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. 2014 Nov;10(6):735-742.e4.
doi: 10.1016/j.jalz.2014.04.520. Epub 2014 Jul 14.

Trajectories of Alzheimer disease-related cognitive measures in a longitudinal sample

Murat Bilgel  1 , Yang An  2 , Andrew Lang  3 , Jerry Prince  4 , Luigi Ferrucci  2 , Bruno Jedynak  5 , Susan M Resnick  2
Affiliations

Trajectories of Alzheimer disease-related cognitive measures in a longitudinal sample

Murat Bilgel et al. Alzheimers Dement. 2014 Nov.

Abstract

Background: The delineation of the relative temporal trajectories of specific cognitive measures associated with Alzheimer's disease (AD) is important for evaluating preclinical markers and monitoring disease progression.

Methods: We characterized the temporal trajectories of measures of verbal episodic memory, short-term visual memory, and mental status using data from 895 participants in the Baltimore Longitudinal Study of Aging.

Results: The California Verbal Learning Test (CVLT) immediate recall was the first measure to decline, followed by CVLT delayed recall. However, further along the disease progression scale, CVLT delayed recall and visual memory changed more rapidly than CVLT immediate recall.

Conclusions: Our findings reconcile reports of early changes in immediate recall with greater reliance on delayed recall performance in clinical settings. Moreover, the utility of cognitive markers in evaluating AD progression depends on the stage of cognitive decline, suggesting that optimal endpoints in therapeutic trials may vary across different stages of the disease process.

Keywords: Alzheimer's disease; California verbal learning test; Disease progression score; Memory.

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Figures

Figure 1
Figure 1
Cognitive data versus age. Cognitively normal and impaired individuals are indicated by black and green dots, respectively. CVLT = California Verbal Learning Test; CVLT-sum = CVLT immediate recall; CVLT-frs = CVLT short delayed free recall; CVLT-frl = CVLT long delayed free recall; BVRT = Benton Visual Retention Test error score; BMS = Blessed Information Memory Concentration score; MMSE = Mini-Mental State Exam.
Figure 2
Figure 2
Sigmoid fits (gray) superimposed on spaghetti plots of fitted data points. Inflection point of each sigmoid curve is indicated with a gray dot. The horizontal axis represents the ADPS estimated for each subject. Longitudinal data points are connected by black lines for individuals who remained cognitively normal throughout the study and by green lines for the cognitively impaired. Red lines were used for subjects who started out as cognitively normal but then became impaired. ADPS = Alzheimer’s Disease Progression Score; CVLT = California Verbal Learning Test; CVLT-sum = CVLT immediate recall; CVLT-frs = CVLT short delayed free recall; CVLT-frl = CVLT long delayed free recall; BVRT = Benton Visual Retention Test error score; BMS = Blessed Information Memory Concentration score; MMSE = Mini-Mental State Exam.
Figure 3
Figure 3
Sigmoid fits for the cognitive markers as a function of the estimated ADPS (top), and the 90% confidence intervals for the inflection points (bottom). The horizontal axis represents the ADPS estimated for each subject. The probabilities of having a certain ADPS conditioned on cognitive status are reflected by the gray and green shaded areas, with gray corresponding to the probabilities associated with the CN individuals and green corresponding to CI. Although we provide confidence intervals around inflection point estimates, statistical significance of their temporal ordering was based on permutation tests. ADPS = Alzheimer’s Disease Progression Score; CVLT = California Verbal Learning Test; CVLT-sum = CVLT immediate recall; CVLT-frs = CVLT short delayed free recall; CVLT-frl = CVLT long delayed free recall; BVRT = Benton Visual Retention Test error score; BMS = Blessed Information Memory Concentration score; MMSE = Mini-Mental State Exam.
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