Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. METHODS: We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. RESULTS: Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. INTERPRETATION: Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

Inflammation-related pathology in the olfactory epithelium: its impact on the olfactory system in psychotic disorders.

Smell deficits and neurobiological changes in the olfactory bulb (OB) and olfactory epithelium (OE) have been observed in schizophrenia and related disorders. The OE is the most peripheral olfactory system located outside the cranium, and is connected with the brain via direct neuronal projections to the OB. Nevertheless, it is unknown whether and how a disturbance of the OE affects the OB in schizophrenia and related disorders. Addressing this gap would be the first step in studying the impact of OE pathology in the disease pathophysiology in the brain. In this cross-species study, we observed that chronic, local OE inflammation with a set of upregulated genes in an inducible olfactory inflammation (IOI) mouse model led to a volume reduction, layer structure changes, and alterations of neuron functionality in the OB. Furthermore, IOI model also displayed behavioral deficits relevant to negative symptoms (avolition) in parallel to smell deficits. In first episode psychosis (FEP) patients, we observed a significant alteration in immune/inflammation-related molecular signatures in olfactory neuronal cells (ONCs) enriched from biopsied OE and a significant reduction in the OB volume, compared with those of healthy controls (HC). The increased expression of immune/inflammation-related molecules in ONCs was significantly correlated to the OB volume reduction in FEP patients, but no correlation was found in HCs. Moreover, the increased expression of human orthologues of the IOI genes in ONCs was significantly correlated with the OB volume reduction in FEP, but not in HCs. Together, our study implies a potential mechanism of the OE-OB pathology in patients with psychotic disorders (schizophrenia and related disorders). We hope that this mechanism may have a cross-disease implication, including COVID-19-elicited mental conditions that include smell deficits.

A comparative neuroimaging perspective of olfaction and higher-order olfactory processing: on health and disease.

Olfactory dysfunction is often the earliest indicator of disease in a range of neurological and psychiatric disorders. One tempting working hypothesis is that pathological changes in the peripheral olfactory system where the body is exposed to many adverse environmental stressors may have a causal role for the brain alteration. Whether and how the peripheral pathology spreads to more central brain regions may be effectively studied in rodent models, and there is successful precedence in experimental models for Parkinson's disease. It is of interest to study whether a similar mechanism may underlie the pathology of psychiatric illnesses, such as schizophrenia. However, direct comparison between rodent models and humans includes challenges under light of comparative neuroanatomy and experimental methodologies used in these two distinct species. We believe that neuroimaging modality that has been the main methodology of human brain studies may be a useful viewpoint to address and fill the knowledge gap between rodents and humans in this scientific question. Accordingly, in the present review article, we focus on brain imaging studies associated with olfaction in healthy humans and patients with neurological and psychiatric disorders, and if available those in rodents. We organize this review article at three levels: 1) olfactory bulb (OB) and peripheral structures of the olfactory system, 2) primary olfactory cortical and subcortical regions, and 3) associated higher-order cortical regions. This research area is still underdeveloped, and we acknowledge that further validation with independent cohorts may be needed for many studies presented here, in particular those with human subjects. Nevertheless, whether and how peripheral olfactory disturbance impacts brain function is becoming even a hotter topic in the ongoing COVID-19 pandemic, given the risk of long-term changes of mental status associated with olfactory infection of SARS-CoV-2. Together, in this review article, we introduce this underdeveloped but important research area focusing on its implications in neurological and psychiatric disorders, with several pioneered publications.

Does Olfactory Training Improve Brain Function and Cognition? A Systematic Review.

Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.

Poor olfaction prior to cardiac surgery: Association with cognition, plasma neurofilament light, and post-operative delirium.

OBJECTIVES: Post-operative delirium (POD) affects up to 50% of cardiac surgery patients, with higher incidence in older adults. There is increasing need for screening tools that identify individuals most vulnerable to POD. Here, we examined the relationship between pre-operative olfaction and both incident POD and POD severity in patients undergoing cardiac surgery. We also examined cross-sectional relationships between baseline olfaction, cognition, and plasma neurofilament light (NfL). METHODS: Individuals undergoing cardiac surgery (n = 189; mean age = 70 years; 75% men) were enrolled in a clinical trial of cerebral autoregulation monitoring. At baseline, odor identification performance (Brief Smell Identification Test), cognitive performance, and plasma concentrations of NfL levels (Simoa™ NF-Light Assay) were measured. Delirium was assessed with the Confusion Assessment Method (CAM) or CAM-ICU, and delirium severity was assessed using the Delirium Rating Scale-Revised-98. The association of baseline olfaction, delirium incidence, and delirium severity was examined in regression models adjusting for age, duration of cardiopulmonary bypass, logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), and baseline cognition. RESULTS: Olfactory dysfunction was present in 30% of patients, and POD incidence was 44%. Pre-operative olfactory dysfunction was associated with both incident POD (OR = 3.17, p = 0.001) and greater severity of POD after cardiac surgery (OR = 3.94 p < 0.001) in models adjusted for age, duration of bypass, and a surgical risk score. The addition of baseline cognition attenuated the strength of the association, but it remained significant for incident POD (OR = 2.25, p = 0.04) and POD severity (OR 2.10, p = 0.04). Poor baseline olfaction was associated with greater baseline cognitive dysfunction (p < 0.001) and increased baseline plasma NfL concentrations (p = 0.04). Neither age, cognition, nor baseline NFL concentration modified the association of impaired olfaction and delirium outcomes. CONCLUSIONS: Olfactory assessment may be a useful pre-surgical screening tool for the identification of patients undergoing cardiac surgery at increased risk of POD. Identifying those at highest risk for severe delirium and poor cognitive outcomes following surgery would allow for earlier intervention and pre-operative rehabilitation strategies, which could ultimately impact the functional disability and morbidity associated with POD.

A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance.

Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and biological markers, we analyzed demographic information, clinical data, structural brain imaging data, and molecular brain imaging data in 7 Tesla magnetic resonance spectroscopy from a first episode psychosis cohort that includes 136 patients. Age, gender, race, smoking status, duration of illness, and antipsychotic dosages were controlled in the analyses. We found that TR patients had a younger age at onset, more hospitalizations, more severe negative symptoms, a reduction in the volumes of the hippocampus (HP) and superior frontal gyrus (SFG), and a reduction in glutathione (GSH) levels in the anterior cingulate cortex (ACC), when compared to non-TR patients. The combination of multiple markers provided a better classification between TR and non-TR patients compared to any individual marker. Our study shows that ACC-GSH, HP and SFG volumes, and age at onset, could potentially be biomarkers for TR diagnosis, while hospitalization and negative symptoms could be used to evaluate the progression of the disease. Multimodal cohorts are essential in obtaining a comprehensive understanding of brain disorders.

The relationship between weight loss and cognitive function in bariatric surgery.

BACKGROUND: Previously, we reported short-term improvements in auditory attention, oromotor processing speed, and executive function during the active weight loss phase following bariatric surgery that persisted out to 3 months. In this study, our aims were to investigate the relationship between weight loss and cognitive performance in these patients 1 year following vertical sleeve gastrectomy (VSG) and Roux-en Y gastric bypass (RYGB) surgery and to determine whether preoperative cognitive performance predicted weight loss. METHODS: Adult women ages 18-55 approved for bariatric surgery completed a cognitive battery prior to and at 2, 12, 24, and 52 weeks following VSG (N = 17) or RYGB (N = 18). Scores from each task were assigned to one of the following cognitive domains: auditory attention, processing speed, memory, and executive functioning. Weight loss and cognitive scores for each domain were calculated and compared between cohorts. RESULTS: RYGB surgery resulted in greater weight loss at 1-year follow-up relative to VSG. Both VSG and RYGB procedures resulted in improved performance on different measures of auditory attention and both surgery groups improved across all processing speed tasks. Within the executive function domain, both groups showed improvements, but only the RYGB procedure resulted in improved performance in the Trail Making Test. Baseline auditory attention and memory performance predicted weight loss at 1 year following RYGB but not VSG surgery. Controlling for baseline cognitive performance, percent total weight loss predicted auditory attention at 1 year following RYGB but not VSG surgery. CONCLUSIONS: Bariatric surgery type may result in selective improvements in cognition during the first year following surgery. Presurgical cognitive performance as well as surgery type appears to influence weight loss outcomes.

Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities-focused research.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.

Investigating relationships between post-prandial gut hormone responses and taste liking ratings prior to and following bariatric surgery: a pilot study.

BACKGROUND: Alterations in gut hormone secretion and reported changes in taste preferences have been suggested to contribute to the weight-reducing effects of bariatric surgery. However, a link between changes in gut hormone secretion and taste preferences following bariatric surgery has yet to be elucidated. METHODS: Here we examined the potential relationships between gut hormone responses (GLP-1 and PYY3-36 peak, ghrelin trough) to a test meal of Ensure and liking ratings for taste mixtures varying in sugar and fat content before and following bariatric surgery (vertical sleeve gastrectomy (VSG): N = 4; Roux-en Y gastric bypass (RYGB): N = 8). RESULTS: Significant increases in GLP-1 and PYY3-36 peak and a significant drop in ghrelin trough were observed following surgery. Pre- and postoperation, patients with higher postprandial GLP-1 or PYY3-36 peaks gave lower liking ratings for mixtures containing a combination of fat and sugar (half and half + 20% added sugar) whereas, for the combined surgery analyses, no relationships were found with solutions comprised of high fat (half and half + 0% sugar), predominantly high sugar (skim milk + 20% added sugar), or low fat and low sugar (skim milk + 0% added sugar). Within the RYGB patients, patients with the greatest increase in postprandial GLP-1 peak from preoperation to postoperation also demonstrated the greatest decrease in liking for half & half + 20% added sugar and skim milk + 20% added sugar, but not the unsweetened version of each solution. No pre- or postoperative relationship between ghrelin and liking ratings were observed. CONCLUSION: Gut hormone responses following bariatric surgery may contribute to taste processing of sugar+fat mixtures and together influence weight loss.

Olfactory Dysfunction Following Moderate to Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

OBJECTIVE: Reports of smell loss following traumatic brain injury (TBI) are a well-documented but understudied phenomenon. Given the broad consequences of olfactory loss, we characterized psychophysical olfactory dysfunction in individuals with moderate to severe TBI using systematic review and meta-analytic methods. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol, five databases (PubMed, EMBASE, Cochrane Library, Web of Science, Scopus) were reviewed for studies investigating olfactory dysfunction in persons with moderate to severe TBI. Of the 5,223 studies reviewed, 19 met our inclusion criteria for the systematic review and 11 met inclusion criteria for meta-analysis. We calculated effect sizes (Hedges' g) to characterize the degree of olfactory dysfunction between patients with moderate to severe TBI and controls. RESULTS: A total of 951 moderate-severe TBI patients from 19 studies were included in the systematic review, which largely demonstrated poorer olfactory psychophysical performances in this patient population. Meta-analysis demonstrated a large effect size for olfactory dysfunction in moderate-severe TBI relative to healthy controls (g=-2.43, 95%CI: -3.16 < δ<-1.69). The magnitude of the effect was moderated by age and patient sex, with larger effect sizes associated with older age (following exclusion of a pediatric population) and larger compositions of women in the patient group. CONCLUSION: Moderate to severe TBI is associated with prominent olfactory dysfunction. Significant research gaps remain regarding the mechanism, recovery and natural history of olfactory dysfunction following moderate to severe TBI, which has significant clinical implications for the identification and treatment for those with post-traumatic olfactory dysfunction.

Perioperative Neurofilament Light Plasma Concentrations and Cognition before and after Cardiac Surgery: A Prospective Nested Cohort Study.

BACKGROUND: Neurofilament light is a marker of neuronal injury and can be measured in blood. Postoperative increases in neurofilament light have been associated with delirium after noncardiac surgery. However, few studies have examined the association of neurofilament light changes with postdischarge cognition in cardiac surgery patients, who are at highest risk for neuronal injury and cognitive decline. The authors hypothesized that increased neurofilament light (both baseline and change) would be associated with worse neuropsychological status up to 1 yr after cardiac surgery. METHODS: This observational study was nested in a trial of cardiac surgery patients, in which blood pressure during bypass was targeted using cerebral autoregulation monitoring. Plasma concentrations of neurofilament light were measured at baseline and postoperative day 1. Neuropsychological testing was performed at baseline, 1 month after surgery, and 1 yr after surgery. Primary outcomes were baseline and change from baseline in a composite z-score of all cognitive tests. RESULTS: Among 167 patients, cognitive outcomes were available in 80% (134 of 167) and 61% (102 of 167) at 1 month and 1 yr after surgery, respectively. The median baseline concentration of neurofilament light was 18.2 pg/ml (interquartile range, 13.4 to 28.1), and on postoperative day 1 was 28.5 pg/ml (interquartile range, 19.3 to 45.0). Higher baseline log neurofilament light was associated with worse baseline cognitive z-score (adjusted slope, -0.60; 95% CI, -0.90 to -0.30; P < 0.001), no change in z-score from baseline to 1 month (0.11; 95% CI, -0.19 to 0.41; P = 0.475), and improvement in z-score from baseline to 1 yr (0.56; 95% CI, 0.31 to 0.81; P < 0.001). Whereas some patients had an improvement in cognition at 1 yr and others a decline, an increase in neurofilament light from baseline to postoperative day 1 was associated with a greater decline in cognition at 1 yr. CONCLUSIONS: Higher baseline neurofilament light concentration was associated with worse baseline cognition but improvement in cognition at 1 yr. A postoperative increase in neurofilament light was associated with a greater cognitive decline at 1 yr.

Psychophysical chemosensory dysfunction in eating disorders: a qualitative systematic review.

PURPOSE: Patients with chemosensory dysfunction experience significant quality of life disruptions, including reduced enjoyment of eating. While chemosensory dysfunction has been associated with eating disorders, the relationship is poorly understood. This systematic review aims to characterize psychophysical gustation and olfaction in patients with eating disorders. METHODS: Systematic review of investigations assessing psychophysical chemosensory function in patients with organic eating disorders. RESULTS: 26 studies were included. Five studies assessed both chemosenses, while 12 and 9 assessed exclusively gustation or olfaction, respectively. In total, 779 patients were included [72.4% anorexia nervosa (AN), 26.7% bulimia nervosa (BN), 0.8% combined AN/BN]. Patients with eating disorders experienced rates of hypogeusia up to 87% in AN and 84.6% in BN. There was evidence for alterations in psychophysical olfaction, but orientation of trends were less clear. Chemosensory dysfunction was more evident in AN patients. Treatment correlated with improved chemosensory function. CONCLUSIONS: Despite heterogeneity in study methodology and results, this review demonstrates that patients with eating disorders experience some degree of chemosensory dysfunction, particularly in gustation. This symptomatology overlaps with those experienced by patients with other causes of chemosensory impairment. These findings suggest potential broad psychosocial, dietary, and mental health implications in patient populations experiencing chemosensory dysfunction. LEVEL OF EVIDENCE: Level II.

Odor identification predicts postoperative seizure control following magnetic resonance-guided laser interstitial thermal therapy.

OBJECTIVE: Olfactory dysfunction has been well documented in individuals with temporal lobe epilepsy, but its use in presurgical planning has yet to be examined. We assessed the role of preoperative odor identification in mesial onset seizure localization utilizing stereoelectroencephalography (S-EEG) and magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) outcome. METHODS: We identified 30 patients who had typical seizures captured during S-EEG monitoring or MRgLiTT of mesial temporal structures (n = 17 S-EEG, n = 13 MRgLiTT); seizure onset zone was classified as unilateral mesial seizure onset, or multifocal with unilateral mesial onset and nonmesial onset. Odor identification ability was assessed using the Sniffin' Sticks Odor Identification Test (SSOIT). Patients also completed measures of confrontation naming and auditory-verbal learning/memory using the Boston Naming Test and Hopkins Verbal Learning Test-Revised, respectively. RESULTS: Overall, patients with intractable focal epilepsy exhibited poor olfactory performance (median [M] = 10.4, interquartile range [IQR] = 9.4-11.8). Of 19 patients who underwent MRgLiTT, 10 patients (52.6%) were seizure-free at last follow-up (M = 13 months, IQR =10-18). Patients who were seizure-free after MRgLiTT (n = 10) had poorer odor identification scores (M = 9, IQR = 7-13) compared to patients with seizure reoccurrence (M = 13, IQR = 12.5-15). Odor identification score was inversely associated with seizure freedom, with odds ratio = 0.60 (95% confidence interval [CI] = 0.38-0.95, P = .03). Receiver operating characteristic analysis revealed that an SSOIT score of 12 was the ideal cutoff for predicting favorable seizure outcome (area under the curve = 0.84, 95% CI = 0.64-1.0). Sensitivity was 88.9% and specificity was 78.9%, with a likelihood ratio of 2.9 of seizure failure in patients who had an odor identification score ≥ 12. SIGNIFICANCE: Interictal olfactory dysfunction is commonly seen in patients with intractable focal epilepsy. Odor identification is a novel, noninvasive presurgical biomarker to distinguish who may or may not benefit from MRgLiTT of mesial temporal structures.

A Meta-Analysis of Neuropsychological Functioning in the Logopenic Variant of Primary Progressive Aphasia: Comparison with the Semantic and Non-Fluent Variants.

OBJECTIVES: The logopenic variant of primary progressive aphasia (lvPPA) has disparate pathological and anatomical features when compared to the semantic (svPPA) and non-fluent (nfvPPA) variants of PPA. As such, there is increasing need for measures that improve diagnostic accuracy particularly when etiology-specific treatments become available. In the current study, we used meta-analytic methods to establish the neuropsychological profile of lvPPA and compare it to recent findings in svPPA and nfvPPA. METHODS: We extracted neuropsychological data from 51 publications representing 663 lvPPA patients and 1379 controls. We calculated Hedges' g effect sizes for nine domains of neuropsychological functioning in lvPPA and assessed the influence of demographic, disease, and task characteristics on effect size magnitude. Results obtained in lvPPA were compared to findings in svPPA and nfvPPA. RESULTS: In lvPPA, the magnitude of deficits in attention, math, visuospatial memory, and executive functioning were as prominent as language deficits. Within the language domain, lvPPA patients demonstrated greater naming than repetition deficits. Compared to svPPA and nfvPPA, lvPPA patients demonstrated greater neuropsychological deficits overall and greater impairment on attention, math, and visual set-shifting tests. CONCLUSIONS: Tests of attention, delayed visuospatial memory, visual set-shifting, and math distinguish lvPPA from svPPA and nfvPPA likely reflecting the posterior temporoparietal atrophy observed early in the course of lvPPA. These findings support the inclusion of these measures in the clinical neuropsychological assessment of lvPPA and underscore the need for additional clinicopathological and longitudinal studies of arithmetic and visuospatial memory across the PPA variants.

Olfactory Testing in Temporal Lobe Epilepsy: a Systematic Review.

PURPOSE OF REVIEW: Olfactory testing is a potentially safe, cost-effective, bedside evaluation tool for diagnosis, monitoring, and risk assessment for surgery in temporal lobe epilepsy (TLE) patients, but testing methods and relevant olfactory domains are not standardized. We conducted a systematic review to evaluate olfactory tests in TLE and summarize the results of the literature. RECENT FINDINGS: Olfactory tests varied significantly in odorant administration tools and devices, target odorants, evaluation timing, and grading scales. The Smell Threshold Test and University of Pennsylvania Smell Identification Test were the most validated single-domain tests for odor detection and odor identification, respectively. For multi-domain tests, Odor Memory/Discrimination Test and the Sniffin' Sticks test were the most validated. Results of olfactory tests in TLE are presented by domain. Rigorous validation, standardization, and comparative analysis of existing olfactory tests by domain is urgently needed to establish the utility and efficacy of olfactory testing in TLE.

Short-term improvements in cognitive function following vertical sleeve gastrectomy and Roux-en Y gastric bypass: a direct comparison study.

BACKGROUND: Cognitive deficits are observed in individuals with obesity. While bariatric surgery can reverse these deficits, it remains unclear whether surgery type differentially influences cognitive outcome. We compared the extent to which vertical sleeve gastrectomy (VSG) and Roux-en Y gastric bypass (RYGB) ameliorated cognitive impairments associated with obesity. METHODS: Female participants approved for VSG (N = 18) or RYGB (N = 18) were administered cognitive measures spanning the domains of attention [Hopkins Verbal Learning Test (HVLT) Trial 1 and Letter Number Sequencing], processing speed [Stroop Color Trial, Symbol Digit Modalities Test, and Trail Making Part A], memory [HVLT Retained and HVLT Discrimination Index], and executive functioning (Stroop Color Word Trials and Trail Making Part B-A) prior to surgery and at 2 weeks and 3 months following surgery. Scores for each cognitive domain were calculated and compared between surgical cohorts using repeated measures analyses of variance. RESULTS: Significant weight loss was observed 2 weeks and 3 months following RYGB and VSG and was accompanied by improvements in processing speed and executive functioning. Patients who received RYGB also experienced improved attention as early as 2 weeks, which persisted at 3 months. This was not observed in individuals who underwent VSG. No changes in memory were observed from baseline measures in either group. CONCLUSIONS: This is the first report of cognitive improvements following VSG and the first direct comparison of cognitive improvements following RYGB and VSG. Short-term improvements in specific domains of cognitive function are observed at the beginning of the active weight loss phase following bariatric surgery that persisted to 3 months. The anatomical distinction between the two surgeries and resulting differential metabolic profiles may be responsible for the improvements in attention observed following RYGB but not following VSG.

Does taste preference predict weight regain after bariatric surgery?

BACKGROUND: While bariatric surgery is well established as a means of inducing sustained weight loss, the rate of weight loss typically declines after a year, and weight regain has been observed. Preoperative taste preferences have been suspected to play a role in weight regain, possibly by influencing post-operative dietary practices. We sought to investigate the association between preoperative taste preferences and weight regain following bariatric surgery. METHODS: Patients who underwent bariatric surgery with at least 2 years of follow-up were included. Demographics and weight were collected in follow-up visits; while patient recall of preoperative taste preference was assessed, using a multiple-choice question in the study survey administered at least 6 months post-surgery. Weight regain was calculated as weight at 2 years minus weight at 1 year post-surgery, with weight regain denoted by positive values and weight loss by negative. Linear regression models were utilized to study associations between weight regain and preoperative taste preferences with and without adjusting for demographic factors and surgery type. RESULTS: Patients undergoing RYGB had less weight regain (- 4.5 kg, p = 0.033) compared to patients undergoing VSG. Compared to patients with no preferences, patients with sweet food or salty food preferences had 5.5 kg (p = 0.038) and 6.1 kg (p = 0.048) weight regain, respectively, at 2 years post-surgery. After adjustment, patients with salty food preference had 6.8 kg (p = 0.027) weight regain compared to patients with no preferences. CONCLUSIONS: Preoperative salty taste preference was associated with weight regain at 2 years post-surgery in patients undergoing bariatric surgery. Findings of this project might have implications for predicting long-term weight loss maintenance for patients with known preoperative taste preferences. Our study suggests that patients with preoperative salty taste preference may need further post-operative psychosocial support and resources to prevent weight regain and to ensure healthy and sufficient weight loss.

A Quantitative Meta-analysis of Olfactory Dysfunction in Epilepsy.

Olfactory dysfunction in epilepsy is well-documented in several olfactory domains. However, the clinical specificity of these deficits remains unknown. The aim of this systematic meta-analysis was to determine which domains of olfactory ability were most impaired in individuals with epilepsy, and to assess moderating factors affecting olfactory ability. Extant peer-reviewed literature on olfaction in epilepsy were identified via a computerized literature search using PubMed, MEDLINE, PsycInfo, and Google Scholar databases. Twenty-one articles met inclusion criteria. These studies included a total of 912 patients with epilepsy and 794 healthy comparison subjects. Included studies measured olfaction using tests of odor identification, discrimination, memory, and detection threshold in patients with different types of epilepsy, including temporal lobe epilepsy (TLE), mixed frontal epilepsy (M-F), and mixed epilepsy (MIX). Olfactory deficits were robust in patients with epilepsy when compared to healthy individuals, with effect sizes in the moderate to large range for several olfactory domains, including odor identification (d = -1.59), memory (d = -1.10), discrimination (d = -1.04), and detection threshold (d = -0.58). Olfactory deficits were most prominent in patients with TLE and M-F epilepsy. Amongst patients with epilepsy, sex, age, smoking status, education, handedness, and age of illness onset were significantly related to olfactory performance. Overall, these meta-analytic findings indicate that the olfactory system is compromised in epilepsy and suggest that detailed neurobiological investigations of the olfactory system may provide further insight into this disorder.

A meta-analysis of neuropsychological, social cognitive, and olfactory functioning in the behavioral and language variants of frontotemporal dementia.

BACKGROUND: Though meta-analyses of neuropsychological and social cognitive deficits in behavioral variant frontotemporal dementia (bvFTD) have been conducted, no study has comprehensively characterized and compared the neuropsychological, social cognitive, and olfactory profiles in the behavioral and language variants of FTD. METHODS: Our search yielded 470 publications meeting inclusion criteria representing 11 782 FTD patients and 19 451 controls. For each domain, we calculated Hedges' g effect sizes, which represent the mean difference between the patient and control group divided by the pooled standard deviation. The heterogeneity of these effects was assessed with Cochran's Q-statistic using a random-effects model. Meta-regressions were employed to analyze the influence of demographic and disease characteristics. RESULTS: Though semantic variant primary progressive aphasia patients showed the greatest impairment across all task types, the three groups showed similar cognitive effect sizes once contributions from the language subdomain were excluded from analysis. Contrary to expectation, the magnitude of deficits in executive functioning, social cognition and olfaction were comparable between the three subgroups. Among indices, a metric of executive errors distinguished the behavioral variant of FTD from the language phenotypes. CONCLUSIONS: These data indicate that social cognitive and traditional executive functioning measures may not capture differences between FTD syndromes. These results have important implications for the interpretation of neuropsychological assessments, particularly when applied to the differential diagnosis of FTD. It is hoped that these findings will guide clinical and research assessments and spur new studies focused on improving the measurement of FTD syndromes.

Observational Study Examining the Association of Baseline Frailty and Postcardiac Surgery Delirium and Cognitive Change.

BACKGROUND: Frailty is a geriatric syndrome thought to identify the most vulnerable older adults, and morbidity and mortality has been reported to be higher for frail patients after cardiac surgery compared to nonfrail patients. However, the cognitive consequences of frailty after cardiac surgery have not been well described. In this study, we examined the hypothesis that baseline frailty would be associated with postoperative delirium and cognitive change at 1 and 12 months after cardiac surgery. METHODS: This study was nested in 2 trials, each of which was conducted by the same research team with identical measurement of exposures and outcomes. Before surgery, patients were assessed with the validated "Fried" frailty scale, which evaluates 5 domains (shrinking, weakness, exhaustion, low physical activity, and slowed walking speed) and classifies patients as nonfrail, prefrail, and frail. The primary outcome was postoperative delirium during hospitalization, which was assessed using the Confusion Assessment Method, Confusion Assessment Method for the Intensive Care Unit, and validated chart review. Neuropsychological testing was a secondary outcome and was generally performed within 2 weeks of surgery and then 4-6 weeks and 1 year after surgery, and the outcome of interest was change in composite Z-score of the test battery. Associations were analyzed using logistic and linear regression models, with adjustment for variables considered a priori (age, gender, race, education, and logistic European System for Cardiac Operative Risk Evaluation). Multiple imputation was used to account for missing data at the 12-month follow-up. RESULTS: Data were available from 133 patients with baseline frailty assessments. Compared to nonfrail patients (13% delirium incidence), the incidence of delirium was higher in prefrail (48% delirium incidence; risk difference, 35%; 95% CI, 10%-51%) and frail patients (48% delirium incidence; risk difference, 35%; 95% CI, 7%-53%). In both univariable and multivariable models, the odds of delirium were significantly higher for prefrail (adjusted odds ratio, 6.43; 95% CI, 1.31-31.64; P = .02) and frail patients (adjusted odds ratio, 6.31; 95% CI, 1.18-33.74; P = .03) compared to nonfrail patients. The adjusted decline in composite cognitive Z-score was greater from baseline to 1 month only in frail patients compared to nonfrail patients. By 1 year after surgery, there were no differences in the association of baseline frailty with change in cognition. CONCLUSIONS: Compared to nonfrail patients, both prefrail and frail patients were at higher risk for the primary outcome of delirium after cardiac surgery. Frail patients were also at higher risk for the secondary outcome of greater decline in cognition from baseline to 1 month, but not baseline to 1 year, after surgery.