Author query sheet
Queries for Author Journal: Journal of Neurology, Neurosurgery & Psychiatry Paper: jnnp-2016-314744 Title: Detecting dysexecutive syndrome in neurodegenerative diseases: are we using an appropriate approach and effective diagnostic tools?
The proof of your manuscript appears on the following page(s). It is the responsibility of the corresponding author to check against the original manuscript and approve or amend these proofs. Please read the proofs carefully, checking for accuracy, verifying the reference order and checking figures and tables. When reviewing your page proof please keep in mind that a professional copyeditor edited your manuscript to comply with the style requirements of the journal. This is not an opportunity to alter, amend or revise your paper; it is intended to be for correction purposes only. The journal reserves the right to charge for excessive author alterations or for changes requested after the proofing stage has concluded. During the preparation of your manuscript for publication, the questions listed below have arisen (the query number can also be found in the gutter close to the text it refers to). Please attend to these matters and return the answers to these questions when you return your corrections. Please note, we will not be able to proceed with your article if these queries have not been addressed. A second proof is not normally provided.
Note Reference
Note
N1
IMPORTANT: Corrections at this stage should be limited to those that are essential. Extensive corrections will delay the time to publication and may also have to be approved by the Editor. Alterations cannot be made after the article has published online.
N2
Author SURNAMES (family names) have been highlighted - please check that these are correct. Please check all names are spelt correctly, and that affiliations and correspondence details are accurate.
N3
Please check funding statement is accurate (and include grant numbers if applicable).
N4
Your article should display in PubMed within 1 week of Online First publication. If you have paid for Open Access, your article will be sent to PubMed Central upon issue publication.
Query Reference
Query No Queries.
If you are happy with the proof as it stands, please email to confirm this. Minor changes that do not require a copy of the proof can be sent by email ( please be as specific as possible). Email:
[email protected]
PE: JKM
CE: AK
QC: SR
Author query sheet If you have any changes that cannot be described easily in an email, please mark them clearly on the proof using the annotation tools and email this by reply to the eProof email. We will keep a copy of any correspondence from you related to the author proof for six months. After six months, correspondence will be deleted.
Please respond within 48 hours
Editorial commentary 1 2 3 4 5 6 7
N1 8 ¶ 9 N2 ¶ 10 N4 ¶ 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45
Detecting dysexecutive syndrome in neurodegenerative diseases: are we using an appropriate approach and effective diagnostic tools? Michele Poletti,1 Marco Cavallo,2,3 Mauro Adenzato4,5 The term ‘dysexecutive syndrome’ refers to a dysregulation of executive functions and is strictly associated to frontal lobe damage. Dysexecutive syndrome typically encompasses emotional, motivational and behavioural symptoms, as well as cognitive deficits.1 This disabling condition can be observed in various clinical domains, and above all characterises degenerative diseases such as frontotemporal dementia (FTD) and—to a lesser degree—corticobasal degeneration (CBD). In recent years, neuropsychological tools have been used to investigate dysexecutive syndrome.2 However, to date this field of clinical research suffers from a significant paradox: while clinicians and caregivers perceive with ease the presence of the symptoms that characterise patients’ clinical picture, surprisingly it has not yet been possible to promptly and reliably detect this cohort of symptoms with effective diagnostic tools. The paper by Gansler et al3 has the merit of making a significant step further in this direction, by proposing the distinction, but also the strict synergy, between the realms of ‘executive functions’ (EF) and ‘dysexecutive behaviours’ (DB), and by supporting the utility of integrating EF and DB measures for diagnostic purposes. In detail, Gansler et al included a large cohort of patients (N=243) affected by
46 47 48 49 50 51 52 53 54 55 56
1
Child and Adolescent Psychiatry Unit, Department of Mental Health and Pathological Addiction, Azienda Unità Sanitaria Locale, Reggio Emilia, Italy; 2eCampus University, Novedrate, Italy; 3Azienda Sanitaria Locale Torino 3, Collegno, Italy; 4Department of Psychology, Center for Cognitive Science, University of Turin, Turin, Italy; 5Neuroscience Institute of Turin, Turin, Italy Correspondence to Mauro Adenzato, Center for Cognitive Science, Department of Psychology, University of Turin, via Po 14, Turin 10123, Italy; mauro.
[email protected]
the behavioural variant of FTD (bvFTD, N=124), primary progressive aphasia (PPA, N=34) or CBD (N=85): for the majority of them, the authors collected patients’ performance on an EF neuropsychological battery (the Delis-Kaplan executive function system), and caregivers’ report of patients’ behaviour through the FrSBe (the frontal behaviour scale). As expected, bvFTD patients got significantly lower scores on EF tests and higher scores on the DB measure, compared to other subgroups. Interestingly, factor analyses showed that EF and DB were distinct but overlapping constructs, and this was corroborated at a neuroimaging level: the EF composite was uniquely associated with left lateral and dorsomedial prefrontal cortex, and with the middle temporal gyrus and temporo-parietal junction, while DB was uniquely associated with cingulate gyrus bilaterally, right subcallosal gyrus, and right frontal anterior pole. The rostral part of the lateral and dorsomedial prefrontal cortex was associated with EF and DB. Finally, the authors’ results showed that by considering EF and DB measures jointly, diagnostic precision increased significantly (even if this was more true for PPA and CDB, than for bvFTD cases where DB measures alone already possessed good explanatory power). In our view, Gansler et al’s study takes the need to improve an early and precise detection of neurodegenerative disease symptoms seriously by considering the interplay between neural, cognitive and behavioural levels. To take the next step, we support the position that future studies in this field should also include an assessment of Theory of Mind (ToM) abilities, that is, the capacity to explain and predict other people’s behaviour by attributing independent mental states to them.
As recently shown,4 5 ToM is another domain significantly involved in dementias and CBD partially dissociated from EF impairment, and interestingly ToM tasks typically present a higher degree of ‘ecological’ validity, compared to standard neuropsychological tests. Researchers and clinicians should, therefore, include a careful ToM assessment to improve diagnostic procedures, with the ultimate goal to implement effective management strategies. Funding MA was supported by an MIUR grant (FIRB 2012–2017, protocol number: RBFR12F0BD_001) and by the University of Torino (Ricerca scientifica finanziata dall’Università ‘Cognizione sociale e attaccamento in popolazioni cliniche e non cliniche)’.
65 66 67 68 69 70 71 72 73 74 75 76 77
N3 ¶ 79 78 80 81
Competing interests None declared.
82
Provenance and peer review Commissioned; internally peer reviewed.
83 84 85 86 87 88
To cite Poletti M, Cavallo M, Adenzato M. J Neurol Neurosurg Psychiatry Published Online First: [ please include Day Month Year] doi:10.1136/jnnp-2016314744
89
Received 24 August 2016 Revised 7 September 2016 Accepted 20 September 2016
93
90 91 92 94 95 96 97 98
▸ http://dx.doi.org/10.1136/jnnp-2016-313576
99 100 101
J Neurol Neurosurg Psychiatry 2016;0:1. doi:10.1136/jnnp-2016-314744
102 103
REFERENCES
104
1
105
2
3
4
5
Godefroy O, Azouvi P, Robert P, et al. Dysexecutive syndrome: diagnostic criteria and validation study. Ann Neurol 2010;68:855–64. da Costa Armentano CG, Porto CS, Nitrini R, et al. Ecological evaluation of executive functions in mild cognitive impairment and Alzheimer disease. Alzheimer Dis Assoc Disord 2013;27:95–101. Gansler DA, Huey ED, Pan JJ, et alAssessing the dysexecutive syndrome in dementia. J Neurol Neurosurg Psychiatr 2016;▪▪▪. Adenzato M, Cavallo M, Enrici I. Theory of Mind ability in the behavioural variant of frontotemporal dementia: an analysis of the neural, cognitive, and social levels. Neuropsychologia 2010;48:2–12. Poletti M, Enrici I, Adenzato M. Cognitive and affective Theory of Mind in neurodegenerative diseases: neuropsychological, neuroanatomical and neurochemical levels. Neurosci Biobehav Rev 2012;36:2147–64.
106 107 108 109 110 111 112 113 114 115 116 117 118 119 120
57
121
58
122
59
123
60
124
61
125
62
126
63
127
64
128
Poletti M, et al. J Neurol Neurosurg Psychiatry Month 2016 Vol 0 No 0
1
