Abstract

AbstractBackgroundEmerging evidence from animal and human studies shows that beta‐amyloid (Aβ) may induce neuronal hyperexcitability in the early stage of Alzheimer’s disease (AD). Electroencephalography (EEG) offers unparalleled temporal resolution in tracing distinct neurophysiological processes even in preclinical AD. The aim of this pilot study was to determine the relationship of Aβ accumulation and event‐related potential (ERP) in cognitively normal older adults.MethodAβ accumulation was characterized with [18F] Florbetapir positron emission tomography (PET) scans. Global Aβ burden was assessed by taking the mean standard uptake value ratios (SUVR) of 6 predefined regions: anterior cingulate, posterior cingulate, precuneus, inferior medial frontal, lateral temporal, and superior parietal cortex. All participants completed a working memory task with three levels of difficulty (0‐,1‐,2‐back). ERP P3 peak amplitude and latency were extracted from the task effect (non‐target minus target). We used Pearson r to calculate associations between mean SUVR and P3 ERP at the midline channels Fz and Cz. Since the working memory task induced frontal cortical activity, we also explored the relationship between SUVR in the inferior medial frontal cortex and the frontal channels Fz, F3, and F4.ResultTwenty‐seven (age: 73.9 ± 5.5; MOCA: 27.37 ± 2.0) completed both PET and EEG scans. Mean SUVR ranged from 0.95 to 1.60 and correlated negatively with P3 latency of the 2‐back at Cz (r = ‐0.40; p = 0.04) and Fz (r = ‐0.58; p = 0.002). SUVR in the inferior medial frontal cortex correlated negatively with P3 peak latency of 1‐back at Fz (r = ‐0.42; p = 0.03) and F3 (r = ‐0.49; p = 0.009), and of 2‐back at Fz (‐0.54; p = 0.004) and F3 (r = ‐0.40; p = 0.045). No correlations were found between global Aβ burden and P3 peak amplitude.ConclusionThe negative relationship between Aβ accumulation and P3 latency provides preliminary support for the neuronal hyperexcitability hypothesis in preclinical AD. However, these findings need to be confirmed in a longitudinal cohort study with larger sample size.

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