Diagnostic accuracy of the MMSE in detecting probable and possible Alzheimer's disease in ethnically diverse highly educated individuals: an analysis of the NACC database.

BACKGROUND: To validate and extend the findings of a raised cut score of O'Bryant and colleagues (O'Bryant SE, Humphreys JD, Smith GE, et al. Detecting dementia with the mini-mental state examination in highly educated individuals. Arch Neurol. 2008;65(7):963-967.) for the Mini-Mental State Examination in detecting cognitive dysfunction in a bilingual sample of highly educated ethnically diverse individuals. METHODS: Archival data were reviewed from participants enrolled in the National Alzheimer's Coordinating Center minimum data set. Data on 7,093 individuals with 16 or more years of education were analyzed, including 2,337 cases with probable and possible Alzheimer's disease, 1,418 mild cognitive impairment patients, and 3,088 nondemented controls. Ethnic composition was characterized as follows: 6,296 Caucasians, 581 African Americans, 4 American Indians or Alaska natives, 2 native Hawaiians or Pacific Islanders, 149 Asians, 43 "Other," and 18 of unknown origin. RESULTS: Diagnostic accuracy estimates (sensitivity, specificity, and likelihood ratio) of Mini-Mental State Examination cut scores in detecting probable and possible Alzheimer's disease were examined. A standard Mini-Mental State Examination cut score of 24 (≤23) yielded a sensitivity of 0.58 and a specificity of 0.98 in detecting probable and possible Alzheimer's disease across ethnicities. A cut score of 27 (≤26) resulted in an improved balance of sensitivity and specificity (0.79 and 0.90, respectively). In the cognitively impaired group (mild cognitive impairment and probable and possible Alzheimer's disease), the standard cut score yielded a sensitivity of 0.38 and a specificity of 1.00 while raising the cut score to 27 resulted in an improved balance of 0.59 and 0.96 of sensitivity and specificity, respectively. CONCLUSIONS: These findings cross-validate our previous work and extend them to an ethnically diverse cohort. A higher cut score is needed to maximize diagnostic accuracy of the Mini-Mental State Examination in individuals with college degrees.

Normative performance on the executive clock drawing task in a multi-ethnic bilingual cohort: a project FRONTIER study.

BACKGROUND: The executive clock drawing task (CLOX) test is a neuropsychological measure intended to aid in the assessment and detection of dementia in older populations. Few studies have provided normative data for this measure, with even less research available regarding the impact of sociodemographic factors on test scores. This study presents normative data for the CLOX in a sample of English and Spanish-speaking Hispanic and non-Hispanic Whites. METHODS: The total sample included 445 cognitively healthy older adults seen as part of an ongoing study of rural cognitive aging, project FRONTIER. Unlike previous studies, criteria for "normality" (i.e., unimpaired) for CLOX1 and CLOX2 were based not merely on global impairment, but also on domain-specific impairment of executive functioning on the Executive Interview 25-item Examination and/or Trail Making Test B, or visuospatial/constructional impairment on the Line Orientation and Figure Copy subtests of the Repeatable Battery for the Assessment of Neuropsychological Status, respectively. RESULTS: Hierarchical regression analyses revealed that CLOX1 scores require adjustment by Age across ethnicities, whereas Education and Gender are necessary stratification markers for CLOX1 performance only in non-Hispanic Whites. None of the demographic variables were valid predictors of CLOX2 performance, negating the need for such adjustments. CONCLUSION: In addition to being the first study to provide separate normative data for CLOX performance in Hispanic and non-Hispanic White samples, the current study offers a novel approach to defining "normal" by cognitive domain. We also highlight the need to directly examine the impact of sociodemographic factors before applying normative corrections based on factors that have negligible impact on test scores.

Low-level groundwater arsenic exposure impacts cognition: a project FRONTIER study.

Arsenic is a ubiquitous environmental toxin with known neurological consequences. Few studies, however, have investigated groundwater arsenic concentrations and cognition among adults and elders. In the study described in this article, the authors examined the potential link between cognitive functioning and low concentrations of arsenic in drinking water. Arsenic concentrations were estimated by the Geographic Information System approach (GIS-arsenic) for 299 rural-dwelling adults and elders. Cognition was assessed with Folstein Mini-Mental State Examination (MMSE). Those in the relatively high GIS-arsenic exposure (> 10.0 microg/L) group had significantly lower MMSE scores than those in the low GIS-arsenic exposure (< or = 10.0 microg/L) group (p < .03). The number of years of education was significantly lower in those in the high GIS-arsenic group(s) than in those in the low GIS-arsenic group (p < .05). These results suggest that poorer cognitive functioning and lower education levels were associated with higher (though still low-level) GIS-arsenic levels in this rural adult cohort.

The influence of thyroid function on cognition in a sample of ethnically diverse, rural-dwelling women: a project FRONTIER study.

This study examined the influence of thyroid markers (TSH and FT4) on cognition in a sample of rural-dwelling women. Data were analyzed from 81 women who were enrolled in an ongoing study of rural health, Project FRONTIER. Cognition was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). TSH levels were significantly related to the RBANS Attention Index, and FT4 levels were significantly related to the RBANS Language Index. The current study found that TSH and FT4 were differentially related to neurocognitive domains, with TSH being related only to measures of attention and FT4 to measures of language.

Serum brain-derived neurotrophic factor levels are specifically associated with memory performance among Alzheimer's disease cases.

AIMS: Our purpose was to study the link between serum brain-derived neurotrophic factor (BDNF) levels and neuropsychological functioning through the Texas Alzheimer's Research Consortium cohort. METHODS: A total of 399 participants [probable Alzheimer's disease (AD) n = 198, controls n = 201] were available for analysis. The BDNF levels were assayed via multiplex immunoassay. Regression analyses were utilized to examine the relation between BDNF levels and neuropsychological functioning. RESULTS: There were no significant mean differences in BDNF levels between cases and controls. In the AD group, the BDNF levels were significantly negatively associated with the scores on immediate [B = -0.07 (0.02), t = -3.55, p = 0.001] and delayed [B = -0.05 (0.02), t = -2.79, p = 0.01] verbal memory and immediate [B = -0.12 (0.05), t = -2.70, p = 0.01] visual memory. No other neuropsychological variables were significantly related to the BDNF levels. The BDNF levels were not significantly related to the neuropsychological test scores in the control group. CONCLUSIONS: Increased serum BDNF levels were associated with poorer visual and verbal memory, but only among AD cases. The current findings point toward an upregulation of serum BDNF as one possible mechanism linked to memory disturbances in AD though it does not appear to be linked to disease severity.

Executive functioning mediates the link between other neuropsychological domains and daily functioning: a Project FRONTIER study.

BACKGROUND: The purpose of this study was to examine the mediating impact of executive functioning on the link between other neuropsychological domain scores and informant-based rating of functional status. METHODS: Data on 181 participants were analyzed from an ongoing epidemiological study of rural health, Project FRONTIER (mean age = 64.6 ± 13.8 years, 69% women, 42% Mexican American). Executive functioning was assessed by the EXIT25 and other neuropsychological domains were assessed via the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Informant-based rating of functional status was assessed via the Clinical Dementia Rating Scale sum of boxes scores (CDR SB). RESULTS: RBANS Index scores were each significantly (p < 0.05) related to CDR SB scores and EXIT25 scores. EXIT25 score was a significant partial mediator of the link between four RBANS indices (Immediate Memory, Attention, Visuospatial/Construction, Delayed Memory) and CDR SB scores, and a complete mediator of the fifth index (Language). CONCLUSION: Executive functioning is a mediator of the link between other neuropsychological domains and daily functioning. Neuropsychological assessments that do not measure executive functioning will provide only a partial clinical picture with adults and elders.

An examination of the Boston Naming Test: calculation of "estimated" 60-item score from 30- and 15-item scores in a cognitively impaired population.

OBJECTIVE: Multiple versions of the Boston Naming Test (BNT) exist, which makes comparison of findings from different studies difficult. The current project sought to determine if estimated 60-item BNT scores could be reliably calculated from 30- and 15-item administrations with patients diagnosed with Alzheimer's disease (AD). METHODS: Estimated 60-item scores were created for 30-item (even and odd) and 15-item Consortium to Establish a Registry for Alzheimer's disease (CERAD) versions of the BNT from a database containing item-level responses for all BNT items. Correlations were conducted between all three estimated 60-item scores and full 60-item version scores administered to all participants in the sample. RESULTS: The estimated versions were all highly correlated with the standard 60-item version of the BNT across the sample and these findings held when the sample was separated out by case (AD) and control status. Mean difference scores were very small for scores estimated from 30-item administrations; however, difference scores for the 15-item CERAD were much larger. CONCLUSIONS: Estimated 60-item versions of the BNT can be created from 30-item BNT administrations, which will enable comparisons across studies and allow integration of data from various AD research groups for increased power in analytic protocols. Creation of an estimated score from the 15-item CERAD version is not warranted.

The acquired capability for suicide: a comparison of suicide attempters, suicide ideators, and non-suicidal controls.

BACKGROUND: The Interpersonal Theory of Suicide states that to make a serious or lethal suicide attempt, a person must experience reductions in fear and pain sensitivity sufficient to overcome self preservation reflexes (i.e., the acquired capability for suicide). The purpose of this study was to examine the fearlessness component of the acquired capability for suicide using self-report assessment instruments and an objective measure of aversion (the affectively modulated startle reflex task). METHODS: Depressed suicide ideators (n=15), depressed suicide attempters (n=15), and a group of control participants (n=14) were compared on their self-report of acquired capability and painful and provocative life events, and completed the affectively modulated startle reflex task. This task compared electromyography recordings of participants' eye-blink response to a startle probe while viewing pictures of varying hedonic valence (neutral, positive, negative, and suicide-related). RESULTS: Suicide attempters reported the highest levels of fearlessness and pain insensitivity and a greater history of painful and provocative life events. Although no group differences were found on the psychophysiology data, participants reacted to suicide-related images with less aversion compared to neutral images with no differences between suicide-related and positive images. CONCLUSIONS: Self-reported fearlessness and pain insensitivity can differentiate suicide attempters and suicide ideators. Results suggest that one's self-perception (i.e., cognitions regarding fear and pain tolerance) are more functionally related to suicide attempts than psychophysiological reactivity to suicide-related stimuli.

Diagnostic accuracy of the RBANS in mild cognitive impairment: limitations on assessing milder impairments.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has demonstrated adequate sensitivity in detecting cognitive impairment in a number of neuropsychiatric conditions, including Alzheimer's disease. However, its ability to detect milder cognitive deficits in the elderly has not been examined. The current study examined the clinical utility of the RBANS by comparing two groups: Patients with Mild Cognitive Impairment (MCI; n = 72) and cognitively intact peers (n = 71). Significant differences were observed on the RBANS Total score, 3 of the 5 Indexes, and 6 of the 12 subtests, with individuals with MCI performing worse than the comparison participants. Specificity was very good, but sensitivity ranged from poor to moderate. Areas under the receiver operating characteristic curves for the RBANS Immediate and Delayed Memory Indexes and the Total Scale score were adequate. Although significant differences were observed between groups and the areas under the curves were adequate, the lower sensitivity values of the RBANS suggests that caution should be used when diagnosing conditions such as MCI.

Validation of the new interpretive guidelines for the clinical dementia rating scale sum of boxes score in the national Alzheimer's coordinating center database.

BACKGROUND: It was recently demonstrated that the Clinical Dementia Rating scale Sum of Boxes (CDR-SB) score can be used to accurately stage severity of Alzheimer dementia and mild cognitive impairment (MCI). However, to our knowledge, the utility of those interpretive guidelines has not been cross-validated or applied to a heterogeneous sample of dementia cases. OBJECTIVE: To cross-validate the staging guidelines proposed in a previous study using the National Alzheimer's Coordinating Center (NACC) database. DESIGN: The previously published cut scores were applied to the NACC sample and diagnostic accuracy estimates obtained. Next, analyses were restricted to NACC participants with a CDR global score (CDR-GS) of 0.5 and receiver operating characteristic curves generated to determine optimal CDR-SB cut scores for distinguishing MCI from very early dementia. SETTING: The 2008 NACC uniform data set. PARTICIPANTS: There were 12 462 participants (5115 controls; 2551 patients with MCI; 4796 patients with dementia, all etiologies) in the NACC data set used for the current analysis. Main Outcome Measure Accurate prediction of diagnoses (MCI or dementia) using the CDR-SB score. RESULTS: The previously proposed CDR-SB ranges successfully classified the vast majority of patients across all impairment ranges with a kappa of 0.91 and 94% overall correct classification rate. Additionally, the CDR-SB score discriminated between patients diagnosed with MCI and dementia when CDR-GS was restricted to 0.5 (overall area under the curve = 0.83). CONCLUSIONS: These findings cross-validate the previously published CDR-SB interpretative guidelines for staging dementia severity and extend those findings to a large heterogeneous sample of patients with dementia. Additionally, the CDR-SB scores distinguished MCI from dementia in patients with reasonable accuracy when CDR-GS was restricted to 0.5.

Diagnostic accuracy of percent retention scores on RBANS verbal memory subtests for the diagnosis of Alzheimer's disease and mild cognitive impairment.

Previous research has supported the use of percent retention scores in the neuropsychological assessment of memory, and many widely used memory measures provide for the calculation and normative comparison of these scores. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), an increasingly utilized assessment tool for cognitive impairment, provides normative data on delayed memory total raw scores only. The current study was aimed at determining the diagnostic accuracy of a novel percent retention score calculated from RBANS verbal memory subtests (delayed recall minus last learning trial) when distinguishing between normal controls, individuals diagnosed with Mild Cognitive Impairment, and individuals diagnosed with Alzheimer's disease. Results revealed excellent diagnostic accuracy of the RBANS percent retention scores when discriminating between the three groups. Findings suggest that RBANS percent retention scores provide excellent diagnostic accuracy offering supplementary information to clinicians and researchers alike.

Identifying functional impairment with scores from the repeatable battery for the assessment of neuropsychological status (RBANS).

OBJECTIVE: To examine the link between RBANS scores and functional impairment. Functional status was evaluated through informant report using the clinical dementia rating (CDR) scale. METHODS: Archival data were reviewed from records of 99 patients in a memory disorder clinic (MDC) research database. Consensus-based diagnoses were Alzheimer's disease (AD; n = 48), mild cognitive impairment (MCI; n = 48), AD with vascular components; (n = 2) and dementia due to psychiatric conditions (n = 1). RESULTS: The RBANS language index score was significantly related to CDR domain scores of community affairs (p < .01), home and hobbies (p < .01), personal care (p < .05), memory (p < 0.01), and judgment (p < 0.01). RBANS immediate memory index scores were significantly related to (p < 0.05) the CDR Memory and judgment and problem solving domains. Based on these findings, follow-up regressions were conducted. Semantic fluency was significantly related to CDR memory (p < 0.01), judgment (p < 0.05), community affairs (p < 0.05), home/hobbies (p < 0.05), and personal care (p < 0.05) functional domains. Picture naming was significantly related to the CDR personal care domain (p < 0.05). List learning was significantly related to CDR memory functional domain (p < 0.01) and judgment (p < 0.05). Lastly, story memory was significantly related to the CDR judgment domain (p < 0.05). CONCLUSIONS: The RBANS may be an indicator of functional impairment as well as a neuropsychological testing tool. The use of the RBANS could reduce the amount of testing that is administered to the patient, or can provide a way to compare other measurements of functional impairment to assess accuracy of findings.

Decreased C-reactive protein levels in Alzheimer disease.

C-reactive protein (CRP) is an acute-phase reactant that has been found to be associated with Alzheimer disease (AD) in histopathological and longitudinal studies; however, little data exist regarding serum CRP levels in patients with established AD. The current study evaluated CRP levels in 192 patients diagnosed with probable AD (mean age = 75.8 +/- 8.2 years; 50% female) as compared to 174 nondemented controls (mean age = 70.6 +/- 8.2 years; 63% female). Mean CRP levels were found to be significantly decreased in AD (2.9 microg/mL) versus controls (4.9 microg/mL; P = .003). In adjusted models, elevated CRP significantly predicted poorer (elevated) Clinical Dementia Rating Scale sum of boxes (CDR SB) scores in patients with AD. In controls, CRP was negatively associated with Mini-Mental State Examination (MMSE) scores and positively associated with CDR SB scores. These findings, together with previously published results, are consistent with the hypothesis that midlife elevations in CRP are associated with increased risk of AD development though elevated CRP levels are not useful for prediction in the immediate prodrome years before AD becomes clinically manifest. However, for a subgroup of patients with AD, elevated CRP continues to predict increased dementia severity suggestive of a possible proinflammatory endophenotype in AD.

Brain-derived neurotrophic factor levels in Alzheimer's disease.

The current search for biomarkers that are diagnostic and/or prognostic of Alzheimer's disease (AD) is of vital importance given the rapidly aging population. It was recently reported that brain-derived neurotrophic factor (BDNF) fluctuated according to AD severity, suggesting that BDNF might have utility for diagnostics and monitoring of therapeutic efficacy. The current study sought to examine whether BDNF levels varied according to AD severity, as previously reported. There were 196 participants (Probable AD, n = 98; Controls, n = 98) in the Texas Alzheimer's Research Consortium (TARC) Longitudinal Research Cohort available for analysis. BDNF levels were assayed via multiplex immunoassay. Regression analyses were utilized to examine the relation between BDNF levels, Mini-Mental Status Examination, and Clinical Dementia Rating scores adjusting for age and gender. In adjusted models, BDNF levels did not distinguish between AD patients and normal controls and did not significantly predict AD severity or global cognitive functioning. In conclusion, these findings do not support the notion that BDNF serves as a diagnostic marker for AD or disease severity. It is likely that the most accurate approach to identifying biomarkers of AD will be through an algorithmic approach that combines multiple markers reflective of various pathways.

Appetitive nature of drug cues re-confirmed with physiological measures and the potential role of stage of change.

RATIONALE: Smokers report pleasant reactions to viewing cigarettes, suggesting that smoking cues may be appetitive in nature. Two studies have investigated this hypothesis through physiological assessment. The first study found that smoking cues were physiologically appetitive in nature, with dampened startle response to smoking pictures in comparison to neutral pictures. The second found that smoking pictures did not modulate the startle response, suggesting such cues may not be physiologically appetitive. OBJECTIVE: The goal of the present study was to further investigate how participants' motivation to quit smoking might modulate responses to smoking cues. MATERIALS AND METHODS: Twenty-two nicotine-dependent smokers viewed standardized pleasant, unpleasant, neutral, and smoking pictures. Eleven of the subjects reported no intent to quit (precontemplators) and 11 reported planning to quit within the next 6 months (contemplators). Acoustic startle probes were randomly administered while subjects viewed the pictures, and eyeblink startle magnitude was measured with electromyography (EMG). RESULTS: As a whole, participants exhibited dampened startle responses during smoking pictures, relative to unpleasant pictures. Precontemplators showed robust startle inhibition to smoking pictures, in comparison to both neutral and unpleasant pictures. Contemplators, however, showed blunted unpleasant picture augmentation and a lack of startle inhibition for pleasant pictures. CONCLUSION: These findings are consistent with the idea that smoking pictures are appetitive in nature. Furthermore, they suggest that smokers at a later stage of change may exhibit a lesser response.