Measuring cognitive change in subjects with prodromal Alzheimer's disease

Abstract

Objective: To investigate the sensitivity of a large set of neuropsychological tests to detect cognitive changes due to prodromal Alzheimer's disease(AD); to compare their metrological properties in order to select a restricted number of these tests for the longitudinal follow-up of subjects with prodromal AD.

Participants: 212 patients with mild cognitive impairment were tested at baseline by a standardised neuropsychological battery, which included: the Free and Cued Selective Reminding test (FCSRT), the Benton Visual Retention test, the Deno100, verbal fluency, a serial digit learning test, the double task of Baddeley, the Wechsler Adult Intelligence Scale (WAIS) similarities, the Trail-Making Test and the WAIS digit symbol test. Patients were monitored every 6 months for up to 3 years in order to identify those who converted to AD (retrospectively classified as prodromal AD). Statistical analyses were performed using a nonlinear multivariate mixed model involving a latent process. This model assumes that the psychometric tests are nonlinear transformations of a common latent cognitive process, and it captures the metrological properties of tests.

Results: 57 patients converted to AD. The most sensitive tests in the detection of cognitive changes due to prodromal AD were the FCSRT, the semantic verbal fluency and the Deno100. Some tests exhibited a higher sensitivity to cognitive changes for subjects with high levels of cognition, such as the free recall, delayed free recall scores of the FCSRT and the semantic verbal fluency, whereas others showed a higher sensitivity at low levels of cognition, such as the total recall score of the FCSRT.

Conclusions: Tests used for the follow-up of prodromal AD subjects should be chosen among those that actually decline in this stage of the disease and should be selected according to the subject's initial scores.

Keywords: Alzheimer's Disease; Cognitive Neuropsychology; Dementia; Statistics.

Figure 1

Conceptualization of the nonlinear mixed model involving a latent process to model cognition from several neuropsychological tests. (a) A linear mixed model describes the change over time in the latent cognitive process and evaluates the common effects of covariates on this latent cognitive trajectory (b) Test-specific measurement models relate each administration of the psychometric tests with the latent cognitive process, by accounting for and describing the metrological properties of the tests and test-specific associations with covariates. (c) Overall effect of a covariate on each specific test is calculated by adding together the effect of the covariate on the latent cognitive process (a) and the test-specific effect (b).

Figure 2

Diagram mapping the administration of the neuropsychological tests and the occurrence of AD during the three-year follow-up (FU) of the study. * In the event of a suspected conversion, the patient underwent an additional neuropsychological evaluation 6 months later.

Figure 3

Mean annual change for each neuropsychological test according to the occurrence of AD during the follow-up (in latent cognitive process units). Mean annual change with 95% confidence interval for each neuropsychological test (in latent cognitive process unit) for a 71.8 year-old woman with a low level of education. *denotes a significant difference (adjusted for age, sex and level of education) between Prodromal-AD and MCI Non-AD (p<0.05), ** for p<0.01 Baddeley Mü was not represented in this figure because of its high level of individual variability; this test did not significantly change over time in any group and was not different between groups.

Figure 4

Metrological properties of the thirteen neuropsychological scores used in the study *according to the previous results display in figure 3