Longitudinal Disability, Cognitive Impairment, and Mood Symptoms in Patients With Anti-NMDA Receptor Encephalitis.

BACKGROUND AND OBJECTIVES: Longitudinal outcomes in anti-NMDA receptor encephalitis (anti-NMDARe) are still not fully understood and may not be adequately captured with the modified Rankin Scale (mRS), often the sole reported outcome. We aim to characterize longitudinal outcomes in anti-NMDARe using multiple outcome measures. METHODS: This single-center, retrospective, observational study examined outcome measures (mRS and Clinical Assessment Scale in Autoimmune Encephalitis [CASE]) in adults with NMDA receptor-IgG in CSF at short- and long-term follow-ups using linear and logistic regression modeling. Patients with evaluations for cognitive impairment (Montreal Cognitive Assessment/Mini-Mental State Examination), depression (Patient Health Questionnaire-9), and anxiety (General Anxiety Disorder-7) >6 months from symptom onset were correlated with final CASE scores. RESULTS: Thirty-eight patients (76% female, median disease onset age = 28 years, range = 1-75 years) were included. The majority received first-line immunosuppressants (97%) at a median of 3.9 weeks (interquartile range [IQR] = 2.1-9.7) from symptom onset and 68% received second-line therapies. At baseline, median/mean mRS and CASE were 4 (IQR = 3-5) and 12.9 (SD = 7.2), respectively. At short-term follow-up (median = 10 weeks, IQR = 6-17), factors associated with higher CASE and mRS included dysautonomia, coma/lethargy, seizures/status epilepticus, and intensive care unit admission (p < 0.05). At long-term follow-up (median = 70 weeks, IQR = 51-174), median/mean mRS and CASE were 2 (IQR = 1-3) and 4.4 (SD = 4.2), respectively. Only weakness at symptom onset predicted higher mRS scores (odds ratio = 5.6, 95% confidence interval 1.02-30.9, p = 0.047). Despite both mRS and CASE improving from baseline (p < 0.001), only 9 patients (31%) returned to their premorbid function. Among patients with cognitive and mood evaluations >6 months from onset, moderate-severe cognitive impairment (42%), depression (28%), and anxiety (30%) were frequent. Cognitive and depression measures were associated with final CASE subscores (including memory, language, weakness, and psychiatric). DISCUSSION: Multiple clinical factors influenced short-term outcomes, but only onset weakness influenced long-term mRS, highlighting that mRS is predominantly affected by global motor function. Although mRS and CASE improved over time for most patients, these outcome measures did not capture the full extent of long-term functional impairment in terms of mood, cognition, and the ability to return to premorbid function. This emphasizes the need for increased utilization of more nuanced cognitive and mood outcome measures.

Cognitive outcomes in anti-LGI-1 encephalitis.

OBJECTIVE: Cognitive impairment is one of the most common symptoms of anti-leucine rich glioma inactivated 1 (anti-LGI-1) encephalitis, but little is known about the cognitive profile of these patients. This study characterized the cognitive profile of patients with anti-LGI-1 encephalitis and compared patterns of impairment to healthy controls and other patient groups with known temporal lobe/limbic involvement. METHODS: A retrospective analysis of adult patients with anti-LGI-1 encephalitis who underwent neuropsychological assessment was conducted. Performance patterns of anti-LGI-1 patients were compared to patients deemed cognitively healthy (HC), as well as patients with amnestic mild cognitive impairment (aMCI) and temporal lobe epilepsy (TLE). RESULTS: Among 10 anti-LGI encephalitis patients (60% male, median age 67.5 years) who underwent neuropsychological testing (median = 38.5 months from symptom onset), cognitive deficits were common, with 100% of patients showing impairment (≤1.5 SD below mean) on 1+ measures and 80% on 2+ measures. Patients with anti-LGI-1 encephalitis performed worse than controls on measures of basic attention, vigilance, psychomotor speed, complex figure copy, and aspects of learning/memory. Of measures which differed from controls, there were no differences between the anti-LGI-1 and TLE patients, while the anti-LGI-1 patients exhibited higher rates of impairment in basic attention and lower rates of delayed verbal memory impairment compared to the aMCI patients. CONCLUSIONS: Long-term cognitive deficits are common in patients with anti-LGI-1 encephalitis and involve multiple domains. Future research in larger samples is needed to confirm these findings.

Neurocognitive Effects of Obesity and Bariatric Surgery.

This review paper will discuss the recent literature examining the relationship between obesity and neurocognitive outcomes, with a particular focus on cognitive changes after bariatric surgery. Obesity is now recognized as an independent risk factor for adverse neurocognitive outcomes, and severely obese persons appear to be at even greater risk. Bariatric surgery is associated with rapid improvements in cognitive function that persist for at least several years, although the mechanisms underlying these improvements are incompletely understood. Assessment of cognitive impairment in bariatric surgery patients is challenging, and improved methods are needed, as poorer performance on neuropsychological tests of memory and executive function leads to poorer clinical weight outcomes. In addition to its clinical importance, further study in this area will provide key insight into obesity-related cognitive dysfunction and clarify the possibility of an obesity paradox for neurological outcomes.

Glucose regulation and cognitive function after bariatric surgery.

INTRODUCTION: Obesity is associated with cognitive impairment, and bariatric surgery has been shown to improve cognitive functioning. Rapid improvements in glycemic control are common after bariatric surgery and likely contribute to these cognitive gains. We examined whether improvements in glucose regulation are associated with better cognitive function following bariatric surgery. METHOD: A total of 85 adult bariatric surgery patients underwent computerized cognitive testing and fasting blood draw for glucose, insulin, and glycated hemoglobin (HbA1c) at baseline and 12 months postoperatively. RESULTS: Significant improvements in both cognitive function and glycemic control were observed among patients. After controlling for baseline factors, 12-month homeostatic model assessment of insulin resistance HOMA-IR predicted 12-month digits backward (ß = -.253, p < .05), switching of attention-A (ß = .156, p < .05), and switching of attention-B (ß = -.181, p < .05). Specifically, as HOMA-IR decreased over time, working memory, psychomotor speed, and cognitive flexibility improved. Decreases in HbA1c were not associated with postoperative cognitive improvements. After controlling for baseline cognitive test performance, changes in body mass index (BMI) were also not associated with 12-month cognitive function. CONCLUSIONS: Small effects of improved glycemic control on improved aspects of attention and executive function were observed following bariatric surgery among severely obese individuals. Future research is needed to identify the underlying mechanisms for the neurocognitive benefits of these procedures.

The role of cognitive function in postoperative weight loss outcomes: 36-month follow-up.

BACKGROUND: Cognitive dysfunction is associated with reduced postoperative weight loss up to 2 years following surgery, though the role of cognition at more extended follow-up is not yet understood. Thirty-six months following bariatric surgery, we retrospectively compared obese and non-obese patients on 12-week postoperative cognitive performance. We hypothesized that early postoperative cognitive dysfunction would predict higher body mass index (BMI) and lower percent weight loss (%WL) in the total sample at 36 month follow-up. MATERIALS AND METHODS: Fifty-five individuals undergoing bariatric surgery completed cognitive testing at preoperative baseline and serial postoperative timepoints, including 12 weeks and 36 months. Cognitive test scores were normed for demographic variables. Percent weight loss (%WL) and body mass index (BMI) were calculated at 36-month follow-up. RESULTS: Adjusting for gender, baseline cognitive function, and 12-week %WL, 12-week global cognitive test performance predicted 36 month postoperative %WL and BMI. Partial correlations revealed recognition memory, working memory, and generativity were most strongly related to weight loss. CONCLUSION: Cognitive function shortly after bariatric surgery is closely linked to extended postoperative weight loss at 36 months. Further work is necessary to clarify mechanisms underlying the relationship between weight loss, durability, and cognitive function, including contribution of adherence, as this may ultimately help identify individuals in need of tailored interventions to optimize postoperative weight loss.

Physical activity and cognitive function in bariatric surgery candidates.

Cognitive impairment is common in severe obesity. Lack of physical activity is a likely contributor to impairment in this population, as many obese persons are inactive and physical activity has been positively and independently associated with cognitive function in healthy and medically-ill samples. This study investigated whether physical activity, measured by self-report of aerobic physical activity in 85 bariatric surgery candidates, was associated with cognitive function. A subset of 31 participants also completed objective activity monitoring. Steps/d and high-cadence min/week, representative of ambulatory moderate to vigorous physical activity (MVPA), were calculated. Approximately one quarter of participants self-reported at least 30 min/d of aerobic MVPA, at least 5 d/week. Median steps/d was 7949 (IQR = 4572) and median MVPA min/week was 105 (IQR = 123). Cognitive deficits were found in 32% of participants (29% memory, 10% executive function, 13% language, 10% attention). Controlling for demographic and medical factors, self-reported aerobic physical activity was weakly correlated with lower attention (r = -0.21, p = 0.04) and executive function (r = -0.27, p < 0.01) and both self-reported aerobic physical activity and objectively-determined MVPA min/week were negatively correlated with memory (r = -0.20, p = 0.04; r = -0.46; p = 0.02, respectively). No other correlations between physical activity measures and cognitive function were significant. Contrary to expectations, greater levels of physical activity were not associated with better cognitive functioning. Such findings encourage future studies to clarify the association among cognitive function and physical activity in obese persons.

The Mini-Mental State Exam (MMSE) is not sensitive to cognitive impairment in bariatric surgery candidates.

BACKGROUND: Cognitive dysfunction is common among bariatric surgery candidates and associated with poorer weight loss outcomes. Identification of a brief screening measure to detect cognitive impairment in this population is needed, because comprehensive neuropsychological evaluations may not be available in all clinical settings. METHODS: The present study examined the utility of the Mini-Mental State Examination (MMSE) for detecting cognitive impairment in 30 bariatric surgery candidates by comparing impairment on the MMSE (at varying cutoffs) to impairment on a comprehensive neuropsychological test battery. RESULTS: Results indicated that the MMSE showed low sensitivity and specificity in identifying impairment, even at the more stringent MMSE cutoffs of 27 and 28. CONCLUSION: These findings suggest that the MMSE is a poor screener for cognitive impairment in bariatric surgery candidates. Future research is needed to identify or develop cognitive screeners for use in this population.

Cognitive function after bariatric surgery: evidence for improvement 3 years after surgery.

BACKGROUND: Bariatric surgery is associated with improved cognition, and it is possible that such improvements are found at extended follow-ups. We hypothesized that cognitive improvement would be maintained 3 years after bariatric surgery. METHODS: Fifty bariatric patients were recruited from the Longitudinal Assessment of Bariatric Surgery parent project. Participants completed a computerized cognitive test battery to assess cognitive function at 12 weeks, 12 months, 24 months, and 36 months after surgery. RESULTS: Repeated measures revealed main effects for attention, executive function, and memory. Attention improved up to 24 months and then slightly declined although it still fell within the average range at 36 months. Improvements in executive function reached their peak at 36 months after surgery. Short-term improvements in memory were maintained at 36 months. No main effect emerged for language. CONCLUSIONS: Bariatric surgery may lead to lasting improvements in cognition. Prospective studies with extended follow-ups (eg, 10 years) should examine whether bariatric surgery can attenuate cognitive decline in severely obese patients.

Adherence and weight loss outcomes in bariatric surgery: does cognitive function play a role?

Although bariatric surgery is the most effective intervention for severe obesity, a significant minority of participants fail to achieve or maintain optimal weight loss at extended follow-up. Accumulating evidence suggests that adherence to prescribed postoperative recommendations, including attendance at follow-up appointments and dietary and physical activity, is related to improved weight loss outcomes. However, adherence to these guidelines presents a significant challenge for many patients, potentially due in part to deficits in cognitive function. In this paper, we briefly examine current literature of adherence on postoperative weight loss outcomes, and review emerging evidence that the cognitive dysfunction present in a subset of obese individuals is related to weight loss outcomes following bariatric procedures. We then extend these findings, positing a role for cognitive function in moderating the relationship between adherence and postoperative outcomes.

Cognitive function is linked to adherence to bariatric postoperative guidelines.

BACKGROUND: Impairment in cognitive function is found in a significant subset of individuals undergoing bariatric surgery, and recent work shows this impairment is associated with smaller postoperative weight loss. Reduced cognitive function could contribute to poorer adherence to postoperative guidelines, although this has not been previously examined. The present study examined the relationship between cognitive function and adherence to bariatric postoperative guidelines. We expected that higher cognitive function would be associated with better adherence to postoperative guidelines. METHODS: Thirty-seven bariatric surgery patients completed cognitive testing and a self-report measure of adherence to postoperative bariatric guidelines during their 4- to 6-week postoperative appointment. RESULTS: Strong correlations were observed between adherence to postoperative guidelines and cognitive indices of attention, executive function, and memory. CONCLUSIONS: Results show that cognitive performance is strongly associated with adherence to postoperative guidelines shortly after bariatric surgery. Further work is needed to clarify whether this relationship is present at later postoperative stages and the degree to which this relationship mediates postoperative weight loss outcomes.

Bariatric surgery patients exhibit improved memory function 12 months postoperatively.

BACKGROUND: Previous work from our group demonstrated improved memory function in bariatric surgery patients at 12 weeks postoperatively relative to controls. However, no study has examined longer-term changes in cognitive functioning following bariatric surgery. METHODS: A total of 137 individuals (95 bariatric surgery patients and 42 obese controls) were followed prospectively to determine whether postsurgery cognitive improvements persist. Potential mechanisms of change were also examined. Bariatric surgery participants completed self-report measurements and a computerized cognitive test battery prior to surgery and at 12-week and 12-month follow-up; obese controls completed measures at equivalent time points. RESULTS: Bariatric surgery patients exhibited cognitive deficits relative to well-established standardized normative data prior to surgery, and obese controls demonstrated similar deficits. Analyses of longitudinal change indicated an interactive effect on memory indices, with bariatric surgery patients demonstrating better performance postoperatively than obese controls. CONCLUSIONS: While memory performance was improved 12 months postbariatric surgery, the mechanisms underlying these improvements were unclear and did not appear attributable to obvious postsurgical changes, such as reductions in body mass index or comorbid medical conditions. Future studies employing neuroimaging, metabolic biomarkers, and more precise physiological measurements are needed to determine the mechanisms underlying memory improvements following bariatric surgery.