Structural and metabolic brain correlates of apathy in Huntington's disease

Martínez‐Horta, Saül; Pérez‐Pérez, Jesús; Sampedro, Frederic; Pagonabarraga, Javier; Horta‐Barba, Andrea; Carceller-Sindreu, Mar; Gómez‐Anson, Beatriz; Lozano-Martinez, Gloria Andrea; López-Mora, Diego Alfonso; Camacho, Valle; Fernández-León, Alejandro; Carrió, Ignasi; Kulisevsky, Jaime

doi:10.1002/mds.27395

Cited by 41 publications

(28 citation statements)

References 37 publications

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“…There is selective early degeneration of the indirect pathway at the level of the striatum compared with the direct pathway in HD, and apathy in HD has been correlated with altered resting‐state activity in a circuit centered on the dorsal striatum . Apathy in HD has also been correlated with amygdala atrophy and hypoperfusion . The amygdala is heavily involved in stimulus‐response learning, and there is evidence to suggest distinct neuronal groups are involved with learning from loss and reward …”

Section: Discussionmentioning

confidence: 99%

“…73 Apathy in HD has also been correlated with amygdala atrophy and hypoperfusion. 74 The amygdala is heavily involved in stimulus-response learning, and there is evidence to suggest distinct neuronal groups are involved with learning from loss and reward. 64,75,76 This work suggests that effort for reward (HD cases had slower reaction times at all levels of reward on the RRTT, despite correction for TMS) was abnormal in HD cases compared with controls, but this deficit did not mediate apathy.…”

Section: Discussionmentioning

confidence: 99%

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Insensitivity to loss predicts apathy in huntington's disease

et al. 2019

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Background Apathy is a deficit in goal‐directed behavior that significantly affects quality of life and function. It is common in Huntington's disease and other disorders affecting corticostriatal pathways. Deficits in processing of reward, altered effort, and executive dysfunction are associated with apathy in other disorders, but the cognitive processes leading to apathy in Huntington's disease remain largely unknown. A previously reported deficit in learning from losses in Huntington's disease raises the possibility of a hitherto unrecognized mechanism leading to apathy. This study's objective was to delineate the cognitive processes associated with apathy in HD. Methods We tested 51 Huntington's disease participants and 26 controls on a battery of novel and established measures to assess the contribution to apathy in Huntington's disease of executive function, reward value, reward‐effort calculations, instrumental learning, and response to reward and loss. Results Huntington's disase participants had deficits in instrumental learning with impaired response to loss, but no evidence to suggest altered reward‐related behavior or effort. We also saw an executive dysfunction contribution to apathy in Huntington's disease. Discussion We report the novel finding that apathy in Huntington's disease is associated with blunted responses to losses and impaired instrumental learning. This association is consistent with the known early degeneration of the indirect pathway and amygdala involvement in apathy in Huntington's disease, but is previously unreported in any disorder. In keeping with the comparative preservation of the ventral striatum and orbitofrontal cortex in Huntington's disease, reward valuation and reward‐effort calculations did not contribute to apathy. © 2019 International Parkinson and Movement Disorder Society

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Insensitivity to loss predicts apathy in huntington's disease

et al. 2019

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“…Microglia activation in the insula has been shown to be associated with neuronal loss in this area early in the disease ( Tai et al, 2007 ). Additionally degeneration of the insula, as well as frontal-striatal circuits has been associated with apathy severity scores in HD ( Martínez-Horta et al, 2018 ). Taken together, insular degeneration appears to be linked strongly with disease symptomology, and future work may look to use the MRI signal in the insula to track HD progression and symptom worsening.…”

Section: Discussionmentioning

confidence: 99%

Altered Intracortical T1-Weighted/T2-Weighted Ratio Signal in Huntington’s Disease

et al. 2018

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Huntington’s disease (HD) is a genetic neurodegenerative disorder that is characterized by neuronal cell death. Although medium spiny neurons in the striatum are predominantly affected, other brain regions including the cerebral cortex also degenerate. Previous structural imaging studies have reported decreases in cortical thickness in HD. Here we aimed to further investigate changes in cortical tissue composition in vivo in HD using standard clinical T1-weighted (T1W) and T2-weighted (T2W) magnetic resonance images (MRIs). 326 subjects from the TRACK-HD dataset representing healthy controls and four stages of HD progression were analyzed. The intracortical T1W/T2W intensity was sampled in the middle depth of the cortex over 82 regions across the cortex. While these previously collected images were not optimized for intracortical analysis, we found a significant increase in T1W/T2W intensity (p < 0.05 Bonferroni-Holm corrected) beginning with HD diagnosis. Increases in ratio intensity were found in the insula, which then spread to ventrolateral frontal cortex, superior temporal gyrus, medial temporal gyral pole, and cuneus with progression into the most advanced HD group studied. Mirroring past histological reports, this increase in the ratio image intensity may reflect disease-related increases in myelin and/or iron in the cortex. These findings suggest that future imaging studies are warranted with imaging optimized to more sensitively and specifically assess which features of cortical tissue composition are abnormal in HD to better characterize disease progression.

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“…Additionally, an MRI-PET study found that in a sample of 40 patients with early stage HD, higher apathy severity was associated with lower grey matter volume in subcortical regions, temporal lobes, and anterior cingulate cortex, as well as lower brain glucose metabolism in the prefrontal cortex, temporal lobes, insula, and precuneus (S. Martinez-Horta et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Apathy predicts rate of cognitive decline over 24 months in premanifest Huntington's disease

et al. 2020

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Background Cognitive impairment is a core feature of Huntington's disease (HD), however, the onset and rate of cognitive decline is highly variable. Apathy is the most common neuropsychiatric symptom of HD, and is associated with cognitive impairment. The aim of this study was to investigate apathy as a predictor of subsequent cognitive decline over 2 years in premanifest and early HD, using a prospective, longitudinal design. Methods A total of 118 premanifest HD gene carriers, 111 early HD and 118 healthy control participants from the multi-centre TRACK-HD study were included. Apathy symptoms were assessed at baseline using the apathy severity rating from the Short Problem Behaviours Assessment. A composite of 12 outcome measures from nine cognitive tasks was used to assess cognitive function at baseline and after 24 months. Results In the premanifest group, after controlling for age, depression and motor signs, more apathy symptoms predicted faster cognitive decline over 2 years. In contrast, in the early HD group, more motor signs, but not apathy, predicted faster subsequent cognitive decline. In the control group, only older age predicted cognitive decline. Conclusions Our findings indicate that in premanifest HD, apathy is a harbinger for cognitive decline. In contrast, after motor onset, in early diagnosed HD, motor symptom severity more strongly predicts the rate of cognitive decline.

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Structural and metabolic brain correlates of apathy in Huntington's disease

Cited by 41 publications

References 37 publications

Insensitivity to loss predicts apathy in huntington's disease

Insensitivity to loss predicts apathy in huntington's disease

Altered Intracortical T1-Weighted/T2-Weighted Ratio Signal in Huntington’s Disease

Apathy predicts rate of cognitive decline over 24 months in premanifest Huntington's disease

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