60 Chapter 3 associations with memory function over time. In addition, we identified a ‘grey zone’ of amyloid burden in cognitively normal individuals, and investigated its clinical significance, by exploring the nature of the relationship between amyloid levels in the subthreshold range and memory slope. METHODS Population We included 162 cognitively normal participants with SCD from the Subjective Cognitive Impairment Cohort (SCIENCe) within the Amsterdam Dementia Cohort at the Alzheimer Centre Amsterdam (27, 28). All subjects with [18F]florbetapir PET, magnetic resonance imaging (MRI) scan and cognitive data available were included. One hundred and fifty-two participants were referred to the memory clinic by their general physician, a neurologist or a geriatrician, and underwent an extensive standardized diagnostic workup that included a neurologic and neuropsychological examination, laboratory testing, and brain MRI (28, 29). In a consensus meeting, participants were labelled SCD when cognitive performance appeared within normal limits compared to peers, and criteria were not met for mild cognitive impairment (MCI), dementia, or other neurological or psychiatric diseases that could possibly cause cognitive complaints. At annual follow-up visits, neuropsychological testing was repeated and diagnoses were re-evaluated. In addition, 10 participants were included as research participants via the Dutch Brain Research Registry (hersenonderzoek. nl). They also experienced cognitive complaints in absence of a diagnosis of MCI or dementia, and received the same baseline work-up. Neuropsychological assessment We previously showed that the relationship between amyloid burden and cognitive decline was strongest for the memory domain, especially for the Rey auditory verbal learning task (RAVLT) - delayed recall (7). Therefore, for this study we used the RAVLT delayed recall as a measure for memory function. We used visits conducted before as well as after the PET scan to accurately estimate the memory slope, resulting in longitudinal cognitive data covering 3.8 ± 3.1 years. Concurrent time points were defined as the visit closest to the PET scan date (median -0.19 (IQR -0.38 – 0.14 years)). We used two different versions of the RAVLT, between which we alternated at the annual follow-up visits. In total, 655 neuropsychological examinations of 162 participants were available (149 ≥ 2 visits; range 1-10; median 3 visits).
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