease and other dementias, Jan 14, 2016
Spatial navigation is one of the cognitive functions known to decline in both normal and patholog... more Spatial navigation is one of the cognitive functions known to decline in both normal and pathological aging. In the present study, we aimed to assess the neural correlates of the decline of topographical memory in patients with amnestic mild cognitive impairment (aMCI). Patients with aMCI and age-matched controls were engaged in an intensive learning paradigm, lasting for 5 days, during which they had to encode 1 path from an egocentric perspective and 1 path from an allocentric perspective. After the learning period, they were asked to retrieve each of these paths using an allocentric or egocentric frame of reference while undergoing a functional magnetic resonance imaging scan. We found that patients with aMCI showed a specific deficit in storing new topographical memories from an allocentric perspective and retrieving stored information to perform the egocentric task. Imaging data suggest that this general decline is correlated with hypoactivation of the brain areas generally inv...
Hybrid PET-MRI is an emerging technique that allows multimodal evaluation of brain structure and ... more Hybrid PET-MRI is an emerging technique that allows multimodal evaluation of brain structure and function. This study evaluates longitudinal PET-MRI in one patient with stage-2 joHD, to assess changes related to disease progression. This approach might be useful to test the efficacy of disease-modifying drugs.
Background Juvenile-onset Huntington’s disease (joHD, neurological onset ≤20 years) is a rare HD ... more Background Juvenile-onset Huntington’s disease (joHD, neurological onset ≤20 years) is a rare HD variant associated with large CAG repeat-size alleles (>60), showing different clinical features from adulthood HD. Aims The aim of this study is twofold: i) To evaluate multimodal hybrid PET-MRI data fusion for characterizing joHD longitudinal brain changes; ii) to identify potential markers of disease progression, which might be useful in future trials to test disease-modifying drugs. Methods A 20-year-old female with stage-2 joHD, 62 CAG repeats and onset at 16 years, underwent 3T [18F]fluorodeoxyglucose (FDG) PET-MRI at two timepoints (Oct 2019, UHDRS-motor score=45 units and Feb 2021, UHDRS-motor score=53 units). The protocol included the simultaneous acquisition of FDG-PET, T1-weighted and resting-state functional MRI (rs-fMRI). Voxel-wise percentage changes at follow-up relative to baseline status were calculated on (i) grey matter (GM) density, (ii) FDG-PET uptake, (iii) rs-fMRI regional homogeneity (ReHo), and (iv) rs-fMRI amplitude of low frequency fluctuation (fALFF). Results Whole-brain GM density decreased by 31.9±21.1%. FDG uptake increased in the frontoparietal network (approx. 20%), while decreasing in the remaining regions, including the thalamus. ReHo and fALFF followed the pattern of PET changes, also highlighting increased functional connectivity in the frontal cortex opposed to decreased connectivity in posterior regions. Conclusion Hybrid PET/MRI is an emerging technique that allows individually-tailored evaluation of brain changes. Preliminary results are promising and showed rapid structural and metabolic changes in an adult patient with stage 2 joHD, resembling the trajectories reported in the literature in advanced adult HD patients, and involving specific regions thought to be key hubs affected by this disease.
The “Spazio Huntington—A Place for Children” program was launched in 2019. The aim was to contact... more The “Spazio Huntington—A Place for Children” program was launched in 2019. The aim was to contact at risk kids within Huntington disease (HD) families, to provide counseling to their parents and to start a prospective follow-up of kids suspicious to manifest pediatric HD (PHD). We met 25 at risk kids in two years, four of whom with PHD and highly expanded (HE) mutations beyond 80 CAG repeats. We rated motor, neuropsychological and behavioral changes in all PHD kids by the Unified HD Rating Scale (UHDRS)-total motor score (TMS) and additional measures of (1) cognitive level (Leiter International Performance Scale), (2) adaptive functioning (Adaptive Behavior Assessment Systems), (3) receptive language (Peabody Picture Vocabulary Test) and (4) behavioral abnormalities (Child Behavior Check List and Children’s Yale–Brown Obsessive Compulsive Scale). All PHD kids showed a severe progression of neurological and psychiatric manifestations including motor, cognitive and behavioral changes....
Cortical hubs play a fundamental role in the functional architecture of brain connectivity at res... more Cortical hubs play a fundamental role in the functional architecture of brain connectivity at rest. However, the anatomical scaffold underlying their centrality is still under debate. Certainly, the brain function and anatomy are significantly entwined through synaptogenesis and pruning mechanisms that continuously reshape structural and functional connections. Thus, if hubs are expected to exhibit a large number of direct anatomical connections with the rest of the brain, such a dense wiring is extremely inefficient in energetic terms. In this work, we investigate these aspects on fMRI and DTI data from a set of know resting‐state networks, starting from the hypothesis that to promote integration, functional, and anatomical connections link different areas at different scales or hierarchies. Thus, we focused on the role of functional hubs in this hierarchical organization of functional and anatomical architectures. We found that these regions, from a structural point of view, are f...
Journal of Neurology, Neurosurgery & Psychiatry, 2014
Background Higher iron concentration in subcortical grey matter structures is documented in Hunti... more Background Higher iron concentration in subcortical grey matter structures is documented in Huntington’s disease (HD) but the disease effects on white matter (WM) is less well documented. We have previously reported macro and microstructural alterations in the corpus callosum (CC) in HD. Aims To investigate the regional iron content in the CC using the Transverse Relations Rate (T2*) and DTI tractography. We examined the CC in its entirety and segmented into its seven anatomical sub regions: the orbital frontal (OF), anterior frontal (AF), superior frontal (SF), superior parietal (SP), posterior parietal (PP), temporal (Temp), and occipital (Occ). Methods Subjects groups included 25 HD patients, 25 presymptomatic HD (PreHD) subjects, 40 healthy controls. Six consecutive T2*-weighted gradient echo-planar whole-brain volumes were acquired at different time of echo. Tractography was performed for each region of the CC by manually drawing two regions of interest on each individuals fractional anisotropy colour map. To test for callosal differences, a Mancova was applied covering for gender and age. Results We found reduced iron content in HD patients across the CC as a whole. Regional results revealed increased iron in the Occ, SP, and OF tracts of Pre-HD subjects when compared with HD patients and decreased iron in the Occ tract of HD patients when compared with controls as well as increased iron in the OF of Pre-HD subjects compared to controls. Conclusion An increase of iron content has been suggested to be associated with remyelination process in attempting to repair myelin damage. Our results are in agreement with this hypothesis and suggest an attemp to repair myelin in the posterior callosal fibre (the Occ) and motor fibres (SP) in presymptomatic stage of HD (higher iron content). This process eventually fails, with the pathology progression, as indicate by lower content of iron in HD. Abstract E09 Figure 1
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