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Background: Patients with Huntington's disease (HD) exhibit a variable predominance of cognitive, behavioral and motor symptoms. A specific instrument focusing on the impact of cognitive impairment in HD over functional capacity is lacking., Objective: To address the need for a brief and specifically developed HD questionnaire able to capture functional aspects suspected to be sensitive to cognitive impairment., Methods: We developed and validated the "Huntington's Disease-Cognitive Functional Rating Scale" (HD-CFRS) in 78 symptomatic carriers of the Huntington's disease mutation. We also administered the HD-CFRS to a knowledgeable informant to measure the level of agreement. To explore the association between HD-CFRS scores and participants' cognitive status, we administered objective measures of cognition. Participants were classified as cognitively preserved (HD-NC), as having mild cognitive impairment (HD-MCI), or as having dementia (HD-Dem)., Results: The HD-CFRS showed concurrent validity and internal consistency in the three groups. HD carriers and informants in the HD-NC group obtained similar HD-CFRS scores. However, in patients with mild cognitive impairment and dementia, informers reported greater functional impairment than HD participants. The HD-CFRS total score showed strong correlations with measures assessing cognition., Conclusions: These findings support the utility of the HD-CFRS as a brief and reliable instrument to measure functional defects associated with cognitive impairment in HD. We believe this questionnaire could be a useful tool both for clinical practice and research., (© 2022. The Author(s).)

Mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with consistent structural and functional brain changes. Whether different approaches for diagnosing PD-MCI are equivalent in their neural correlates is presently unknown. We aimed to profile the neuroimaging changes associated with the two endorsed methods of diagnosing PD-MCI. We recruited 53 consecutive non-demented PD patients and classified them as PD-MCI according to comprehensive neuropsychological examination as operationalized by the Movement Disorders Task Force. Voxel-based morphometry, cortical thickness, functional connectivity and graph theoretical measures were obtained on a 3-Tesla MRI scanner. 18 patients (32%) were classified as PD-MCI with Level-II criteria, 19 (33%) with the Parkinson's disease Cognitive Rating Scale (PD-CRS) and 32 (60%) with the Montreal Cognitive Assessment (MoCA) scale. Though regions of atrophy differed across classifications, reduced gray matter in the precuneus was found using both Level-II and PD-CRS classifications in PD-MCI patients. Patients diagnosed with the PD-CRS also showed extensive changes in cortical thickness, concurring with the MoCA in regions of the cingulate cortex, and again with Level-II regarding cortical thinning in the precuneus. Functional connectivity analysis found higher coherence within salience network regions of interest, and decreased anticorrelations between salience/central executive and default-mode networks in the PD-CRS classification for PD-MCI patients. Graph theoretical metrics showed a widespread decrease in node degree for the three classifications in PD-MCI, whereas betweenness centrality was increased in select nodes of the default mode network (DMN). Clinical and neuroimaging commonalities between the endorsed methods of cognitive assessment suggest a corresponding set of neural correlates in PD-MCI: loss of structural integrity in DMN structures, mainly the precuneus, and a loss of weighted connections in the salience network that might be counterbalanced by increased centrality in the DMN. Furthermore, the similarity of the results between exhaustive Level-II and screening Level-I tools might have practical implications in the search for neuroimaging biomarkers of cognitive impairment in Parkinson's disease., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cognitive deficits are common in Parkinson's disease (PD), with some PD patients meeting criteria for mild cognitive impairment (MCI). An unaddressed question is whether linguistic prediction is preserved in PD. This ability is nowadays deemed crucial for achieving fast and efficient comprehension, and it may be negatively impacted by cognitive deterioration in PD. To fill this gap of knowledge, we used event-related potentials (ERPs) to evaluate mechanisms of linguistic prediction in a sample of PD patients (on dopamine compensation) with and without MCI. To this end, participants read sentence contexts that were predictive or not about a sentence-final word. The final word appeared after one sec, matching or mismatching the prediction. The introduction of the interval allowed to capture neural responses both before and after sentence-final words, reflecting semantic anticipation and semantic processing. PD patients with normal cognition (N = 58) showed ERP responses comparable to those of matched controls. Specifically, in predictive contexts, a slow negative potential developed prior to sentence-final words, reflecting semantic anticipation. Later, expected words elicited reduced N400 responses (compared to unexpected words), indicating facilitated semantic processing. PD patients with MCI (N = 20) showed, in addition, a prolongation of the N400 congruency effect (compared to matched PD patients without MCI), indicating that further cognitive decline impacts semantic processing. Finally, lower verbal fluency scores correlated with prolonged N400 congruency effects and with reduced pre-word differences in all PD patients (N = 78). This relevantly points to a role of deficits in temporal-dependent mechanisms in PD, besides prototypical frontal dysfunction, in altered semantic anticipation and semantic processing during sentence comprehension., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Context: Type 1 diabetes (T1D) is associated with an increased risk of cognitive decline, where severe hypoglycemia (SH) and impaired awareness of hypoglycemia (IAH) may play a role. While there is evidence of a possible association between IAH and brain damage, the potential brain changes remain poorly characterized by magnetic resonance imaging (MRI)., Objective: To investigate whether there are structural brain differences in a group of T1D patients with IAH compared with normal awareness of hypoglycemia (NAH)., Design: General practice, population-based, cross-sectional study (July 2018 to July 2019)., Setting: Endocrinology Department, Hospital Santa Creu i Sant Pau., Participants: A total of 40 T1D patients (20 each with IAH and NAH) matched for age, sex, T1D duration, and education level., Main Outcome Measures: Using different neuroimaging techniques, we compared whole-brain gray matter (GM) and white matter (WM) differences. We used voxel-based morphometry and cortical surface area analysis methods to assess GM differences, and fractional anisotropy (FA) to assess WM differences., Results: Compared with patients with T1D-NAH, patients with T1D-IAH had reduced GM volumes and cortical surface areas, especially in frontal and parietal regions (P < 0.05 corrected), and also showed reduced FA values in major WM tracts. The observed MRI differences correlated with both SH frequency and IAH severity., Conclusions: MRI for patients with T1D show that IAH is associated with brain changes involving both GM and WM. Further research is needed to elucidate whether the observed differences are a consequence of increased SH episode frequency and increased IAH severity., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2019 Wiley Periodicals, Inc.)

Lack of validated data on cutoff scores for mild cognitive impairment (MCI) and sensitivity to change in predementia stages of Parkinson's disease (PD) limit the utility of instruments measuring global cognition as screening and outcome measures in therapeutic trials. Investigators who were blinded to PD-Cognitive Rating Scale (PD-CRS) scores classified a cohort of prospectively recruited, nondemented patients into a PD with normal cognition (PD-NC) group and a PD with MCI (PD-MCI) group using Clinical Dementia Rating (CDR) and the Mattis Dementia Rating Scale-2 (MDRS-2). The discriminative power of the PD-CRS for PD-MCI was examined in a representative sample of 234 patients (145 in the PD-NC group; 89 in the PD-MCI group) and in a control group of 98 healthy individuals. Sensitivity to change in the PD-CRS score (the minimal clinically important difference was examined with the Clinical Global Impression of Change scale and was calculated with a combination of distribution-based and anchor-based approaches) was explored in a 6-month observational multicenter trial involving a subset of 120 patients (PD-NC, 63; PD-MCI, 57). Regression analysis demonstrated that PD-CRS total scores (P < 0.001) and age (P = 0.01) independently differentiated PD-NC from PD-MCI. Area under the receiver operating characteristic curve (AUC) analysis (AUC, 0.85; 95% confidence interval, 0.80-0.90) indicated that a score ≤ 81 of 134 was the optimal cutoff point on the total score for the PD-CRS (sensitivity, 79%; specificity, 80%; positive predictive value, 59%; negative predictive value, 91%). A range of change from 10 to 13 points on the PD-CRS total score was indicative of clinically significant change. These findings suggest that the PD-CRS is a useful tool to identify PD-MCI and to track cognitive changes in nondemented patients with PD., (© 2013 International Parkinson and Movement Disorder Society.)

Cognitive impairment can be demonstrated in Parkinson's disease (PD) from the very beginning of the disease. Clinical manifestations range from slight deficits, only demonstrable by means of neuropsychological testing, up to dementia. If a linear involution is supposed for the cognitive worsening in PD, then the relatively subtle cognitive defects should be taken as the earliest signs of dementia implying that PD-MCI concept would be thoroughly equivalent to that used for the early prediction of other dementias among healthy population. Cognitive defects in PD, however, may not follow a normal distribution. While fronto-striatal deficits, such as working memory, set-shifting and free-recall verbal memory appear altered in most patients during long periods of time, certain functions depending on more posterior-cortical regions, such as copying or naming, usually characterize patients with dementia. Fronto-striatal and posterior-cortical cognitive defects may have a different pathophysiological substrates, evolution and prognosis. While fronto-striatal defects appear more related to dopaminergic defects, posterior-cortical defects may obey multiple neurotransmitter failure. Designing criteria to accurately diagnose PD-MCI is highly relevant for clinical treatment, research, care-giving and decision-making. Besides quantitative defects, an operative definition of MCI in PD should clearly distinguish a "risky cognitive profile" among the broad cognitive defects intrinsic to PD. Thus, along with other possible biological markers, from a neuropsychological point of view, posterior-cortical defects probably represent the very syndrome of MCI in PD.