Comparing the North American Adult Reading Test (NAART) and the Test of Premorbid Functioning (TOPF) to estimate premorbid Wechsler Adult Intelligence Scale - 4th edition FSIQ in a clinical sample with epilepsy.

Estimating premorbid general cognitive functioning is an essential component to the neuropsychological evaluation process. The North American Adult Reading Test (NAART) is a method to predict premorbid general cognitive functioning based on word reading skills developed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R), which is currently in its fourth edition (WAIS-IV). The Test of Premorbid Function (TOPF) was developed using the WAIS-IV, based on the same method as the NAART, to estimate premorbid intellectual ability. There is a paucity of research comparing estimates of premorbid general intellectual ability between the NAART and TOPF. This study evaluated the clinical utility of premorbid estimates of FSIQ derived from the NAART and TOPF in a sample of 101 patients with temporal lobe epilepsy (TLE). Differences between NAART-derived premorbid FSIQs and TOPF simple demographic predicted FSIQs were significant (p < .001) with large effect sizes. NAART estimated premorbid FSIQ (M = 104.04, SD = 8.42) was significantly greater than TOPF premorbid estimates (M = 99.83, SD = 9.26). Results suggested NAART-derived estimates of premorbid FSIQ may be more accurate than TOPF-based estimates, which likely underestimated premorbid FSIQ in this sample of patients with epilepsy. Limitations and future directions are discussed.

Lower Cardiac Output Relates to Longitudinal Cognitive Decline in Aging Adults.

BACKGROUND: Subclinical reductions in cardiac output correspond to lower cerebral blood flow (CBF), placing the brain at risk for functional changes. OBJECTIVES: This study aims to establish the consequences of reduced cardiac output on longitudinal cognitive outcomes in aging adults. METHODS: Vanderbilt Memory and Aging Project participants free of clinical dementia and heart failure (n = 306, 73 ± 7, 58% male) underwent baseline echocardiography to assess cardiac output (L/min) and longitudinal neuropsychological assessment at baseline, 18 months, 3 and 5 years. Linear mixed-effects regressions related cardiac output to trajectory for each longitudinal neuropsychological outcome, adjusting for age, sex, race/ethnicity, education, body surface area, Framingham Stroke Risk Profile score, apolipoprotein E (APOE) ε4 status and follow-up time. Models were repeated, testing interactions with cognitive diagnosis and APOE-ε4 status. RESULTS: Lower baseline cardiac output related to faster declines in language (ß = 0.11, p = 0.01), information processing speed (ß = 0.31, p = 0.006), visuospatial skills (ß = 0.09, p = 0.03), and episodic memory (ß = 0.02, p = 0.001). No cardiac output x cognitive diagnosis interactions were observed (p > 0.26). APOE-ε4 status modified the association between cardiac output and longitudinal episodic memory (ß = 0.03, p = 0.047) and information processing speed outcomes (ß = 0.55, p = 0.02) with associations stronger in APOE-ε4 carriers. CONCLUSION: The present study provides evidence that even subtle reductions in cardiac output may be associated with more adverse longitudinal cognitive health, including worse language, information processing speed, visuospatial skills, and episodic memory performances. Preservation of healthy cardiac functioning is important for maintaining optimal brain aging among older adults.

Lower Left Ventricular Ejection Fraction Relates to Cerebrospinal Fluid Biomarker Evidence of Neurodegeneration in Older Adults.

BACKGROUND: Subclinical cardiac dysfunction is associated with decreased cerebral blood flow, placing the aging brain at risk for Alzheimer's disease (AD) pathology and neurodegeneration. OBJECTIVE: This study investigates the association between subclinical cardiac dysfunction, measured by left ventricular ejection fraction (LVEF), and cerebrospinal fluid (CSF) biomarkers of AD and neurodegeneration. METHODS: Vanderbilt Memory & Aging Project participants free of dementia, stroke, and heart failure (n = 152, 72±6 years, 68% male) underwent echocardiogram to quantify LVEF and lumbar puncture to measure CSF levels of amyloid-ß42 (Aß42), phosphorylated tau (p-tau), and total tau (t-tau). Linear regressions related LVEF to CSF biomarkers, adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E ɛ4 status. Secondary models tested an LVEF x cognitive diagnosis interaction and then stratified by diagnosis (normal cognition (NC), mild cognitive impairment (MCI)). RESULTS: Higher LVEF related to decreased CSF Aß42 levels (ß= -6.50, p = 0.04) reflecting greater cerebral amyloid accumulation, but this counterintuitive result was attenuated after excluding participants with cardiovascular disease and atrial fibrillation (p = 0.07). We observed an interaction between LVEF and cognitive diagnosis on CSF t-tau (p = 0.004) and p-tau levels (p = 0.002), whereas lower LVEF was associated with increased CSF t-tau (ß= -9.74, p = 0.01) and p-tau in the NC (ß= -1.41, p = 0.003) but not MCI participants (p-values>0.13). CONCLUSIONS: Among cognitively normal older adults, subclinically lower LVEF relates to greater molecular evidence of tau phosphorylation and neurodegeneration. Modest age-related changes in cardiovascular function may have implications for pathophysiological changes in the brain later in life.

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition.

INTRODUCTION: Neuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage. METHODS: Plasma and cerebrospinal fluid (CSF) neurofilament light (NFL) were related to neuropsychological performance among Vanderbilt Memory & Aging Project participants (plasma n = 333, 73 ± 7 years; CSF n = 149, 72 ± 6 years) ranging from normal cognition (NC) to mild cognitive impairment (MCI). Models adjusted for age, sex, race/ethnicity, education, apolipoprotein E ε4 carriership, and Framingham Stroke Risk Profile. RESULTS: Plasma NFL was related to all domains (P values ≤ .008) except processing speed (P values ≥ .09). CSF NFL was related to memory and language (P values ≤ .04). Interactions with cognitive diagnosis revealed widespread plasma associations, particularly in MCI participants, which were further supported in head-to-head comparison models. DISCUSSION: Plasma and CSF NFL (reflecting neuroaxonal injury) relate to cognition among non-demented older adults albeit with small to medium effects. Plasma NFL shows particular promise as an accessible biomarker with relevance to cognition in MCI.

Adverse Vascular Risk Relates to Cerebrospinal Fluid Biomarker Evidence of Axonal Injury in the Presence of Alzheimer's Disease Pathology.

BACKGROUND: Vascular risk factors promote cerebral small vessel disease and neuropathological changes, particularly in white matter where large-caliber axons are located. How Alzheimer's disease pathology influences the brain's vulnerability in this regard is not well understood. OBJECTIVE: Systemic vascular risk was assessed in relation to cerebrospinal fluid concentrations of neurofilament light, a biomarker of large-caliber axonal injury, evaluating for interactions by clinical and protein markers of Alzheimer's disease. METHODS: Among Alzheimer's Disease Neuroimaging Initiative participants with normal cognition (n = 117), mild cognitive impairment (n = 190), and Alzheimer's disease (n = 95), linear regression related vascular risk (as measured by the modified Framingham Stroke Risk Profile) to neurofilament light, adjusting for age, sex, education, and cognitive diagnosis. Interactions were assessed by cognitive diagnosis, and by cerebrospinal fluid markers of Aß42, hyperphosphorylated tau, and total tau. RESULTS: Vascular risk and neurofilament light were not related in the main effect model (p = 0.08). However, interactions emerged for total tau (p = 0.01) and hyperphosphorylated tau (p = 0.002) reflecting vascular risk becoming more associated with cerebrospinal fluid neurofilament light in the context of greater concentrations of tau biomarkers. An interaction also emerged for the Alzheimer's disease biomarker profiles (p = 0.046) where in comparison to the referent 'normal' biomarker group, individuals with abnormal levels of both Aß42 and total tau showed stronger associations between vascular risk and neurofilament light. CONCLUSION: Older adults may be more vulnerable to axonal injury in response to higher vascular risk burdens in the context of concomitant Alzheimer's disease pathology.

Apolipoprotein E Genotype Modifies the Association Between Cardiac Output and Cognition in Older Adults.

Background Subtle reductions in cardiac output relate to lower cerebral blood flow, especially in regions where Alzheimer's disease pathology first develops. Apolipoprotein E (APOE)-ε4 is a genetic susceptibility risk factor for Alzheimer's disease that also moderates vascular damage. This study investigated whether APOE-ε4 carrier status modifies the cross-sectional association between cardiac output and cognition. Methods and Results Vanderbilt Memory & Aging Project participants free of clinical stroke and dementia (n=306, 73±7 years, 42% female) underwent echocardiography to determine cardiac output (L/min), comprehensive neuropsychological assessment, and venous blood draw to determine APOE genotype and ε4 carrier status. Linear regressions related cardiac output to neuropsychological test performance, adjusting for age, sex, education, race/ethnicity, body surface area, cognitive diagnosis, Framingham Stroke Risk Profile, and APOE-ε4 status. Main effect models were null (P>0.19). With identical covariates, models were repeated testing a cardiac output×APOE-ε4 status interaction and again stratified by ε4 carrier status. Cardiac output×APOE-ε4 status related to naming (ß=0.91, P=0.0009), category fluency (ß=1.2, P=0.01), information processing speed (ß=-5.4, P=0.001), visuospatial skill (ß=0.85, P=0.003), and executive function performances (ß=0.22, P=0.002). Stratified models suggested that lower cardiac output was associated with worse neuropsychological performances among APOE-ε4 carriers. Conclusions APOE-ε4 carrier status appears to modify the cross-sectional association between cardiac output and neuropsychological performance such that lower cardiac output relates to poorer performances among carriers of the ε4 allele. These findings add to increasing evidence that APOE-ε4 carrier status has important implications for associations between vascular and brain health in aging adults.

White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities.

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia.

Perivascular spaces contribute to cognition beyond other small vessel disease markers.

OBJECTIVE: To cross-sectionally relate multiple small vessel disease (SVD) neuroimaging markers to cognition among older adults. METHODS: Vanderbilt Memory & Aging Project participants free of clinical dementia and stroke (n = 327, age 73 ± 7 years, 59% male, 40% with mild cognitive impairment) completed neuropsychological assessment and 3T MRI to measure white matter hyperintensities (WMH), perivascular spaces (PVS), cerebral microbleeds (CMBs), and lacunes. Linear regressions related each SVD marker to neuropsychological performances and adjusted for age, sex, race/ethnicity, education, cognitive diagnosis, APOE ε4 presence, Framingham Stroke Risk Profile, and intracranial volume. RESULTS: WMH related to the most neuropsychological measures, including the Boston Naming Test, Animal Naming, Coding, Number Sequencing, Executive Function Composite, and Hooper Visual Organization Test performances (p ≤ 0.01). PVS related to multiple information processing and executive function performances (p ≤ 0.02). Lacunes and CMBs related to fewer measures than expected. Combined models simultaneously testing multiple statistically significant SVD predictors suggested that WMH, PVS, and CMBs each independently related to information processing and executive function performances; however, compared to other SVD markers, PVS remained statistically significant in models related to information processing and executive functioning performances. CONCLUSIONS: As expected, increased WMH corresponded to poorer performances across multiple cognitive domains. PVS, previously considered a benign neuroimaging feature in older adults, may have important clinical implications because PVS was related to information processing and executive function performances even in combined models. On the basis of models with multiple SVD predictors, WMH, PVS, and CMBs may each reflect a separate pathway of small vessel injury.

Neurofilament relates to white matter microstructure in older adults.

Cerebrospinal fluid (CSF) neurofilament light (NFL) is a protein biomarker of axonal injury. To study whether NFL is associated with diffusion tensor imaging (DTI) measurements of white matter (WM) microstructure, Vanderbilt Memory & Aging Project participants with normal cognition (n = 77), early mild cognitive impairment (n = 15), and MCI (n = 55) underwent lumbar puncture to obtain CSF and 3T brain MRI. Voxel-wise analyses cross-sectionally related NFL to DTI metrics, adjusting for demographic and vascular risk factors. Increased NFL correlated with multiple DTI metrics (p-values < 0.05). An NFL × diagnosis interaction (excluding early mild cognitive impairment) on WM microstructure (p-values < 0.05) was detected, with associations strongest among MCI. Multiple NFL × CSF biomarker interactions were detected. Associations between NFL and worse WM metrics were strongest among amyloid-ß42-negative, tau-positive, and suspected nonamyloid pathology participants. Findings suggest increased NFL, a biomarker of axonal injury, is correlated with compromised WM microstructure. Results highlight the role of elevated NFL in predicting WM damage in cognitively impaired older adults who are amyloid-negative, tau-positive, or meet suspected nonamyloid pathology criteria.

APOE genotype modifies the association between central arterial stiffening and cognition in older adults.

Arterial stiffening is associated with cognitive impairment and prodromal Alzheimer's disease. This study tested the interaction between arterial stiffening and an Alzheimer's disease genetic risk factor (apolipoprotein E [APOE] genotype) on cognition among older adults. Vanderbilt Memory & Aging Project participants with normal cognition (n = 162, 72 ± 7 years, 29% APOE-ε4 carrier) and mild cognitive impairment (n = 121, 73 ± 8 years, 42% APOE-ε4 carrier) completed neuropsychological assessment and cardiac MRI to assess aortic stiffening using pulse wave velocity (PWV, m/s). Linear regression models stratified by cognitive diagnosis related aortic PWV × APOE-ε4 status to neuropsychological performances, adjusting for demographic and vascular risk factors. PWV × APOE-ε4 related to poorer performance on measures of lexical retrieval (ß = -0.29, p = 0.01), executive function (ß = -0.44, p = 0.02), and episodic memory (ß = -3.07, p = 0.02). Among participants with higher aortic PWV, APOE-ε4 modified the association between central arterial stiffening and cognition, such that carriers had worse performances than noncarriers. Findings add to a growing body of evidence for APOE-vascular interactions on cognition in older adults and warrant further research into less heart-healthy cohorts where the association between PWV and cognition among older adults might be stronger.

Cerebrospinal fluid ß-amyloid42 and neurofilament light relate to white matter hyperintensities.

White matter hyperintensities (WMHs) are associated with poorer brain health, but their pathophysiological substrates remain elusive. To better understand the mechanistic underpinnings of WMHs among older adults, this study examined in vivo cerebrospinal fluid biomarkers of ß-amyloid42 deposition (Aß42), hyperphosphorylated tau pathology, neurodegeneration (total tau), and axonal injury (neurofilament light [NFL]) in relation to log-transformed WMHs volume. Participants free of clinical stroke and dementia were drawn from the Vanderbilt Memory & Aging Project (n = 148, 72 ± 6 years). Linear regression models adjusted for age, sex, race/ethnicity, education, intracranial volume, modified Framingham Stroke Risk Profile (excluding points assigned for age), cognitive diagnosis, and APOE-ε4 carrier status. Aß42 (ß = -0.001, p = 0.007) and NFL (ß = 0.0003, p = 0.01) concentrations related to WMHs but neither hyperphosphorylated tau nor total tau associations with WMHs reached statistical significance (p-values > 0.21). In a combined model, NFL accounted for 3.2% of unique variance in WMHs and Aß42 accounted for an additional 4.3% beyond NFL, providing novel evidence of the co-occurrence of at least 2 distinct pathways for WMHs among older adults, including amyloid deposition and axonal injury.

Subclinical Compromise in Cardiac Strain Relates to Lower Cognitive Performances in Older Adults.

BACKGROUND: Global longitudinal strain (GLS), reflecting total shortening of the myocardium during the cardiac cycle, has emerged as a more precise myocardial function measure than left ventricular ejection fraction (LVEF). Longitudinal strain may be selectively affected in subclinical heart disease, even in the presence of normal LVEF. This study examines subclinical cardiac dysfunction, assessed by GLS and LVEF, and cognition among older adults. METHODS AND RESULTS: Vanderbilt Memory and Aging Project participants who were free of clinical dementia, stroke, and heart failure (n=318, 73±7 years, 58% male) completed neuropsychological assessment and cardiac magnetic resonance to quantify GLS and LVEF. Linear regression models related GLS and LVEF to neuropsychological performances, adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile, cognitive diagnosis, and APOE*ε4 status. Models were repeated with a cardiac×cognitive diagnosis interaction term. Compromised GLS (reflected by higher values) related to worse naming (ß=-0.07, P=0.04), visuospatial immediate recall (ß=-0.83, P=0.03), visuospatial delayed recall (ß=-0.22, P=0.03), and verbal delayed recall (ß=-0.11, P=0.007). LVEF did not relate to worse performance on any measure (P>0.18). No diagnostic interactions were observed. CONCLUSIONS: Our study results are among the first to suggest that compromised GLS relates to worse episodic memory and language performance among older adults who are free of clinical dementia, stroke, and heart failure. Subclinical cardiac dysfunction may correlate with cognitive health in late life, even when LVEF remains normal. The results add to growing evidence that GLS may be a more sensitive and preferred method for quantifying subclinical changes in cardiac function.

The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data.

BACKGROUND/AIMS: This study evaluated neuroimaging and biological correlates, psychometric properties, and regression-based normative data of the 12-word Philadelphia Verbal Learning Test (PVLT), a list-learning test. METHODS: Vanderbilt Memory and Aging Project participants free of clinical dementia and stroke (n = 230, aged 73 ± 7 years) completed a neuropsychological protocol and brain MRI. A subset (n = 111) underwent lumbar puncture for analysis of Alzheimer's disease (AD) and axonal integrity cerebrospinal fluid (CSF) biomarkers. Regression models related PVLT indices to MRI and CSF biomarkers adjusting for age, sex, race/ethnicity, education, APOE-ε4 carrier status, cognitive status, and intracranial volume (MRI models). Secondary analyses were restricted to participants with normal cognition (NC; n = 127), from which regression-based normative data were generated. RESULTS: Lower PVLT performances were associated with smaller medial temporal lobe volumes (p < 0.05) and higher CSF tau concentrations (p < 0.04). Among NC, PVLT indices were associated with white matter hyperintensities on MRI and an axonal injury biomarker (CSF neurofilament light; p < 0.03). CONCLUSION: The PVLT appears sensitive to markers of neurodegeneration, including temporal regions affected by AD. Conversely, in cognitively normal older adults, PVLT performance seems to relate to white matter disease and axonal injury, perhaps reflecting non-AD pathways to cognitive change. Enhanced normative data enrich the clinical utility of this tool.

Physician Preferences to Communicate Neuropsychological Results: Comparison of Qualitative Descriptors and a Proposal to Reduce Communication Errors.

OBJECTIVE: Errors in communication are a leading cause of medical errors. A potential source of error in communicating neuropsychological results is confusion in the qualitative descriptors used to describe standardized neuropsychological data. This study sought to evaluate the extent to which medical consumers of neuropsychological assessments believed that results/findings were not clearly communicated. In addition, preference data for a variety of qualitative descriptors commonly used to communicate normative neuropsychological test scores were obtained. METHODS: Preference data were obtained for five qualitative descriptor systems as part of a larger 36-item internet-based survey of physician satisfaction with neuropsychological services. A new qualitative descriptor system termed the Simplified Qualitative Classification System (Q-Simple) was proposed to reduce the potential for communication errors using seven terms: very superior, superior, high average, average, low average, borderline, and abnormal/impaired. A non-random convenience sample of 605 clinicians identified from four United States academic medical centers from January 1, 2015 through January 7, 2016 were invited to participate. RESULTS: A total of 182 surveys were completed. A minority of clinicians (12.5%) indicated that neuropsychological study results were not clearly communicated. When communicating neuropsychological standardized scores, the two most preferred qualitative descriptor systems were by Heaton and colleagues (26%) and a newly proposed Q-simple system (22%). Comprehensive norms for an extended Halstead-Reitan battery: Demographic corrections, research findings, and clinical applications. Odessa, TX: Psychological Assessment Resources) (26%) and the newly proposed Q-Simple system (22%). DISCUSSION: Initial findings highlight the need to improve and standardize communication of neuropsychological results. These data offer initial guidance for preferred terms to communicate test results and form a foundation for more standardized practice among neuropsychologists.

A randomized, double-blind, placebo-controlled crossover study of the effects of levetiracetam on cognition, mood, and balance in healthy older adults.

OBJECTIVE: The cognitive and mood effects of levetiracetam (LEV) in older adults are not known. This study compared the cognitive and mood effects of LEV to placebo in healthy older adults. METHODS: Cognitive, mood, and balance variables were compared between LEV and placebo using a randomized, double-blind, placebo-controlled crossover study with two 5-week treatment periods. Healthy volunteers (n = 20) aged 65-80 (mean age 72.4) received either LEV or placebo in which the LEV target dose was 1,000 mg/day. Volunteers, aged 65-80, were without epilepsy to limit potentially confounding the impact of seizures and/or underlying neuropathology on outcomes. LEV was initiated at 250 mg twice a day for 2 weeks, then increased to 500 mg twice a day for 2 weeks, and then tapered to 250 mg twice a day for 1 week. This was randomized with placebo for the two treatment arms. Measures included standardized neuropsychological, mood, and balance tests yielding 32 variables. Balance was assessed using subjective report (e.g., A-B neurotoxicity scale) and objective data (e.g., Berg Balance Scale). RESULTS: Average LEV serum concentration was 16.9 (standard deviation [SD} 7.7). Repeated-measures analysis of variance (ANOVA) found no differences between LEV and placebo phases for 29 (90.6%) of 32 variables including no change in balance. Performance on LEV was better than placebo on a visual memory (MCG Complex Figure Recall; p = 0.007) and two attention tests (Trail Making Test, Part A, p = 0.009; Stroop Interference, p = 0.004). There was a trend for greater irritability and fatigue (POMS Anger and Fatigue) during the LEV phase (p = 0.029, p = 0.035). Effect-size changes were generally small (Cohen d < 0.5). SIGNIFICANCE: LEV was well tolerated in this elderly population in terms of cognition, mood, and balance. When anticonvulsant medication is indicated for older adults, LEV has pharmacokinetic advantages, and these data indicate no adverse impact on cognition or balance.

Taxonomy for Education and Training in Clinical Neuropsychology: past, present, and future.

OBJECTIVE: Historically, the clinical neuropsychology training community has not clearly or consistently defined education or training opportunities. The lack of consistency has limited students' and trainees' ability to accurately assess and compare the intensity of neuropsychology-specific training provided by programs. To address these issues and produce greater 'truth in advertising' across programs, CNS, with SCN's Education Advisory Committee (EAC), ADECN, AITCN, and APPCN constructed a specialty-specific taxonomy, namely, the Taxonomy for Education and Training in Clinical Neuropsychology. The taxonomy provides consensus in the description of training offered by doctoral, internship, and postdoctoral programs, as well as at the post-licensure stage. Although the CNS approved the taxonomy in February 2015, many programs have not adopted its language. Increased awareness of the taxonomy and the reasons behind its development and structure, as well as its potential benefits, are warranted. METHODS: In 2016, a working group of clinical neuropsychologists from the EAC and APPCN, all authors of this manuscript, was created and tasked with disseminating information about the taxonomy. Group members held regular conference calls, leading to the generation of this manuscript. RESULTS: This manuscript is the primary byproduct of the working group. Its purpose is to (1) outline the history behind the development of the taxonomy, (2) detail its structure and utility, (3) address the expected impact of its adoption, and (4) call for its adoption across training programs. CONCLUSIONS: This manuscript outlines the development and structure of the clinical neuropsychology taxonomy and addresses the need for its adoption across training programs.

Addressing potential role of magnesium dyshomeostasis to improve treatment efficacy for epilepsy: A reexamination of the literature.

Magnesium (Mg(2+) ) is an abundant mineral in the body serving many biochemical functions. Magnesium supplementation has been shown to raise seizure threshold in animal and human studies, but the etiological contribution of magnesium deficiency to the onset and maintenance of epilepsy, as well as the degree to which it impacts antiepileptic drug efficacy, remains poorly understood. This may be due, at least in part, to the inherent limitations of commonly used serum levels as a measure of functional magnesium status, as well as insufficient data regarding relative bioavailabilities of various magnesium salts and chelates for use with humans. To date, 1 randomized clinical trial has been conducted assessing Mg(2+) supplementation in epilepsy, and findings yielded promising results. Yet a notable dearth in the literature remains, and more studies are needed. To better understand the potential role of magnesium deficiency as a causal factor in epilepsy, more convenient and accurate measurement methods should to be developed and employed in randomized, controlled trials of oral magnesium supplementation in epilepsy. Findings from such studies have the potential to facilitate far-reaching clinical and economic improvements in epilepsy treatment standards.

Utility of Green's Word Memory Test Free Recall Subtest as a Measure of Verbal Memory: Initial Evidence from a Temporal Lobe Epilepsy Clinical Sample.

This study investigated the Word Memory Test (WMT) Free Recall (FR) subtest as a conventional memory measure. Nineteen participants with pharmacoresistant left temporal lobe epilepsy (LTLE) and 16 with right temporal lobe epilepsy (RTLE) completed the WMT, Rey Auditory Verbal Learning Test (RAVLT), and Wechsler Memory Scale-Fourth Edition Logical Memory (LM) subtest during presurgical evaluation. LTLE participants performed significantly worse on FR subtest (p < .05, [Formula: see text]) and RAVLT Trial 7 (p < .01, [Formula: see text]), but not on LM subtest. Age was a significant covariate for FR (p < .01, [Formula: see text]). Logistic regression revealed FR plus age and RAVLT age-adjusted T-scores both yielded 77.1% classification accuracy and respective diagnostic odds ratios of 11.36 and 11.84. Receiver operating characteristic curves to classify seizure laterality found that RAVLT and FR were significant (area under the curve [AUC] = 0.82 and 0.74), whereas LM was nonsignificant (AUC = 0.67). Cut scores and positive/negative predictive values were established for improved clinical classification.

Predictors of surgical outcome in medically-resistant temporal lobe epilepsy with bilateral features on pre-operative evaluation.

OBJECTIVE: This study identifies potential prognostic factors for favorable anterior mesial temporal lobe (AMTL) resection outcomes in patients with medically refractory temporal lobe epilepsy (TLE) with bilateral features on pre-operative examination. METHODS: Thirty-one patients demonstrated bilateral features defined as: bilateral independent temporal or bitemporal ictal onsets on surface or intracranial EEG, or bitemporal interictal epileptiform abnormalities on surface EEG with bilateral radiographic mesial temporal sclerosis. Surgical outcomes were classified according to reduction in seizure frequency: I (100% reduction), II (≥75% reduction), III (50-74% reduction), IV (<50% reduction). RESULTS: Of 31 patients, 14 (45%) improved to class I and 9 (29%) had a class II outcome at an average of 4 years after surgery. Eight (26%) patients did not exhibit good surgical outcome (class III, class IV). We found that neuropsychological and Wada memory scores were significantly correlated (p<0.05) with surgical outcome, and logistic regression found neuropsychological evaluation significantly predicted better surgical outcome (p<0.05). CONCLUSIONS: When bilateral features are present on pre-operative evaluation, neuropsychological and Wada test results can provide unique data to better identify those patients more likely to achieve substantial seizure reduction.

Laser ablation therapy: An alternative treatment for medically resistant mesial temporal lobe epilepsy after age 50.

Selective anterior mesial temporal lobe (AMTL) resection is considered a safe and effective treatment for medically refractory mesial temporal lobe epilepsy (MTLE). However, as with any open surgical procedure, older patients (aged 50+) face greater risks. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has shown recent potential as an alternative treatment for MTLE. As a less invasive procedure, MRgLITT could be particularly beneficial to older patients. To our knowledge, no study has evaluated the safety and efficacy of MRgLITT in this population. Seven consecutive patients (aged 50+) undergoing MRgLITT for MTLE were followed prospectively to assess surgical time, complications, postoperative pain control, length of stay (LOS), operating room (OR) charges, total hospitalization charges, and seizure outcome. Five of these patients were assessed at the 1-year follow-up for seizure outcome. These data were compared with data taken from 7 consecutive patients (aged 50+) undergoing AMTL resection. Both groups were of comparable age (mean: 60.7 (MRgLITT) vs. 53 (AMTL)). One AMTL resection patient had a complication of aseptic meningitis. One MRgLITT patient experienced an early postoperative seizure, and two MRgLITT patients had a partial visual field deficit. Seizure-freedom rates were comparable (80% (MRgLITT) and 100% (AMTL) (p>0.05)) beyond 1year postsurgery (mean follow-up: 1.0years (MRgLITT) vs. 1.8years (AMTL)). Mean LOS was shorter in the MRgLITT group (1.3days vs. 2.6days (p<0.05)). Neuropsychological outcomes were comparable. Short-term follow-up suggests that MRgLITT is safe and provides outcomes comparable to AMTL resection in this population. It also decreases pain medication requirement and reduces LOS. Further studies are necessary to assess the long-term efficacy of the procedure.