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Research paper
Measuring cognitive change in subjects with prodromal Alzheimer's disease
  1. T Mura1,2,3,4,
  2. C Proust-Lima5,6,
  3. H Jacqmin-Gadda5,6,
  4. T N Akbaraly1,2,7,
  5. J Touchon1,2,8,
  6. B Dubois9,
  7. C Berr1,2,8
  1. 1INSERM, U1061, Neuropsychiatrie: Recherche Epidémiologique et Clinique, Montpellier, Cedex, France
  2. 2Université Montpellier I, Montpellier, Cedex, France
  3. 3Département d'Information Médicale & Centre d'Investigation Clinique, CHRU Montpellier, Montpellier, France
  4. 4INSERM, CIC 1001, Montpellier, France
  5. 5INSERM U897, Equipe de Biostatistique, Centre de Recherche en Epidémiologie et Biostatistique, Bordeaux, France
  6. 6ISPED, Université Bordeaux Segalen,  Bordeaux, France
  7. 7Department of Epidemiology and Public Health, University College London, London, UK
  8. 8CMRR Languedoc Roussillon, service de Neurologie, CHRU Montpellier, Montpellier, France
  9. 9INSERM-UPMC UMRS 975, Institut de la Mémoire et de la Maladie d'Alzheimer, ICM, APHP, Salpétrière Hospital, University Paris 6, Paris, France
  1. Correspondence to Dr Thibault Mura, Inserm U1061, Hôpital La Colombière, Pavillon 42 39 av. Charles Flahault, 34493 Montpellier, Cedex 5, France; t-mura{at}


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.

  • Alzheimer's Disease
  • Cognitive Neuropsychology
  • Dementia
  • Statistics

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