Development and assessment of a composite score for memory in the Alzheimer's Disease Neuroimaging Initiative (ADNI)

Abstract

We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer's Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score.

Fig. 1

Bi-factor model path diagram for baseline data. RAVLT=Rey Auditory Verbal Learning Test. ADAS=Alzheimer’s Disease Assessment Schedule. MMSE=Mini-Mental State Examination. Covariation across all the indicators is modeled with loadings on the primary “Memory” factor shown to the right. Shared covariation beyond that shared with all of the items is shown in secondary factors (for three or more indicators) and residual correlations (for two indicators, shown as two-headed curved arrows) to the left. For example, shared covariation for the 6 word list learning trials for the RAVLT (five with list A, one with list B) beyond that shared with all the other indicators is modeled with the “RAVLT Learning” factor. We specified a unit variance for each of the factors, and they were mutually uncorrelated with each other

Fig. 2

Difficulty levels for the elements of the two versions of the Rey Auditory Verbal Learning Test. The five learning trials are indicated by the numbers 1 through 5; the interference trial by the letter B, the first recall trial by the number 6; delayed recall by “Recall”, and the recognition task by “Recognition”. Version A difficulty thresholds are denoted with blue circles, while version B difficulty thresholds are denoted with green diamonds. In this plot, the difficulty levels are plotted on the y axis in z-statistic units; higher numbers indicate higher memory ability / higher item difficulty. Considering the two versions of learning trial 1, version A is easier for each threshold. At an overall memory ability level of −0.5, for example, higher proportions of people will be above the first threshold for version A, and lower proportions of people above that same threshold for version B. At every threshold the green diamonds are higher than the blue dots. For the second through 5^th learning trials, this difference is dramatic at the top end, as the top threshold on version A is only as difficult as the 2^nd to highest threshold on version B

Fig. 3

Difficulty levels for the elements of the three versions of the Alzheimer’s Disease Assessment Scale – Cognitive Subscale. Recog=Recognition. Version A threshold difficulty levels are depicted with blue circles, Version B with green diamonds, and Version C with red triangles. In this plot, the difficulty levels are plotted on the y axis in z-statistic units; higher numbers indicate higher memory ability / higher item difficulty Version A has greater spread than Version B and to a lesser extent than version C, meaning it will have slightly smaller ceiling and floor effects. Unlike the Rey, no version appears to be consistently easier or harder than the other versions