The ADAS-cog in Alzheimer's disease clinical trials: psychometric evaluation of the sum and its parts

Cano, Stefan; Posner, Holly; Moline, Margaret; Hurt, Stephen W.; Swartz, Jina; Hsu, Tim; Hobart, Jeremy

doi:10.1136/jnnp.2009.204008

Cited by 168 publications

(131 citation statements)

References 34 publications

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“…For longitudinal studies, 20 additional patients with AD were identified retrospectively based on their provision of blood twice at the Mayo Clinic or the University of Kentucky, first when cognitively intact and later at diagnosis of AD (table 1). Intervals between the 2 blood samples (number of patients) were 1 to 5 years (7) and 6 to 10 years (13). Each patient in both cross-sectional and longitudinal groups had mental status testing and an MRI, and some had measurements of CSF Ab1-42, total tau, and P-T181-tau.…”

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confidence: 99%

“…7,8 Those with probable AD and mild to moderate dementia were diagnosed by Dubois criteria 11 Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale were conducted as described. 12,13 Twenty-four of the 26 cross-sectional patients with AD were taking an acetyl-cholinesterase inhibitor and/or memantine, and 5 were on antidepressant medications.…”

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Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease

et al. 2015

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Objective: Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy.Methods: Blood exosomes obtained once from patients with AD (n 5 26) or frontotemporal dementia (n 5 16), other patients with AD (n 5 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker.Results: Mean exosomal levels of cathepsin D, lysosome-associated membrane protein 1 (LAMP-1), and ubiquitinylated proteins were significantly higher and of heat-shock protein 70 significantly lower for AD than controls in cross-sectional studies (p # 0.0005). Levels of cathepsin D, LAMP-1, and ubiquitinylated protein also were significantly higher for patients with AD than for patients with frontotemporal dementia (p # 0.006).Step-wise discriminant modeling of the protein levels correctly classified 100% of patients with AD. Exosomal levels of all proteins were similarly significantly different from those of matched controls in 20 patients 1 to 10 years before and at diagnosis of AD (p # 0.0003).Conclusions: Levels of autolysosomal proteins in neurally derived blood exosomes distinguish patients with AD from case controls and appear to reflect the pathology of AD up to 10 years before clinical onset. These preliminary results confirm in living patients with AD the early appearance of neuronal lysosomal dysfunction and suggest that these proteins may be useful biomarkers in large prospective studies. There is an urgent need for biomarkers that accurately detect pathogenic components of Alzheimer disease (AD) before appearance of neurologic signs. Early treatments directed to such targets could limit or reverse neuronal damage and prevent development of overt AD. Recent analyses of neurally derived plasma exosomal proteins have shown significantly higher levels of the pathogenic proteins P-T181-tau, P-S396-tau, and b-amyloid (Ab)1-42 in AD than in case controls.1 Discriminant modeling of these exosomal protein levels correctly classified more than 96% of patients with AD. Neurally derived plasma exosomal levels of P-T181-tau, P-S396-tau, and Ab1-42 also were significantly higher in preclinical AD than for controls up to 10 years before appearance of neurologic signs. Altered levels of phosphorylated forms of the insulin receptor proximal signaling protein, termed insulin receptor substrate (IRS), in neurally derived plasma exosomes supported the

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Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease

et al. 2015

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“…Scaling assumptions determine whether summing subscales of the instrument to create a single scale score is appropriate. Targeting evaluates whether the range of cognitive performance measured by the battery corresponds to the range of the sample (Cano et al, 2010). Effect size correlations can provide convenient and informative indices of construct validity (Westen, & Rosenthal, 2003).…”

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confidence: 99%

A systematic review of validity procedures used in neuropsychological batteries.

Pawlowski¹,

Segabinazi²,

Wagner³

et al. 2013

Psychology & Neuroscience

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This study presents a systematic review of validity evidence for neuropsychological batteries. Studies published in international databases between 2005 and 2012 were examined. Considering the specificity of neuropsychological batteries, the aim of the study was to review the statistical analyses and procedures that have been used to validate these instruments. A total of 1,218 abstracts were read, of which 147 involved studies of neuropsychological batteries or tests that evaluated at least three cognitive processes. The full text of each article was analyzed according to publication year, focal instrument of the study, sample type, sample age range, characterization of the participants, and procedures and analyses used to provide evidence of validity. The results showed that the studies primarily analyzed patterns of convergence and divergence by correlating the instruments with other tests. Measures of reliability, such as internal consistency and test-retest reliability, were also frequently employed. To provide evidence of relationships between test scores and external criteria, the most common procedures were evaluations of sensitivity and specificity, and comparisons were made between contrasting groups. The statistical analyses frequently used were Receiver Operating Characteristic analysis, Pearson correlation, and Cronbach's alpha. We discuss the necessity of incorporating both classic and modern psychometric procedures and presenting a broader scope of validity evidence, which would represent progress in this field. Finally, we hope our findings will help researchers better plan the validation process for new neuropsychological instruments and batteries.

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“…Cano et al 13 evaluated the psychometric properties of both the individual components of the ADAS-Cog and the total score. Convergent validity with respect to Mini Mental Status Exam scores was satisfactory (0.63) and ADAS-Cog scores were not affected by age or gender.…”

Section: Short Communicationmentioning

confidence: 99%

Assessment of outcome in clinical trials in mild Alzheimer�s disease: Urgent time for a rethink?

Morrison¹,

Wilson²,

Kelly³

et al. 2013

OA Elderly Medicine

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The ADAS-cog in Alzheimer's disease clinical trials: psychometric evaluation of the sum and its parts

Cited by 168 publications

References 34 publications

Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease

Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease

A systematic review of validity procedures used in neuropsychological batteries.

Assessment of outcome in clinical trials in mild Alzheimer�s disease: Urgent time for a rethink?

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