Event-related potentials, inhibition and Alzheimer's disease risk in cognitively intact elders

Abstract

Despite advances in understanding Alzheimer’s disease (AD), prediction of AD prior to symptom onset remains severely limited, even when primary risk factors such as the apolipoprotein-E (APOE) ε4 allele are known. Although executive dysfunction is highly prevalent and is a primary contributor to loss of independence in those with AD, few studies have examined neural differences underlying executive functioning as an indicator of risk for AD prior to symptom onset, when intervention might be effective. This study examined event-related potential (ERP) differences during inhibitory control in 44 cognitively intact older adults (20 ε4+, 24 ε4-), relative to 41 young adults. All participants completed go/no-go and stop-signal tasks. Overall, both older adult groups exhibited slower reaction times and longer ERP latencies compared to young adults. Older adults also had generally smaller N200 and P300 amplitudes, except at frontal electrodes and for N200 stop-signal amplitudes, which were larger in older adults. These patterns, along with intact task accuracy, support prior studies evidencing age-related neural compensation. Although ε4 did not distinguish elders during go or no-go tasks, this study uniquely showed that the more demanding stop-signal task was sensitive to ε4 differences, despite comparable task and neuropsychological performance with non-carriers. Specifically, ε4+ elders had slower frontal N200 latency and larger N200 amplitude, which was most robust at frontal sites, compared with ε4-. Thus N200 during a stop-signal task was sensitive to AD risk, prior to any evidence of cognitive dysfunction, suggesting that stop-signal ERPs may be an important protocol addition to neuropsychological testing.

Early Event-Related Potential components as potential biomarkers for Alzheimer's Disease and their relationship with attentional capacity.

“…However, this conclusion is tentative, as a majority of these studies employed an oddball paradigm (49%), whilst the few studies that did report significant differences in N200 amplitude between AD patients and controls utilised more complex tests of attention than the oddball task, such as the Erickson Flanker Task (Wang et al, 2013) attentionally cued discrimination task (Lockwood et al, 2018), and go/no-go tasks, (Crawford, 2015). This indicates that oddball paradigms may not be complex enough to demonstrate differences in N200 amplitude, a result supported by Elverman et al, (2021), who observed that as attentional task complexity increased, differences between older adults carrying the E4 apolipoprotein allele, a risk factor for AD, became more distinguishable. Studies indicating differences in N200 latency between AD and controls also present mixed results, however most studies do present significantly prolonged N200 latencies in AD patients (see Howe, 2014).…”

“…As poor impulse control has been noted as a potential symptom of AD (Mendez & Shapira, 2013), it may indicate why AD patients elicit lower N200 amplitudes than controls in tests like the go/no go, as they have less cognitive resources available to allocate to impulse control. This theory is contentious however, particularly as a study by Elverman et al, (2021) showed that participants with the ɛ4+ Apolipoprotein E gene, a primary risk factor in AD development, showed higher peak amplitudes as part of a no/go task than controls.…”