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BackgroundCognitive reserve may protect against cognitive decline. However, its effect on physiological measures of cognitive workload in adults with cognitive impairments is unclear.ObjectiveThe aim was to determine the association between cognitive reserve and physiological measures of cognitive workload in older adults with and without cognitive impairments.Methods29 older adults with cognitive impairment (age: 75±6, 11 (38%) women, MOCA scores 20±7) and 19 with normal cognition (age: 74±6; 11 (58%) women; MOCA 28±2) completed a working memory test of increasing task demand (0-, 1-, 2-back). Cognitive workload was indexed using amplitude and latency of the P3 event-related potential (ERP) at electrode sites Fz, Cz, and Pz, and changes in pupillary size, converted to an index of cognitive activity (ICA). The Cognitive Reserve Index questionnaire (CRIq) evaluated Education, Work Activity, and Leisure Time as a proxy of cognitive reserve.ResultsHigher CRIq total scores were associated with larger P3 ERP amplitude (p=0.048), independent of cognitive status (p=0.80), task demand (p=0.003), and electrode site (pConclusionCognitive reserve affects cognitive workload and neural efficiency, regardless of cognitive status. Future longitudinal studies should investigate the causal relationship between cognitive reserve and physiological processes of neural efficiency across cognitive aging.

Background: Growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer’s disease (AD). The aim of this study was to compare neuronal excitability between cognitively normal amyloid positive (CNAβ+) and those without elevated amyloid (CNAβ-) older adults. We hypothesized CNAβ+ participants would show hyperexcitability, indexed by greater peak P3 event-related potential peak amplitude, shorter peak latency, and changes in event-related power, compared to CNAβ-.Methods: CNAβ+ participants (n = 17, age: 73 ± 5, 11 women, MOCA scores 26 ± 2) and 17 CNAβ- participants group-matched for age, sex, and MOCA completed the a working memory task (n-back with n = 0, 1, 2) test while wearing a 256-channel EEG net. P3 peak amplitude and latency of the nontarget, target and task difference (nontarget – target), and event-related power, extracted from Fz (main outcome), Cz, and Pz were compared between groups using linear mixed models. Mean Aβ standard uptake value ratios (SUVR) were correlated with P3 amplitude and latency using Pearson r.Results: P3 peak amplitude of the task difference (p = 0.048) and P3 peak latency of non-targets trials (p = 0.006) at Fz differed between groups. Similarly, power was lower in the delta band (p = 0.04) for nontargets at Fz in CNAβ+ participants. CNAβ+ participants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERP. Strong correlations were found between mean Aβ SUVR and latency of the 1-back (r = -0.69; p = 0.003) and 2-back (r = -0.69; p = 0.004) of the task difference at channel Fz in the CNAβ+ group.Conclusions: Our pilot data suggests that elevated amyloid in cognitive normal older adults is associated with hyperexcitability in P3 ERP. Further research is warranted to determine the validity of ERP in predicting clinical, neurobiological, and functional manifestations of AD.

Background Although growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer’s disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated Aβ (Aβ+) and cognitive processes measured by the P3 event-related potential (ERP) in cognitively normal (CN) older adults. The second aim was to compare the event-related power between CNAβ+ and CNAβ−. Methods Seventeen CNAβ+ participants (age: 73 ± 5, 11 females, Montreal Cognitive Assessment [MoCA] score 26 ± 2) and 17 CNAβ- participants group-matched for age, sex, and MOCA completed a working memory task (n-back with n = 0, 1, 2) test while wearing a 256-channel electro-encephalography net. P3 peak amplitude and latency of the target, nontarget and task difference effect (nontarget−target), and event-related power in the delta, theta, alpha, and beta bands, extracted from Fz, Cz, and Pz, were compared between groups using linear mixed models. P3 amplitude of the task difference effect at Fz and event-related power in the delta band were considered main outcomes. Correlations of mean Aβ standard uptake value ratios (SUVR) using positron emission tomography with P3 amplitude and latency of the task difference effect were analyzed using Pearson Correlation Coefficient r. Results The P3 peak amplitude of the task difference effect at Fz was lower in the CNAβ+ group (P = 0.048). Similarly, power was lower in the delta band for nontargets at Fz in the CNAβ+ participants (P = 0.04). The CNAβ+ participants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERP. Strong correlations were found between the mean Aβ SUVR and the latency of the 1-back (r = − 0.69; P = 0.003) and 2-back (r = − 0.69; P = 0.004) of the task difference effect at channel Fz in the CNAβ+ group. Conclusions Our data suggest that the elevated amyloid in cognitively normal older adults is associated with neuronal hyperexcitability. The decreased P3 task difference likely reflects early impairments in working memory processes. Further research is warranted to determine the validity of ERP in predicting clinical, neurobiological, and functional manifestations of AD.