The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update
Cognitive dysfunction is an important non-motor symptom in amyotrophic lateral sclerosis (ALS) that has a negative impact on survival and caregiver burden. It shows a wide spectrum ranging from subjective cognitive decline to frontotemporal dementia (FTD) and covers various cognitive domains, mainly...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/19/14647 |
| _version_ | 1797575789977272320 |
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| author | Kurt A. Jellinger |
| author_facet | Kurt A. Jellinger |
| author_sort | Kurt A. Jellinger |
| collection | DOAJ |
| description | Cognitive dysfunction is an important non-motor symptom in amyotrophic lateral sclerosis (ALS) that has a negative impact on survival and caregiver burden. It shows a wide spectrum ranging from subjective cognitive decline to frontotemporal dementia (FTD) and covers various cognitive domains, mainly executive/attention, language and verbal memory deficits. The frequency of cognitive impairment across the different ALS phenotypes ranges from 30% to 75%, with up to 45% fulfilling the criteria of FTD. Significant genetic, clinical, and pathological heterogeneity reflects deficits in various cognitive domains. Modern neuroimaging studies revealed frontotemporal degeneration and widespread involvement of limbic and white matter systems, with hypometabolism of the relevant areas. Morphological substrates are frontotemporal and hippocampal atrophy with synaptic loss, associated with TDP-43 and other co-pathologies, including tau deposition. Widespread functional disruptions of motor and extramotor networks, as well as of frontoparietal, frontostriatal and other connectivities, are markers for cognitive deficits in ALS. Cognitive reserve may moderate the effect of brain damage but is not protective against cognitive decline. The natural history of cognitive dysfunction in ALS and its relationship to FTD are not fully understood, although there is an overlap between the ALS variants and ALS-related frontotemporal syndromes, suggesting a differential vulnerability of motor and non-motor networks. An assessment of risks or the early detection of brain connectivity signatures before structural changes may be helpful in investigating the pathophysiological mechanisms of cognitive impairment in ALS, which might even serve as novel targets for effective disease-modifying therapies. |
| first_indexed | 2024-03-10T21:44:17Z |
| format | Article |
| id | doaj.art-fd4b86639e7d482389ecc15eebc12cbb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:44:17Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fd4b86639e7d482389ecc15eebc12cbb2023-11-19T14:29:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191464710.3390/ijms241914647The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An UpdateKurt A. Jellinger0Institute of Clinical Neurobiology, Alberichgasse 5/13, A-1150 Vienna, AustriaCognitive dysfunction is an important non-motor symptom in amyotrophic lateral sclerosis (ALS) that has a negative impact on survival and caregiver burden. It shows a wide spectrum ranging from subjective cognitive decline to frontotemporal dementia (FTD) and covers various cognitive domains, mainly executive/attention, language and verbal memory deficits. The frequency of cognitive impairment across the different ALS phenotypes ranges from 30% to 75%, with up to 45% fulfilling the criteria of FTD. Significant genetic, clinical, and pathological heterogeneity reflects deficits in various cognitive domains. Modern neuroimaging studies revealed frontotemporal degeneration and widespread involvement of limbic and white matter systems, with hypometabolism of the relevant areas. Morphological substrates are frontotemporal and hippocampal atrophy with synaptic loss, associated with TDP-43 and other co-pathologies, including tau deposition. Widespread functional disruptions of motor and extramotor networks, as well as of frontoparietal, frontostriatal and other connectivities, are markers for cognitive deficits in ALS. Cognitive reserve may moderate the effect of brain damage but is not protective against cognitive decline. The natural history of cognitive dysfunction in ALS and its relationship to FTD are not fully understood, although there is an overlap between the ALS variants and ALS-related frontotemporal syndromes, suggesting a differential vulnerability of motor and non-motor networks. An assessment of risks or the early detection of brain connectivity signatures before structural changes may be helpful in investigating the pathophysiological mechanisms of cognitive impairment in ALS, which might even serve as novel targets for effective disease-modifying therapies.https://www.mdpi.com/1422-0067/24/19/14647ALScognitive impairmentfrontotemporal lobe degenerationmultimodal neuroimagingbrain hypometabolismfunctional connectivity |
| spellingShingle | Kurt A. Jellinger The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update International Journal of Molecular Sciences ALS cognitive impairment frontotemporal lobe degeneration multimodal neuroimaging brain hypometabolism functional connectivity |
| title | The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update |
| title_full | The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update |
| title_fullStr | The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update |
| title_full_unstemmed | The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update |
| title_short | The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update |
| title_sort | spectrum of cognitive dysfunction in amyotrophic lateral sclerosis an update |
| topic | ALS cognitive impairment frontotemporal lobe degeneration multimodal neuroimaging brain hypometabolism functional connectivity |
| url | https://www.mdpi.com/1422-0067/24/19/14647 |
| work_keys_str_mv | AT kurtajellinger thespectrumofcognitivedysfunctioninamyotrophiclateralsclerosisanupdate AT kurtajellinger spectrumofcognitivedysfunctioninamyotrophiclateralsclerosisanupdate |