{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:32:28Z","timestamp":1790271148356,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>In elderly people loneliness represents a risk factor for dementia and may negatively impact on mental and physical health. The specific contribute of loneliness to cognitive and behavioral functioning have not yet been determined in amyotrophic lateral sclerosis (ALS). Our hypothesis was that loneliness may be related to motor dysfunction with a negative impact on cognitive and behavioral decline, possibly related to specific cortical involvement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In 200 ALS patients (ALSpts) and 50 healthy controls (HCs) we measured loneliness, mood, and quality of life (QoL). ALSpts underwent comprehensive clinical, genetic, and neuropsychological assessment to define phenotypes. Seventy\u2010seven ALSpts performed 3T MRI scans to measure cortical thickness. Between\u2010group, partial correlation and regression analyses were used to examined clinical, neuropsychological, and cortical signatures of loneliness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Feelings of loneliness were documented in 38% of ALSpts (ALS\/L+pts) and in 47% of HCs. In both groups loneliness was associated with anxiety (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), depression (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.005), and poor QoL (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). ALS\/L+pts had similar motor dysfunctions and cognitive abilities than non\u2010lonely ALSpts, but distinct behavioral profiles (<jats:italic>P<\/jats:italic>\u2009\u2264\u20090.005) and frontoparietal involvement (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Loneliness in ALS is related to behavioral changes, apathy, and emotional dysregulation (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our cross\u2010sectional study indicates that, in ALS, the satisfaction of social environment is associated with a sense of life well\u2010being that is not limited to the motor status, proving instead that loneliness can impact on disease\u2010related neurobehavioral changes with a possible flashback on brain architecture. This suggests that sociality could promote personal resilience against behavioral and affective decline in ALS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52028","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T05:37:06Z","timestamp":1708666626000},"page":"1122-1134","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Loneliness as neurobehavioral issue in amyotrophic lateral sclerosis"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0479-2290","authenticated-orcid":false,"given":"Monica","family":"Consonni","sequence":"first","affiliation":[{"name":"3rd Neurology Unit and Motor Neuron Disease Centre Fondazione IRCCS Istituto Neurologico Carlo Besta  via Luigi Celoria 11 Milan 20133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Faltracco","sequence":"additional","affiliation":[{"name":"3rd Neurology Unit and Motor Neuron Disease Centre Fondazione IRCCS Istituto Neurologico Carlo Besta  via Luigi Celoria 11 Milan 20133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Dalla Bella","sequence":"additional","affiliation":[{"name":"3rd Neurology Unit and Motor Neuron Disease Centre Fondazione IRCCS Istituto Neurologico Carlo Besta  via Luigi Celoria 11 Milan 20133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Telesca","sequence":"additional","affiliation":[{"name":"3rd Neurology Unit and Motor Neuron Disease Centre Fondazione IRCCS Istituto Neurologico Carlo Besta  via Luigi Celoria 11 Milan 20133 Italy"},{"name":"Ph.D. Program in Neuroscience School of Medicine and Surgery, University of Milano\u2010Bicocca  Via Cadore 48 Monza 20900 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Bersano","sequence":"additional","affiliation":[{"name":"3rd Neurology Unit and Motor Neuron Disease Centre Fondazione IRCCS Istituto Neurologico Carlo Besta  via Luigi Celoria 11 Milan 20133 Italy"},{"name":"Department of Medical Biotechnology and Translational Medicine University of Milan  Via Vanvitelli 32 Milan 20133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1197-5458","authenticated-orcid":false,"given":"Anna","family":"Nigri","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  via Luigi Celoria 11 Milan 20133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Demichelis","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  via Luigi Celoria 11 Milan 20133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6450-0202","authenticated-orcid":false,"given":"Jean 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