Background

We previously created a serum-based algorithm that yielded excellent diagnostic accuracy in Alzheimer's disease. The current project was designed to refine that algorithm by reducing the number of serum proteins and by including clinical labs. The link between the biomarker risk score and neuropsychological performance was also examined.

Methods

Serum-protein multiplex biomarker data from 197 patients diagnosed with Alzheimer's disease and 203 cognitively normal controls from the Texas Alzheimer's Research Consortium were analyzed. The 30 markers identified as the most important from our initial analyses and clinical labs were utilized to create the algorithm.

Results

The 30-protein risk score yielded a sensitivity, specificity, and AUC of 0.88, 0.82, and 0.91, respectively. When combined with demographic data and clinical labs, the algorithm yielded a sensitivity, specificity, and AUC of 0.89, 0.85, and 0.94, respectively. In linear regression models, the biomarker risk score was most strongly related to neuropsychological tests of language and memory.

Conclusions

Our previously published diagnostic algorithm can be restricted to only 30 serum proteins and still retain excellent diagnostic accuracy. Additionally, the revised biomarker risk score is significantly related to neuropsychological test performance.

Background

The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score is commonly used, although the utility regarding this score in staging dementia severity is not well established.

Obiective

To investigate the effectiveness of CDRSOB scores in staging dementia severity compared with the global CDR score.

Design

Retrospective study.

Setting

Texas Alzheimer's Research Consortium minimum data set cohort.

Participants

A total of 1577 participants (110 controls, 202 patients with mild cognitive impairment, and 1265 patients with probable Alzheimer disease) were available for analysis.

Main Outcome Measures

Receiver operating characteristic curves were generated from a derivation sample to determine optimal cutoff scores and ranges, which were then applied to the validation sample.

Results

Optimal ranges of CDR-SOB scores corresponding to the global CDR scores were 0.5 to 4.0 for a global score of 0.5, 4.5 to 9.0 for a global score of 1.O, 9.5 to 15.5 for a global score of 2.0, and 16.0 to 18.0 for a global score of 3.0. When applied to the validation sample, κ scores ranged from 0.86 to 0.94 (P <.001 for all), with 93.0% of the participants falling within the new staging categories.

Conclusions

The CDR-SOB score compares well with the global CDR score for dementia staging. Owing to the increased range of values, the CDR-SOB score offers several advantages over the global score, including increased utility in tracking changes within and between stages of dementia severity. Interpretive guidelines for CDR-SOB scores are provided.

Traumatic axonal injury (TAI) is a common mechanism of traumatic brain injury not readily identified using conventional neuroimaging modalities. Novel imaging modalities such as diffusion tensor imaging (DTI) can detect microstructural compromise in white matter (WM) in various clinical populations including TAI. DTI-derived data can be analyzed using global methods (i.e., WM histogram or voxel based approaches) or a regional approach (i.e., tractography). While each of these methods produce qualitatively comparable results, it is not clear which is most useful in clinical research and ultimately in clinical practice. This study compared three methods of analyzing DTI-derived data with regard to detection of WM injury and their association with clinical outcomes. Thirty patients with TAI and 19 demographically similar normal controls were scanned using a 3T magnet. Patients were scanned approximately eight months post-injury, and underwent an outcomes assessment at that time. Histogram analysis of FA and MD showed global WM integrity differences between patients and controls. Voxel-based and tractography analyses showed significant decreases in FA within centroaxial structures involved in TAI. All three techniques were associated with functional and cognitive outcomes. DTI measures of microstructural integrity appear robust, as the three analysis techniques studied showed adequate utility for detecting WM injury.

Objective:

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.

Method:

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, MMSE, and CDR scores adjusting for age and gender.

Results:

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.

Conclusions:

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.

Neuropsychological evaluations conducted in the United States and abroad commonly include the use of tests translated from English to Spanish. The use of translated naming tests for evaluating predominately Spanish-speakers has recently been challenged on the grounds that translating test items may compromise a test’s construct validity. The Texas Spanish Naming Test (TNT) has been developed in Spanish specifically for use with Spanish-speakers; however, it is unlikely patients from diverse Spanish-speaking geographical regions will perform uniformly on a naming test. The present study evaluated and compared the internal consistency and patterns of item-difficulty and -discrimination for the TNT and two commonly used translated naming tests in three countries (i.e., United States, Colombia, Spain). Two hundred fifty two subjects (126 demented, 116 nondemented) across three countries were administered the TNT, Modified Boston Naming Test-Spanish, and the naming subtest from the CERAD. The TNT demonstrated superior internal consistency to its counterparts, a superior item difficulty pattern than the CERAD naming test, and a superior item discrimination pattern than the MBNT-S across countries. Overall, all three Spanish naming tests differentiated nondemented and moderately demented individuals, but the results suggest the items of the TNT are most appropriate to use with Spanish-speakers. Preliminary normative data for the three tests examined in each country are provided.

Objective

To determine if a direct measure of instrumental activities of daily living (IADL) scale designed for use with dementia patients can detect differences between persons with mild cognitive impairment (MCI) and normal elderly control subjects (NC).

Methods

This study used cross-sectional and longitudinal IADL scale data from MCI and NC subjects followed at an Alzheimer’s Disease Center.

Results

On a 52-point scale, MCI subjects (n = 30) scored significantly lower than NC subjects (n = 30) on the IADL scale (total score 47.17 vs. 48.77 points; t (58) = 2.34, p = .011) and its Memory subscale (5.27 vs. 6.6 points; t (58) = 3.29, p = .002).Examination of annualized IADL scale change scores revealed that 50% of MCI subjects had declined by one point, compared with 29% of NC.

Conclusion

A direct IADL measure for dementia patients is able to detect small differences between MCI and NC and cross-sectionally and longitudinally, but does not distinguish between groups.