A systematic review of behavioural changes in motor neuron disease
Abstract
Motor neuron disease (MND) and the behavioural variant of frontotemporal dementia (bvFTD) are thought to be part of a disease spectrum. There is uncertainty about the frequency and characteristics of behavioural changes in MND, and similarly, about a relation between bvFTD and the site of onset of MND. Our aim was to perform a systematic review of the publications on behavioural changes in MND. An extensive search for articles on behavioural changes in MND patients was performed. First, cohort studies of MND patients were reviewed to summarize the prevalence of bvFTD and mild behavioural changes. Secondly, data on bvFTD symptoms (mostly from case reports) of individual MND-bvFTD patients were used to analyse characteristics and pooled prevalences of bvFTD symptoms. In addition, site of onset, survival and demographic variables of MND-bvFTD patients were analysed. Results showed that in cohorts, 8.1% (95% CI 5.6 - 11.5%) of MND patients had bvFTD. In 170 individual patients with MND-bvFTD, perseveration (40%), apathy (29%) and disinhibition (26%) were the most frequently reported behavioural changes; 43% had memory disturbances and bulbar onset was found in 48%. In conclusion, 8% of MND patients have bvFTD, with perseveration being reported most frequently. MND-bvFTD is often accompanied by memory disturbances and is related to bulbar onset.
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Informal caregivers of patients with ALS or PMA face stressful demands due to the prospect of an early death and severe impairments of the patient.
“Informal caregivers of patients with ALS or PMA face stressful demands due to the prospect of an early death and severe impairments of the patient.”
The prevalence of frontotemporal dementia has been identified in around 8.1% (CI: 5.6-11.5%) of patients, with apathy, disinhibition and perseveration being the most commonly reported changes.
“the prevalence of frontotemporal dementia has been identified in around 8.1% (CI: 5.6–11.5%) of patients, with apathy, disinhibition and perseveration being the most commonly reported changes (Raaphorst et al., 2012).”
From Patients experiences of maintaining mental well-being and hope within motor neuron disease: a thematic synthesis (2015) · cites this paper as Raaphorst et al., 2012
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“Previous reports showed that this prevalence varied greatly from 17% to 88% in patients with MND, partly due to diverging definitions and diagnostic tools adopted among different studies.[26]”
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“of bulbar onset in patients with FTD-ALS compared 311 to ALS without dementia [26, 35].”
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Identification of potential pathways and biomarkers linked to progression in ALS
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“Whilst ALS is primarily driven by the degeneration of motor neurons, cognitive and behavioural changes corresponding to frontotemporal dysfunction occur in up to 40% of cases.(3) There is also vast genetic heterogeneity.”
Backgroundde Wit, J., Beelen, A., Drossaert, C. H. C., Kolijn, R., van den Berg, L. H., Visser-Meily, J. M. A., & Schröder, C. D. (2018) · BMC Psychology · doi:10.1186/s40359-018-0232-5 · Cited by 12 · see citing works
The spectrum of behavioral disorders in amyotrophic lateral sclerosis: current view
Jellinger, K. A. (2024) · Journal of Neural Transmission · doi:10.1007/s00702-024-02841-8 · Cited by 13 · see citing works
“The ALS-FTD-Q shows construct validity and correlates highest with other behavioral measures but poorly with anxiety and motor impairment (Raaphorst et al. 2012b).”
Clinicians' attitudes towards cognitive and behavioural screening in motor neurone disease
Crockford, C., Stockton, C., & Abrahams, S. (2017) · British Journal of Neuroscience Nursing · doi:10.12968/bjnn.2017.13.3.116 · Cited by 10 · see citing works
“Difficulties in executive functions (e.g., problem solving, decision making, social perception), language (e.g., word finding, comprehension), and behaviours such as apathy are commonly reported (Raaphorst et al., 2012; Beeldman et al. 2015).”
BackgroundTarot, P., Lasbleiz, C., & Liévens, J.-C. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385283 · Cited by 9 · see citing works
Intrusion errors during verbal fluency task in amyotrophic lateral sclerosis
Pérez, M., Amayra, I., Lázaro, E., García, M., Martínez, Ó., Caballero, P., Berrocoso, S., Paz, J. F. L., Al-Rashaida, M. A. H., Rodríguez, A. A., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0233349 · Cited by 9 · see citing works
“The FBI incorporates symptoms of habitual behaviour of FTD, according to the criteria set by Lund and Manchester [43].”
BackgroundInfluentialRespiratory Assessment of ALS Patients: A Nationwide Survey of Current Dutch Practice
Tilanus, T. B. M., Groothuis, J. T., ten Broek-Pastoor, J. M. C., Doorduin, J., van Engelen, B. G. M., Kampelmacher, M. J., & Raaphorst, J. (2018) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-180302 · Cited by 9 · see citing works
“Moderate to severe cognitive and behavioural impairment occurs in up to 30% of ALS patients and fron-totemporal dementia in 8–15% [27].”
Self-citationPoletti, B., Aiello, E. N., Consonni, M., Iazzolino, B., Torre, S., Solca, F., Faltracco, V., Telesca, A., Palumbo, F., Bella, E. D., et al. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12658-w · Cited by 8 · see citing works
“%) involvement [6, 7] in this population are moderately hetero-geneous—possibly as a result of (1) the paucity of large-scale studies and (2) the unsystematic employment of gold-standard, ALS-specific measures of cognition and behaviour”
Exploring clinical management of cognitive and behavioural deficits in MND. A scoping review
Francis, R. L., Attrill, S., Radaković, R., & Doeltgen, S. (2023) · Patient Education and Counseling · doi:10.1016/j.pec.2023.107942 · Cited by 8 · see citing works
Valotassiou, V. J., Sifakis, N., Tzavara, C. K., Lykou, E., Tsinia, N., Kamtsadeli, V., Sali, D., Angelidis, G., Psimadas, D., Tsougos, I., et al. (2020) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651501.2020.1846752 · Cited by 8 · see citing works
“It is also common in progressive supranuclear palsy (PSP) (Belvisi et al. 2018), while patients with FTD motor neuron disease (FTD-MND) may also exhibit the symptom (Raaphorst et al. 2012).”
BackgroundCase Report: Cognitive Conversion in a Non-brazilian VAPB Mutation Carrier (ALS8)
Temp, A. G. M., Dyrba, M., Kasper, E., Teipel, S. J., & Prudlo, J. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.668772 · Cited by 8 · see citing works
Motor neuron disease beginning with frontotemporal dementia: clinical features and progression
Gromicho, M., Kuźma‐Kozakiewicz, M., Szacka, K., Nieporęcki, K., Andersen, P. M., Großkreutz, J., Petri, S., Pinto, S., Uysal, H., Swash, M., et al. (2021) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2021.1910309 · Cited by 8 · see citing works
“A higher prevalence of bulbar impairment in FTD-MND patients has been noted in several studies (12,31,32,34) although bulbar-onset disease has no reported effect on overall behavioral impairment (38).”
BackgroundLoss of “insight” into behavioral changes in ALS: Differences across cognitive profiles
Temp, A. G. M., Kasper, E., Vielhaber, S., Machts, J., Hermann, A., Teipel, S. J., & Prudlo, J. (2021) · Brain and Behavior · doi:10.1002/brb3.2439 · Cited by 8 · see citing works
“German translations of alternative, ALSspecific behavioral instruments would certainly be desirable (Elamin et al., 2017; Mioshi et al., 2014; Raaphorst et al., 2012).”
BackgroundResultInfluentialSteigerwald, C. G., Bertolini, C., McElhiney, M. C., Bergner, A. L., Harms, M. B., & Harrington, E. A. (2024) · Journal of Genetic Counseling · doi:10.1002/jgc4.1890 · Cited by 8 · see citing works
“The co-occurrence of frontotemporal dementia (FTD) may range from 5% to 27% based on various reports and typically includes apathy, personality change, and declines in judgment and self control (Raaphorst et al., 2012).”
Katerelos, A., Alexopoulos, P., Εconomou, P., Polychronopoulos, P., & Chroni, E. (2023) · Neurological Sciences · doi:10.1007/s10072-023-07262-1 · Cited by 7 · see citing works
“According to the literature, patients with bulbar onset ALS showed more significant deficits in executive function than patients with spinal onset [13, 48, 49], which was also demonstrated in our study.”
BackgroundRespiratory Assessment of ALS Patients: A Nationwide Survey of Current Dutch Practice
Tilanus, T. B. M., Groothuis, J. T., ten Broek-Pastoor, J. M. C., Doorduin, J., van Engelen, B. G. M., Kampelmacher, M. J., & Raaphorst, J. (2018) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-18302 · Cited by 7 · see citing works
Self-citationTrucco, A. P., Backhouse, T., & Mioshi, E. (2024) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001293 · Cited by 7 · see citing works
Faltracco, V., Pain, D., Bella, E. D., Riva, N., Telesca, A., Soldini, E., Gandini, G., Radici, A., Poletti, B., Lauria, G., et al. (2025) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2024.123378 · Cited by 6 · see citing works
Neuropsychiatric Manifestations of Amyotrophic Lateral Sclerosis
Kutlubaev, M. A., Владимировна, П. Е., Areprintseva, D. K., Mendelevich, В. D., & Brylev, L. (2023) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-023-01366-z · Cited by 6 · see citing works
“The incidence of mental disorders in ALS without symptoms of dementia ranges from 14% to 40% [4].”
BackgroundNeuropsychiatric presentations of amyotrophic lateral sclerosis
Kutlubaev, M. A., Владимировна, П. Е., Areprintseva, D. K., Mendelevich, V. D., & Brylev, L. (2022) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro202212205136 · Cited by 5 · see citing works
Response to ‘Exploring limits of neuropsychological screening in ALS: The FAB problem’
Raaphorst, J., Beeldman, E., Schmand, B. A., van den Berg, L. H., de Visser, M., & de Haan, R. J. (2013) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.3109/21678421.2012.747541 · Cited by 5 · see citing works
Self-citationHemispheric asymmetry in neurodegenerative diseases
Cappa, S. F. (2025) · Handbook of clinical neurology · doi:10.1016/b978-0-443-15646-5.00009-9 · Cited by 4 · see citing works
Behavioral and Psychological Changes in Alzheimer’s and Other Neurodegenerative Disorders
Diamantopoulos, M. (2022) · Springer eBooks · doi:10.1007/978-3-319-75479-6_2-1 · Cited by 4 · see citing works
Assessing and Managing Depression and Fatigue in Motor Neuron Disease
Sidey-Gibbons, C. J., & Young, C. A. (2012) · Neurodegenerative Disease Management · doi:10.2217/nmt.12.42 · Cited by 4 · see citing works
Taule, T., Eide, I. S., Fjær, L., Myrberget, M.-A., Oseland, M. S., Renså, M. A., Revheim, T., Tysnes, O., Aßmus, J., & Rekand, T. (2023) · PLoS ONE · doi:10.1371/journal.pone.0285307 · Cited by 3 · see citing works
Illness Cognitions in ALS: New Insights Into Clinical Management of Behavioural Symptoms
Caga, J., Devenney, E. M., Huynh, W., Zoing, M. C., Ahmed, R. M., & Kiernan, M. C. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.740693 · Cited by 3 · see citing works
“In addition to significant cognitive problems, ALS patients may experience behavioural symptoms that include perseveration, disinhibition and most commonly apathy (4, 5).”
BackgroundNeuromuscular Disease A Case-Based Approach
Wokke, J. H. J., van Doorn, P. A., Hoogendijk, J. E., & de Visser, M. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9780511735905 · Cited by 3 · see citing works
Wexler, E. (2013) · Neurologic Clinics · doi:10.1016/j.ncl.2013.04.016 · Cited by 2 · see citing works
Troubles cognitifs et SLA. Au-delà de l’atteinte motrice
Viader, F., Mondou, A., Desgranges, B., & Carluer, L. (2014) · La Presse Médicale · doi:10.1016/j.lpm.2013.11.020 · Cited by 2 · see citing works
Segerstrom, S. C., & Kasarskis, E. J. (2024) · Health Psychology and Behavioral Medicine · doi:10.1080/21642850.2024.2396137 · Cited by 1 · see citing works
“Behavioral impairments occur in 30–40% of pwALS, and behavioral variant frontotemporal dementia occurs in 7–13% (Garcia-Willingham, 2018; Raaphorst et al., 2012).”
Barker, M. S., Shneider, N. A., Manoochehri, M., Huey, E. D., & Lindenberger, E. C. (2025) · Psychiatry Research Case Reports · doi:10.1016/j.psycr.2025.100247 · Cited by 1 · see citing works
“It is not clear which ALS patients will develop FTD (Raaphorst et al., 2012), but the risk of progression to non-motor frontal areas may increase with the progression of the motor illness (Lillo et al., 2012).”
Cognitive impairment in amyotrophic lateral sclerosis: the hidden challenges
Ghosh, M., Callagher, P., Addison–Jones, R., Bennett, W., Parkes, A., Chhetri, S. K., & Majeed, T. (2016) · British Journal of Neuroscience Nursing · doi:10.12968/bjnn.2016.12.1.17 · Cited by 1 · see citing works
Oh, S., Kim, H.-J., Park, A., Oh, K., Gwak, H. S., & Kim, S. H. (2014) · Dementia and Neurocognitive Disorders · doi:10.12779/dnd.2014.13.1.1
“고 있었던 행동심리증상인 무감동 등이 많이 나타나는 것과는 다 른 양상으로 나타나는 것을 알 수 있었다[6, 20].”
Cognition and behavior in motor neuron disease
Raaphorst, J. (2015) · UvA-DARE (University of Amsterdam)
Self-citationAmyotrophic lateral sclerosis with frontotemporal dementia
Wokke, J. H. J., van Doorn, P. A., Hoogendijk, J. E., & de Visser, M. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9780511735905.004
Behavioral and Psychological Changes in Alzheimer’s and Other Neurodegenerative Disorders
Diamantopoulos, M. (2023) · Springer eBooks · doi:10.1007/978-3-319-75922-7_2
Shaka, Z., Mojtabavi, H., Taebi, M., Mahmoodi‐Bakhtiari, B., & Sarraf, P. (2025) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2025.2509615
“These changes, including deficits in executive functions, language, memory, visuospatial abilities, and behavioral regulation, can significantly impair patients ’ quality of life, treatment adherence, and caregiving (7 – 9).”
Unravelling the tangle of motor neuron diseases : insights from neuroimaging and neurophysiology
Querin, G. (2019) · theses.fr (ABES) · doi:10.70675/30ad3e2az5051z4364z9ec1z4b8d1f952b7b
Iazzolino, B., Palumbo, F., Canosa, A., Callegaro, S., Passidomo, V., Manera, U., Vasta, R., Matteoni, E., Cabras, S., Pellegrino, G., et al. (2026) · European Journal of Neurology · doi:10.1111/ene.70778
“First, behavioural change in ALS is generally milder than the florid syndromes of bvFTD, with apathy and irritability pre-dominating and overt disinhibition much less common [3, 14], so a bvFTD-calibrated threshold is expected to be overly conservative.”
- Authors
- Raaphorst, J., Beeldman, E., De Visser, M., De Haan, R. J., & Schmand, B.
- Affiliations
- Department of Neurology
- Clinical Research Unit, Academic Medical Centre, University of Amsterdam
- University of Amsterdam (NL)
- Corresponding author
- Raaphorst, Joost
- Venue
- Amyotrophic Lateral Sclerosis
- Publisher
- Informa UK Limited
- Published
- 2012-03-16
- Volume
- 13
- Issue
- 6
- Pages
- 493-501
- ISSN
- 1471-180X (ISSN-L)
- 1748-2968
- OpenAlex
- W2065577030
- Cited by
- 75
- References
- 38
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 10 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 6 · 2013: 6 · 2012: 3
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Amyotrophic Lateral Sclerosis (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Ulster University
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- motor neuron disease, behavioral variant frontotemporal dementia, behavior change, perseveration, apathy, disinhibition, memory impairment, bulbar onset, disease spectrum, prevalence
- MeSH terms
- Behavior, Cognition Disorders, Humans, Databases, Factual, Motor Neuron Disease, Frontotemporal Dementia
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