Age of Onset as a Moderator of Cognitive Decline in Pediatric-Onset Multiple Sclerosis

2014 ◽  
Vol 20 (8) ◽  
pp. 796-804 ◽  
Author(s):  
Banafsheh Hosseini ◽  
David B. Flora ◽  
Brenda L. Banwell ◽  
Christine Till
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Decline ◽  
Social Status ◽  
Cognitive Reserve ◽  
Disease Onset ◽  
Rate Of Change ◽  
Childhood And Adolescence ◽  
Younger Age ◽  
Pediatric Onset ◽  
Cognitive Maturation

AbstractCognitive impairment is often reported in pediatric-onset multiple sclerosis (MS). Using serial cognitive data from 35 individuals with pediatric-onset MS, this study examined how age at disease-onset and proxies of cognitive reserve may impact cognitive maturation over the course of childhood and adolescence. Neuropsychological evaluations were conducted at baseline and up to four more assessments. Of the 35 participants, 7 completed only one assessment, 5 completed two assessments, 13 completed three assessments, 10 completed four or more assessments. Growth curve modeling was used to assess longitudinal trajectories on the Trail Making Test-Part B (TMT-B) and the Symbol Digit Modalities (SDMT; oral version) and to examine how age at disease onset, baseline Full Scale IQ, and social status may moderate rate of change on these measures. Mean number of evaluations completed per patient was 2.8. Younger age at disease onset was associated with a greater likelihood of cognitive decline on both the TMT-B (p=.001) and SDMT (p=.005). Baseline IQ and parental social status did not moderate any of the cognitive trajectories. Findings suggest that younger age at disease-onset increases the vulnerability for disrupted performance on measures of information processing, visual scanning, perceptual/motor speed, and working memory. Proxies of cognitive reserve did not protect against the progression of decline on these measures. Young patients with MS should be advised to seek follow-up cognitive evaluation to assess cognitive maturation and to screen for the potential late emergence of cognitive deficits. (JINS, 2014, 20, 1–9)

scholarly journals Cognitive Issues in Pediatric Multiple Sclerosis

2021 ◽  
Vol 11 (4) ◽  
pp. 442
Author(s):  
Emilio Portaccio ◽  
Ermelinda De Meo ◽  
Angelo Bellinvia ◽  
Maria Pia Amato
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Pediatric Patients ◽  
Leisure Activities ◽  
Disease Onset ◽  
Cognitive Profiles ◽  
Brain Growth ◽  
Network Activation ◽  
Definition Of

Multiple sclerosis (MS) is one of the leading causes of disability in young adults. The onset of MS during developmental age makes pediatric patients particularly susceptible to cognitive impairment, resulting from both disease-related damage and failure of age-expected brain growth. Despite different test batteries and definitions, cognitive impairment has been consistently reported in approximately one-third of pediatric patients with MS. However, the lack of a uniform definition of cognitive impairment and the adoption of different test batteries have led to divergent results in terms of cognitive domains more frequently affected across the cohorts explored. This heterogeneity has hampered large international collaborative studies. Moreover, research aimed at the identification of risk factors (e.g., demographic, clinical, and radiological features) or protective factors (e.g., cognitive reserve, leisure activities) for cognitive decline is still scanty. Mood disorders, such as depression and anxiety, can be detected in these patients alongside cognitive decline or in isolation, and can negatively affect quality of life scores as well as academic performances. By using MRI, cognitive impairment was attributed to damage to specific brain compartments as well as to abnormal network activation patterns. However, multimodal MRI studies are still needed in order to assess the contribution of each MRI metric to cognitive impairment. Importantly, longitudinal studies have recently demonstrated failure of age-expected brain growth and of white matter (WM) and gray matter (GM) maturation plays a relevant role in determining cognitive dysfunction, in addition to MS-related direct damage. Whether these growth retardations might result in specific cognitive profiles according to the age at disease onset has not been studied, yet. A better characterization of cognitive profiles in pediatric MS patients, as well as the definition of neuroanatomical substrates of cognitive impairment and their longitudinal evolution are needed to develop efficient therapeutic strategies against cognitive impairment in this patient population.

Cognitive reserve moderates the impact of subcortical gray matter atrophy on neuropsychological status in multiple sclerosis

2015 ◽  
Vol 22 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Claire M Modica ◽  
Niels Bergsland ◽  
Michael G Dwyer ◽  
Deepa P Ramasamy ◽  
Ellen Carl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Decline ◽  
Cognitive Processing ◽  
Gray Matter ◽  
Cognitive Reserve ◽  
Cognitive Outcome ◽  
Brain Reserve ◽  
The Impact ◽  
Normal Controls

Background: Cognitive decline is characterized in multiple sclerosis (MS), but the rate and severity vary. The reserve hypothesis proposes that baseline neurological differences impact cognitive outcome in neurodegenerative disease. Objective: To elucidate how brain reserve and cognitive reserve influence subcortical gray matter (SCGM) atrophy and cognitive decline in MS over 3 years. Methods: Seventy-one MS patients and 23 normal controls underwent magnetic resonance imaging and cognitive assessment at baseline and 3-year follow-up. The influence of reserve on cognitive processing speed (CPS) and memory was examined. Results: SCGM volume and cognitive scores were lower in MS than normal controls ( P⩽0.001). Accounting for baseline, comparison of follow-up means yielded a difference between groups in SCGM volume ( P<0.001) but not cognition (NS). Cognitive reserve ( P=0.005), but not brain reserve, contributed to CPS, with only low cognitive reserve MS subjects showing decline in CPS ( P=0.029). SCGM change predicted CPS outcome in MS with low cognitive reserve ( P=0.002) but not high cognitive reserve. There were no effects in the domain of memory. Conclusions: SCGM atrophy occurs in normal controls, but significantly more so in MS. While CPS did not change in normal controls, low cognitive reserve was associated with CPS decline in MS. High cognitive reserve protect MS patients from cognitive decline related to SCGM atrophy.

scholarly journals Cognitive Reserve and Brain Reserve in Prodromal Huntington's Disease

2013 ◽  
Vol 19 (7) ◽  
pp. 739-750 ◽  
Author(s):  
Aaron Bonner-Jackson ◽  
Jeffrey D. Long ◽  
Holly Westervelt ◽  
Geoffrey Tremont ◽  
Elizabeth Aylward ◽  
...  
Keyword(s):  
Cognitive Reserve ◽  
Morphological Changes ◽  
Occupational Status ◽  
Disease Onset ◽  
Brain Structures ◽  
Rate Of Change ◽  
Longitudinal Change ◽  
Brain Volumes ◽  
Cognitive Measure ◽  
Intellectual Level

AbstractHuntington disease (HD) is associated with decline in cognition and progressive morphological changes in brain structures. Cognitive reserve may represent a mechanism by which disease-related decline may be delayed or slowed. The current study examined the relationship between cognitive reserve and longitudinal change in cognitive functioning and brain volumes among prodromal (gene expansion-positive) HD individuals. Participants were genetically confirmed individuals with prodromal HD enrolled in the PREDICT-HD study. Cognitive reserve was computed as the composite of performance on a lexical task estimating premorbid intellectual level, occupational status, and years of education. Linear mixed effects regression (LMER) was used to examine longitudinal changes on four cognitive measures and three brain volumes over approximately 6 years. Higher cognitive reserve was significantly associated with a slower rate of change on one cognitive measure (Trail Making Test, Part B) and slower rate of volume loss in two brain structures (caudate, putamen) for those estimated to be closest to motor disease onset. This relationship was not observed among those estimated to be further from motor disease onset. Our findings demonstrate a relationship between cognitive reserve and both a measure of executive functioning and integrity of certain brain structures in prodromal HD individuals. (JINS, 2013, 19, 1–12).

The cognitive reserve theory in the setting of pediatric-onset multiple sclerosis

2016 ◽  
Vol 22 (13) ◽  
pp. 1741-1749 ◽  
Author(s):  
Luisa Pastò ◽  
Emilio Portaccio ◽  
Benedetta Goretti ◽  
Angelo Ghezzi ◽  
Silvia Lori ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Reserve ◽  
Reliable Change Index ◽  
Neuropsychological Performance ◽  
Regression Analyses ◽  
Neuropsychological Battery ◽  
Healthy Control ◽  
Multivariable Regression ◽  
Potential Impact ◽  
Pediatric Onset

Background: The study of cognitive reserve (CR) in relationship with cognitive impairment (CI) in pediatric-onset multiple sclerosis (POMS) may provide cues to identifying subjects at higher risk of impairment and scope for therapeutic strategies. Objectives: To assess the potential impact of CR on cognition in a cohort of POMS patients. Methods: In all, 48 POMS patients were followed up for 4.7 ± 0.4 years. CI was defined as the failure of ⩾3 tests on an extensive neuropsychological battery. Change of neuropsychological performance was assessed through the Reliable Change Index (RCI) method. At baseline, CR was estimated by measuring the intelligence quotient (IQ). The relationships were assessed through multivariable regression analyses. Results: At baseline, CI was detected in 14/48 (29.2%) patients. Two out of 57 healthy control (HC; 3.5%) met the same criteria of CI ( p < 0.001). A deteriorating cognitive performance using the RCI method was observed in 18/48 patients (37.6%). Among the 34 cases who were cognitively preserved at baseline, a higher reserve predicted stable/improving performance (odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.03–1.20; p = 0.006). Conclusion: Our results suggest that higher CR in POMS patients may protect from CI, particularly in subjects with initial cognitive preservation, providing relevant implications for counseling and rehabilitation strategies.

scholarly journals Alemtuzumab-related thyroid disease in people with multiple sclerosis is associated with age and brainstem phenotype at disease onset

2020 ◽  
Vol 6 (2) ◽  
pp. 205521732093392 ◽  
Author(s):  
Siew Mei Yap ◽  
Mary Dillon ◽  
Rachel K Crowley ◽  
Christopher McGuigan
Keyword(s):  
Multiple Sclerosis ◽  
Thyroid Disease ◽  
Chart Review ◽  
Disease Onset ◽  
Human Leukocyte ◽  
Cross Reactivity ◽  
Autoimmune Thyroid ◽  
Leukocyte Antigen ◽  
Younger Age ◽  
Thyroid Medication

Background Autoimmune thyroid disease (AITD) occurs in 40%–50% of alemtuzumab-treated persons with multiple sclerosis (pwMS), most of whom will develop Graves’ Disease (GD). Objective To explore contributory factors for alemtuzumab-related AITD in pwMS. Methods A retrospective patient chart review was performed. Results Sixteen out of 52 (30.8%) pwMS developed AITD. GD occurred in 56.3% ( n = 9), the majority ( n = 7, 77.8%) symptomatic. All but one (85.7%) pwMS with symptomatic GD developed atypical, large and rapid fluctuations in thyroid hormone levels unexplained by effect of anti-thyroid medication alone. All symptomatic GD cases were age ≤32 years when starting alemtuzumab (ɸ = 0.60, p = 0.03). PwMS who started alemtuzumab at a younger age developed thyroid disease earlier ( r = 0.51, p = 0.04). PwMS with clinical and radiological evidence of brainstem involvement at onset of multiple sclerosis were 11 times more likely to develop symptomatic GD compared with those with other phenotypes ( p < 0.01). Conclusion Alemtuzumab-induced reconstitution GD may result from early and increased cross-reactivity between antigens common to the brainstem and thyroid, or presence of shared Human Leukocyte Antigen (HLA) alleles that determine brainstem and thyroid involvement. We suggest cautious use of alemtuzumab in younger (≤32 years) pwMS with early brainstem involvement, especially those actively planning pregnancy, where alternative therapies are readily available.

scholarly journals Multiple sclerosis starting before the age of 18 years: the Brazilian experience

2013 ◽  
Vol 71 (10) ◽  
pp. 783-787 ◽  
Author(s):  
Yara Dadalti Fragoso ◽  
Maria Lucia Brito Ferreira ◽  
Nivea de Macedo Oliveira Morales ◽  
Walter Oleschko Arruda ◽  
Joseph Bruno Bidin Brooks ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Data Collection ◽  
Disease Duration ◽  
Disease Onset ◽  
Severe Form ◽  
Childhood And Adolescence ◽  
Retrospective Data ◽  
Mild Form ◽  
Retrospective Data Collection ◽  
The Mean

Multiple sclerosis (MS) starting in childhood and adolescence poses a challenge for diagnosis and management of the disease. The aim of the present study was to assess the characteristics of early onset MS in Brazilian patients. Methods Retrospective data collection from specialized MS units. Results From 20 MS units in 11 Brazilian states, 117 cases of MS starting before the age of 18 years were collected. These patients had an average of 10 years of disease duration, still typically with low disability and one relapse every 2.5 years. The mean age for disease onset was 13.7 years. Conclusion The present study introduces a large series of Brazilian cases of pediatric MS. Although some patients presented a very severe form of MS, on the whole the group of patients with MS starting in childhood or adolescence presented a relatively mild form of this disease in Brazil.

Cognitive reserve moderates decline in information processing speed in multiple sclerosis patients

2010 ◽  
Vol 16 (5) ◽  
pp. 829-835 ◽  
Author(s):  
RALPH H.B. BENEDICT ◽  
SARAH A. MORROW ◽  
BIANCA WEINSTOCK GUTTMAN ◽  
DIANE COOKFAIR ◽  
DAVID J. SCHRETLEN
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Decline ◽  
Cognitive Dysfunction ◽  
Processing Speed ◽  
Cognitive Reserve ◽  
Cognitive Testing ◽  
Information Processing Speed ◽  
The North ◽  
Premorbid Intelligence ◽  
Multiple Sclerosis Patients

AbstractCognitive reserve is widely recognized as a moderator of cognitive decline in patients with senile dementias such as Alzheimer’s disease. The same effect may occur in multiple sclerosis (MS), an immunologic disorder affecting the central nervous system. While MS is traditionally considered an inflammatory, white matter disease, degeneration of gray matter is increasingly recognized as the primary contributor to progressive cognitive decline. Our aim was to determine if individual differences in estimated cognitive reserve protect against the progression of cognitive dysfunction in MS. Ninety-one patients assessed twice roughly 5 years apart were identified retrospectively. Cognitive testing emphasized mental processing speed. Cognitive reserve was estimated by years of education and by performance on the North American Adult Reading Test (NAART). After controlling for baseline characteristics, both years of education (p = .013) and NAART scores (p = .049) significantly improved regression models predicting cognitive decline. Symbol Digit Modalities Test (SDMT) performance showed no significant change in patients with > 14 years of education, whereas it declined significantly in patients with ≤ 14 years of education. We conclude that greater cognitive reserve as indexed by either higher premorbid intelligence or more years of education protects against the progression of cognitive dysfunction in MS. (JINS, 2010, 16, 829–835.)

scholarly journals Long-term disability progression of pediatric-onset multiple sclerosis

Neurology ◽  
2019 ◽  
Vol 92 (24) ◽  
pp. e2764-e2773 ◽  
Author(s):  
Kyla A. McKay ◽  
Jan Hillert ◽  
Ali Manouchehrinia
Keyword(s):  
Multiple Sclerosis ◽  
Proportional Hazards ◽  
Clinical Information ◽  
Cox Proportional Hazards ◽  
Disability Progression ◽  
Kaplan Meier ◽  
Younger Age ◽  
Risk Of Progression ◽  
Pediatric Onset

ObjectiveTo evaluate long-term disability progression in pediatric-onset multiple sclerosis (POMS) and compare to adult-onset multiple sclerosis (AOMS).MethodsThis was a retrospective cohort study using prospectively collected clinical information from the Swedish MS Registry. Clinical features were compared and Kaplan-Meier and Cox proportional hazards regression were used to assess the risk of reaching sustained Expanded Disability Status Scale (EDSS) 3, 4, and 6 in POMS (multiple sclerosis [MS] onset <18 years) and AOMS (MS onset ≥18 years).ResultsA total of 12,482 persons were included; 549 (4.4%) were classified as POMS. The POMS cohort took longer to reach all 3 disability milestones from their MS onset, but did so at a younger age than the AOMS cohort. Primary progressive course (hazard ratio [HR] 4.63; 95% confidence interval [CI] 1.46–14.7), higher relapse rate in the first 5 years of disease (HR 5.35; 95% CI 3.37–8.49), and complete remission from the initial relapse (HR 0.41; 95% CI 0.18–0.94) were associated with an altered risk of progression to EDSS 4 among POMS cases. The same pattern emerged for the risk of reaching EDSS 3 and 6.ConclusionsPatients with pediatric-onset MS follow a distinctive clinical course, which should be considered in the treatment and management of the disease.

Timing of birth and disease progression in multiple sclerosis

2008 ◽  
Vol 14 (6) ◽  
pp. 793-798 ◽  
Author(s):  
M Koch ◽  
J De Keyser ◽  
H Tremlett
Keyword(s):  
Multiple Sclerosis ◽  
Natural History ◽  
Disease Progression ◽  
Disease Onset ◽  
Later Life ◽  
Season Of Birth ◽  
Month Of Birth ◽  
Birth Month ◽  
Kaplan Meier ◽  
Younger Age

Background The timing of birth has recently been associated with the risk of developing multiple sclerosis (MS) in later life. Whether the timing of birth also influences the disease course of MS is unknown. Objective To investigate whether the season or month of birth influences the timing of secondary progression or the time to landmark disability outcomes in MS. Methods To allow confirmation of findings, all analyses were performed in duplicate in two large natural history cohorts from geographically distinct but seasonally similar locations in Europe and North America. Kaplan–Meier survival analyses were used to investigate the influence of month and season of birth on 1) the time to and age at the development of secondary progression in patients with a relapsing disease onset and 2) the time to reach an Expanded Disability Status Scale (EDSS) score of 6.0 in patients with primary progressive and relapsing MS. Results No association between the month or season of birth and disease progression could be found, which was reproducible in both natural history cohorts. A seasonal trend was observed for the time to and age at secondary progression in Groningen, with March babies exhibiting a shorter time to and younger age at secondary progression. The birth month affected time to EDSS 6 for those with relapsing MS in British Columbia, with January babies exhibiting a longer time to EDSS 6. Neither finding could be reciprocated in the other natural history cohort. Conclusion The season or month of birth does not appear to influence disease progression of MS.

Cognitive processing speed in pediatric-onset multiple sclerosis: Baseline characteristics of impairment and prediction of decline

2019 ◽  
Vol 26 (14) ◽  
pp. 1938-1947 ◽  
Author(s):  
Asya I Wallach ◽  
Michael Waltz ◽  
T Charles Casper ◽  
Gregory Aaen ◽  
Anita Belman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Cognitive Processing ◽  
Processing Speed ◽  
Disease Onset ◽  
Initial Assessment ◽  
The Mean ◽  
Cognitive Screen ◽  
Pediatric Onset

Background: Cognitive impairment occurs in approximately one-third of pediatric-onset multiple sclerosis (POMS) patients. The Symbol Digit Modalities Test (SDMT), a widely used cognitive screen in adults, has yet to be incorporated early into the standard care of POMS. Objective: To screen for cognitive impairment early in the course of POMS and analyze predictive factors. Methods: Of the 955 POMS or clinically isolated syndrome (CIS) patients prospectively assessed from March 2014 to July 2018, 500 POMS and 116 CIS patients met inclusion criteria (disease onset before the age of 18, one or more SDMTs, and 8 years or older at the time of testing). Those with relapse were analyzed separately from those who were relapse-free. Results: At initial assessment, the mean (interquartile range (IQR)) age at symptom onset was 13.5 years (12.0, 15.9) and the mean (±SD) disease duration was 3.0 ± 2.9 years. Impaired processing speed occurred in 23.4% of POMS and in 16.4% of CIS. On serial testing ( n = 383, mean follow-up: 1.8 years), 14.1% had clinically meaningful decline predicted by older age of multiple sclerosis (MS) onset and male gender. Disease relapse or steroid use led to transient worsening on the SDMT. Conclusion: Early in the disease, some POMS and CIS patients are at risk for cognitive impairment and subsequent decline.

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