Memory markers can help trace the Alzheimer’s disease continuum: Evidence from the GERO Cohort

Background: Cognitive assessments able to detect impairments as early as neuropathological changes that occur in neurodegenerative diseases initiate are urgently needed. The Visual Short-Term Memory Binding Test (VSTMBT) and the Free and Cued Selective Reminding Test (FCRST) have been recently recommended by the Neurodegenerative Diseases Working Group (Costa et al., 2017) as promising preclinical markers of AD. They have never been used before to assess elderlies with cognitive complain recruited from the community. Method: A total of 271 subjects (37 healthy controls (HC), 112 subjective cognitive complain (SCC), 96 mild cognitive impairment (MCI) and 26 Alzheimer's disease dementia (ADD)), recruited from Geroscience Center for Brain Health and Metabolism (GERO) Cohort and the Memory and Neuropsychiatric Clinic (CMYN), underwent assessment with the VSTMBT and the Visual Version of the FCRST (FCRST-Visual). Two memory loads were used for the VSTMBT (low and high). The ability of these tests to discriminate between groups. Result: Significant differences were found between HC, MCI and ADD using the VSTMBT and the FCRST-Visual version. Notably, the STMB was the only test that "marginally" differentiated between HC from SCC (p = 0.055). Moreover, whereas the FCRST-Visual showed a gradient (HC = SCC) > MCI > AD, the VSTMBT's gradient was HC > (SCC = MCI = ADD) suggesting that the function assessed by the latter test may be sensitive to the very early stages of the disease dropping to levels that cannot decline further. Conclusion: Our results suggest that the VSTMBT and FCSRT are sensitive to the early stages of dementia. Whereas the former detects changes in the early subjective stages, the latter is more sensitive to later objective stages of cognitive decline. The latter but not the former could help monitor disease progression. These results raise important questions about the usefulness of cognitive screening tools to detect and monitor disease progression and to separate normal and abnormal ageing trajectories. We propose the need of cognitive assessments that detect subtle differences as early as neuropathological changes occur in the brain, which will lead to the development of new "cognitive biomarkers" for dementia.