Structural brain correlates of cognitive and behavioral impairment in <scp>MND</scp>

Agosta, Federica; Ferraro, Pilar M.; Riva, Nilo; Spinelli, Edoardo Gioele; Chiò, Adriano; Canu, Elisa; Valsasina, Paola; Lunetta, Christian; Iannaccone, Sandro; Copetti, Massimiliano; Prudente, Evelina; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

doi:10.1002/hbm.23124

Cited by 90 publications

(88 citation statements)

References 71 publications

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“…This is consistent with previous studies supporting the notion that the right hemisphere has a critical role in complex social behaviours 5 25 26. It is interesting to note that the right superior frontal gyrus involvement has been found in motor neuron disease with comorbid FTD,27 suggesting that its early involvement in patients with ALS might be marker for the development of bvFTD.…”

Section: Discussionmentioning

confidence: 99%

Cortical correlates of behavioural change in amyotrophic lateral sclerosis

Consonni

Cappa

Bella

et al. 2018

J Neurol Neurosurg Psychiatry

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BackgroundBehavioural changes in amyotrophic lateral sclerosis (ALS) are heterogeneous. The study aim was to identify the behavioural profiles of non-demented patients with ALS and their neuroimaging correlates and to elucidate if they are comparable to those reported in studies of the behavioural-variant of frontotemporal dementia (bvFTD).MethodsBehavioural changes of 102 non-demented patients with ALS were assessed through the Frontal Behavioural Inventory (FBI), a 24-item scale assessing different behavioural modifications, mainly chosen from the core clinical features of FTD. Principal component analysis (PCA) was used to detect distinct clusters of behavioural changes based on FBI subscores. The cortical thinning related to each behavioural profile was analysed in 29 patients with ALS. Cronbach’s α was used to test the reliability of bvFTD-related FBI clustering in our cohort.ResultsSixty patients with ALS had FBI score≥1. PCA identified three phenotypic clusters loading on disinhibited/hostile, dysexecutive and apathetic FBI subscores. Imaging analyses revealed that the thinning of bilateral orbitofrontal cortex was related to apathy, the right frontotemporal and cingular cortex to the disinhibited/hostile profile and the left precuneus cortex to the dysexecutive behaviours. The bvFTD-associated aggressive profile reliably applied to our cohort.ConclusionsIn non-demented patients with ALS, different behavioural profiles could be identified. The right frontotemporal and cingular cortex thinning was the hallmark of the behavioural profile mostly overlapping that described in bvFTD. Our findings provide the unbiased identification of determinants relevant for a novel stratification of patients with ALS based on their behavioural impairment, which might be useful as proxy of cognitive decline.

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Section: Discussionmentioning

confidence: 99%

Cortical correlates of behavioural change in amyotrophic lateral sclerosis

Consonni

Cappa

Bella

et al. 2018

J Neurol Neurosurg Psychiatry

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“…DTI metrics have consistently demonstrated significant white matter alterations in the corticospinal tracts (CSTs) in ALS compared with healthy controls, reporting reduced FA [42–50] and increased MD and RD [51, 52]. DTI studies have specifically noted altered indices in the corpus callosum in ALS [53–55], as well extensive extramotor white matter involvement [56–58]. Asymptomatic carriers of pathogenic mutations in SOD1 were also reported to have lower FA in the CSTs [59], though a result not replicated in a subsequent study [60].…”

Section: Emerging Imaging Biomarkers In Alsmentioning

confidence: 99%

“…Furthermore, surface-based analysis of the precentral gyrus revealed that compared with patients with ALS, patients with a UMN phenotype displayed reduced cortical thickness [70]. The involvement of extramotor cortical regions is more severe in patients with ALS with cognitive impairment and ALS-FTD [58]. …”

Section: Emerging Imaging Biomarkers In Alsmentioning

confidence: 99%

Neuroimaging Endpoints in Amyotrophic Lateral Sclerosis

et al. 2017

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative, clinically heterogeneous syndrome pathologically overlapping with frontotemporal dementia. To date, therapeutic trials in animal models have not been able to predict treatment response in humans, and the revised ALS Functional Rating Scale, which is based on coarse disability measures, remains the gold-standard measure of disease progression. Advances in neuroimaging have enabled mapping of functional, structural, and molecular aspects of ALS pathology, and these objective measures may be uniquely sensitive to the detection of propagation of pathology in vivo. Abnormalities are detectable before clinical symptoms develop, offering the potential for neuroprotective intervention in familial cases. Although promising neuroimaging biomarker candidates for diagnosis, prognosis, and disease progression have emerged, these have been from the study of necessarily select patient cohorts identified in specialized referral centers. Further multicenter research is now needed to establish their validity as therapeutic outcome measures.Electronic supplementary materialThe online version of this article (doi:10.1007/s13311-016-0484-9) contains supplementary material, which is available to authorized users.

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“…Even less evidence exists of the imaging alterations observed in non-demented patients with ALS but with mild cognitive impairment. Recently, Agosta et al, in a study with DTI, demonstrated the association of the degeneration of white matter tracts with neuropsychological deficits in patients with ALS 22 . In our study, we highlight that all patients were evaluated at an early stage of the disease with a full battery of neuropsychological tests adapted to ALS patients, which included all cognitive areas.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile

Chaves

Bettini

Fernández

et al. 2017

Arq. Neuro-Psiquiatr.

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The objective of this preliminary study was to correlate diffusion tensor imaging (DTI) alterations with the cognitive profile of patients with amyotrophic lateral sclerosis (ALS). Methods This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA) was analyzed in the white matter using the tract based spatial statistics program. Results Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3) and 13 healthy controls (four females, average age 66.9 + - 2) were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001). Discussion In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.

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Structural brain correlates of cognitive and behavioral impairment in MND

Abstract: Cortical thinning and WM degeneration are highly associated with neuropsychological and behavioral symptoms in patients with MND. DT MRI metrics seem to be the most sensitive markers of extra-motor deficits within the MND spectrum.

Cited by 90 publications

References 71 publications

Cortical correlates of behavioural change in amyotrophic lateral sclerosis

Cortical correlates of behavioural change in amyotrophic lateral sclerosis

Neuroimaging Endpoints in Amyotrophic Lateral Sclerosis

Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile

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