The relation between cognitive functioning and activities of daily living in normal aging, mild cognitive impairment, and dementia: a meta-analysis.

Literature suggests that dementia and, more generally, cognitive impairment affect the capacity to carry out activities of daily living (ADL) in aging. However, it is important to decipher the weight of specific cognitive domains and neurodegenerative profiles mainly related to ADL difficulties. A meta-analysis was conducted to investigate the nature and strength of the association between cognitive functioning and ADL in healthy older adults, mild cognitive impairment (MCI), and dementia. A comprehensive search of the PubMed, PsycINFO (PROQUEST), and Scopus databases for cross-sectional or longitudinal studies up until December 2022. Our meta-analytic results revealed that: overall, instrumental ADL (IADL) showed a significant association with executive functioning, in particular, abstraction ability/concept formation, set-shifting, and processing speed/complex attention/working memory, regardless of type of participants (i.e., healthy older adults, MCI, and dementia); whereas ADL (both basic ADL, BADL, and IADL) significantly correlated with global cognitive functioning and long-term verbal memory, with a moderator effect of clinical condition (e.g., increasing ES based on the level of cognitive impairment). Moreover, visuospatial and language abilities significantly correlated with ADL, mainly when performance-based tasks were used for ADL assessment. These findings emphasize the importance of neuropsychological assessment in aging to early identify people most at risk of functional decline and shed light on the need to consider specific cognitive abilities in rehabilitation programs.

The Cognitive Profile of Atypical Parkinsonism: A Meta-Analysis.

Atypical Parkinsonism (AP) syndromes are characterized by a wide spectrum of non-motor symptoms including prominent attentional and executive deficits. However, the cognitive profile of AP and its differences and similarities with that of Parkinson's Disease (PD) are still a matter of debate. The present meta-analysis aimed at identifying patterns of cognitive impairment in AP by comparing global cognitive functioning, memory, executive functions, visuospatial abilities, language, non-verbal reasoning, and processing speed test performances of patients with AP relative to healthy controls and patients with PD. All investigated cognitive domains showed a substantial impairment in patients with AP compared to healthy controls. When AP syndromes were considered separately, their cognitive functioning was distributed along a continuum from Multiple Systemic Atrophy at one extreme, with the least impaired cognitive profile (similar to that observed in PD) to Progressive Supranuclear Palsy, with the greatest decline in global cognitive and executive functioning (similar to Corticobasal Syndrome). These findings indicate that widespread cognitive impairment could represent an important clinical indicator to distinguish AP from other movement disorders.

Comparing face-to-face and videoconference assessment of the Brief Repeatable Battery of Neuropsychological Tests in people with multiple sclerosis.

BACKGROUND: The COVID-19 pandemic has underlined the need to evaluate cognitive profile via videoconferencing (teleneuropsychology, TeleNP) as a suitable alternative to face-to-face assessment (F-F). OBJECTIVE: To evaluate the feasibility and the reliability of Rao's Brief Repeatable Battery of Neuropsychological Tests (R-BRB) remote administration in people with multiple sclerosis (PwMS). METHODS: Sixty PwMS underwent R-BRB in two conditions: F-F and TeleNP, 1 month apart. RESULTS: Cognitive test performance was similar, regardless of the administration type, but visuospatial test performance was better in F-F. CONCLUSION: These data suggest that TeleNP is feasible and highly reliable in MS clinical practice.

Body Representation Alterations in Patients with Unilateral Brain Damage.

OBJECTIVE: Systematic studies about the impact of unilateral brain damage on the different body representations (body schema, body structural representation, and body semantics) are still rare. Aim of this study was to evaluate body representation deficits in a relatively large sample of patients with unilateral brain damage and to investigate the impact of right or left brain damage on body representations (BRs), independently from deficits in other cognitive processes. METHOD: Sixty-four patients with unilateral stroke (22 with left brain damage, LBD; 31 with right brain damage without neglect, RBD-N; 11 with right brain damage with neglect, RBD+N) and 41 healthy individuals underwent a specific battery including BR as well as control tasks. RESULTS: In more than a third of the sample, selective (37.5%) and pure (31%) deficits of BR were presented and equally distributed among the different BRs (˜10% for each representation), with selective (27.2%) and pure (22.7%) body schema deficit mainly presented after left brain damage. As a group, patients with unilateral brain damage, independently of the side of lesion (LBD, RBD-N, RBD+N), had significantly worse performance on body structural representation with respect to healthy individuals, whereas LBD had numerically worse performance on body schema with respect to healthy individuals and RBD-N. No significant differences among groups were found on body semantics. CONCLUSION: BR deficits are not a rare consequence of unilateral brain damage and are independent of a more general cognitive dysfunction. Accordingly, the need for an accurate assessment and specific neuropsychological training in clinical settings is discussed.

The Neural Bases of Drawing. A Meta-analysis and a Systematic Literature Review of Neurofunctional Studies in Healthy Individuals.

Drawing is a multi-component process requiring a wide range of cognitive abilities. Several studies on patients with focal brain lesions and functional neuroimaging studies on healthy individuals demonstrated that drawing is associated with a wide brain network. However, the neural structures specifically related to drawing remain to be better comprehended. We conducted a systematic review complemented by a meta-analytic approach to identify the core neural underpinnings related to drawing in healthy individuals. In analysing the selected studies, we took into account the type of the control task employed (i.e. motor or non-motor) and the type of drawn stimulus (i.e. geometric, figurative, or nonsense). The results showed that a fronto-parietal network, particularly on the left side of the brain, was involved in drawing when compared with other motor activities. Drawing figurative images additionally activated the inferior frontal gyrus and the inferior temporal cortex, brain areas involved in selection of semantic features of objects and in visual semantic processing. Moreover, copying more than drawing from memory was associated with the activation of extrastriate cortex (BA 18, 19). The activation likelihood estimation coordinate-based meta-analysis revealed a core neural network specifically associated with drawing which included the premotor area (BA 6) and the inferior parietal lobe (BA 40) bilaterally, and the left precuneus (BA 7).These results showed that a fronto-parietal network is specifically involved in drawing and suggested that a crucial role is played by the (left) inferior parietal lobe, consistent with classical literature on constructional apraxia.

Subjective cognitive failures and their psychological correlates in a large Italian sample during quarantine/self-isolation for COVID-19.

OBJECTIVE: The quarantine/self-isolation measures implemented to retard the spread of the 2019 coronavirus disease (COVID-19) may negatively affect the mental health of the population. The present study aimed to explore the impact of the psychological symptoms on the occurrence of cognitive failures in a large sample of home-dwelling Italian individuals during quarantine/self-isolation for COVID-19. METHODS: We employed an online questionnaire using a virtual platform of Google Moduli. The questionnaire included an assessment of cognitive failures evaluated by the Perceived Memory and Attentional Failures Questionnaire (PerMAFaQ) and of resilience, coping style, depression, anger, and anxiety. RESULTS: The online questionnaire was completed by 4175 participants revealing that about 30% of participants complained of cognitive failures at least sometimes during quarantine/self-isolation, whereas some respondents reported very frequent cognitive failures. Moreover, resilience was found to mediate the relationships between depressive and anger symptoms and cognitive failures. Although no difference was found on PerMAFaQ among smart-workers, non-smart-workers, and those currently not at work, people not working at the moment complained of more frequent cognitive failures. CONCLUSIONS: These findings indicate the need to implement psychological support intervention, particularly for vulnerable groups, to reduce anxiety, depression, and anger, and of psychoeducational interventions to enhance resilience reducing possible long-term cognitive consequences of the quarantine.

Vitamin D as a possible biomarker of mild cognitive impairment in parkinsonians.

INTRODUCTION: Mild Cognitive Impairment in Parkinson's Disease (PD-MCI) is a transitional state between normal cognition and dementia. Cross-sectional studies revealed that low Vitamin D levels were associated with worse performance on cognitive tests in Parkinson's Disease. The present longitudinal study aimed to examine the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels at baseline and possible development of PD-MCI at 24 and 48 months. MATERIALS AND METHODS: Sixty untreated, de novo PD patients underwent clinical and cognitive evaluations and measurement of serum 25(OH)D at baseline assessment (T0). After 24 (T1) and 48 months (T2), cognitive status (presence or absence of PD-MCI) of PD patients were re-evaluated. RESULTS: Vitamin D insufficiency occurred in 93.3% at T0. At T1, significant differences among patients with PD-MCI at both baseline and follow-up, patients with PD-MCI at follow-up and patients who never developed PD-MCI were found on age, age at onset of PD, and education; no significant difference was found on vitamin D levels at T0. A binary logistic regression analysis showed that a lower level of 25(OH)D at T0 (B= -0.158, Wald= 5.280, p = 0.022, Exp (B)=0.854; CI 95%: 0.746-0.977) and lower education (B= -0.214, Wald= 3.859, p = 0.049, Exp (B)=0.807; CI 95%: 0652-1.000) were predictors of PD-MCI occurrence at T2. DISCUSSION: Our results demonstrated that a lower level of 25(OH)D is conceivable as a biomarker of development of PD-MCI throughout the disease. Early diagnosis of Vitamin D insufficiency and its management might be useful to prevent cognitive decline in PD patients.

Apathy as a herald of cognitive changes in multiple sclerosis: A 2-year follow-up study.

BACKGROUND: Behavioral symptoms, such as apathy and depression, are common in multiple sclerosis (MS) but their relationship with cognitive and clinical characteristics often remains underinvestigated and not monitored over time. OBJECTIVE: The aim of this study was to assess the evolution of cognitive profile of patients affected by MS in relation to apathy and depression using a 2-year follow-up study. METHODS: Two years after the first assessment, 100 of 125 MS patients were re-evaluated on a comprehensive neuropsychological battery, and on specific scales for assessment of apathy (Apathy Evaluation Scale-Self-reported) and depression (Hamilton Depression Rating Scale). RESULTS: After 2 years (T1), we found a relatively consistent prevalence of apathy (about 40%) and a reduction in prevalence of depression (from 44% to 30%). Higher level of apathy at baseline predicted the progressive cognitive changes at follow-up; and patients with apathy without depression ("pure" apathy) than patients without apathy had poorer performance on the interference task of the Stroop test assessing inhibitory control. CONCLUSION: The present results suggested that apathy in MS was associated with more severe executive dysfunctions (in particular cognitive control). Apathy rather than depression predicted cognitive impairment in MS over time.

Interoceptive awareness in focal brain-damaged patients.

BACKGROUND: Interoception is the basic process enabling evaluation of one's own internal state of body, but its alteration in brain-damaged patients has not been adequately investigated. Our study aimed to investigate awareness of visceral and somatosensorial sensations in brain-damaged patients with unilateral stroke. METHODS: Sixty patients (22 with left brain damage, LP; 25 with right brain damage without neglect, RPN-; and 13 with right brain-damage and extrapersonal and/or personal neglect, RPN+) and 45 healthy controls (HC) completed the Self-Awareness Questionnaire (SAQ), a self-report tool for assessing interoceptive awareness with two domains related to visceral (VD) and somatosensory feelings (SD), respectively. RESULTS: Comparing the SAQ subdomains scores between three groups of patients (LP, RPN-, and RPN+) and HC, we found that RPN+ had significantly lower scores on VD than HC and LP, whereas no significant difference was found on scores of SD between groups. CONCLUSION: Our results support the hypothesis of a right-hemispheric dominance for "interoceptive neural network" suggesting that processing of visceral sensations would be located mainly in the right hemisphere. Therefore, a careful assessment of interoceptive awareness in clinical practice would be useful to improve rehabilitation and to engage patients with deficit of interoceptive awareness in developing greater accuracy of body signals.

Usefulness of nutraceuticals in migraine prophylaxis.

Several studies have supported the efficacy of complementary and alternative medicine approaches (physical, behavioral and nutraceutical therapies) in the treatment of headache disorders. Nutraceutical treatment consists of taking vitamins, supplements (magnesium, riboflavin, coenzyme Q10, and alpha lipoic acid) and herbal preparations (feverfew and butterbur), and its usage is frequently determined by dissatisfaction with conventional medical therapies. There is a growing body of research on nutraceutical use for migraine prophylaxis. This brief overview provides information about the potential efficacy and side effects of various nutraceutical products summarizing randomized controlled trials of some of the most commonly used non-pharmacological treatments for the prophylaxis and treatment of migraine, including magnesium, coenzyme Q10, riboflavin (vitamin B2), petasites, and feverfew.

Assessment of apathy independent of physical disability: validation of the Dimensional Apathy Scale in Italian healthy sample.

Apathy is well described in neurodegenerative diseases characterized by motor disability; therefore, assessment of apathy avoiding possible confounding effects of motor impairments is necessary in neurological diseases. Recently, the Dimensional Apathy Scale (DAS) was developed to assess apathy as multifaceted construct, independent of physical disability. We developed the Italian version of the Dimensional Apathy Scale (I-DAS) and explored its psychometric properties in a sample of 309 healthy individuals. Participants also completed Apathy Evaluation Scale, Beck Depression Inventory-II and Addenbrooke's Cognitive Examination-Revised. The I-DAS showed high internal consistency, good convergent and divergent validity. The I-DAS had a three-factor structure, such as the original scale. The I-DAS scored was significantly correlated with individuals' education, but not with age or gender. We, therefore, computed correction factor for education and provided percentile distribution of the adjusted scores to identify individuals with high levels of apathy. The I-DAS showed good psychometric properties and can be a valid and reliable tool to assess multidimensional apathy.

The Addenbrooke's Cognitive Examination Revised (ACE-R) and its sub-scores: normative values in an Italian population sample.

The Addenbrooke's Cognitive Examination Revised (ACE-R) is a rapid screening battery, including five sub-scales to explore different cognitive domains: attention/orientation, memory, fluency, language and visuospatial. ACE-R is considered useful in discriminating cognitively normal subjects from patients with mild dementia. The aim of present study was to provide normative values for ACE-R total score and sub-scale scores in a large sample of Italian healthy subjects. Five hundred twenty-six Italian healthy subjects (282 women and 246 men) of different ages (age range 20-93 years) and educational level (from primary school to university) underwent ACE-R and Montreal Cognitive Assessment (MoCA). Multiple linear regression analysis revealed that age and education significantly influenced performance on ACE-R total score and sub-scale scores. A significant effect of gender was found only in sub-scale attention/orientation. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-offs score were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a good significant correlation between ACE-R adjusted scores with MoCA adjusted scores (r = 0.612, p < 0.001). The present study provided normative data for the ACE-R in an Italian population useful for both clinical and research purposes.

Psychometric properties of the Hamilton Depression Rating Scale in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is frequently associated with depressive symptoms and major depression. OBJECTIVE: We assessed psychometric properties of the Hamilton Depression Rating Scale (HDRS, 17-item version) for assessing depressive symptomatology in a sample of MS patients. METHODS: Seventy patients (aged 43.3 ± 10.3 years) completed the HDRS and a thorough clinical and neuropsychological assessment, including diagnosis of major depression according to the established clinical criteria. RESULTS: HDRS was easy to administer and acceptable, and showed fair internal consistency (Cronbach's alpha = 0.8). The HDRS showed good convergent validity with respect to neuropsychiatric inventory (NPI) subdomain of depression (r rho = .85) and good divergent validity with respect to remaining NPI subdomains (r rho < .30). Moreover, HDRS's total score correlated moderately with functional disability and apathetic symptomatology, and poorly with general cognitive status. Receiver operating characteristics curve analysis demonstrated that a cutoff >14.5 can identify clinically relevant depressive symptoms with good sensitivity (93 %) and specificity (97 %) with respect to the diagnosis of major depression. Such a cutoff identified clinically relevant depressive symptoms in 42 % of our MS sample, whereas 44.2 % patients met established clinical criteria for major depression. CONCLUSION: The HDRS can be considered as an easy, reliable, and valid tool to assess depressive symptomatology for clinical and research purposes in non-demented MS patients.

The multidimensional assessment of body representation and interoception in multiple sclerosis.

BACKGROUND: The mental representation of the body (or body representation, BR) derives from the processing of multiple sensory and motor inputs and plays a crucial role in guiding our actions and in how we perceive our body. Fundamental inputs for BR construction come also from the interoceptive systems which refer to the whole bidirectional processes between the brain and the body. People with Multiple sclerosis (MS) show an abnormal multisensory integration which may compromise BR and interoception integrity. However, no study has evaluated possible deficits on distinct and dissociable dimensions of body representation (i.e., action-oriented, aBR; and a nonaction-oriented body representation, NaBR) and interoception (i.e., interoceptive accuracy, interoceptive sensibility, and interoceptive awareness) in MS. OBJECTIVE: In the present study, we aimed to determine whether participants with MS present changes in BR and interoceptive dimensions. METHODS: We performed comparison analyses on tasks and questionnaires tapping all BR and interoceptive dimensions between 36 people with relapsing-remitting MS (RRMS) and 42 healthy controls, and between 23 people with progressive MS (PMS) and 33 healthy controls. RESULTS: Overall, patients with MS exhibited lower interoceptive accuracy than matched controls. The RRMS group also showed higher visceral interoceptive sensibility levels. No differences were found in BR accuracy measures, but the PMS reported longer response times when performing the aBR task. CONCLUSION: These findings open a new issue on the role of inner-signal monitoring in the body symptomatology of MS and highlight the need for an accurate BR and interoceptive assessment in a clinical setting.

Distinct Neuropsychological Correlates of Apathy Sub-Domains in Multiple Sclerosis.

BACKGROUND: Apathy is relatively frequent and significantly associated with clinical and cognitive outcomes in Multiple Sclerosis (MS), even if previous research has produced mixed results. This varied picture could be due to most studies treating apathy as a unitary construct, despite the evidence showing that apathy is a multifaceted syndrome including three different sub-domains (i.e., cognitive, affective, and behavioral). This study aims to investigate the neuropsychological correlates of apathy fractionated into its three sub-domains in participants with MS. METHODS: Eighty-five participants with MS underwent a comprehensive neuropsychological battery. The severity of apathy symptoms was assessed by the self-report version of the Apathy Evaluation Scale. RESULTS: Correlational analysis showed that cognitive apathy sub-domain scores had a high correlation with the performances obtained at cognitive tests tapping into inhibitory control (i.e., IML and Strop test-interference task), whereas the affective apathy sub-domain scores had a high correlation with the performances obtained at cognitive test tapping into the use of executive functions in visuospatial abilities (i.e., Clock Drawing Test). Moreover, linear regression analysis results showed that the cognitive apathy sub-domain scores predicted executive functioning domain scores and that the cognitive and affective apathy sub-domains scores predicted visuospatial abilities domain scores. CONCLUSION: These results confirm that apathy is a multidimensional concept with important neuropsychological correlates, visible only when it is fractionated into its sub-domains.

Combining the Inner Self with the Map of the Body: Evidence for White Matter Contribution to the Relation Between Interoceptive Sensibility and Nonaction-oriented Body Representation.

Very recent studies on healthy individuals suggest that changes in the sensibility toward internal bodily sensations across the lifespan affect the ability to mentally represent one's body, in terms of action-oriented and nonaction-oriented body representation (BR). Little is known about the neural correlates of this relation. Here we fill this gap using the neuropsychological model provided by focal brain damage. Sixty-five patients with unilateral stroke (20 with left and 45 with right brain damage, LBD and RBD, respectively) participated in this study. Both action-oriented BR and nonaction-oriented BR were tested; interoceptive sensibility was assessed as well. First, we tested whether interoceptive sensibility predicted action-oriented BR and nonaction-oriented BR, in RBD and LBD separately. Then, a track-wise hodological lesion-deficit analysis was performed in a subsample of twenty-four patients to test the brain network supporting this relation. We found that interoceptive sensibility predicted the performances in the task tapping nonaction-oriented BR. The higher interoceptive sensibility was, the worse patients performed. This relation was associated with the disconnection probability of the corticospinal tract, the fronto-insular tract, and the pons. We expand over the previous findings on healthy individuals, supporting the idea that high levels of interoceptive sensibility negatively affect BR. Specific frontal projections and frontal u-shaped tracts may play a pivotal role in such an effect, likely affecting the development of a first-order representation of the self within the brainstem autoregulatory centers and posterior insula and of a second-order representation of the self within the anterior insula and higher-order prefrontal areas.

Neural substrates of interoceptive sensibility: An integrated study in normal and pathological functioning.

In early studies interoception strictly referred to the awareness of visceral sensations, but recent theories have expanded this concept to denote the ongoing status of the body, including somatosensory feelings. Here, we integrated data from normal and pathological functioning to disclose neural underpinnings of interoceptive sensibility, taking into account the crucial distinction between visceral and somatosensory feelings. Twenty-seven healthy young individuals underwent structural MRI (including T1w images and DTI). Voxel-wise analyses of the gyrification index (GI) and fractional anisotropy (FA) data were performed to assess the relation between interoceptive sensibility and surface morphometry and anatomical connectivity. Thirty-three unilateral brain-damaged patients took part in this study for Voxel-Based Lesion-Symptom Mapping (VLSM) and track-wise hodological lesion-deficit analysis (TWH). All participants completed the Self-Awareness Questionnaire (SAQ), a self-report tool assessing interoceptive sensibility of visceral (F1) and somatosensory feelings (F2). Tract-Based Spatial Statistics showed that F2 was positively associated with FA in the bilateral anterior thalamic radiation, corticospinal tract, cingulum, forceps, inferior longitudinal, fronto-occipital, superior longitudinal, and uncinate fasciculi; no significant association was detected for F1. However, F1 was positively associated with GI in the left anterior cingulate cortex. VLSM showed that F1 mainly relies on the right posterior insula, whereas F2 is related mostly to subcortical nuclei and surrounding white matter in the right hemisphere. Accordingly, patients with disconnection of the anterior thalamic projection, corticospinal tract, inferior fronto-occipital, inferior longitudinal, uncinate and superior longitudinal fasciculus III showed lower scores on F2. Overall, results support the dissociation between interoceptive sensibility of visceral and somatosensory feelings.

The bodily fundament of empathy: The role of action, nonaction-oriented, and interoceptive body representations.

Mental representations with bodily contents or in various bodily formats have been suggested to play a pivotal role in social cognition, including empathy. However, there is a lack of systematic studies investigating, in the same sample of participants and using an individual differences approach, whether and to what extent the sensorimotor, perceptual, and interoceptive representations of the body could fulfill an explanatory role in the empathic abilities.To address this goal, we carried out two studies in which healthy adults were given measures of interoceptive sensibility (IS), action (aBR), and nonaction-oriented body representations (NaBR), and affective, cognitive, and motor empathy. A higher tendency to be self-focused on interoceptive signals predicted higher affective, cognitive, and motor empathy levels. A better performance in tasks probing aBR and NaBR predicted, respectively, higher motor and cognitive empathy levels.These findings support the view that the various facets of the empathic response are differently grounded in the body since they diversely involve representations with a different bodily format.Individual differences in the focus on one's internal body state representation can directly modulate all the components of the empathic experience. Instead, a body representation used interpersonally to represent both one's own body and others' bodies, in particular in its spatial specificity, could be necessary to accurately understand other people's minds (cognitive empathy), while a sensorimotor body representation used to represent both one's own body and others' bodies actions, could be fundamental for the self-awareness of feelings expressed in actions (motor empathy).

Sensitivity of conventional cognitive tests in multiple sclerosis: Application of item response theory.

BACKGROUND: Cognitive impairment (CI) is common in Multiple Sclerosis (MS), and its prevalence rate ranges between 22% and 70%. Because CI significantly impacts vocational status, caregiver burden, and quality of life, an accurate neuropsychological assessment is required. Three widely used and validated batteries for MS-associated CI are the Brief Repeatable Neuropsychological Battery (BRN-B), the Minimal Assessment of Cognitive Function (MACFIMS), and the Brief International Cognitive Assessment (BICAMS). Although similar, these batteries differ in time-consuming and in specific tests employed. This study aims to assess the sensitivity of cognitive tests included in these batteries through an Item Response Theory approach. METHODS: Ninety-seven patients with MS and 91 demographically matched controls (HC) were consecutively assessed using the three neuropsychological batteries (i.e., BRN-B, MACFIMS, and BICAMS). Continuous Response Model (CRM) was used to identify the cognitive test(s) that best discriminate patients with MS from HC. Receiver Operating Characteristic (ROC) curve analysis was used to determine the accuracy of the CRM results. RESULTS: Cognitive tests loaded on two different latent variables: the 'higher-order executive functioning,' consisting of tests assessing concept formation, problem-solving, and inhibitory control, and the 'memory and information processing speed,' comprising tests assessing long-term, working memory, and information processing speed. The Delis Kaplan Executive Functioning System-Sorting Test and the Stroop Test were the most sensitive tests in differentiating cognitive functioning between MS and HC. CONCLUSIONS: This study confirms the importance of including a more extensive executive assessment in MS clinical practice since higher-order executive functions (e.g., abstraction and inhibitory control) significantly impact patients' quality of life and functional autonomy. Clinical implications of careful dissection of executive functioning in MS neuropsychological assessment are discussed.