Pub Date : 2024-09-04eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae250
Jeremy Hogeveen, Ethan M Campbell, Teagan S Mullins, Cidney R Robertson-Benta, Davin K Quinn, Andrew R Mayer, James F Cavanagh
Depression is a common consequence of traumatic brain injury. Separately, spontaneous depression-arising without brain injury-has been linked to abnormal responses in motivational neural circuitry to the anticipation or receipt of rewards. It is unknown if post-injury and spontaneously occurring depression share similar phenotypic profiles. This issue is compounded by the fact that nearly all examinations of these psychiatric sequelae are post hoc: there are rarely any prospective assessments of mood and neural functioning before and after a brain injury. In this Stage 2 Registered Report, we used the Adolescent Brain Cognitive Development Consortium dataset to examine if a disruption in functional neural responses to rewards is present in patients with depression after a mild traumatic brain injury. Notably, this study provides an unparalleled opportunity to examine the trajectory of neuropsychiatric symptoms longitudinally within-subjects. This allowed us to isolate mild traumatic brain injury-specific variance independent from pre-existing functioning. Here, we focus on a case-control comparison between 43 youth who experienced a mild traumatic brain injury between MRI visits, and 43 well-matched controls. Contrary to pre-registered predictions (https://osf.io/h5uba/), there was no statistically credible increase in depression in mild traumatic brain injury cases relative to controls. Mild traumatic brain injury was associated with subtle changes in motivational neural circuit recruitment during the anticipation of incentives on the Monetary Incentive Delay paradigm. Specifically, changes in neural recruitment appeared to reflect a failure to deactivate 'task-negative' brain regions (ventromedial prefrontal cortex), alongside blunted recruitment of 'task-positive' regions (anterior cingulate, anterior insula and caudate), during the anticipation of reward and loss in adolescents following mild brain injuries. Critically, these changes in brain activity were not correlated with depressive symptoms at either visit or depression change scores before and after the brain injury. Increased time since injury was associated with a recovery of cognitive functioning-driven primarily by processing speed differences-but depression did not scale with time since injury. These cognitive changes were also uncorrelated with neural changes after mild traumatic brain injury. This report provides evidence that acquired depression may not be observed as commonly after a mild traumatic brain injury in late childhood and early adolescence, relative to findings in adult cases. Several reasons for these differing findings are considered, including sampling enrichment in retrospective cohort studies, under-reporting of depressive symptoms in parent-report data, and neuroprotective factors in childhood and adolescence.
{"title":"Neural response to monetary incentives in acquired adolescent depression after mild traumatic brain injury: Stage 2 Registered Report.","authors":"Jeremy Hogeveen, Ethan M Campbell, Teagan S Mullins, Cidney R Robertson-Benta, Davin K Quinn, Andrew R Mayer, James F Cavanagh","doi":"10.1093/braincomms/fcae250","DOIUrl":"10.1093/braincomms/fcae250","url":null,"abstract":"<p><p>Depression is a common consequence of traumatic brain injury. Separately, spontaneous depression-arising without brain injury-has been linked to abnormal responses in motivational neural circuitry to the anticipation or receipt of rewards. It is unknown if post-injury and spontaneously occurring depression share similar phenotypic profiles. This issue is compounded by the fact that nearly all examinations of these psychiatric sequelae are <i>post hoc</i>: there are rarely any prospective assessments of mood and neural functioning before and after a brain injury. In this Stage 2 Registered Report, we used the Adolescent Brain Cognitive Development Consortium dataset to examine if a disruption in functional neural responses to rewards is present in patients with depression after a mild traumatic brain injury. Notably, this study provides an unparalleled opportunity to examine the trajectory of neuropsychiatric symptoms longitudinally within-subjects. This allowed us to isolate mild traumatic brain injury-specific variance independent from pre-existing functioning. Here, we focus on a case-control comparison between 43 youth who experienced a mild traumatic brain injury between MRI visits, and 43 well-matched controls. Contrary to pre-registered predictions (https://osf.io/h5uba/), there was no statistically credible increase in depression in mild traumatic brain injury cases relative to controls. Mild traumatic brain injury was associated with subtle changes in motivational neural circuit recruitment during the anticipation of incentives on the Monetary Incentive Delay paradigm. Specifically, changes in neural recruitment appeared to reflect a failure to deactivate 'task-negative' brain regions (ventromedial prefrontal cortex), alongside blunted recruitment of 'task-positive' regions (anterior cingulate, anterior insula and caudate), during the anticipation of reward and loss in adolescents following mild brain injuries. Critically, these changes in brain activity were not correlated with depressive symptoms at either visit or depression change scores before and after the brain injury. Increased time since injury was associated with a recovery of cognitive functioning-driven primarily by processing speed differences-but depression did not scale with time since injury. These cognitive changes were also uncorrelated with neural changes after mild traumatic brain injury. This report provides evidence that acquired depression may not be observed as commonly after a mild traumatic brain injury in late childhood and early adolescence, relative to findings in adult cases. Several reasons for these differing findings are considered, including sampling enrichment in retrospective cohort studies, under-reporting of depressive symptoms in parent-report data, and neuroprotective factors in childhood and adolescence.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae273
Amanda Bischoff-Grethe, Susan A Stoner, Edward P Riley, Eileen M Moore
Studies of youth and young adults with prenatal alcohol exposure (PAE) have most consistently reported reduced volumes of the corpus callosum, cerebellum and subcortical structures. However, it is unknown whether this continues into middle adulthood or if individuals with PAE may experience premature volumetric decline with aging. Forty-eight individuals with fetal alcohol spectrum disorders (FASD) and 28 healthy comparison participants aged 30 to 65 participated in a 3T MRI session that resulted in usable T1-weighted and T2-weighted structural images. Primary analyses included volumetric measurements of the caudate, putamen, pallidum, cerebellum and corpus callosum using FreeSurfer software. Analyses were conducted examining both raw volumetric measurements and subcortical volumes adjusted for overall intracranial volume (ICV). Models tested for main effects of age, sex and group, as well as interactions of group with age and group with sex. We found the main effects for group; all regions were significantly smaller in participants with FASD for models using raw volumes (P's < 0.001) as well as for models using volumes adjusted for ICV (P's < 0.046). Although there were no significant interactions of group with age, females with FASD had smaller corpus callosum volumes relative to both healthy comparison females and males with FASD (P's < 0.001). As seen in children and adolescents, adults aged 30 to 65 with FASD showed reduced volumes of subcortical structures relative to healthy comparison adults, suggesting persistent impact of PAE. Moreover, the observed volumetric reduction of the corpus callosum in females with FASD could suggest more rapid degeneration, which may have implications for cognition as these individuals continue to age.
{"title":"Subcortical volume in middle-aged adults with fetal alcohol spectrum disorders.","authors":"Amanda Bischoff-Grethe, Susan A Stoner, Edward P Riley, Eileen M Moore","doi":"10.1093/braincomms/fcae273","DOIUrl":"10.1093/braincomms/fcae273","url":null,"abstract":"<p><p>Studies of youth and young adults with prenatal alcohol exposure (PAE) have most consistently reported reduced volumes of the corpus callosum, cerebellum and subcortical structures. However, it is unknown whether this continues into middle adulthood or if individuals with PAE may experience premature volumetric decline with aging. Forty-eight individuals with fetal alcohol spectrum disorders (FASD) and 28 healthy comparison participants aged 30 to 65 participated in a 3T MRI session that resulted in usable T<sub>1</sub>-weighted and T<sub>2</sub>-weighted structural images. Primary analyses included volumetric measurements of the caudate, putamen, pallidum, cerebellum and corpus callosum using FreeSurfer software. Analyses were conducted examining both raw volumetric measurements and subcortical volumes adjusted for overall intracranial volume (ICV). Models tested for main effects of age, sex and group, as well as interactions of group with age and group with sex. We found the main effects for group; all regions were significantly smaller in participants with FASD for models using raw volumes (<i>P</i>'s < 0.001) as well as for models using volumes adjusted for ICV (<i>P</i>'s < 0.046). Although there were no significant interactions of group with age, females with FASD had smaller corpus callosum volumes relative to both healthy comparison females and males with FASD (<i>P</i>'s < 0.001). As seen in children and adolescents, adults aged 30 to 65 with FASD showed reduced volumes of subcortical structures relative to healthy comparison adults, suggesting persistent impact of PAE. Moreover, the observed volumetric reduction of the corpus callosum in females with FASD could suggest more rapid degeneration, which may have implications for cognition as these individuals continue to age.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae266
Tara L Spires-Jones
Our editor discusses taking a vacation without a computer and some neuroscience evidence supporting the need for work-life balance.
我们的编辑讨论了在没有电脑的情况下度假的问题,以及支持工作与生活平衡必要性的一些神经科学证据。
{"title":"Summer days: research culture and the neuroscience of taking a break.","authors":"Tara L Spires-Jones","doi":"10.1093/braincomms/fcae266","DOIUrl":"10.1093/braincomms/fcae266","url":null,"abstract":"<p><p>Our editor discusses taking a vacation without a computer and some neuroscience evidence supporting the need for work-life balance.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae288
Maximilian Vidovic, Hanna Sophie Lapp, Constanze Weber, Lydia Plitzko, Michael Seifert, Petra Steinacker, Markus Otto, Andreas Hermann, René Günther
Diagnosis of the fatal neurodegenerative disease amyotrophic lateral sclerosis is challenging. Neurofilaments, indicative of neuronal damage, along with creatine kinase, creatinine, myoglobin, and troponin T, representing muscular damage, have been identified as promising fluid biomarkers. This study aims to comprehensively assess and compare their diagnostic and prognostic potential in a 'real-world' cohort of patients with amyotrophic lateral sclerosis. About 77 patients with amyotrophic lateral sclerosis and its clinical variants, and 26 age- and sex-matched controls with various neuromuscular and neurodegenerative diseases, were retrospectively included in this monocentric, cross-sectional study. Neurofilaments in cerebrospinal fluid and biomarkers of muscular damage in serum were measured and correlated with demographic features, motor function, survival time, clinical phenotypes, and the extent of upper and lower motor neuron involvement. Neurofilament, myoglobin, and troponin T concentrations were higher in patients with amyotrophic lateral sclerosis compared to disease controls. Higher neurofilament levels correlated with lower motor function and faster disease progression rate, while higher creatine kinase and creatinine concentrations were linked to preserved motor function. In contrast, troponin T elevation indicated poorer fine and gross motor functions. Increased neurofilament levels were associated with shorter survival, whereas biomarkers of muscular damage lacked survival correlation. Neurofilament concentrations were higher in classical amyotrophic lateral sclerosis than in progressive muscular atrophy, while myoglobin and troponin T levels were elevated in progressive muscular atrophy compared to primary lateral sclerosis. Neurofilaments were predominantly linked to upper motor neuron involvement. Our findings confirmed the robust diagnostic and prognostic value of neurofilaments in amyotrophic lateral sclerosis. Elevated neurofilament concentrations were associated with higher disease severity, faster disease progression, shorter survival, and predominant upper motor neuron degeneration. Biomarkers of muscular damage were inferior in distinguishing amyotrophic lateral sclerosis from other neuromuscular and neurodegenerative diseases. However, they may serve as complementary biomarkers and support in discriminating clinical variants of amyotrophic lateral sclerosis.
{"title":"Comparative analysis of neurofilaments and biomarkers of muscular damage in amyotrophic lateral sclerosis.","authors":"Maximilian Vidovic, Hanna Sophie Lapp, Constanze Weber, Lydia Plitzko, Michael Seifert, Petra Steinacker, Markus Otto, Andreas Hermann, René Günther","doi":"10.1093/braincomms/fcae288","DOIUrl":"10.1093/braincomms/fcae288","url":null,"abstract":"<p><p>Diagnosis of the fatal neurodegenerative disease amyotrophic lateral sclerosis is challenging. Neurofilaments, indicative of neuronal damage, along with creatine kinase, creatinine, myoglobin, and troponin T, representing muscular damage, have been identified as promising fluid biomarkers. This study aims to comprehensively assess and compare their diagnostic and prognostic potential in a 'real-world' cohort of patients with amyotrophic lateral sclerosis. About 77 patients with amyotrophic lateral sclerosis and its clinical variants, and 26 age- and sex-matched controls with various neuromuscular and neurodegenerative diseases, were retrospectively included in this monocentric, cross-sectional study. Neurofilaments in cerebrospinal fluid and biomarkers of muscular damage in serum were measured and correlated with demographic features, motor function, survival time, clinical phenotypes, and the extent of upper and lower motor neuron involvement. Neurofilament, myoglobin, and troponin T concentrations were higher in patients with amyotrophic lateral sclerosis compared to disease controls. Higher neurofilament levels correlated with lower motor function and faster disease progression rate, while higher creatine kinase and creatinine concentrations were linked to preserved motor function. In contrast, troponin T elevation indicated poorer fine and gross motor functions. Increased neurofilament levels were associated with shorter survival, whereas biomarkers of muscular damage lacked survival correlation. Neurofilament concentrations were higher in classical amyotrophic lateral sclerosis than in progressive muscular atrophy, while myoglobin and troponin T levels were elevated in progressive muscular atrophy compared to primary lateral sclerosis. Neurofilaments were predominantly linked to upper motor neuron involvement. Our findings confirmed the robust diagnostic and prognostic value of neurofilaments in amyotrophic lateral sclerosis. Elevated neurofilament concentrations were associated with higher disease severity, faster disease progression, shorter survival, and predominant upper motor neuron degeneration. Biomarkers of muscular damage were inferior in distinguishing amyotrophic lateral sclerosis from other neuromuscular and neurodegenerative diseases. However, they may serve as complementary biomarkers and support in discriminating clinical variants of amyotrophic lateral sclerosis.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae285
Crista A Minderhoud, Amber Postma, Floor E Jansen, Janneke R Zinkstok, Judith S Verhoeven, Bianca Berghuis, Wim M Otte, Marian J Jongmans, Kees P J Braun, Eva H Brilstra
This cohort study aims to describe the evolution of disease features and health-related quality of life per life stage in Dravet syndrome and other SCN1A-related non-Dravet seizure disorders which will enable treating physicians to provide tailored care. Health-related quality of life and disease features were assessed cross-sectionally in participants with a SCN1A-related seizure disorder, categorized per age group for Dravet syndrome, and longitudinally over seven years follow-up (2015-2022). Data were collected from questionnaires, medical records, and semi-structured telephonic interviews. Health-related quality of life was measured with the Paediatric Quality of Life Inventory, proxy-reported for participants with Dravet syndrome and for participants with non-Dravet aged younger than 18 years old and self-reported for participants with non-Dravet over 18 years old. Associations between health-related quality of life and disease features were explored with multivariable regression analyses, cross-sectionally in a cohort of 115 patients with Dravet and 48 patients with generalized epilepsy with febrile seizures plus and febrile seizures (non-Dravet) and longitudinally in a cohort of 52 Dravet patients and 13 non-Dravet patients. In the cross-sectional assessment in 2022, health-related quality of life was significantly lower in Dravet syndrome, compared to non-Dravet and normative controls. Health-related quality of life in the School and Psychosocial domain was significantly higher in older Dravet age groups. A higher health-related quality of life was associated with fewer behavioural problems [β = -1.1; 95% confidence interval (CI), (-1.4 to -0.8)], independent walking (β = 8.5; 95%CI (4.2-12.8)), compared to the use of a wheelchair), and fewer symptoms of autonomic dysfunction (β = -2.1, 95%CI (-3.2 to -1.0)). Longitudinally, health-related quality of life was significantly higher seven years later in the course of disease in Dravet participants (Δ8.9 standard deviation (SD) 18.0, P < 0.05), mediated by a lower prevalence of behavioural problems (β = -1.2, 95%CI (-2.0 to -0.4)), lower seizure frequency (β = -0.1, 95%CI (-0.2 to -0.0)) and older age (β = 0.03, 95%CI (0.01-0.04)). In summary, health-related quality of life was significantly higher at older age in Dravet syndrome. This finding may reflect the benefits of an advanced care strategy in recent years and a ceiling of severity of disease symptoms, possibly resulting in an increased wellbeing of parents and patients. The strong association with behavioural problems reinforces the need to incorporate a multidisciplinary approach, tailored to the age-specific needs of this patient group, into standard care.
这项队列研究旨在描述德拉维特综合征和其他与 SCN1A 相关的非德拉维特癫痫发作性疾病在每个生命阶段的疾病特征和健康相关生活质量的演变情况,从而使治疗医生能够提供有针对性的护理。我们对患有 SCN1A 相关癫痫发作障碍的参与者进行了健康相关生活质量和疾病特征的横向评估,并按年龄组别对 Dravet 综合征进行了分类,还对七年的随访(2015-2022 年)进行了纵向评估。数据通过问卷、病历和半结构化电话访谈收集。健康相关生活质量采用儿科生活质量量表(Pediatric Quality of Life Inventory)进行测量,年龄在18岁以下的德拉维特综合征患者和非德拉维特患者采用代理报告,18岁以上的非德拉维特患者采用自我报告。研究人员通过多变量回归分析探讨了健康相关生活质量与疾病特征之间的关系,横向研究对象包括115名德拉韦综合征患者和48名伴有发热性癫痫发作和发热性癫痫发作的全身性癫痫患者(非德拉韦),纵向研究对象包括52名德拉韦综合征患者和13名非德拉韦综合征患者。在 2022 年进行的横向评估中,与非德拉维特患者和正常对照组相比,德拉维特综合征患者的健康相关生活质量明显较低。在学校和社会心理领域中,年龄较大的 Dravet 患者的健康相关生活质量明显较高。较高的健康相关生活质量与较少的行为问题(β = -1.1; 95% 置信区间 (CI), (-1.4 to -0.8))、独立行走(β = 8.5; 95%CI (4.2-12.8))(与使用轮椅相比)和较少的自主神经功能紊乱症状(β = -2.1, 95%CI (-3.2 to -1.0) )相关。纵向观察发现,在病程的七年后,Dravet 患者的健康相关生活质量明显提高(Δ8.9 标准差(SD)18.0,P < 0.05),这与行为问题发生率较低(β = -1.2, 95%CI (-2.0 to -0.4))、癫痫发作频率较低(β = -0.1, 95%CI (-0.2 to -0.0))和年龄较大(β = 0.03, 95%CI (0.01-0.04))有关。总之,年龄越大,德雷韦综合征患者的健康相关生活质量越高。这一发现可能反映了近年来先进的护理策略所带来的益处以及疾病症状严重程度的上限,这可能会增加父母和患者的幸福感。与行为问题密切相关的研究结果表明,有必要在标准护理中纳入多学科方法,以满足该患者群体的特定年龄需求。
{"title":"Quality of life in <i>SCN1A</i>-related seizure disorders across the lifespan.","authors":"Crista A Minderhoud, Amber Postma, Floor E Jansen, Janneke R Zinkstok, Judith S Verhoeven, Bianca Berghuis, Wim M Otte, Marian J Jongmans, Kees P J Braun, Eva H Brilstra","doi":"10.1093/braincomms/fcae285","DOIUrl":"10.1093/braincomms/fcae285","url":null,"abstract":"<p><p>This cohort study aims to describe the evolution of disease features and health-related quality of life per life stage in Dravet syndrome and other <i>SCN1A</i>-related non-Dravet seizure disorders which will enable treating physicians to provide tailored care. Health-related quality of life and disease features were assessed cross-sectionally in participants with a <i>SCN1A-</i>related seizure disorder, categorized per age group for Dravet syndrome, and longitudinally over seven years follow-up (2015-2022). Data were collected from questionnaires, medical records, and semi-structured telephonic interviews. Health-related quality of life was measured with the Paediatric Quality of Life Inventory, proxy-reported for participants with Dravet syndrome and for participants with non-Dravet aged younger than 18 years old and self-reported for participants with non-Dravet over 18 years old. Associations between health-related quality of life and disease features were explored with multivariable regression analyses, cross-sectionally in a cohort of 115 patients with Dravet and 48 patients with generalized epilepsy with febrile seizures plus and febrile seizures (non-Dravet) and longitudinally in a cohort of 52 Dravet patients and 13 non-Dravet patients. In the cross-sectional assessment in 2022, health-related quality of life was significantly lower in Dravet syndrome, compared to non-Dravet and normative controls. Health-related quality of life in the School and Psychosocial domain was significantly higher in older Dravet age groups. A higher health-related quality of life was associated with fewer behavioural problems [<i>β</i> = -1.1; 95% confidence interval (CI), (-1.4 to -0.8)], independent walking (<i>β</i> = 8.5; 95%CI (4.2-12.8)), compared to the use of a wheelchair), and fewer symptoms of autonomic dysfunction (<i>β</i> = -2.1, 95%CI (-3.2 to -1.0)). Longitudinally, health-related quality of life was significantly higher seven years later in the course of disease in Dravet participants (Δ8.9 standard deviation (SD) 18.0, <i>P</i> < 0.05), mediated by a lower prevalence of behavioural problems (<i>β</i> = -1.2, 95%CI (-2.0 to -0.4)), lower seizure frequency (<i>β</i> = -0.1, 95%CI (-0.2 to -0.0)) and older age (<i>β</i> = 0.03, 95%CI (0.01-0.04)). In summary, health-related quality of life was significantly higher at older age in Dravet syndrome. This finding may reflect the benefits of an advanced care strategy in recent years and a ceiling of severity of disease symptoms, possibly resulting in an increased wellbeing of parents and patients. The strong association with behavioural problems reinforces the need to incorporate a multidisciplinary approach, tailored to the age-specific needs of this patient group, into standard care.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae275
Yawen Xiang, Mark A Rodrigues, Christine Lerpiniere, Tom J Moullaali, James J M Loan, Tim Wilkinson, Catherine A Humphreys, Colin Smith, Rustam Al-Shahi Salman, Neshika Samarasekera
Little is known about whether clinical, radiological or neuropathological features are associated with cognitive impairment before intracerebral haemorrhage. We conducted a community-based cohort study of 125 adults with intracerebral haemorrhage (lobar n = 71, non-lobar n = 54) with consent to brain autopsy. We compared small vessel disease biomarkers on diagnostic CT head and neuropathological findings including neurofibrillary tangles and amyloid plaques in adults without cognitive impairment versus cognitive impairment without dementia versus dementia before intracerebral haemorrhage, stratified by lobar and non-lobar intracerebral haemorrhage. In non-lobar intracerebral haemorrhage, severe cortical atrophy was less common in those without cognitive impairment (8/36, 22%) and cognitive impairment without dementia (0/9, 0%) versus dementia (5/9, 56%); P = 0.008. Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder neurofibrillary tangle pathology measured by median Braak stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [interquartile range, 2-3] versus cognitive impairment without dementia 4 [2-6] versus dementia 5.5 [4-6]; P = 0.004; non-lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [1-2] versus dementia 5 [3-6]; P < 0.001). Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder amyloid plaque pathology measured by median Thal stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [2-3] versus dementia 2.5 [2-3.5]; P = 0.033; non-lobar intracerebral haemorrhage: no cognitive impairment 1 [0-1] versus cognitive impairment without dementia 0 [0-2] versus dementia 3 [2-3]; P = 0.002). Our findings suggest that irrespective of intracerebral haemorrhage location, adults with cognitive impairment before an intracerebral haemorrhage have more Alzheimer's disease neuropathologic change.
{"title":"Factors associated with cognitive impairment before intracerebral haemorrhage: community-based neuropathological study.","authors":"Yawen Xiang, Mark A Rodrigues, Christine Lerpiniere, Tom J Moullaali, James J M Loan, Tim Wilkinson, Catherine A Humphreys, Colin Smith, Rustam Al-Shahi Salman, Neshika Samarasekera","doi":"10.1093/braincomms/fcae275","DOIUrl":"10.1093/braincomms/fcae275","url":null,"abstract":"<p><p>Little is known about whether clinical, radiological or neuropathological features are associated with cognitive impairment before intracerebral haemorrhage. We conducted a community-based cohort study of 125 adults with intracerebral haemorrhage (lobar <i>n</i> = 71, non-lobar <i>n</i> = 54) with consent to brain autopsy. We compared small vessel disease biomarkers on diagnostic CT head and neuropathological findings including neurofibrillary tangles and amyloid plaques in adults without cognitive impairment versus cognitive impairment without dementia versus dementia before intracerebral haemorrhage, stratified by lobar and non-lobar intracerebral haemorrhage. In non-lobar intracerebral haemorrhage, severe cortical atrophy was less common in those without cognitive impairment (8/36, 22%) and cognitive impairment without dementia (0/9, 0%) versus dementia (5/9, 56%); <i>P</i> = 0.008. Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder neurofibrillary tangle pathology measured by median Braak stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [interquartile range, 2-3] versus cognitive impairment without dementia 4 [2-6] versus dementia 5.5 [4-6]; <i>P</i> = 0.004; non-lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [1-2] versus dementia 5 [3-6]; <i>P</i> < 0.001). Irrespective of intracerebral haemorrhage location, adults without cognitive impairment had milder amyloid plaque pathology measured by median Thal stage (lobar intracerebral haemorrhage: no cognitive impairment 2 [1-2] versus cognitive impairment without dementia 2 [2-3] versus dementia 2.5 [2-3.5]; <i>P</i> = 0.033; non-lobar intracerebral haemorrhage: no cognitive impairment 1 [0-1] versus cognitive impairment without dementia 0 [0-2] versus dementia 3 [2-3]; <i>P</i> = 0.002). Our findings suggest that irrespective of intracerebral haemorrhage location, adults with cognitive impairment before an intracerebral haemorrhage have more Alzheimer's disease neuropathologic change.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae284
Erin C Conrad, Alfredo Lucas, William K S Ojemann, Carlos A Aguila, Marissa Mojena, Joshua J LaRocque, Akash R Pattnaik, Ryan Gallagher, Adam Greenblatt, Ashley Tranquille, Alexandra Parashos, Ezequiel Gleichgerrcht, Leonardo Bonilha, Brian Litt, Saurabh R Sinha, Lyle Ungar, Kathryn A Davis
Patients with drug-resistant temporal lobe epilepsy often undergo intracranial EEG recording to capture multiple seizures in order to lateralize the seizure onset zone. This process is associated with morbidity and often ends in postoperative seizure recurrence. Abundant interictal (between-seizure) data are captured during this process, but these data currently play a small role in surgical planning. Our objective was to predict the laterality of the seizure onset zone using interictal intracranial EEG data in patients with temporal lobe epilepsy. We performed a retrospective cohort study (single-centre study for model development; two-centre study for model validation). We studied patients with temporal lobe epilepsy undergoing intracranial EEG at the University of Pennsylvania (internal cohort) and the Medical University of South Carolina (external cohort) between 2015 and 2022. We developed a logistic regression model to predict seizure onset zone laterality using several interictal EEG features derived from recent publications. We compared the concordance between the model-predicted seizure onset zone laterality and the side of surgery between patients with good and poor surgical outcomes. Forty-seven patients (30 female; ages 20-69; 20 left-sided, 10 right-sided and 17 bilateral seizure onsets) were analysed for model development and internal validation. Nineteen patients (10 female; ages 23-73; 5 left-sided, 10 right-sided, 4 bilateral) were analysed for external validation. The internal cohort cross-validated area under the curve for a model trained using spike rates was 0.83 for a model predicting left-sided seizure onset and 0.68 for a model predicting right-sided seizure onset. Balanced accuracies in the external cohort were 79.3% and 78.9% for the left- and right-sided predictions, respectively. The predicted concordance between the laterality of the seizure onset zone and the side of surgery was higher in patients with good surgical outcome. We replicated the finding that right temporal lobe epilepsy was harder to distinguish in a separate modality of resting-state functional MRI. In conclusion, interictal EEG signatures are distinct across seizure onset zone lateralities. Left-sided seizure onsets are easier to distinguish than right-sided onsets. A model trained on spike rates accurately identifies patients with left-sided seizure onset zones and predicts surgical outcome. A potential clinical application of these findings could be to either support or oppose a hypothesis of unilateral temporal lobe epilepsy when deciding to pursue surgical resection or ablation as opposed to device implantation.
{"title":"Interictal intracranial EEG asymmetry lateralizes temporal lobe epilepsy.","authors":"Erin C Conrad, Alfredo Lucas, William K S Ojemann, Carlos A Aguila, Marissa Mojena, Joshua J LaRocque, Akash R Pattnaik, Ryan Gallagher, Adam Greenblatt, Ashley Tranquille, Alexandra Parashos, Ezequiel Gleichgerrcht, Leonardo Bonilha, Brian Litt, Saurabh R Sinha, Lyle Ungar, Kathryn A Davis","doi":"10.1093/braincomms/fcae284","DOIUrl":"10.1093/braincomms/fcae284","url":null,"abstract":"<p><p>Patients with drug-resistant temporal lobe epilepsy often undergo intracranial EEG recording to capture multiple seizures in order to lateralize the seizure onset zone. This process is associated with morbidity and often ends in postoperative seizure recurrence. Abundant interictal (between-seizure) data are captured during this process, but these data currently play a small role in surgical planning. Our objective was to predict the laterality of the seizure onset zone using interictal intracranial EEG data in patients with temporal lobe epilepsy. We performed a retrospective cohort study (single-centre study for model development; two-centre study for model validation). We studied patients with temporal lobe epilepsy undergoing intracranial EEG at the University of Pennsylvania (internal cohort) and the Medical University of South Carolina (external cohort) between 2015 and 2022. We developed a logistic regression model to predict seizure onset zone laterality using several interictal EEG features derived from recent publications. We compared the concordance between the model-predicted seizure onset zone laterality and the side of surgery between patients with good and poor surgical outcomes. Forty-seven patients (30 female; ages 20-69; 20 left-sided, 10 right-sided and 17 bilateral seizure onsets) were analysed for model development and internal validation. Nineteen patients (10 female; ages 23-73; 5 left-sided, 10 right-sided, 4 bilateral) were analysed for external validation. The internal cohort cross-validated area under the curve for a model trained using spike rates was 0.83 for a model predicting left-sided seizure onset and 0.68 for a model predicting right-sided seizure onset. Balanced accuracies in the external cohort were 79.3% and 78.9% for the left- and right-sided predictions, respectively. The predicted concordance between the laterality of the seizure onset zone and the side of surgery was higher in patients with good surgical outcome. We replicated the finding that right temporal lobe epilepsy was harder to distinguish in a separate modality of resting-state functional MRI. In conclusion, interictal EEG signatures are distinct across seizure onset zone lateralities. Left-sided seizure onsets are easier to distinguish than right-sided onsets. A model trained on spike rates accurately identifies patients with left-sided seizure onset zones and predicts surgical outcome. A potential clinical application of these findings could be to either support or oppose a hypothesis of unilateral temporal lobe epilepsy when deciding to pursue surgical resection or ablation as opposed to device implantation.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-20eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae272
Alice Tisserand, Frédéric Blanc, Candice Muller, Hélène Durand, Catherine Demuynck, Alix Ravier, Léa Sanna, Paulo Loureiro de Sousa, Anne Botzung, Mary Mondino, Nathalie Philippi
Although deficits in learning and retrieving new information are well characterized in dementia with Lewy bodies, autobiographical memory has never been explored in this disease. Yet, autobiographical memory impairments are a pervasive feature of dementia, well characterized in other neurodegenerative diseases. Moreover, autobiographical memory corresponds to an extension over time of the self, which we hypothesize is altered in dementia with Lewy bodies and impairment of which could be linked to the insular atrophy occurring from an early stage of the disease. In this study, we sought to characterize autobiographical memory impairments and explore their neural correlates in dementia with Lewy bodies, on the assumption that insular damage could impact the self, including its most elaborate components, such as autobiographical memory. Twenty patients with prodromal to mild dementia with Lewy bodies were selected to participate in this exploratory study along with 20 healthy control subjects. The Autobiographical Interview was used to assess autobiographical memory. Performances were compared between patients and control subjects, and an analysis across life periods and recall conditions was performed. 3D magnetic resonance images were acquired for all participants, and correlational analyses were performed in the patient group using voxel-based morphometry. The behavioural results of the Autobiographical Interview showed that autobiographical memory performances were significantly impaired in dementia with Lewy body patients compared to control subjects in a temporally ungraded manner, for both the free recall and the specific probe conditions (P < 0.0001), though with greater improvement after probing in the patient group. Furthermore, autobiographical memory impairments were correlated with grey matter volume within right insular cortex, temporoparietal junction, precuneus, putamen, left temporal cortex, bilateral parahippocampus and cerebellum, using a threshold of P = 0.005 uncorrected. The behavioural results confirm the existence of temporally ungraded autobiographical memory impairments in dementia with Lewy bodies, from the early stage of the disease. As we expected, neuroimaging analysis revealed a role for the insula and the precuneus in autobiographical memory retrieval, two regions associated with elementary aspects of the self, among other brain regions classically associated with autobiographical memory, such as medial temporal lobe and temporoparietal junction. Our findings provide important insights regarding the involvement of the insula in the self and suggest that insular damage could lead to a global collapse of the self, including its more elaborated components, such as autobiographical memory.
尽管路易体痴呆症患者在学习和检索新信息方面存在缺陷,但对这种疾病的自传体记忆却从未进行过研究。然而,自传体记忆障碍是痴呆症的一个普遍特征,也是其他神经退行性疾病的显著特征。此外,自传体记忆与自我的时间延伸相对应,我们推测路易体痴呆症患者的自传体记忆会发生改变,而自传体记忆的损伤可能与疾病早期出现的岛叶萎缩有关。在这项研究中,我们试图描述路易体痴呆症患者自传体记忆损伤的特征,并探索其神经相关性,假设岛叶损伤会影响自我,包括其最复杂的组成部分,如自传体记忆。这项探索性研究选取了 20 名路易体痴呆前驱期至轻度患者和 20 名健康对照组受试者。自传体访谈被用来评估自传体记忆。对患者和对照组受试者的表现进行了比较,并对不同生活时期和回忆条件进行了分析。研究人员为所有参与者采集了三维磁共振图像,并使用体素形态测量法对患者组进行了相关分析。自传体访谈的行为结果显示,与对照组相比,路易体痴呆症患者的自传体记忆能力在自由回忆和特定探查条件下均明显受损(P < 0.0001),但患者组在探查后改善程度更大。此外,自传体记忆障碍与右侧岛叶皮层、颞顶交界处、楔前区、普鲁门、左侧颞叶皮层、双侧海马旁和小脑的灰质体积相关,未校正阈值为 P = 0.005。行为学结果证实,路易体痴呆症患者从疾病早期开始就存在时间上未分级的自传体记忆障碍。正如我们所预期的那样,神经影像学分析表明,岛叶和楔前叶在自传体记忆检索中发挥作用,这两个区域与自我的基本方面有关,其他脑区通常与自传体记忆有关,如内侧颞叶和颞顶交界处。我们的研究结果提供了有关岛叶参与自我的重要见解,并表明岛叶损伤可能导致自我的全面崩溃,包括其更精细的组成部分,如自传体记忆。
{"title":"Neuroimaging of autobiographical memory in dementia with Lewy bodies: a story of insula.","authors":"Alice Tisserand, Frédéric Blanc, Candice Muller, Hélène Durand, Catherine Demuynck, Alix Ravier, Léa Sanna, Paulo Loureiro de Sousa, Anne Botzung, Mary Mondino, Nathalie Philippi","doi":"10.1093/braincomms/fcae272","DOIUrl":"https://doi.org/10.1093/braincomms/fcae272","url":null,"abstract":"<p><p>Although deficits in learning and retrieving new information are well characterized in dementia with Lewy bodies, autobiographical memory has never been explored in this disease. Yet, autobiographical memory impairments are a pervasive feature of dementia, well characterized in other neurodegenerative diseases. Moreover, autobiographical memory corresponds to an extension over time of the self, which we hypothesize is altered in dementia with Lewy bodies and impairment of which could be linked to the insular atrophy occurring from an early stage of the disease. In this study, we sought to characterize autobiographical memory impairments and explore their neural correlates in dementia with Lewy bodies, on the assumption that insular damage could impact the self, including its most elaborate components, such as autobiographical memory. Twenty patients with prodromal to mild dementia with Lewy bodies were selected to participate in this exploratory study along with 20 healthy control subjects. The Autobiographical Interview was used to assess autobiographical memory. Performances were compared between patients and control subjects, and an analysis across life periods and recall conditions was performed. 3D magnetic resonance images were acquired for all participants, and correlational analyses were performed in the patient group using voxel-based morphometry. The behavioural results of the Autobiographical Interview showed that autobiographical memory performances were significantly impaired in dementia with Lewy body patients compared to control subjects in a temporally ungraded manner, for both the free recall and the specific probe conditions (<i>P</i> < 0.0001), though with greater improvement after probing in the patient group. Furthermore, autobiographical memory impairments were correlated with grey matter volume within right insular cortex, temporoparietal junction, precuneus, putamen, left temporal cortex, bilateral parahippocampus and cerebellum, using a threshold of <i>P</i> = 0.005 uncorrected. The behavioural results confirm the existence of temporally ungraded autobiographical memory impairments in dementia with Lewy bodies, from the early stage of the disease. As we expected, neuroimaging analysis revealed a role for the insula and the precuneus in autobiographical memory retrieval, two regions associated with elementary aspects of the self, among other brain regions classically associated with autobiographical memory, such as medial temporal lobe and temporoparietal junction. Our findings provide important insights regarding the involvement of the insula in the self and suggest that insular damage could lead to a global collapse of the self, including its more elaborated components, such as autobiographical memory.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-20eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae247
John B Coulton, Yingxin He, Nicolas R Barthélemy, Hong Jiang, David M Holtzman, Randall J Bateman
Although neurofilament light chain is a well-known marker of neuronal damage, its characterization at the proteoform level is underdeveloped. Here, we describe a new method to profile and quantify neurofilament light chain in plasma at the peptide level, using three in-house monoclonal antibodies targeting distinct protein domains and nano-liquid chromatography coupled to high-resolution tandem mass spectrometry. This study profiled and compared plasma neurofilament light chain to CSF in 102 older individuals (73.9 ± 6.3 years old), 37 of which had a clinical dementia rating greater than 0. We observed elevated neurofilament light chain in preclinical Alzheimer's disease plasma for two measures (NfL101 and NfL324) and CSF for seven measures (NfL92, NfL101, NfL117, NfL137, NfL148, NfL165 and NfL530). We found five plasma peptides (NfL92, NfL101, NfL117, NfL324 and NfL530) significantly associated with age and two (NfL148 and NfL324) with body mass index.
{"title":"Multi-peptide characterization of plasma neurofilament light chain in preclinical and mild Alzheimer's disease.","authors":"John B Coulton, Yingxin He, Nicolas R Barthélemy, Hong Jiang, David M Holtzman, Randall J Bateman","doi":"10.1093/braincomms/fcae247","DOIUrl":"10.1093/braincomms/fcae247","url":null,"abstract":"<p><p>Although neurofilament light chain is a well-known marker of neuronal damage, its characterization at the proteoform level is underdeveloped. Here, we describe a new method to profile and quantify neurofilament light chain in plasma at the peptide level, using three in-house monoclonal antibodies targeting distinct protein domains and nano-liquid chromatography coupled to high-resolution tandem mass spectrometry. This study profiled and compared plasma neurofilament light chain to CSF in 102 older individuals (73.9 ± 6.3 years old), 37 of which had a clinical dementia rating greater than 0. We observed elevated neurofilament light chain in preclinical Alzheimer's disease plasma for two measures (NfL101 and NfL324) and CSF for seven measures (NfL92, NfL101, NfL117, NfL137, NfL148, NfL165 and NfL530). We found five plasma peptides (NfL92, NfL101, NfL117, NfL324 and NfL530) significantly associated with age and two (NfL148 and NfL324) with body mass index.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-20eCollection Date: 2024-01-01DOI: 10.1093/braincomms/fcae193
Makoto T Tanaka, Yasuo Miki, Fumiaki Mori, Tomoya Kon, Tomonori Furukawa, Shuji Shimoyama, Yota Tatara, Taku Ozaki, Conceição Bettencourt, Thomas T Warner, Koichi Wakabayashi
Abnormal α-synuclein (αSyn), including an oligomeric form of αSyn, accumulates and causes neuronal dysfunction in the brains of patients with multiple system atrophy. Neuroprotective drugs that target abnormal αSyn aggregation have not been developed for the treatment of multiple system atrophy. In addition, treating diseases at an early stage is crucial to halting the progress of neuronal damage in neurodegeneration. In this study, using early-stage multiple system atrophy mouse model and in vitro kinetic analysis, we investigated how intranasal and oral administration of trehalose can improve multiple system atrophy pathology and clinical symptoms. The multiple system atrophy model showed memory impairment at least four weeks after αSyn induction. Behavioural and physiological analyses showed that intranasal and oral administration of trehalose reversed memory impairments to near-normal levels. Notably, trehalose treatment reduced the amount of toxic αSyn and increased the aggregated form of αSyn in the multiple system atrophy model brain. In vitro kinetic analysis confirmed that trehalose accelerated the aggregate formation of αSyn. Based on our findings, we propose a novel strategy whereby accelerated αSyn aggregate formation leads to reduced exposure to toxic αSyn oligomers, particularly during the early phase of disease progression.
{"title":"Intranasal administration of trehalose reduces α-synuclein oligomers and accelerates α-synuclein aggregation.","authors":"Makoto T Tanaka, Yasuo Miki, Fumiaki Mori, Tomoya Kon, Tomonori Furukawa, Shuji Shimoyama, Yota Tatara, Taku Ozaki, Conceição Bettencourt, Thomas T Warner, Koichi Wakabayashi","doi":"10.1093/braincomms/fcae193","DOIUrl":"10.1093/braincomms/fcae193","url":null,"abstract":"<p><p>Abnormal α-synuclein (αSyn), including an oligomeric form of αSyn, accumulates and causes neuronal dysfunction in the brains of patients with multiple system atrophy. Neuroprotective drugs that target abnormal αSyn aggregation have not been developed for the treatment of multiple system atrophy. In addition, treating diseases at an early stage is crucial to halting the progress of neuronal damage in neurodegeneration. In this study, using early-stage multiple system atrophy mouse model and <i>in vitro</i> kinetic analysis, we investigated how intranasal and oral administration of trehalose can improve multiple system atrophy pathology and clinical symptoms. The multiple system atrophy model showed memory impairment at least four weeks after αSyn induction. Behavioural and physiological analyses showed that intranasal and oral administration of trehalose reversed memory impairments to near-normal levels. Notably, trehalose treatment reduced the amount of toxic αSyn and increased the aggregated form of αSyn in the multiple system atrophy model brain. <i>In vitro</i> kinetic analysis confirmed that trehalose accelerated the aggregate formation of αSyn. Based on our findings, we propose a novel strategy whereby accelerated αSyn aggregate formation leads to reduced exposure to toxic αSyn oligomers, particularly during the early phase of disease progression.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}