Background and purpose
Cognitive impairment is a central feature of Huntington's disease (HD), but it is unclear to what extent more aggressive cognitive phenotypes exist in HD among individuals with ...the same genetic load and equivalence in other clinical and sociodemographic variables.
Methods
We included Enroll‐HD study participants in early and early–mid stages of HD at baseline and with three consecutive yearly follow‐ups for whom several clinical and sociodemographic as well as cognitive measures were recorded. We excluded participants with low and large CAG repeat length (CAG < 39 & > 55), with juvenile or late onset HD, and with dementia at baseline. We explored the existence of different groups according to the profile of cognitive progression using a two‐step k‐means cluster analysis model based on the combination of different cognitive outcomes.
Results
We identified a slow cognitive progression group of 293 participants and an aggressive progression group (F‐CogHD) of 235 for which there were no differences at the baseline visit in any of the measures explored, with the exception of a slightly higher motor score in the F‐CogHD group. This group showed a more pronounced annual loss of functionality and a more marked motor and psychiatric deterioration.
Conclusions
The rate of progression of cognitive deterioration in HD is strongly variable even between patients sharing, among other variables, equivalent CAG repeat length, age, and disease duration. We can recognize at least two phenotypes that differ in terms of rate of progression. Our findings open new avenues to study additional mechanisms contributing to HD heterogeneity.
Individuals with pre‐manifest and early symptomatic Huntington's disease (HD) have shown deficits in solving arithmetic word‐problems. However, the neural correlates of these deficits in HD are ...poorly understood. We explored the structural (gray‐matter volume; GMV) and metabolic (18F‐FDG PET; SUVr) brain correlates of arithmetic performance using the recently developed HD‐word problem arithmetic task (HD‐WPA) in seventeen preHD and sixteen HD individuals. Symptomatic participants showed significantly lower scores in the HD‐WPA than preHD participants. Lower performance in the HD‐WPA was associated with reduced GMV in subcortical, medial frontal, and several posterior‐cortical clusters in HD participants. No significant GMV loss was found in preHD participants. 18F‐FDG data revealed a widespread pattern of hypometabolism in association with lower arithmetic performance in all participants. In preHD participants, this pattern was restricted to the ventrolateral and orbital prefrontal cortex, the insula, and the precentral gyrus. In HD participants, the pattern extended to several parietal–temporal regions. Word‐problem solving arithmetic deficits in HD is subserved by a pattern of asynchronous metabolic and structural compromise across the cerebral cortex as a function of disease stage. In preHD individuals, arithmetic deficits were associated with prefrontal alterations, whereas in symptomatic HD patients, more severe arithmetic deficits are associated with the compromise of several frontal‐subcortical and temporo‐parietal regions. Our results support the hypothesis that cognitive deficits in HD are not exclusively dominated by frontal‐striatal dysfunctions but also involve fronto‐temporal and parieto‐occipital damage.
Approximately 20% of type 1 diabetes (T1D) patients have an impaired awareness of hypoglyceamia (IAH). IAH represents a risk factor for severe and recurrent hypoglycaemic events, which can lead to ...brain damage. Because no effective treatments are currently available to prevent IAH in this population, characterising the set of brain alterations associated with IAH may reveal novel preclinical diagnostic or therapeutic strategies. Using state‐of‐the art neuroimaging techniques, we compared 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) uptake at rest between 10 T1D patients with IAH and nine patients with normal awareness of hypoglycaemia (NAH). T1D‐IAH patients showed a pattern of increased FDG‐PET uptake with respect to NAH patients (P < .05 corrected). Topographically, glucose metabolism was increased in the frontal and precuneus regions. Importantly, within the IAH group, this abnormal hypermetabolism correlated with IAH severity. This hypermetabolic state appeared to be unrelated to compensatory mechanisms as a result of reduced grey matter density or a neuroinflammatory state. We observed an abnormal increase in FDG‐uptake in T1D patients with IAH in brain regions strongly related to cognition. Because this hypermetabolic state correlated with IAH severity, its biological characterisation could reveal new preventive or therapeutic strategies. A possible mechanism could be that glucose transport is increased in hypoglycaemia unawareness to compensate for recurrent hypoglycaemia, although this need to be confirmed in further research.
With respect to type 1 diabetes (T1D) patients with normal awareness of hypoglycaemia, T1D patients with impaired awareness of hypoglyceamia patients showed increased 18F‐fluorodeoxyglucose‐positron emission tomography uptake both in the voxelwise standardised uptake values (SUVr) analysis (top) and in the intracortical vertexwise partial volume correction‐SUVR analysis (bottom) (P < .05 corrected).
Cognitive decline is a major disabling feature in Parkinson's disease (PD). Multimodal imaging studies have shown functional disruption in neurocognitive networks related to cognitive impairment. ...However, it remains unknown whether these changes are related to gray matter loss, or whether they outline network vulnerability in the early stages of cognitive impairment. In this work, we intended to assess functional connectivity and graph theoretical measures and their relation to gray matter loss in Parkinson's disease with mild cognitive impairment (PD‐MCI). We recruited 53 Parkinson's disease patients and classified them for cognitive impairment using Level‐1 Movement Disorders Society‐Task Force Criteria. Voxel‐based morphometry, functional connectivity and graph theoretical measures were obtained on a 3‐Tesla MRI scanner. Loss of gray matter was observed in the default mode network (bilateral precuneus), without a corresponding disruption of functional or graph theoretical properties. However, functional and graph theoretical changes appeared in salience network nodes, without evidence of gray matter loss. Global cognition and executive scores showed a correlation with node degree in the right anterior insula. We also found a correlation between visuospatial scores and right supramarginal gyrus node degree. Our findings highlight the loss of functional connectivity and topological features without structural damage in salience network regions in PD‐MCI. They also underline the importance of multimodal hubs in the transition to mild cognitive impairment. This functional disruption in the absence of gray matter atrophy suggests that the salience network is a key vulnerable system at the onset of mild cognitive impairment in PD.
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