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Introduction Lipocalin-2 is an acute-phase protein with pleotropic functions that has been implicated in several diseases including Alzheimer's disease (AD). However, it is unknown if circulating lipocalin-2 levels are altered in the preclinical stage of AD, where AD pathology has accumulated but cognition remains relatively intact. Methods In this cross-sectional study, we used an immunoassay to measure plasma lipocalin-2 levels in cognitively normal (Clinical Dementia Rating 0) elderly individuals. 38 of 156 subjects were classified as preclinical AD by cerebrospinal fluid criteria. Results Plasma lipocalin-2 levels were higher in preclinical AD compared with control subjects and associated with cerebrospinal fluid amyloid-beta42 levels but not cerebrospinal fluid tau or phosphorylated-tau181 levels. Exploratory analyses revealed that plasma lipocalin-2 was associated with executive function but not episodic memory. Discussion Collectively, these results raise the possibility that circulating lipocalin-2 is involved early in AD pathogenesis and may represent an early blood biomarker of amyloid-beta pathology.

Objectives:Antidepressants have limited efficacy in older adults with depression and cognitive impairment, and psychosocial interventions for this population have been inadequately investigated. Problem Adaptation Therapy (PATH) is a psychosocial intervention for older adults with major depression, cognitive impairment, and disability.Design:This study tests the efficacy of PATH versus Supportive Therapy for Cognitively Impaired Older Adults (ST-CI) in reducing depression (Montgamery Asberg Depression Rating Scale [MADRS]) and disability (World Health Organization Disability Assessments Schedule-II [WHODAS-II]) and improving cognitive outcomes (Mini Mental State Examination [MMSE]) over 24 weeks (12 weeks of treatment and 12-week post-treatment follow-up).Setting:Participants were recruited through collaborating community agencies of Weill Cornell Institute of Geriatric Psychiatry. Both interventions and all research assessments were conducted at home.Participants:Thirty-five older adults (age ≥ 65 years) with major depression and cognitive impairment no dementia (CIND).Interventions:PATH aims to increase emotion regulation by incorporating a problem-solving approach, teaching compensatory strategies, and inviting caregiver participation. Supportive Therapy aims to facilitate the expression of affect, as well as promote empathy.Measurements:Depression was measured using the MADRS, disability using the WHODAS-II, and cognition using the MMSE.Results:PATH participants showed significantly greater reduction in MADRS total score (7.04 points at 24 weeks, treatment group by time interaction:F[1,24.4]= 7.61,p= 0.0108), greater improvement in MMSE total score (2.30 points at 24 weeks, treatment group by time interaction:F[1,39.8]= 13.31,p= 0.0008), and greater improvement in WHODAS-II total score (2.95 points at 24 weeks, treatment group by time interaction:F[1,89]= 4.93,p= 0.0290) than ST-CI participants over the 24-week period.Conclusions:PATH participants had better depression, cognitive, and disability outcomes than ST-CI participants over 6 months. PATH may provide relief to depressed older adults with CIND who currently have limited treatment options.

Objective Our aim is to define the extent of comorbidities in order to improve clinical care of patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) utilizing the REM Sleep Behavior Disorder Associations with Parkinson's Disease Study (RAPiDS) cohort. Methods Consecutive adult study participants with iRBD confirmed on polysomnogram (PSG) were prospectively recruited from the Weill Cornell Center for Sleep Medicine. Evaluations comprised multiple facets of sleep, neurological, autonomic, and psychiatric function. Results Participants evaluated included 30 individuals with iRBD, with mean 1.5 ± 2.3 years from PSG to neuropsychiatric evaluation. Mean age was 59.5 ± 16.0 years at time of PSG, and 6/30 were women. Urinary difficulties were reported in 14/30 (47%): slight 7 (23%), mild 4 (13%), moderate 2 (7%), and severe 1 (3.0%). Ten out of 29 (34%) had abnormal Montreal Cognitive Assessment (MoCA) scores and the mean was 26.5 ± 3.2. The distribution of MoCA scores was significantly associated with urinary problems insofar as the more severe urinary problems were, the lower the MoCA scores (p = 0.04). Conclusions In this RAPiDS cohort, we detected an unexpectedly high occurrence of non-motor dysfunction. Our results point to the need for screening patients with iRBD for complaints that are actionable, for example those affecting mood, cognition, urinary function, and bowel function. We propose the term RBD+ to be used to identify such individuals. For the quality of life in patients diagnosed with RBD, a closer look by the clinician should be enacted, with appropriate referrals and workup., Highlights • Comorbidities in idiopathic rapid eye movement sleep behavior disorder (iRBD) is further defined. • REM Sleep Behavior Disorder Associations with Parkinson's Disease Study (RAPiDS) cohort • There was a high occurrence of non-motor dysfunction in this cohort. • The need for screening patients with iRBD for complaints that are actionable was demonstrated. • We proposed the term “RBD+” to be used to identify such individuals.

Objectives The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. Background TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. Methods SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤−1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below −1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume. Results Among 234 patients tested, the mean composite z-score was −0.65 SD below the normative mean. Domain scores ranged from −0.15 SD for attention to −1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p Conclusions There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.

The LUCINDA Trial (Leuprolide plus Cholinesterase Inhibition to reduce Neurologic Decline in Alzheimer’s) is a 52 week, randomized, placebo-controlled trial of leuprolide acetate (Eligard) in women with Alzheimer’s disease (AD). Leuprolide acetate is a gonadotropin analogue commonly used for hormone-sensitive conditions such as prostate cancer and endometriosis. This repurposed drug demonstrated efficacy in a previous Phase II clinical trial in those women with AD who also received a stable dose of the acetylcholinesterase inhibitor donepezil (Bowen et al., 2015). Basic biological, epidemiological and clinical trial data suggest leuprolide acetate mediates improvement and stabilization of neuropathology and cognitive performance via the modulation of gonadotropin and/or gonadotropin-releasing hormone signaling. LUCINDA will enroll 150 women with mild-moderate AD who are receiving a stable dose of donepezil from three study sites in the United States. Cognition and function are the primary outcome measures as assessed by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale. Blood and MRI biomarkers are also measured to assess hormonal, inflammatory and AD biomarker changes. We present the protocol for LUCINDA and discuss trial innovations and challenges including changes necessitated by the covid-19 pandemic and study drug procurement issues.

The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer’s Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes. In this work, we present a combined framework, cascaded multiview canonical correlation (CaMCCo), for fusion and cascaded classification that incorporates all diagnostic categories and optimizes classification by selectively combining a subset of modalities at each level of the cascade. CaMCCo is evaluated on a data cohort comprising 149 patients for whom neurophysiological, neuroimaging, proteomic and genomic data were available. Results suggest that fusion of select modalities for each classification task outperforms (mean AUC = 0.92) fusion of all modalities (mean AUC = 0.54) and individual modalities (mean AUC = 0.90, 0.53, 0.71, 0.73, 0.62, 0.68). In addition, CaMCCo outperforms all other multi-class classification methods for MCI prediction (PPV: 0.80 vs. 0.67, 0.63).

BACKGROUND AND PURPOSE: Oxidative stress has been implicated as an important pathologic mechanism in the development of Alzheimer disease. The purpose of this study was to assess whether glutathione levels, detected noninvasively with proton MR spectroscopy, are associated with brain amyloidosis and memory in a community-dwelling cohort of healthy older adults. MATERIALS AND METHODS: Fifteen cognitively healthy subjects were prospectively enrolled in this study. All subjects underwent 1H-MR spectroscopy of glutathione, a positron-emission tomography scan with an amyloid tracer, and neuropsychological testing by using the Repeatable Battery for the Assessment of Neuropsychological Status. Associations among glutathione levels, brain amyloidosis, and memory were assessed by using multivariate regression models. RESULTS: Lower glutathione levels were associated with greater brain amyloidosis in the temporal (P = .03) and parietal (P = .05) regions, adjusted for apolipoprotein E e4 carrier status. There were no significant associations between glutathione levels and cognitive scores. CONCLUSIONS: This study found an association between cortical glutathione levels and brain amyloidosis in healthy older adults, suggesting a potential role for 1H-MR spectroscopy measures of glutathione as a noninvasive biomarker of early Alzheimer disease pathogenesis.

Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer’s disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, ‘shape connections’ between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus.

Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD.A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared with condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Preplanned co-primary outcomes were anxiety and depression scales 12 months after disclosure.Three hundred and forty-three adults (mean age 58.3, range 33-86 years, 71% female, 23% African American) were randomly assigned to the SP-GC protocol (n = 115), CP-GC protocol (n = 116), or CP-MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC with SP-GC, the 97.5% upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P.001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans.These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information.

The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging.TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease.SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤-1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below -1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume.Among 234 patients tested, the mean composite z-score was -0.65 SD below the normative mean. Domain scores ranged from -0.15 SD for attention to -1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p 0.001), verbal memory (p 0.001), and visual memory (p 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations.There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.

Brain imaging genetics intends to uncover associations between genetic markers and neuroimaging quantitative traits. Sparse canonical correlation analysis (SCCA) can discover bi-multivariate associations and select relevant features, and is becoming popular in imaging genetic studies. The L1-norm function is not only convex, but also singular at the origin, which is a necessary condition for sparsity. Thus most SCCA methods impose $${\ell }_{{\bf{1}}}$$ ℓ 1 -norm onto the individual feature or the structure level of features to pursuit corresponding sparsity. However, the $${\ell }_{{\bf{1}}}$$ ℓ 1 -norm penalty over-penalizes large coefficients and may incurs estimation bias. A number of non-convex penalties are proposed to reduce the estimation bias in regression tasks. But using them in SCCA remains largely unexplored. In this paper, we design a unified non-convex SCCA model, based on seven non-convex functions, for unbiased estimation and stable feature selection simultaneously. We also propose an efficient optimization algorithm. The proposed method obtains both higher correlation coefficients and better canonical loading patterns. Specifically, these SCCA methods with non-convex penalties discover a strong association between the APOE e4 rs429358 SNP and the hippocampus region of the brain. They both are Alzheimer’s disease related biomarkers, indicating the potential and power of the non-convex methods in brain imaging genetics.

Accurate prediction of Alzheimer’s disease (AD) is important for the early diagnosis and treatment of this condition. Mild cognitive impairment (MCI) is an early stage of AD. Therefore, patients with MCI who are at high risk of fully developing AD should be identified to accurately predict AD. However, the relationship between brain images and AD is difficult to construct because of the complex characteristics of neuroimaging data. To address this problem, we present a longitudinal measurement of MCI brain images and a hierarchical classification method for AD prediction. Longitudinal images obtained from individuals with MCI were investigated to acquire important information on the longitudinal changes, which can be used to classify MCI subjects as either MCI conversion (MCIc) or MCI non-conversion (MCInc) individuals. Moreover, a hierarchical framework was introduced to the classifier to manage high feature dimensionality issues and incorporate spatial information for improving the prediction accuracy. The proposed method was evaluated using 131 patients with MCI (70 MCIc and 61 MCInc) based on MRI scans taken at different time points. Results showed that the proposed method achieved 79.4% accuracy for the classification of MCIc versus MCInc, thereby demonstrating very promising performance for AD prediction.

Background To determine the effects of Type 2 diabetes (DM2) on levels of brain amyloidosis and cognition in a community-dwelling cohort of nondemented elderly individuals. Methods 33 subjects (16 DM2, 17 nondiabetic) were prospectively recruited. Subjects underwent a PET scan using the amyloid tracer, Pittsburgh Compound B, and a neuropsychological evaluation. Associations between DM2, brain amyloidosis, and cognition were assessed using multivariate regressions, adjusting for age and APOE4 status. Results DM2 subjects had lower global cognitive function (p = 0.018), as measured by the Repeatable Battery for the Assessment of Neuropsychological Status. There was no difference in brain amyloidosis between groups (p = 0.25). Conclusions Community-dwelling, nondemented individuals with DM2 had greater cognitive deficits, which do not appear to be mediated by brain amyloidosis. Further studies exploring potential mediators of these cognitive deficits should be performed.

Aim: We sought to identify markers of motor and nonmotor function in Parkinson's disease (PD) using advanced neuroimaging techniques in subjects with PD. Methods: We enrolled 26 nondemented PD subjects and 12 control subjects. All subjects underwent [18F]fluorodeoxyglucose positron emission computed tomography (FDG-PET) and magnetic resonance imaging, and a complete neuropsychological battery. Results: FDG-PET of subjects with PD revealed significant metabolic elevations in the bilateral posterior lentiform nucleus, posterior cingulate, and parahippocampus, and metabolic reductions in the bilateral temporoparietal association cortex and occipital lobe versus controls. PD subjects had significant reductions in executive/attention function, memory/verbal learning, and speed of thinking, and significantly increased depression, anxiety and apathy scores compared with controls. Motor dysfunction correlated with increased metabolism in the posterior lentiform nucleus, pons, and cerebellum, and decreased metabolism in the temporoparietal lobe. Cognitive dysfunction correlated with increased posterior cingulate metabolism and decreased temporoparietal lobe metabolism. Depressive symptoms correlated with increased amygdala metabolism; anxiety scores correlated with decreased caudate metabolism, and apathy scores correlated with increased metabolism in the anterior cingulate and orbitofrontal lobe and decreased metabolism in the temporoparietal association cortex. Conclusions: Our findings showed that motor, cognitive, and emotional dysfunction in PD are associated with distinct patterns of cerebral metabolic changes.

Objective: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder presenting with gait, cognitive, and bladder symptoms in the context of ventricular enlargement. Although gait is the primary indicator for treatment candidacy and outcome, additional monitoring tools are needed. Line Tracing Test (LTT) and Serial Dotting Test (SDT), two psychomotor tasks, have been introduced as potential outcome measures but have not been widely studied. This preliminary study examined whether LTT and SDT are sensitive to motor dysfunction in INPH and determined if accuracy and time are important aspects of performance. Methods: Eighty-four INPH subjects and 36 healthy older adults were administered LTT and SDT. Novel error scoring procedures were developed to make scoring practical and efficient; interclass correlation showed good reliability of scoring procedures for both tasks (0.997; pResults: The INPH group demonstrated slower performance on SDT (pppp≤.001) and SDT (pConclusions: These findings indicate LTT and SDT may prove useful for monitoring psychomotor skills in INPH. While completion time reflects impaired processing speed, reduced accuracy may suggest planning and self-monitoring difficulties, aspects of executive functioning known to be compromised in INPH. This is the first study to underscore the importance of performance accuracy in INPH and introduce practical/reliable error scoring for these tasks. Future work will establish reliability and validity of these measures and determine their utility as outcome tools. (JINS, 2016, 22, 341–349)

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by disturbed gait, cognition, and urinary symptoms in the context of enlargement of the ventricular system. Typically, gait impairment is the most prominent feature, yet cognitive decline can predate other symptoms and contribute to functional impairments.1 The cognitive profile of iNPH is generally characterized by frontal-systems dysfunction, which includes executive deficits, compromised learning and recall, and reduced information processing and psychomotor speed. Improvement in gait has been well documented after shunt placement,2,3 yet controversy remains regarding the extent and pattern of postsurgical cognitive changes. Some studies report no change in mental status; others suggest improvement in up to 90% of patients.4–7 Conflicting findings may be explained by variations in the depth of cognitive examination, the way in which cognitive improvement is defined, and study follow-up intervals. Furthermore, most investigations lack a control group, making it difficult to disentangle practice effects from a true treatment effect. One recent study on iNPH treatment response used comparison data from a control sample and found that iNPH patients improved on most tasks; however, effects of prior exposure to test material could not be examined because the control subjects were tested at only 1 time point.7 Neuropsychological test performance can change as a result of measurement error, statistical considerations (ie, regression to the mean), or the effects of prior exposure to the testing material (ie, practice effects). Although the use of alternative test forms can alleviate some concerns regarding repeat testing, the most rigorous methodology involves a controlled study design in which both patients and control subjects undergo repeat assessment. We sought to examine postshunt changes in a sample of well-characterized iNPH participants compared with a group of age- and education-matched healthy control subjects.

Victoria M Wilkins1, Dimitris Kiosses1, Lisa D Ravdin21Department of Psychiatry, Weill Medical College of Cornell University, White Plains, NY, USA; 2Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Less than half of older adults with depression achieve remission with antidepressant medications, and rates of remission are even poorer for those with comorbid conditions. Psychosocial interventions have been effective in treating geriatric depression, either alone or better yet, in combination with antidepressant medications. Traditional strategies for nonpharmacological treatment of late-life depression do not specifically address the co-occurring cognitive impairment and disability that is prevalent in this population. Newer therapies are recognizing the need to simultaneously direct treatment efforts in late-life depression towards the triad of depressive symptoms, cognitive dysfunction, and functional disability that is so often found in geriatric depression, and this comprehensive approach holds promise for improved treatment outcomes.Keywords: geriatric depression, dementia, functional impairment, psychotherapy

Background Perioperative hypothermia has been reported to increase the occurrence of cardiovascular complications. By increasing the activity of sympathetic nervous system, perioperative hypothermia also has the potential to increase cardiac injury and dysfunction associated with subarachnoid hemorrhage. Methods The Intraoperative Hypothermia for Aneurysm Surgery Trial randomized patients undergoing cerebral aneurysm surgery to intraoperative hypothermia (n = 499, 33.3 degrees +/- 0.8 degrees C) or normothermia (n = 501, 36.7 degrees +/- 0.5 degrees C). Cardiovascular events (hypotension, arrhythmias, vasopressor use, myocardial infarction, and others) were prospectively followed until 3-month follow-up and were compared in hypothermic and normothermic patients. A subset of 62 patients (hypothermia, n = 33; normothermia, n = 29) also had preoperative and postoperative (within 24 h) measurement of cardiac troponin-I and echocardiography to explore the association between perioperative hypothermia and subarachnoid hemorrhage-associated myocardial injury and left ventricular function. Results There was no difference between hypothermic and normothermic patients in the occurrence of any single cardiovascular event or in composite cardiovascular events. There was no difference in mortality (6%) between groups, and there was only a single primary cardiovascular death (normothermia). There was no difference between hypothermic and normothermic patients in postoperative versus preoperative left ventricular regional wall motion or ejection fraction. Compared with preoperative values, hypothermic patients had no postoperative increase in cardiac troponin-I (median change 0.00 microg/l), whereas normothermic patients had a small postoperative increase (median change + 0.01 microg/l, P = 0.038). Conclusion In patients undergoing cerebral aneurysm surgery, perioperative hypothermia was not associated with an increased occurrence of cardiovascular events.

Background Although hypothermia and barbiturates improve neurologic outcomes in animal temporary focal ischemia models, the clinical efficacy of these interventions during temporary occlusion of the cerebral vasculature during intracranial aneurysm surgery (temporary clipping) is not established. Methods A post hoc analysis of patients from the Intraoperative Hypothermia for Aneurysm Surgery Trial who underwent temporary clipping was performed. Univariate and multivariate logistic regression methods were used to test for associations between hypothermia, supplemental protective drug, and short- (24-h) and long-term (3-month) neurologic outcomes. An odds ratio more than 1 denotes better outcome. Results Patients undergoing temporary clipping (n = 441) were assigned to intraoperative hypothermia (33.3 degrees +/- 0.8 degrees C, n = 208) or normothermia (36.7 degrees +/- 0.5 degrees C, n = 233), with 178 patients also receiving supplemental protective drug (thiopental or etomidate) during temporary clipping. Three months after surgery, 278 patients (63%) had good outcome (Glasgow Outcome Score = 1). Neither hypothermia (P = 0.847; odds ratio = 1.043, 95% CI = 0.678-1.606) nor supplemental protective drug (P = 0.835; odds ratio = 1.048, 95% CI = 0.674-1.631) were associated with 3-month Glasgow Outcome Score. The effect of supplemental protective drug did not significantly vary with temperature. The effects of hypothermia and protective drug did not significantly vary with temporary clip duration. Similar findings were made for 24-h neurologic status and 3-month Neuropsychological Composite Score. Conclusion In the Intraoperative Hypothermia for Aneurysm Surgery Trial, neither systemic hypothermia nor supplemental protective drug affected short- or long-term neurologic outcomes of patients undergoing temporary clipping.

The Tap Test (TT) is a commonly used method for predicting shunt responsiveness in patients with Normal Pressure Hydrocephalus (NPH). The present study investigates whether measures of upper extremity motor function are useful for assessing response to spinal fluid drainage.42 subjects undergoing evaluations for idiopathic NPH (iNPH) participated in this study. A standardized gait evaluation, a neuropsychological battery, and objective tests of upper extremity motor functions were administered. A Neurologist skilled in NPH assessment independently rated patients as TT Responders (n=26) or Non-Responders (n=16) based on clinical impression of change 2-4h after 40-50 cm(3) drainage of spinal fluid by lumbar puncture (LP). In the subset of subjects who underwent shunt placement, operative outcome was also evaluated.TT Responders improved significantly more than TT Non-Responders in Upper Extremity Coordination/Speed tasks (p.001). The groups did not differ on other neuropsychological measures post-LP. A possible association was observed between pre- and post-TT changes in Upper Extremity Coordination/Speed and post-shunt improvement. Among Upper Extremity Coordination/Speed measures, Line Tracing displayed the greatest sensitivity (76%) to change post-LP.Our data suggest that measures of upper extremity motor functions may be useful as measures of Tap Test response in patients with iNPH. These upper extremity motor tasks can be rapidly administered (5 min) in clinical practice and may provide an additional dimension beyond gait and cognition for evaluating response to LP.

Low-grade or minimal hepatic encephalopathy (MHE) is characterised by relatively mild neurocognitive impairments, and occurs in a substantial percentage of patients with liver disease. The presence of MHE is associated with a significant compromise of quality of life, is predictive of the onset of overt hepatic encephalopathy and is associated with a poorer prognosis for outcome. Early identification and treatment of MHE can improve quality of life and may prevent the onset of overt encephalopathy, but to date, there has been little agreement regarding the optimum method for detecting MHE. The International Society on Hepatic Encephalopathy and Nitrogen Metabolism convened a group of experts for the purpose of reviewing available data and making recommendations for a standardised approach for neuropsychological assessment of patients with liver disease who are at risk of MHE. Specific recommendations are presented, along with a proposed methodology for further refining these assessment procedures through prospective research.

Boxing has held appeal for many athletes and audiences for centuries, and injuries have been part of boxing since its inception. Although permanent and irreversible neurologic dysfunction does not occur in the majority of participants, an association has been reported between the number of bouts fought and the development of neurologic, psychiatric, or histopathological signs and symptoms of encephalopathy in boxers. The purpose of this paper is to (i) provide clinical neuropsychologists, other health-care professionals, and the general public with information about the potential neuropsychological consequences of boxing, and (ii) provide recommendations to improve safety standards for those who participate in the sport.

Background and Purpose Systemic lupus erythematosus (SLE) is an autoimmune disease in which almost all the organs are involved. Neuropsychiatric SLE is of one of the major concerns in the clinical evaluation of this disease. Routine magnetic resonance imaging (MRI) findings are often nonspecific or negative. In this study, we explored the use of diffusion tensor imaging in assisting with the diagnosis of SLE. Methods Data from 34 SLE patients (age range, 18–73 years) and 29 age-matched volunteers (age range, 29–64 years) were analyzed. MRI was performed on a 1.5-T clinical MR scanner with a quadrature head coil. The average diffusion constant (Dav) and diffusion anisotropy maps [fractional anisotropy (FA)] were determined on a pixel-by-pixel basis. Regional diffusion measurements were made by region of interest in the genu and splenium of the corpus callosum (CC), anterior and posterior limb of the internal capsule (IC) and frontal lobe and thalamus. The diffusion distribution was fitted to a triple-Gaussian model. The mean of the brain tissue distribution was determined as a mean diffusion constant for the whole brain (BDav). Student's t test was used to determine the diffusion difference between SLE patients and control subjects. The SLE patients were separated into two groups according to their MRI results. A P value lower than .05 was considered to be statistically significant. Results Twenty of the 34 SLE patients with abnormal MRI results showed findings dominated by nonspecific white matter disease. The BDav and Dav values of the frontal lobe, splenium CC and anterior IC were significantly higher in all SLE patients as compared with the control subjects. The SLE patients with normal MRI results also showed higher BDav and Dav values in the frontal lobe, splenium and anterior and posterior limbs of the IC as compared with the control subjects. There was no significant difference in the Dav values of the thalamus between the SLE patients and the control subjects. The BDav value in the SLE patient group was robustly correlated with the Dav values of the frontal lobe, splenium and thalamus. These correlations were found to be similarly significant for the SLE patients with normal MRI findings. The diffusion anisotropy measurements showed that splenium CC had the highest FA value in both the control subjects and SLE patients. Overall, SLE patients had lower FA values in the genu and splenium CC as compared with the control subjects. In the group of patients with normal MRI findings, the FA values of the genu and splenium CC as well as the anterior IC were also lower than those in the control subjects. Pearson's correlation statistics revealed robust correlations between the measurements of Dav and FA values in the SLE patient group. Conclusion Quantitative diffusion imaging and diffusion anisotropy showed early changes in the brains of the SLE patients. Increased BDav and Dav values of the frontal lobe as well as decreased anisotropy in the genu CC and anterior IC may represent preclinical signs of central nervous system involvement of SLE even when the routine MRI findings are negative or nonspecific. Quantitative diffusion analysis may prove to be useful in detecting the initial brain involvement of SLE and may enable monitoring of early disease progression and treatment efficacy.

Objective To assess the association between serum NR2a antibodies and cognitive dysfunction in systemic lupus erythematosus (SLE). Methods The study population consisted of English-speaking adults who met American College of Rheumatology (ACR) criteria for SLE and had at least 1 serum sample stored in the Hospital for Special Surgery Autoimmune Registry and Repository. Demographic and clinical information was obtained, and patients completed the neuropsychological test battery recommended by the ACR, the Center for Epidemiologic Studies Depression Scale, and the Spielberger State-Trait Anxiety Inventory. Cognitive impairment was defined as scores >1.5 SD below the mean of age-matched published normative data on at least 2 neuropsychological tests. Sera were tested for NR2a antibodies by enzyme-linked immunosorbent assay. Performance on neuropsychological tests was compared between NR2a-positive and NR2a-negative patients. Results Of the 93 patients, 24 (25.8%) were positive for NR2a antibodies. Of the 48 patients who were cognitively impaired based on test results, 31% were positive for NR2a antibodies, compared with 20% of those who were not cognitively impaired (P = 0.24). Among antibody-positive patients, the mean ± SD number of neuropsychological tests with abnormal results was 2.3 ± 2.2, compared with 2.0 ± 1.8 in the antibody-negative group (P = 0.59). Similar nonsignificant differences were found when impairment was defined using a more stringent definition (i.e., test scores >2.0 SD below the mean) and using a neuropsychologist's clinical ratings. No association was detected between NR2a antibody positivity and depressive symptoms (P = 0.73) or anxiety (P = 0.42). Conclusion No significant association was found between NR2a antibody positivity and cognitive dysfunction, depressive symptoms, or anxiety. These results indicate that the presence of these antibodies alone does not have a direct effect on cognitive functioning or any other neuropsychiatric manifestation of SLE.

Purpose: Alzheimer’s disease, for which one form of the apolipoprotein E (APOE) genotype is a risk factor, provides a paradigm in which to examine response to susceptibility testing for common, complex diseases. This study’s main purposes were to estimate interest in such testing and to examine demographic predictors of study participation. Methods: In this 3-site, randomized clinical trial (RCT), the intervention was a risk assessment program wherein genetic counselors educated adult children of AD patients about lifetime risk of disease based on their gender, family history, and APOE genotype. Two groups of participants were followed from initial contact to RCT enrollment: those who were systematically contacted through research registries, and those who were self-referred. Results: Of 196 systematically contacted participants, 47, or 24%, progressed from initial contact to RCT enrollment. These participants were more likely to be below age 60 (adjusted OR = 3.83, P < 0.01) and college educated (adjusted OR = 3.48, P < 0.01). Of 179 self-referred participants, 115, or 64%, progressed from initial contact to RCT enrollment. Most self-referred participants had a college education and were female (79%). Conclusions: In the first RCT to examine genetic susceptibility testing for AD, uptake rates were sufficiently high to merit concern that future test demand may strain available education and counseling resources. Findings suggest that susceptibility testing for AD may be of particular interest to women, college educated persons, and persons below age 60.

Depression induced cognitive impairment, also referred to as the dementia syndrome of depression or pseudodementia, has been well characterized, yet the extent to which the more common mild depressive symptoms influence cognition has not been well studied. We sought to identify the influence of mild depressive symptoms on verbal fluency performance in a large sample of healthy community dwelling older adults. Letter and semantic fluency testing was conducted on 188 participants (ages 60-92 years) with no known history of neurologic or psychiatric disease. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS). A total of 39 subjects obtained GDS scores consistent with mild depressive symptoms (GDS=10-19), and 149 subjects were identified as not depressed (GDS10). ANOVA indicated that subjects with mild depressive symptoms performed significantly worse than normal controls on letter fluency (p.05), but there was no significant difference between the groups on semantic fluency. Analysis of the nondepressed group stratified into young-old, middle-old, and oldest-old revealed a significant decline in semantic (p.001) but not letter fluency with age. The nondepressed young-old showed the expected advantage for word list generation to semantic as compared to letter categories, yet this pattern was reversed in the older age groups, where letter fluency scores exceeded semantic fluency scores. Our results suggest that the presence of even mild depressive symptoms may confound using letter versus category discrepancies in the differential diagnosis of dementia. Further, our findings suggest that the commonly used strategy of examining letter-semantic fluency discrepancies may not be relevant for individuals of advanced age. Age-stratified normative data for fluency testing in older adults is also provided.

Neuropsychiatric syndromes associated with systemic lupus erythematosus are common, but diverse in etiology and presentation. Cognitive dysfunction is prevalent among these syndromes, but exhibit a significant degree of heterogeneity both within and between patient variability. Earlier studies of SLE-associated cognitive dysfunction addressed its identification and description. Common associations were repeatedly acknowledged, including concomitant or past neuropsychiatric disease, use of corticosteroids, disease activity, emotional disturbance, and antiphospholipid antibodies. The past several years have focused more on elucidating the relative strengths of various risk associations, patterns of cognitive abnormalities, both cross-sectionally and longitudinally (ie, clinical course), and novel means to identify cognitive impairment, both functionally and biologically.

Chronic pain is highly prevalent in older adults, contributes to activity restriction and social isolation, disrupts family and interpersonal relationships, and poses a significant economic burden to society. Negative emotions such as sadness, anxiety, helplessness, and hopelessness are associated with chronic pain and contribute to poor quality of life, impaired interpersonal and social functioning, and increased disability. Psychosocial interventions for older adults with chronic pain have been historically developed for, and are almost exclusively delivered to, cognitively intact patients. Therefore, many older adults with chronic pain and comorbid cognitive deficits have limited treatment options. Our multidisciplinary team developed Problem Adaptation Therapy for Pain in Primary Care (PATH-Pain), a psychosocial intervention for older adults with chronic pain, negative emotions, and a wide range of cognitive functioning, including mild-to-moderate cognitive impairment. In the current article, we describe the principles underlying PATH-Pain, review the steps taken to adapt the original PATH protocol, outline the treatment process, and present a case illustrating its potential value.

Summary: Purpose: The purpose of this study was to obtain preliminary information about the effect of menopause and perimenopause on the course of epilepsy, and to determine whether seizure type, use of hormone-replacement therapy (HRT), or a history of catamenial seizure pattern would influence this course. Methods: We performed a questionnaire study of women with epilepsy currently in menopause and perimenopause, requesting information regarding the course of their epilepsy and treatment. Statistical analysis was performed by using Pearson X2 with 95% confidence limits. Results: Forty-two menopausal women (ages 41–86 years) responded. Twelve subjects reported no change in seizures at menopause, 17 reported a decrease in seizure frequency, and 13 reported an increase. Sixteen (38%) took synthetic HRT. Sixteen (38%) additional subjects (having some overlap with the HRT group) reported having a catamenial seizure pattern before menopause. HRT was significantly associated with an increase in seizures during perimenopause (p = 0.001). A history of catamenial seizure pattern was significantly associated with a decrease in seizures at menopause (p = 0.013). Thirty-nine perimenopausal women (ages 38–55 years) responded. Nine subjects reported no change in seizures at perimenopause, five reported a decrease in seizure frequency, and 25 reported an increase. Eight (15%) subjects took synthetic HRT, and 28 (72%) reported having a catamenial seizure pattern before menopause. HRT had no significant effect on seizures; however, a history of catamenial seizure pattern was significantly associated with an increase in seizures at perimenopause (p = 0.02). Conclusions: These pilot data suggest that synthetic HRT may be associated with an increase in seizure frequency in menopausal women with epilepsy. A catamenial seizure pattern may be associated with seizure decrease during menopause but with an increase during perimenopause.

This study examined the relation between complaints of memory disturbance and measures of mood and memory functioning in 55 patients with serological evidence of late-stage Lyme Borreliosis (LB). Patients completed the Self-Ratings of Memory Questionnaire (SRMQ) and the Beck Depression Inventory. Memory functioning was assessed with the California Verbal Learning Test. Depressed patients exhibited more frequent complaints of memory disturbance on the SRMQ, although their pattern of responses did not differ from nondepressed patients. There was a significant correlation between subjective memory ratings and self-reported depression (Spearman rho = -.57, p.001). No relation was observed between subjective memory ratings and objective memory performance. The results indicate subjective complaints of more severe memory disturbance in patients with LB and depression. Particular attention should be paid to the assessment of depression and subjective symptoms of memory disturbance when administering neuropsychological tests of memory functioning in patients with LB.

We sought to identify markers of motor and nonmotor function in Parkinson's disease (PD) using advanced neuroimaging techniques in subjects with PD.We enrolled 26 nondemented PD subjects and 12 control subjects. All subjects underwent [(18)F]fluorodeoxyglucose positron emission computed tomography (FDG-PET) and magnetic resonance imaging, and a complete neuropsychological battery.FDG-PET of subjects with PD revealed significant metabolic elevations in the bilateral posterior lentiform nucleus, posterior cingulate, and parahippocampus, and metabolic reductions in the bilateral temporoparietal association cortex and occipital lobe versus controls. PD subjects had significant reductions in executive/attention function, memory/verbal learning, and speed of thinking, and significantly increased depression, anxiety and apathy scores compared with controls. Motor dysfunction correlated with increased metabolism in the posterior lentiform nucleus, pons, and cerebellum, and decreased metabolism in the temporoparietal lobe. Cognitive dysfunction correlated with increased posterior cingulate metabolism and decreased temporoparietal lobe metabolism. Depressive symptoms correlated with increased amygdala metabolism; anxiety scores correlated with decreased caudate metabolism, and apathy scores correlated with increased metabolism in the anterior cingulate and orbitofrontal lobe and decreased metabolism in the temporoparietal association cortex.Our findings showed that motor, cognitive, and emotional dysfunction in PD are associated with distinct patterns of cerebral metabolic changes.

Idiopathic normal pressure hydrocephalus (INPH) is characterized by the clinical triad of gait disturbance, cognitive dysfunction, and urinary symptoms, observed in the context of enlargement of the cerebral ventricular system. Mean age of onset is approximately 60 years, which complicates the diagnosis since there is the potential for multiple age-related comorbidities in this population. Typically, gait disturbance is the presenting symptom that brings an individual to medical attention, but cognitive decline can be the initial symptom in some cases. NPH is an important diagnostic entity for the neuropsychologist working with older adults to be familiar with, since it is one of the few progressive cognitive disturbances that can be effectively treated. The current standard of care treatment is placement of a ventriculoperitoneal shunt, which can lead to reversal of symptoms, but shunt surgery is not without complications and careful patient selection is prudent. The neuropsychologist can be a key contributor in clinical settings for diagnostic considerations and in the evaluation of treatment response. In this chapter, we present a discussion of the clinical presentation and characteristic features of INPH, explore recent evidence-based diagnostic criteria, and provide guidelines for neuropsychological evaluation of INPH. A case example documenting post-shunt recovery of function is presented.

Subtle cognitive deficits persist in schizophrenia even after active periods of psychosis subside. Even though early attempts to ameliorate cognitive impairments were relatively successful, the endeavor was abandoned nearly 30 years ago. We contrast this state of affairs with that of closed-head injury, in which less well-designed and less successful attempts to treat similar impairments have been greeted with much enthusiasm. Objections to cognitive remediation in schizophrenia are evaluated and the attempt is encouraged.

OBJECTIVE: We examined the incidence of perioperative fever and its relationship to outcome among patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial. METHODS: One thousand patients with initial World Federation of Neurological Surgeons grades of I to III undergoing clipping of intracranial aneurysms after subarachnoid hemorrhage were randomized to intraoperative normothermia (36 degrees C-37 degrees C) or hypothermia (32.5 degrees C-33.5 degrees C). Fever (> or =38.5 degrees C) and other complications (including infections) occurring between admission and discharge (or death) were recorded. Functional and neuropsychologic outcomes were assessed 3 months postoperatively. The primary outcome variable for the trial was dichotomized Glasgow Outcome Scale (good outcome versus all others). RESULTS: Fever was reported in 41% of patients. In 97% of these, fever occurred in the postoperative period. The median time from surgery to first fever was 3 days. All measures of outcome were worse in patients who developed fever, even in those without infections or who were World Federation of Neurological Surgeons grade I. Logistic regression analyses were performed to adjust for differences in preoperative factors (e.g., age, Fisher grade, initial neurological status). This demonstrated that fever continued to be significantly associated with most outcome measures, even when infection was added to the model. An alternative stepwise model selection process including all fever-related measures from the preoperative and intraoperative period (e.g., hydrocephalus, duration of surgery, intraoperative blood loss) resulted in the loss of significance for dichotomized Glasgow Outcome Scale, but significant associations between fever and several other outcome measures remained. After adding postoperative delayed ischemic neurological deficits to the model, only worsened National Institutes of Health Stroke Scale score, Barthel Activities of Daily Living index, and discharge destination (home versus other) remained independently associated with fever. CONCLUSION: These findings suggest that fever is associated with worsened outcome in surgical subarachnoid hemorrhage patients, although, because the association between fever and the primary outcome measure for the trial is dependent on the covariates used in the analysis (particularly operative events and delayed ischemic neurological deficits), we cannot rule out the possibility that fever is a marker for other events. Only a formal trial of fever treatment or prevention can address this issue.

Objective: To identify components of gait associated with a positive tap test (TT) in patients with idiopathic normal pressure hydrocephalus (iNPH). Patients and methods: Thirty-three patients with iNPH underwent clinical evaluation pre- and post-TT and were classified as responders (Rs) or non-responders (NRs). Elements of gait were assessed with a formal standardized Gait Scale and compared between groups. Results: Analysis of pre/post-TT group differences revealed an interaction for Total Gait Score and Walking Score, with improvements in responders only. Total Gait Scores improved by 29% in the Rs and 4.85% in the NRs. Rs showed significant post-TT improvements on a timed 10 m walk, turning, and balance. Tandem walking, turning, truck balance and start stop hesitation showed trends toward improvement. Conclusions: The classic features of gait often used in determining diagnosis of NPH (wide based stride, reduced foot-floor clearance, and small steps) were not helpful in identifying responders to the TT. Walking speed, steps for turning, and tendency towards falling were most likely to improve post-TT. These straightforward measures can readily be adapted into clinical practice to assist in determination of shunt candidacy.

Importance Problem adaptation therapy (PATH) is a treatment for older adults with major depression, cognitive impairment (from mild cognitive deficits to moderate dementia), and disability. Antidepressants have limited efficacy in this population and psychosocial interventions are inadequately investigated. Objective To test the efficacy of 12-week PATH vs supportive therapy for cognitively impaired patients (ST-CI) in reducing depression and disability in 74 older adults with major depression, cognitive impairment, and disability. Design, Setting, and Participants A randomized clinical trial at the Weill Cornell Institute of Geriatric Psychiatry from April 1, 2006, to September 31, 2011. Interventions were administered at the participants’ homes. Participants included 74 older individuals (age ≥65 years) with major depression and cognitive impairment to the level of moderate dementia. They were recruited through collaborating community agencies of Weill Cornell Institute of Geriatric Psychiatry and were randomly assigned to 12 weekly sessions of PATH or ST-CI (14.8% attrition rate). Interventions Home-delivered PATH vs home-delivered ST-CI. Problem adaptation therapy integrates a problem-solving approach with compensatory strategies, environmental adaptations, and caregiver participation to improve patients’ emotion regulation. Supportive therapy for cognitively impaired patients focuses on expression of affect, understanding, and empathy. Main Outcomes and Measures Mixed-effects models for longitudinal data compared the efficacy of PATH with that of ST-CI in reducing depression (Montgomery-Asberg Depression Rating Scale) and disability (World Health Organization Disability Assessment Schedule II) during 12 weeks of treatment. Results Participants in PATH had significantly greater reduction in depression (Cohen d , 0.60; 95% CI, 0.13-1.06; treatment × time, F 1,179 = 8.03; P = .005) and disability (Cohen d , 0.67; 95% CI, 0.20-1.14; treatment × time, F 1,169 = 14.86; P = .001) than ST-CI participants during the 12-week period (primary outcomes). Furthermore, PATH participants had significantly greater depression remission rates than ST-CI participants (37.84% vs 13.51%; χ 2 = 5.74; P = .02; number needed to treat = 4.11) (secondary outcome). Conclusions and Relevance Problem adaptation therapy was more efficacious than ST-CI in reducing depression and disability. Problem adaptation therapy may provide relief to a large group of depressed and cognitively impaired older adults who have few treatment options. Trials Registration Clinicaltrials.gov Identifier:NCT00368940

Purpose: To determine whether individuals recall their apolipoprotein E genotype and numeric lifetime risk estimates after undergoing a risk assessment for Alzheimer's disease. Methods: One-hundred and four participants underwent Alzheimer's disease risk assessment that included disclosure of apolipoprotein E genotype and a numeric lifetime risk estimate. Results: At six weeks and one year post-disclosure, 59% and 48% of participants, respectively, recalled their lifetime risk estimate, and 69% and 63% recalled their apolipoprotein E genotype. Participants were more likely to remember their genotype than numeric lifetime risk estimate at one year (P < 0.05). Apolipoprotein E ɛ4-positive participants had better recall of their genotype at both time points (P < 0.05). Participants were more likely to recall whether they carried the “risk-enhancing form of apolipoprotein E” than their specific genotype (P < 0.05). Conclusions: These data suggest that apolipoprotein E genotype, especially the presence of an ɛ4 allele, is more memorable than a numeric risk estimate for Alzheimer's disease. Participants recalled genotype information in a more simplified, binary form. Health professionals testing for complex disorders such as Alzheimer's disease must find an appropriate balance between communicating risk in an understandable format and addressing the probabilistic nature of the information.

The authors developed an 8-week psychoeducational group intervention for patients with systemic lupus erythematosus (SLE) who reported cognitive dysfunction but were not globally impaired on neuropsychological testing. Results of a nonrandomized, uncontrolled pilot study of this program in 17 women with SLE suggest that metamemory and memory self-efficacy improve after participation. One hundred percent retention throughout the study further suggests that patients with SLE are willing and capable of successfully completing the program.

Some aspects of memory and other thinking abilities decline as part of the normal aging process. Normal age-related cognitive decline and disease-associated cognitive impairment can be difficult to differentiate in the typical patient-physician interaction, especially in the geriatric primary care setting where patients may present with multiple physical complaints that consume the physician's attention. It is essential that clinician's recognize even modest changes in thinking abilities in the geriatric patient since these changes may be an early warning sign of an impending dementing disorder. At the very least, reduced cognitive functioning can decrease one's quality of life as well as threaten their independence. When cognitive decline is suspected, a neuropsychological evaluation can provide an objective assessment of cognitive functioning that is useful for differential diagnosis, assessing presence and progression of cognitive disorders, and providing information relevant to treatment and planning. This article explores the challenges of cognitive assessment in older adults and provides an overview of the neuropsychological evaluation, its advantages and limitations, as well as common referral questions from primary care physicians.

Context. Antiepileptic drugs (AEDs) are frequently used for their beneficial mood effects.Objective. We sought to determine if there was a quantifiable effect on mood of the vagus nerve stimulator (VNS) when used as an antiseizure treatment.Design. Mood was assessed before and 3 months after VNS implantation in adult epilepsy patients. A group of adult epilepsy patients on stable AED regimens were used as a comparison group. AED regimens were unchanged during the study. The change in mood scale scores across time was assessed by t test (intragroup) and two-factor repeated-measures ANOVA (intergroup).Setting. An epilepsy center in a university hospital was the setting.Subjects. Twenty consecutive adult epilepsy patients undergoing VNS implantation to improve seizure control and twenty adult seizure patients with no intervention were enrolled.Main outcome measures. The mood scales used were the Cornell Dysthymia Rating Scale (CDRS) and the Hamilton Depression (Ham-D), Hamilton Rating Scale for Anxiety (Ham-A), and Beck Depression Inventory (BDI) scales.Results. The VNS group showed a significant decrease in mood scale scores across time (t test CDRS P = 0.001, Ham-D P = 0.017, BDI P = 0.045), indicating a decrease in depressive symptoms. The Ham-A scores in the VNS group and the comparison group scores did not significantly change across time. There were no significant differences between groups across time, although the BDI approached significance at P = 0.07. The VNS group had a significant decrease in seizure frequency compared with the comparison group (P = 0.01). There was no difference in mood scales over time between the VNS treatment responders (defined by >50% decrease in seizure frequency) and nonresponders, suggesting dissociation between seizure frequency reduction and mood change.Conclusion. VNS treatment is associated with mood improvement as measured by multiple scales, but differences in mood scale scores over time between the VNS and a comparison group were not found.