Cognitive Reserve In Multiple Sclerosis Research Articles

Vocabulary knowledge as a reliable proxy of cognitive reserve in multiple sclerosis: a validation study

IntroductionThe present study aimed to explore the suitability of the vocabulary knowledge (VOC) test as an accurate and reliable proxy of cognitive reserve (CR) by evaluating its psychometric properties and discrimination accuracy compared with other CR measures in multiple sclerosis (MS).MethodsSixty-eight consecutive people with multiple sclerosis (pwMS), followed at our MS outpatient clinic, completed a clinical evaluation and neuropsychological assessment including: VOC, Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Cognitive Reserve Index Questionnaire (CRIq), Beck Depression Inventory-II, and State-Trait Anxiety Inventory. Reliability, convergent and divergent validity, and discrimination accuracy of the VOC were assessed using educational level as reference standard. The possible effects of sociodemographic and clinical factors on VOC and their role in predicting global cognitive status were also explored.ResultsVOC demonstrated good internal consistency (Cronbach’s α = 0.894) and adequate construct validity. It showed an acceptable level of discrimination between pwMS with high and low CR, comparable to the CRIq score. Education strongly affected VOC scores, which in turn were independent of MS features. VOC emerged as an independent predictor of global cognitive status together with MS-related disability.ConclusionWe demonstrated the validity of VOC as a reliable CR measure in pwMS. Thus, CR may also be estimated using fixed objective measures, independent of brain pathology and clinical features. Early CR estimation may help clinicians identify pwMS at a higher risk of cognitive decline and plan strict neuropsychological monitoring and cognitive interventions.

Systematic review of cognitive reserve in multiple sclerosis: Accounting for physical disability, fatigue, depression, and anxiety.

Cognitive reserve (CR) describes an individual's ability to adapt cognitive processes in response to brain atrophy, and has been reported to explain some of the discrepancy between brain atrophy and cognitive functioning outcomes in multiple sclerosis (MS). CR in MS is typically investigated by assessing an individual's pre- and/or post-diagnosis enrichment, which includes premorbid intellectual abilities, educational level, occupational attainment, and engagement in cognitively enriching leisure activities. Common MS symptoms (e.g., physical disability, fatigue, depression, anxiety) may impact an individual's ability to engage in various CR-enhancing activities post-diagnosis. It is unknown to what extent these MS symptoms have been taken into account in MS research on CR. As such, we identified whether studies assessed CR using measures of premorbid or continuous (including post-diagnosis) enrichment. For studies investigating continuous enrichment, we identified whether studies accounted for MS-impact, which MS symptoms were accounted for, and how, and whether studies acknowledged MS symptoms as potential CR-confounds. Three electronic databases (PsycINFO, PubMed, Scopus) were searched. Eligible studies investigated CR proxies (e.g., estimated premorbid intellectual abilities, vocabulary knowledge, educational level, occupational attainment, cognitively enriching leisure activities, or a combination thereof) in relation to cognitive, brain atrophy or connectivity, or daily functioning outcomes in adult participants with MS. We extracted data on methods and measures used, including any MS symptoms taken into account. Objectives were addressed using frequency analyses and narrative synthesis. 115 studies were included in this review. 47.8% of all studies investigated continuous enrichment. Approximately half of the studies investigating continuous enrichment accounted for potential MS-impact in their analyses, with only 31.0% clearly identifying that they treated MS symptoms as potential confounds for CR-enhancement. A narrative synthesis of studies which investigated CR with and without controlling statistically for MS-impact indicated that accounting for MS symptoms may impact findings concerning the protective nature of CR. Fewer than half of the studies investigating CR proxies in MS involved continuous enrichment. Just over half of these studies accounted for potential MS-impact in their analyses. To achieve a more complete and accurate understanding of CR in MS, future research should investigate both pre-MS and continuous enrichment. In doing so, MS symptoms and their potential impact should be considered. Establishing greater consistency and rigour across CR research in MS will be crucial to produce an evidence base for the development of interventions aimed at improving quality of care and life for pwMS.

Cognitive reserve in multiple sclerosis

One of the most common symptoms of multiple sclerosis is a cognitive impairment, which becomes severe in the late stage of disease. It is difficult to evaluate the probability of cognitive deficit development and the rate of its progression. Evaluation of neurological status and neuroimaging data in neurodegenerative diseases patients show an inconsistency in the severity of cognitive symptoms. This served as the basis for creating the concept of cognitive reserve, which reflects the brain’s ability to compensate cognitive impairment resulting from damage to brain structures. the term «cognitive reserve» has acquired several «concepts». Despite these concepts are used only for scientific researches, it has a good potential for implementation in clinical practice. This review contains information about the supposed physiological mechanisms of the cognitive reserve, role for preventing of the development of cognitive and motor deficit, methods of cognitive reserve quantitative assessment by clinical and neuroimaging methods, and possible ways of increase.

Anterior Insular Resting-State Functional Connectivity is Related to Cognitive Reserve in Multiple Sclerosis.

Cognitive dysfunction is common in multiple sclerosis (MS). The dorsal anterior insula (dAI) is a key hub of the salience network (SN) orchestrating access to critical cognitive brain regions. The aim of this study was to assess whole-brain dAI intrinsic functional connectivity (iFC) using resting-state functional MRI (rs-fMRI) in people with MS and healthy controls (HC) and test the relationship between cognitive reserve (CR) and dAI iFC in people with MS. We studied 28 people with relapsing-remitting MS and 28 HC. CR index was quantified by combining premorbid IQ, leisure activities, and education level. For whole-brain iFC analyses, the bilateral dAI were used as seeds. Individual subject correlation maps were entered into general linear models for group comparison and to analyze the effect of CR index on dAI iFC, controlling for multiple comparisons. The correlation between CR index and iFC was assessed using a linear regression model. rs-fMRI analyses revealed a negative relationship between CR index and iFC within the left dAI and a left occipital cluster in people with MS including regions of the cuneus, superior occipital gyrus, and parieto-occipital sulcus. The regression analysis showed that people with MS and a higher CR index had a statistically significantly reduced iFC within the left dAI and the cluster. CR is relevant to functional connectivity within one of the main nodes of the SN, the dAI, and occipital regions in MS. These results have implications for how CR may modulate the susceptibility to cognitive dysfunction in MS.

The role of cognitive reserve in multiple sclerosis: A cross-sectional study in 526 patients

BackgroundCognitive impairment (CI) affects about 40–70% of multiple sclerosis (MS) patients. Brain MRI explains about 33–50% of the CI variance in MS. The cognitive reserve (CR) hypothesis has been postulated to identify other factors that can account for more variance in this outcome. The objective of this study was to explore the impact of CR on cognitive performance in MS patients. MethodsA total of 526 MS outpatients were recruited (70.9% females, 41.7 ± 11.1 years old). CR was cross-sectionally assessed by the CR Index questionnaire (CRIq). Cognitive assessment was performed using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) tool to evaluate information processing speed, verbal memory and visuospatial memory. The role of CRIq in MS cognition was investigated by using multiple linear regression models to account for possible confounders. ResultsIn total 202 (38.4%) patients were found with CI (i.e. failure in at least one of the three cognitive tests used based on normative data from 212 healthy controls). The CRIq score of CI patients was lower than that of non-CI patients (p < 0.001). CRIq score was significantly correlated with information processing speed (rho = 0.364, p < 0.001), verbal memory (rho = 0.237, p < 0.001) and visuospatial memory (rho = 0.331, p < 0.001), having adjusted for age and sex. CRIq was also significantly associated with disability (rho = -0.188, p < 0.001) and depressive symptoms (rho = -0.220, p < 0.001). Roughly, CRIq, disability and depressive symptoms significantly explained 12.2–23.7% of cognitive performance in MS. A significant interaction between CRIq and disability was also found for information processing speed. ConclusionCR has a protective role in MS-related cognitive dysfunction. The differential effect of CR on distinct cognitive domains is supported. Interventions targeting CR to prevent cognitive impairment in MS patients are warranted by the study findings.

Preserved network functional connectivity underlies cognitive reserve in multiple sclerosis.

Cognitive reserve is one's mental resilience or resistance to the effects of structural brain damage. Reserve effects are well established in people with multiple sclerosis (PwMS) and Alzheimer's disease, but the neural basis of this phenomenon is unclear. We aimed to investigate whether preservation of functional connectivity explains cognitive reserve. Seventy‐four PwMS and 29 HCs underwent neuropsychological assessment and 3 T MRI. Structural damage measures included gray matter (GM) atrophy and network white matter (WM) tract disruption between pairs of GM regions. Resting‐state functional connectivity was also assessed. PwMS exhibited significantly impaired cognitive processing speed (t = 2.14, p = .037) and visual/spatial memory (t = 2.72, p = .008), and had significantly greater variance in functional connectivity relative to HCs within relevant networks (p < .001, p < .001, p = .016). Higher premorbid verbal intelligence, a proxy for cognitive reserve, predicted relative preservation of functional connectivity despite accumulation of GM atrophy (standardized‐β = .301, p = .021). Furthermore, preservation of functional connectivity attenuated the impact of structural network WM tract disruption on cognition (β = −.513, p = .001, for cognitive processing speed; β = −.209, p = .066, for visual/spatial memory). The data suggests that preserved functional connectivity explains cognitive reserve in PwMS, helping to maintain cognitive capacity despite structural damage.

Cognitive and brain reserve in multiple sclerosis––A cross-sectional study

BackgroundCognitive impairment (CI) is detected in 40–70% of multiple sclerosis (MS) patients, but only 33–50% of the CI variance is explained by the disease burden assessed by MRI. The cognitive reserve (CR) hypothesis has been postulated to account for this discrepancy. So far, most previous studies have confirmed the CR hypothesis in MS but failed to examine CR indices collectively or use clinically relevant neuropsychological assessments. The aim of this study was to replicate previous findings for the effect of CR (and its counterpart; brain reserve-BR) in MS by considering these caveats. Methods128 RRMS and 13 SPMS patients were recruited in this cross-sectional study (mean age 43.5 ± 10.4 years old, 73% females, mean disease duration 153.7 ± 89.4). CR was assessed by the Cognitive Reserve Index questionnaire (CRIq) and BR by the intracranial volume. Neuropsychological assessment was made by using the recommended for clinicians Brief International Cognitive Assessment for MS (BICAMS) tool. Other measurements included clinical characteristics, psychological status, fatigue, and MRI volumetric imaging parameters. Multiple linear regression models were implemented to ascertain the putative moderating role (i.e. interaction terms) of CR and BR in cognition. ResultsExploratory univariate analyses revealed significant negative correlations between both disability and depression with cognitive scores (rho = −0.382, p < 0.001, rho = −0.278, p = 0.001, respectively), only. After controlling for gender, disability and depression, a significant moderating protective effect of CR on the associations between both grey and peripheral grey matter volumes with verbal memory was found (beta = 1.834, p = 0.045, beta = 1.936, p = 0.04 for the interaction terms, respectively). Also, BR moderated the effect of the total brain volume on verbal memory (beta = 1.516, p = 0.043). ConclusionThis study showed that by using composite measures of CR and simple, clinically-orientated neuropsychological assessments, the protective role of CR and BR is mostly restricted to memory function. Future research should embark on investigating interventions that will aim to enhance CR for the prevention of CI in MS.

Concordance Between Structural and Functional Connectivity Reflects Available Cognitive Reserve in Multiple Sclerosis During Cognitive Rehabilitation (P1.1-025)

Concordance Between Structural and Functional Connectivity Reflects Available Cognitive Reserve in Multiple Sclerosis During Cognitive Rehabilitation (P1.1-025)

Cognitive reserve and neuropsychological performance in multiple sclerosis: A meta-analysis.

Cognitive dysfunction is frequent in multiple sclerosis (MS), and its relationship with cognitive reserve (CR) has been investigated in several studies with conflicting results. In this meta-analysis, we here sought to determine the relationship between CR and cognition in MS patients and to ascertain whether demographic or clinical variables could moderate the above-mentioned relationship. We searched three electronic databases for studies assessing the relationship between CR and performance in 6 cognitive domains or processes (verbal and spatial memory, attention, processing speed, verbal fluency, inhibitory control). The initial literature search yielded 1,452 articles; 245 full-texts were evaluated, and 18 studies were entered into the meta-analysis. Mean weighted effect sizes (ES) were calculated using Hedges' g. Sensitivity analyses and examinations of funnel plots served to reduce heterogeneity. A total number of 1,903 MS patients were included, analyzing each aspect of cognition separately. ES for the relationship between CR and cognition were significant (except for verbal fluency) and moderate. After applying specific techniques to reduce heterogeneity, the verbal fluency ES became significant. Metaregression analysis revealed that older age and female sex increased the ES for attention and verbal memory outcomes. High levels of CR were associated with better cognitive task performance in verbal and spatial memory, attention, processing speed, verbal fluency, and inhibitory control. The results indirectly emphasize the value of early cognitive assessments of cognitive status and CR levels to enable timely initiation of cognitive interventions to increase CR in MS in patients with low levels of CR. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Exploring cognitive reserve in multiple sclerosis: New findings from a cross-sectional study

ABSTRACTIntroduction: The cognitive reserve (CR) hypothesis attempts to explain the discrepancy between brain damage and clinical manifestations in neurodegenerative diseases. Recently the concept of CR was applied to the multiple sclerosis (MS) model. Our aim is to investigate the impact of demographic and clinical variables on cognitive outcome in MS patients. Method: A total of 72 MS patients were assessed by Rao’s Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Cognitive Reserve Index Questionnaire (CRIq), and high field magnetic resonance examination. We performed a multivariate linear regression analysis, including each cognitive test scores as dependent variables and CRI together with age, normalized brain volume (NBV), normalized cortical volume (NCV), expanded disability severity scale (EDSS) score, and disease duration as independent variables. Moreover, we assessed whether one of the CRI subscores (CRI–Education, CRI–WorkingActivity, CRI–LeisureTime) predicted cognitive performance more than the other. Finally, to assess the CR hypothesis in our sample, we conducted the same analyses including the interaction term CRI × NCV. Results: From the multiple regression analysis, it emerged that the CRI total score influenced sustained attention, concentration, information processing speed, and verbal learning. Among the three CRI subscores, CRI–Education and CRI–WorkingActivity had the most influence. Age and EDSS score were the other significant predictors. We did not find evidence for a moderation effect of CR on negative influence of atrophy on cognitive status. Conclusions: This study focused on the contribution of CR to predict neuropsychological outcome in MS. We used a new standardized questionnaire to provide a global index including three main source of CR: education, working activity, and leisure time activities. Our preliminary findings suggest that the CR is an important predictor of better performance on cognitive tests in MS patients. However, at this stage of the study, we are unable to confirm the CR hypothesis.

Cognitive reserve in multiple sclerosis: Protective effects of education

Background: Recent data suggest that cognitive reserve modulates the adverse effects of multiple sclerosis (MS) pathology on cognitive functioning; however, the protective effects of education in MS are still unclear. Objective: To explore education as an indicator of cognitive reserve, while controlling for demographic, clinical and genetic features. Methods: A total of 419 MS patients and 159 healthy comparison (HC) subjects underwent a comprehensive neuropsychological (NP) assessment, and answered the Hospital Anxiety and Depression Scale. Based on the HC data, MS patients’ NP scores were adjusted for sex, age and education; and the estimated 5th percentile (or 95th percentile, when appropriate) was used to identify any deficits. Patients also performed the Mini-Mental State Examination (MMSE); and their human leucocyte antigen HLA-DRB1 and apolipoprotein E (ApoE) genotypes were investigated. Results: Patients with higher education were less likely (p < 0.05) to have cognitive deficits than those with lower education, even when controlling for other covariates. Other significant predictors of cognitive deficit were: age, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), and a progressive course. No significant association was found with the HLA-DRB1*15:01 or ApoE ε4 alleles. Conclusions: These results provide support to the use of education as a proxy of cognitive reserve in MS and stress the need to take into account education when approaching cognition in MS.

Cognitive processess and cognitive reserve in multiple sclerosis.

Multiple Sclerosis (MS) is characterized by motor, cognitive, and neuropsychiatric symptoms, which can occur independently. While MS is traditionally considered an inflammatory disease of the white matter, degeneration of gray matter is increasingly recognized as an important contributor to the progressive cognitive decline. A protective factor against the progression of cognitive dysfunction in MS could be the cognitive reserve, defined as resistance to brain dysfunction. Aim of the present study is to evaluate the role of cognitive reserve for different aspects of cognitive dysfunction of patients with MS. We found that patients with MS and lower cognitive reserve have poorer neuropsychological performance and slower information speed processing. These findings support the notion that intellectual reserve may protect some aspects of cognitive function in patients with MS.

Cognitive processess and cognitive reserve in multiple sclerosis

Multiple Sclerosis (MS) is characterized by motor, cognitive, and neuropsychiatric symptoms, which can occur independently. While MS is traditionally considered an inflammatory disease of the white matter, degeneration of gray matter is increasingly recognized as an important contributor to the progressive cognitive decline. A protective factor against the progression of cognitive dysfunction in MS could be the cognitive reserve, defined as resistance to brain dysfunction. Aim of the present study is to evaluate the role of cognitive reserve for different aspects of cognitive dysfunction of patients with MS. We found that patients with MS and lower cognitive reserve have poorer neuropsychological performance and slower information speed processing. These findings support the notion that intellectual reserve may protect some aspects of cognitive function in patients with MS.

Cognitive Reserve in Multiple Sclerosis Modulates Hippocampal Functional Connectivity and Protects from Memory Deficits (P6.124)

Cognitive Reserve in Multiple Sclerosis Modulates Hippocampal Functional Connectivity and Protects from Memory Deficits (P6.124)

Brain reserve and cognitive reserve in multiple sclerosis: What you’ve got and how you use it

In the article “Brain reserve and cognitive reserve in multiple sclerosis: What you’ve got and how you use it” by J.F. Sumowski et al. ( Neurology ® 2013;80:2186–2193), there is an error in figures 1 and 2 where the lines are switched. The corrected figures are below. The editorial staff regrets the error.

Cognitive reserve in multiple sclerosis

Cognitive impairment is common among persons with multiple sclerosis (MS), but some patients are able to withstand considerable disease burden (e.g. white matter lesions, cerebral atrophy) without cognitive impairment (cognitive inefficiency, memory decline). What protects these patients from cognitive impairment? We review the literature on cognitive reserve in MS, which shows that heritable (larger maximal lifetime brain growth) and environmental (greater intellectual enrichment) factors attenuate the negative effect of disease burden on cognitive status. That is, persons with larger maximal lifetime brain growth, greater vocabulary knowledge, and/or greater early life participation in cognitive leisure activities (e.g. reading, hobbies) are better able to cope with MS disease without cognitive impairment. We review evidence that benefits of intellectual enrichment on cognitive status may stem from more efficient patterns of brain function. We discuss clinical implications and highlight important unanswered questions for future research on reserve against cognitive impairment in MS.

Brain reserve and cognitive reserve in multiple sclerosis

We first tested the brain reserve (BR) hypothesis in multiple sclerosis (MS) by examining whether larger maximal lifetime brain volume (MLBV; determined by genetics) protects against disease-related cognitive impairment, and then investigated whether cognitive reserve (CR) gained through life experience (intellectually enriching leisure activities) protects against cognitive decline independently of MLBV (BR). Sixty-two patients with MS (41 relapsing-remitting MS, 21 secondary progressive MS) received MRIs to estimate BR (MLBV, estimated with intracranial volume [ICV]) and disease burden (T2 lesion load; atrophy of gray matter, white matter, thalamus, and hippocampus). Early-life cognitive leisure was measured as a source of CR. We assessed cognitive status with tasks of cognitive efficiency and memory. Hierarchical regressions were used to investigate whether higher BR (ICV) protects against cognitive impairment, and whether higher CR (leisure) independently protects against cognitive impairment over and above BR. Cognitive status was positively associated with ICV (R(2) = 0.066, p = 0.017). An ICV × disease burden interaction (R(2) = 0.050, p = 0.030) revealed that larger ICV attenuated the impact of disease burden on cognition. Controlling for BR, higher education (R(2) = 0.047, p = 0.030) and leisure (R(2) = 0.090, p = 0.001) predicted better cognition. A leisure × disease burden interaction (R(2) = 0.037, p = 0.030) showed that leisure independently attenuated the impact of disease burden on cognition. Follow-up analyses revealed that BR protected against cognitive inefficiency, not memory deficits, whereas CR was more protective against memory deficits than cognitive inefficiency. We provide evidence of BR in MS, and show that CR independently protects against disease-related cognitive decline over and above BR. Lifestyle choices protect against cognitive impairment independently of genetic factors outside of one's control.

Evidence for Brain Reserve and Cognitive Reserve in Multiple Sclerosis: Lifetime Maximal Brain Growth and Early Life Cognitive Leisure Independently but Differentially Protect Against Disease-Related Cognitive Decline (P04.109)

Evidence for Brain Reserve and Cognitive Reserve in Multiple Sclerosis: Lifetime Maximal Brain Growth and Early Life Cognitive Leisure Independently but Differentially Protect Against Disease-Related Cognitive Decline (P04.109)

Occupational Attainment as a Marker of Cognitive Reserve in Multiple Sclerosis

Cognitive dysfunction affects half of MS patients. Although brain atrophy generally yields the most robust MRI correlations with cognition, significant variance in cognition between individual MS patients remains unexplained. Recently, markers of cognitive reserve such as premorbid intelligence have emerged as important predictors of neuropsychological performance in MS. In the present study, we aimed to extend the cognitive reserve construct by examining the potential contribution of occupational attainment to cognitive decline in MS patients. Brain atrophy, estimated premorbid IQ, and occupational attainment were assessed in 72 MS patients. The Minimal Assessment of Cognitive Functioning in MS was used to evaluate indices of information processing speed, memory, and executive function. Results showed that occupational attainment was a significant predictor of information processing speed, memory, and executive function in hierarchical linear regressions after accounting for brain atrophy and premorbid IQ. These data suggest that MS patients with low occupational attainment fare worse cognitively than those with high occupational attainment after controlling for brain atrophy and premorbid IQ. Occupation, like premorbid IQ, therefore may make an independent contribution to cognitive outcome in MS. Information regarding an individual's occupation is easily acquired and may serve as a useful proxy for cognitive reserve in clinical settings.

Premorbid cognitive leisure independently contributes to cognitive reserve in multiple sclerosis

Consistent with the cognitive reserve hypothesis, higher education and vocabulary help persons with Alzheimer disease (AD) and multiple sclerosis (MS) better withstand neuropathology before developing cognitive impairment. Also, premorbid cognitive leisure (e.g., reading, hobbies) is an independent source of cognitive reserve for elders with AD, but there is no research on the contribution of leisure activity to cognition in MS. We investigated whether premorbid cognitive leisure protects patients with MS from cognitive impairment. Premorbid cognitive leisure was surveyed in 36 patients with MS. Neurologic disease severity was estimated with brain atrophy, measured as third ventricle width on high-resolution MRI. Cognitive status was measured with a composite score of processing speed and memory. Controlling for brain atrophy, premorbid cognitive leisure was positively associated with current cognitive status (r(p) = 0.49, p < 0.01), even when controlling for vocabulary (r(p) = 0.39, p < 0.05) and education (r(p) = 0.47, p < 0.01). Also, premorbid cognitive leisure was unrelated to brain atrophy (r = 0.03, p > 0.5), but a positive partial correlation between leisure and atrophy emerged when controlling for cognitive status (r(p) = 0.37, p < 0.05), which remained when also controlling for vocabulary (r(p) = 0.34, p < 0.05) and education (r(p) = 0.35, p < 0.05). Premorbid cognitive leisure contributes to cognitive status in patients with MS independently of vocabulary and education. Also, patients with MS who engaged in more cognitive leisure were able to withstand more severe brain atrophy at a given cognitive status. Premorbid cognitive leisure is supported as an independent source of cognitive reserve in patients with MS.