Alzheimer's Disease Biomarker Protocol

We retrospectively included patients who had been evaluated and followed up in the memory clinic of the Amsterdam UMC Alzheimer center, or who participated in a multicenter AD clinical trial with central EEG analysis at the Amsterdam UMC EEGlab, between October 15, 2003, and January 1, 2019. All participants provided written informed consent for the use of their data for research purposes. Although AD represents a seamless disease continuum, patients can be assigned to progressive phases based on physical, cognitive, and functional assessments [1 (link)]. We differentiated between patients with MCI and dementia due to AD based on established clinical guidelines [40 (link)]. For a detailed description of all investigations that were performed as part of our routine diagnostic screening, see Van der Flier et al. [41 (link)]. Two or more EEG recordings were available for all participants. Recordings that were heavily contaminated with artifacts were excluded from analysis. Follow-up durations shorter than 3 months or longer than 3 years are not commonly employed in AD clinical trials. We therefore only evaluated follow-up recordings that were obtained within this time-frame. All participants were positive for Aβ deposition, as assessed using CSF Aβ42 (cut-off < 813 pg/ml, Tijms et al. (2018)) [42 ] or [¹¹C] PiB amyloid PET investigation (the routine PET protocol has been described elsewhere [43 (link), 44 (link)]). Tau pathology and neurodegeneration were characterized at baseline using CSF p-tau (cut-off > 52 pg/ml) and t-tau levels (cut-off > 375 pg/ml) [45 (link)]. Tau and neurodegeneration positive and negative patients (T +/- , N +/-) were included in this study. Medial temporal lobe atrophy (MTA), ranging from 0 (no atrophy) to 4 (severe atrophy), was rated on coronal T1-weighted MRI images. To evaluate the potential effect of pharmacological agents (i.e., cholinesterase inhibitors, anti-depressants, anti-epileptic drugs, anti-psychotics, benzodiazepines) on our findings, medication use was evaluated and scored.