The 'when' matters: evidence from memory markers in the clinical continuum of Alzheimer's disease

Gonzalo Forno, Mario A. Parra, Daniela Thumala, Roque Villagra, Mauricio Cerda, Pedro Zitko, Agustin Ibanez, Patricia Lillo, Andrea Slachevsky

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Objective: Cognitive assessment able to detect impairments in the early neuropathological stages of Alzheimer's disease (AD) are urgently needed. The Visual Short-Term Memory Binding Task (VSTMBT) and the Free and Cued Selective Reminding Test (FCSRT) have been recommended by the Neurodegenerative Disease Working Group as promising tests to aid in the early detection of AD. In this study, we investigated their complementary value across the clinical stages of the AD continuum. Methods: 117 older adults with subjective cognitive complaint (SCC), 79 with mild cognitive impairment (MCI), 31 patients with AD dementia (ADD) and 37 cognitively unimpaired (CU) subjects, underwent assessment with the VSTMBT and the Picture version of the Spanish FCSRT. Results: After controlling for multiple comparisons, significant differences were found across groups. The VSTMBT was the only test that ‘marginally’ differentiated between CU and SCC (d = 0.47, p = 0.052). Moreover, whereas the FCSRT showed a gradient (CU = SCC) > MCI > ADD, the VSTMBT gradient was CU > SCC > (MCI = ADD) suggesting that conjunctive binding deficits assessed by the latter may be sensitive to the very early stages of the disease. Conclusions: Our results suggest that the VSTMBT and the FCSRT are sensitive to the clinical continuum of AD. Whereas the former detects changes in the early prodromal stages, the latter is more sensitive to the advanced prodromal stages of AD. These novel tests can aid in the early detection, monitor disease progression and response to treatment, and thus support drug development programs.
Original languageEnglish
Number of pages37
Publication statusAccepted/In press - 25 Nov 2022


  • Alzheimer's disease
  • memory markers
  • early detection
  • memory binding
  • relational memory
  • cognitive complaint


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