Valerie Hobson

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 Alzheimers 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.

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 µg/mL) versus controls (4.9 µg/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 Alzheimers 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 Alzheimers 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.

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 Alzheimers 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.

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.

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

To examine the link between RBANS scores and functional impairment. Functional status was evaluated through informant report using the clinical dementia rating (CDR) scale.

An examination of the Boston Naming Test: calculation of “estimated” 60‐item score from 30‐ and 15‐item scores in a cognitively impaired population

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 Alzheimers disease (AD).

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.

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 Alzheimers 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.

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

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.