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1.  Staging Dementia Using Clinical Dementia Rating Scale Sum of Boxes Scores 
Archives of neurology  2008;65(8):1091-1095.
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.
doi:10.1001/archneur.65.8.1091
PMCID: PMC3409562  PMID: 18695059
2.  The CERAD Neuropsychological Battery Total Score and the Progression of Alzheimer's Disease 
Objective
To establish the CERAD neuropsychological battery as a valid measure of cognitive progression in Alzheimer's disease (AD) by deriving annualized CERAD Total Change Scores and corresponding confidence intervals in AD and controls from which to define clinically meaningful change.
Method
Subjects included 383 Normal Control (NC) and 655 AD subjects with serial data from the CERAD registry database. Annualized CERAD Total Change Scores were derived and Reliable Change Indexes (RCIs) calculated to establish statistically reliable change values. CERAD Change Scores were compared to annualized change scores from the MMSE, Clinical Dementia Rating Scale (CDR) Sum of Boxes, and Blessed Dementia Rating Scale (BDRS).
Results
For the CERAD Total Score, the AD sample showed significantly greater decline than the NC sample over the four year interval, with AD subjects declining an average of 22.2 points compared to the NCs' improving an average 2.8 points from baseline to last visit [Group × Time interaction (F(4,1031) = 246.08, p < .001)]. By Visit 3, the majority of AD subjects (65.2%) showed a degree of cognitive decline that fell outside the RCI. CERAD Change Scores significantly correlated (p<0.001) with MMSE (r = -.66), CDR (r = -.42), and BDRS (r = -.38) change scores.
Conclusion
Results support the utility of the CERAD Total Score as a measure of AD progression and provide comparative data for annualized change in CERAD Total Score and other summary measures.
doi:10.1097/WAD.0b013e3181b76415
PMCID: PMC2920638  PMID: 20505431
3.  Brain-Derived Neurotrophic Factor Levels in Alzheimer's Disease 
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.
doi:10.3233/JAD-2009-1051
PMCID: PMC2787708  PMID: 19363274
Alzheimer's disease; Biomarkers; BDNF; Dementia Severity; Clinical Dementia Rating
4.  Can a Direct IADL Measure Detect Deficits in Persons with MCI? 
Current Alzheimer research  2009;6(1):48-51.
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.
PMCID: PMC2655701  PMID: 19199874
Mild cognitive impairment; IADL; texas functional living scale

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