Compassion Versus Accuracy: Lenient Scoring of the Spatial Orientation Items on the Mini-mental State Exam Lowers Sensitivity.

The Mini-mental State Examination (MMSE) is a commonly used screening tool for cognitive impairment. Lenient scoring of spatial orientation errors (SOEs) on the MMSE is common and negatively affects its diagnostic utility. We examined the effect of lenient SOE scoring on MMSE classification accuracy in a consecutive case series of 103 older adults (age 60 or above) clinically referred for neuropsychological evaluation. Lenient scoring of SOEs on the MMSE occurred in 53 (51.4%) patients and lowered the sensitivity by 7% to 18%, with variable gains in specificity (0% to 11%) to psychometrically operationalized cognitive impairment. Results are consistent with previous reports that lenient scoring is widespread and attenuates the sensitivity of the MMSE. Given the higher clinical priority of correctly detecting early cognitive decline over specificity, a warning against lenient scoring of SOEs (on the MMSE and other screening tools) during medical education and in clinical practice is warranted.

Differentiating epilepsy from psychogenic nonepileptic seizures using neuropsychological test data.

OBJECTIVE: Differentiating epileptic seizures (ES) from psychogenic nonepileptic seizures (PNES) represents a challenging differential diagnosis with important treatment implications. This study was designed to explore the utility of neuropsychological test scores in differentiating ES from PNES. METHOD: Psychometric data from 72 patients with ES and 33 patients with PNES were compared on various tests of cognitive ability and performance validity. Individual measures that best discriminated the diagnoses were then entered as predictors in a logistic regression equation with group membership (ES vs. PNES) as the criterion. RESULTS: On most tests of cognitive ability, the PNES sample outperformed the ES sample (medium-large effect) and was less likely to fail the Reliable Digit Span. However, patients with PNES failed two embedded validity indicators at significantly higher rates (risk ratios (RR): 2.45-4.16). There were no group differences on the Test of Memory Malingering (TOMM). A logistic regression equation based on seven neuropsychological tests correctly classified 85.1% of patients. The cutoff with perfect specificity was associated with 0.47 sensitivity. CONCLUSIONS: Consistent with previous research, the utility of psychometric methods of differential diagnosis is limited by the complex neurocognitive profiles associated with ES and PNES. Although individual measures might help differentiate ES from PNES, multivariate assessment models have superior discriminant power. The strongest psychometric evidence for PNES appears to be a consistent lack of impairment on tests sensitive to diffuse neurocognitive deficits such as processing speed, working memory, and verbal fluency. While video-electroencephalogram (EEG) monitoring is the gold standard of differential diagnosis, psychometric testing has the potential to enhance clinical decision-making, particularly in complex or unclear cases such as patients with nondiagnostic video-EEGs. Adopting a standardized, fixed neuropsychological battery at epilepsy centers would advance research on the differential diagnostic power of psychometric testing.

Replicating a Meta-Analysis: The Search for the Optimal Word Choice Test Cutoff Continues.

This study was designed to expand on a recent meta-analysis that identified ≤42 as the optimal cutoff on the Word Choice Test (WCT). We examined the base rate of failure and the classification accuracy of various WCT cutoffs in four independent clinical samples (N = 252) against various psychometrically defined criterion groups. WCT ≤ 47 achieved acceptable combinations of specificity (.86-.89) at .49 to .54 sensitivity. Lowering the cutoff to ≤45 improved specificity (.91-.98) at a reasonable cost to sensitivity (.39-.50). Making the cutoff even more conservative (≤42) disproportionately sacrificed sensitivity (.30-.38) for specificity (.98-1.00), while still classifying 26.7% of patients with genuine and severe deficits as non-credible. Critical item (.23-.45 sensitivity at .89-1.00 specificity) and time-to-completion cutoffs (.48-.71 sensitivity at .87-.96 specificity) were effective alternative/complementary detection methods. Although WCT ≤ 45 produced the best overall classification accuracy, scores in the 43 to 47 range provide comparable objective psychometric evidence of non-credible responding. Results question the need for designating a single cutoff as "optimal," given the heterogeneity of signal detection environments in which individual assessors operate. As meta-analyses often fail to replicate, ongoing research is needed on the classification accuracy of various WCT cutoffs.

The doubtful benefits of giving the benefit of the doubt: Lenient scoring of the spatial orientation items on the mini-Mental Status Exam increases false negative rates.

Lenient scoring of spatial orientation errors (SOE) on the Mini-Mental State Exam (MMSE) is common practice, even though it deviates from standard protocol and may compromise its diagnostic power. This study was designed to empirically evaluate the effect of lenient scoring on the MMSE's classification accuracy. Participants were 113 community dwelling older adults recruited for a research study, representing a wide range of range of neurological status from cognitively healthy to Alzheimer's disease. Clinical classification was determined by expert assessors based on multiple sources of clinical evidence. Lenient scoring significantly inflated MMSE total scores (d = .88, large effect), and suppressed failure rates (from 26% to 14%). Standard scoring produced superior overall classification accuracy (75% vs. 67%) over lenient scoring and, more importantly, increased sensitivity from .33 to .53, with minimal loss in specificity (from 1.00 to .95). SOEs are empirical markers of cognitive decline and should not be adjusted based on clinical judgment. Results indicate that diminished sensitivity to cognitive impairment is an unintended consequence of lenient scoring and argue against this practice.

Memory of a drug lapse: Role of noradrenaline.

Memory processes may be involved in the transition from drug lapses to relapse. This study explored the role of noradrenaline (NA) in reacquisition of place preference, an animal model of relapse that involves the updating of memories about drugs and associated stimuli. Experiments involved 7 phases: habituation, conditioning (1 mg/kg heroin and vehicle; 4 pairings each), test of conditioning (Test I), extinction (vehicle and vehicle; 4 pairings each), test of extinction (Test II), reconditioning (1 mg/kg heroin and vehicle; 1 re-pairing each), and test of reconditioning (Test III). To target memory stabilization processes, various treatments were administered post-reconditioning: systemic clonidine (0, 10, 40, 100 µg/kg; α2 adrenergic receptor agonist); intra-locus coeruleus (LC) clonidine (0, 4.5, 18 nmol); and intra-basolateral amygdala (BLA) propranolol/prazosin (0, 34/2.4 nmol; ß and α1 adrenergic receptor antagonists, respectively). The effect of post-reconditioning systemic clonidine on BLA c-fos expression was also assessed. It was found that systemic clonidine dose-dependently blocked heroin reacquisition when given immediately or 4 h post-reconditioning, but not 8 h later or 4 h prior to Test III. Similar effects were observed following intra-LC clonidine infusions. Post-reconditioning systemic clonidine also blocked reacquisition of cocaine place preference (20 mg/kg). Finally, BLA c-fos expression was reduced by clonidine, and blockade of BLA ß and α1 receptors prevented heroin reacquisition. These findings in rats support the hypothesis that relapse involves memory stabilization processes that can be disrupted by suppression of central NA activity.

Fructose:glucose ratios--a study of sugar self-administration and associated neural and physiological responses in the rat.

This study explored whether different ratios of fructose (F) and glucose (G) in sugar can engender significant differences in self-administration and associated neurobiological and physiological responses in male Sprague-Dawley rats. In Experiment 1, animals self-administered pellets containing 55% F + 45% G or 30% F + 70% G, and Fos immunoreactivity was assessed in hypothalamic regions regulating food intake and reward. In Experiment 2, rats self-administered solutions of 55% F + 42% G (high fructose corn syrup (HFCS)), 50% F + 50% G (sucrose) or saccharin, and mRNA of the dopamine 2 (D2R) and mu-opioid (MOR) receptor genes were assessed in striatal regions involved in addictive behaviors. Finally, in Experiment 3, rats self-administered HFCS and sucrose in their home cages, and hepatic fatty acids were quantified. It was found that higher fructose ratios engendered lower self-administration, lower Fos expression in the lateral hypothalamus/arcuate nucleus, reduced D2R and increased MOR mRNA in the dorsal striatum and nucleus accumbens core, respectively, as well as elevated omega-6 polyunsaturated fatty acids in the liver. These data indicate that a higher ratio of fructose may enhance the reinforcing effects of sugar and possibly lead to neurobiological and physiological alterations associated with addictive and metabolic disorders.