title: Alzheimer's Disease Assessment Scale-Cognitive subscale variants in mild cognitive impairment and mild Alzheimer's disease: change over time and the effect of enrichment strategies.
abstract: BACKGROUND
  Development of new treatments for Alzheimer's disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline. The 11-item version of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) was originally developed to measure cognition in patients with mild to moderate AD. Attempts to improve its properties for early AD by removing items prone to ceiling and/or by adding cognitive measures known to be impaired early have yielded a number of ADAS-Cog variants. Using Alzheimer's Disease Neuroimaging Initiative data, we compared the performance of the 3-, 5-, 11- and 13-item ADAS-Cog variants in subjects with early AD. Given the interest in enrichment strategies, we also examined this aspect with a focus on cerebrospinal fluid (CSF) markers.
  
  
  METHODS
  Subjects with mild cognitive impairment (MCI) and mild AD with available ADAS-Cog 13 and CSF data were analysed. The decline over time was defined by change from baseline. Direct cross-comparison of the ADAS-Cog variants was performed using the signal-to-noise ratio (SNR), with higher values reflecting increased sensitivity to detect change over time.
  
  
  RESULTS
  The decline over time on any of the ADAS-Cog variants was minimal in subjects with MCI. Approximately half of subjects with MCI fulfilled enrichment criteria for positive AD pathology. The impact of enrichment was detectable but subtle in MCI. The annual decline in mild AD was more pronounced but still modest. More than 90 % of subjects with mild AD had positive AD pathology. SNRs were low in MCI but greater in mild AD. The numerically largest SNRs were seen for the ADAS-Cog 5 in MCI and for both the 5- and 13-item ADAS-Cog variants in mild AD, although associated confidence intervals were large.
  
  
  CONCLUSIONS
  The possible value of ADAS-Cog expansion or reduction is less than compelling, particularly in MCI. In mild AD, adding items known to be impaired at early stages seems to provide more benefit than removing items on which subjects score close to ceiling.
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, Ingelheim/Rhein, 55218, Germany. jana.podhorna@boehringer-ingelheim.com.
authors: Jana
authors: J
authors: Podhorna
authors: Cogitars GmbH, Heidelberg, Germany. tillmann.krahnke.ext@boehringer-ingelheim.com.
authors: Tillmann
authors: T
authors: Krahnke
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/Riss, Germany. michael.shear@boehringer-ingelheim.com.
authors: Michael
authors: M
authors: Shear
authors: VU University Medical Center Amsterdam, Amsterdam, The Netherlands. johncpc@btinternet.com.
authors: John E
authors: JE
authors: Harrison
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002986:Clinical Trials as Topic; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012720:Severity of Illness Index; D059629:Signal-To-Noise Ratio; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C497285:amyloid beta-protein (1-41); D016875:tau Proteins