Cognitive mediated eye movements during the SDMT reveal the challenges with processing speed faced by people with MS.

BACKGROUND: The Symbol Digit Modalities Test (SDMT) is regarded as the cognitive test of choice for people with MS (pwMS). While deficits are linked to impaired processing speed, the mechanisms by which they arise are unclear. Cognitive-mediated eye movements offer one putative explanation. The objective of this study was to determine the association between eye movements and performance on the SDMT. METHODS: Thirty-three people with confirmed MS and 25 matched healthy control subjects (HC) were administered the oral SDMT while eye movements were recorded. RESULTS: Mean SDMT scores were significantly lower in pwMS (p < 0.038). Shorter mean saccade distance in the key area (p = 0.007), more visits to the key area per response (p = 0.014), and more total number of fixations in the test area (p = 0.045) differentiated pwMS from HCs. A hierarchical regression analysis revealed that the number of visits to the key area per response (p < 0.001; ΔR2 = 0.549) and total number of fixations in the test area (p < 0.001; ΔR2 = 0.782) were the most robust predictors of SDMT scores. CONCLUSION: Cognitive-mediated eye movements help elucidate the processing speed challenges confronted by people with MS. Mechanistic insights such as these can potentially help inform new cognitive rehabilitation strategies.

Why Sex Matters: A Cognitive Study of People With Multiple Sclerosis.

BACKGROUND: Cognitive dysfunction affects 40% to 70% of people with multiple sclerosis (MS). Sex may influence a person's cognition. Although a few studies have reported greater cognitive deficits in men than women, it is unclear whether specific cognitive domains are more vulnerable than others to the effects of sex or whether cognition is influenced by neurologic or psychiatric variables. METHODS: A chart review was undertaken of 408 people with MS referred to neuropsychological services. Demographic and MS-related variables were extracted from the patients' records. We used the Minimal Assessment of Cognitive Functioning in Multiple Sclerosis for the neuropsychological assessment. Raw test scores were converted to z scores using Canadian regression-based normative means. A general linear model was conducted on the adjusted scores, controlling for age; years of education; disease course; illness duration; and disability, anxiety, and depression scores. RESULTS: Men were more likely than women to have primary progressive MS (χ=6.415, P=0.011). There were no other sex differences with respect to demographic, neurologic, or psychiatric data. Women performed significantly better than men on the California Verbal Learning Test-Second Edition Total Learning index (F=7.846, P=0.006). CONCLUSIONS: An analysis of a large, consecutive sample of people with MS demonstrated that sex, independent of demographic, neurologic, or psychiatric factors, is an important determinant in cognitive impairment, with men being more impaired than women on tests of verbal learning and memory.

The link between depression and performance on the Symbol Digit Modalities Test: Mechanisms and clinical significance.

OBJECTIVE: To determine the mechanism and clinical significance of depression-related differences in performance on the Symbol Digit Modalities Test (SDMT). METHODS: The influence of depression on two versions of a computerized SDMT (i.e. fixed versus variable code) was assessed. Both versions involve processing speed, but the fixed c-SDMT also encompasses incidental visual memory. RESULTS: Depression was associated with a 19.06% slowing on the variable ( p = 0.002) and an 8.10% slowing on the fixed ( p = 0.219) c-SDMT. CONCLUSION: Depression-associated differences in performance on the SDMT appear linked more to a reduction in processing speed than a decline in incidental visual memory and exceed the 10% threshold considered clinically significant.

Revisiting cognitive reserve and cognition in multiple sclerosis: A closer look at depression.

BACKGROUND: The protective effect of cognitive reserve (CR) on cognition in people with multiple sclerosis (PwMS) has been well described. OBJECTIVE: To explore the relationship between aspects of CR, namely, leisure pursuits and depression. METHODS: In a cross-sectional study, a sample of 155 PwMS and 115 healthy controls (HC) underwent cognitive testing with the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. Leisure activity was retrospectively recorded using the Leisure Activity Scale (LAS). Depression was assessed using the Hospital Anxiety and Depression Scale. RESULTS: PwMS demonstrated greater decreases in leisure activity over time compared to the HC group, particularly in the past year ( p < 0.001). Here, depression accounted for 17% of the variance in determining the level of leisure activity ( p < 0.001). Premorbid IQ and leisure activity within the past year emerged as significant predictors of information processing speed, learning, memory and executive function. After controlling for depression, the influence of leisure activity on cognition was insignificant. CONCLUSION: Depression can cause significant changes in behaviour which can influence indices of CR, such as leisure pursuits. Successfully treating depression may lead to a more active lifestyle thereby offsetting in part the cognitive burden of disease.

Comparison of Two Versions of the Hospital Anxiety and Depression Scale in Assessing Depression in a Neurologic Setting.

BACKGROUND: The Hospital Anxiety and Depression Scale-Depression Subscale (HADS-D) is widely used to assess depression in people with multiple sclerosis (MS). Developed specifically for use in a medical setting, the scale has one item, "I feel as if I am slowed down," that might represent a significant somatic confounder, possibly biasing the assessment. OBJECTIVE: We sought to determine whether inclusion or exclusion of the "slowed down" item in the HADS-D affects the detection of depression and the scale's associations with impaired cognition, fatigue, and employment status. METHODS: A sample of 193 people with confirmed MS completed the HADS. To identify depressed participants, we used previously established cutoff scores for the HADS-D with (≥8) and without (≥6) the "slowed down" item. Linear and logistic regression models were used to determine predictors of cognition and employment status. RESULTS: The HADS-D with and without the "slowed down" item detected similar rates of depression: 30.6% and 31.6%, respectively. Both versions of the HADS-D predicted processing speed and executive functioning, but not memory. Neither version predicted employment status. CONCLUSIONS: The HADS-D is an easy-to-use and clinically relevant self-report psychometric scale for detecting depression in MS. Removing the "slowed down" item from the HADS-D does not influence its internal consistency, and both versions have similar associations with clinical outcomes.

Deconstructing the symbol digit modalities test in multiple sclerosis: The role of memory.

BACKGROUND: The Symbol Digit Modalities Test (SDMT) is a sensitive measure of impaired cognition in people with MS. While the SDMT is primarily considered a test of information processing speed, other components such as visual scanning and oral-motor ability have also been linked to performance. The objective of this study was to determine the role of memory in the performance of the SDMT. METHODS: Two version of a modified computerized SDMT (c-SDMT) were employed, a fixed and a variable. For each group 50 MS and 33 healthy control (HC) participants were recruited. In the fixed c-SDMT, the symbol-digit code is kept constant for the entire test whereas in the variable version, it changes eight times. Unlike the traditional SDMT which records the correct number of responses, the c-SDMT presented here measures the mean response time (in seconds) for the eight trials. RESULTS: MS participants were slower than HC on the fixed (p < 0.001) and variable (p = 0.005) c-SDMT. Trend analysis showed performance improvement on the fixed, but not on the variable c-SDMT in both MS and HC groups. Furthermore, immediate visual memory recall was associated with the fixed (ß = -0.299, p = 0.017), but not variable (B = -0.057, p = 0.260) c-SDMT. Immediate verbal memory was not associated with either versions of the c-SDMT. CONCLUSIONS: Given that the fixed and variable c-SDMTs are identical in every way apart from the fixity of the code, the ability of participants to speed up responses over the course of the fixed version only points to the contribution of incidental visual memory in test performance.

Cannabis and cognitive functioning in multiple sclerosis: The role of gender.

BACKGROUND: Cognitive function in people with multiple sclerosis (PwMS) is associated with gender differences and the use of smoked/ingested cannabis. OBJECTIVE: The objective of this report is to explore a possible gender-cannabis interaction associated with cognitive dysfunction in PwMS. METHODS: A retrospective analysis was undertaken of cognitive data collected from 140 PwMS. A general linear model was conducted to determine gender and cannabis effects on processing speed (SDMT), verbal (CVLT-II) and visual (BVMT-R) memory, and executive functions (D-KEFS), while controlling for age and years of education. RESULTS: Cannabis was smoked at least once a month by 33 (23.6%) participants. Cannabis users were more impaired on the SDMT (p = 0.044). Men, who comprised 30.7% of the entire sample and 42.2% of cannabis users, were more impaired on the CVLT-II (total learning, p = 0.001; delayed recall, p = 0.004). A cannabis-gender interaction was found with the CVLT-II delayed recall (p = 0.049) and BVMT-R total learning (p = 0.014), where male cannabis users performed more poorly than female. CONCLUSION: Males with MS may be particularly vulnerable to the cognitive side effects of smoked cannabis use.

Processing speed and distractibility in multiple sclerosis: the role of sleep.

BACKGROUND: The effects of sleep disturbances on cognitive performance under distraction in multiple sclerosis (MS) are not known. The objective of the present study was to explore the association between an index of sleep (i.e. daytime somnolence), distractibility and the hallmark cognitive deficit in people with MS (i.e. processing speed). METHODS: MS participants (n=102) were recruited from outpatient neurology clinics. All participants completed the traditional Symbol Digit Modalities Test (SDMT). In addition, half the sample (n=52) completed a computerized version with distracters (c-SDMT) and half (n=50) without distracters. Excessive daytime sleepiness was explored with the Epworth Sleepiness Scale. Mood, anxiety and fatigue were also assessed. A linear regression analyses was conducted to determine predictors of cognitive performance. RESULTS: Participants with excessive daytime sleepiness performed significantly slower on the distracter c-SDMT than those with normal sleepiness (p=0.01). No significant differences were found on the c-SDMT without distracters or the traditional SDMT. Depression and excessive daytime sleepiness predicted performance on the distracter c-SDMT, whereas only the former predicted performance on the traditional test. CONCLUSIONS: Excessive daytime sleepiness in people with MS adversely influences their processing speed in the presence of real-world distracters. This finding suggests that a more complete understanding of processing speed deficits in people with MS should entail a closer look at sleep and the relationship with distractibility.

Distraction adds to the cognitive burden in multiple sclerosis.

BACKGROUND: Cognitive dysfunction in multiple sclerosis (MS) causes numerous limitations in activities of daily living. OBJECTIVES: To develop an improved method of cognitive assessment in people with MS using novel real-world distracters. METHODS: A sample of 99 people with MS and 55 demographically matched healthy controls underwent testing with the Minimal Assessment of Cognitive Functioning in Multiple Sclerosis (MACFIMS) and a modified version of the computerized Symbol Digit Modalities Test (c-SDMT). Half of the subjects completed the c-SDMT with built-in real-world distracters and half without. RESULTS: The mean time on the c-SDMT was significantly greater in MS subjects than healthy controls for both distracter ( p = 0.001) and non-distracter ( p < 0.001) versions. Significantly more MS subjects were impaired on the c-SDMT with distracters than the traditional SDMT (47.1% vs 30.3%, p = 0.04). There were no differences in impairment between the c-SDMT with and without distracters (47.1% vs 37.5%, p = 0.34). The distracter version had a sensitivity of 81% and specificity of 88% in detecting global cognitive impairment. CONCLUSIONS: The incorporation of distracters improves the sensitivity of a validated computerized version of the SDMT relative to the non-distracter and traditional versions and offers a quick and easy means of detecting cognitive impairment in people with MS.

Distractibility in multiple sclerosis: The role of depression.

The present study assesses the influence of depression and anxiety on the effects of cognitive distracters in people with multiple sclerosis (MS). Participants completed computerized versions of the Symbol Digit Modalities Test (c-SDMT) with (n = 51) and without (n = 51) auditory distracters. Based on the Hospital Anxiety and Depression Scale (HADS), 29 (28.4%) and 51 (50%) participants were classified as depressed or anxious, respectively. A regression analysis revealed that depression (p = 0.034), not anxiety (p = 0.264), further impaired performance on the c-SDMT, particularly in the presence of distracters. These results suggest that distracter effects are influenced by depression more than anxiety. Given that distracters are ubiquitous in real-world environments, their use in a cognitive assessment adds to the ecological validity of the results.

The rationale and design of Insight into Nephrotic Syndrome: Investigating Genes, Health and Therapeutics (INSIGHT): a prospective cohort study of childhood nephrotic syndrome.

BACKGROUND: Nephrotic syndrome is one of the most commonly diagnosed kidney diseases in childhood and its progressive forms can lead to chronic kidney disease (CKD) and/or end-stage renal disease (ESRD). There have been few longitudinal studies among a multi-ethnic cohort to determine potential risk factors influencing disease susceptibility, treatment response, and progression of nephrotic syndrome. Temporal relationships cannot be studied through cross-sectional study design. Understanding the interaction between various factors is critical to developing new strategies for treating children with kidney disease. We present the rationale and the study design of a longitudinal cohort study of children with nephrotic syndrome, the Insight into Nephrotic Syndrome: Investigating Genes, Health and Therapeutics (INSIGHT) study. The specific aims are to determine: 1) socio-demographic, environmental, and genetic factors that influence disease susceptibility; 2) rates of steroid treatment resistance and steroid treatment dependence, and identify factors that may modify treatment response; 3) clinical and genetic factors that influence disease susceptibility and progression to CKD and ESRD; and 4) the interaction between the course of illness and socio-demographic, environmental, and clinical risk factors. METHODS/DESIGN: INSIGHT is a disease-based observational longitudinal cohort study of children with nephrotic syndrome. At baseline, participants complete questionnaires and provide biological specimen samples (blood, urine, and toenail clippings). Follow-up questionnaires and repeat biological specimen collections are performed annually for up to five years. DISCUSSION: The proposed cohort will provide the structure to test various risk factors predicting or influencing disease susceptibility, treatment response, and progression to CKD among children with nephrotic syndrome. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01605266.