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Slide Slam S10 Sandbox Series

Age-related changes in semantic processing: towards a neurophysiological marker of early Alzheimer’s disease

Slide Slam Session S, Friday, October 8, 2021, 12:00 - 2:30 pm PDT Log In to set Timezone

Pietari Nurmi1, Heidi Ala-Salomäki1, Hanna Renvall1,2, Mia Liljeström1,2; 1Aalto University, 2Helsinki University Hospital

Early detection of Alzheimer’s disease (AD) is crucial for delaying the disease progression. Synaptic dysfunction, measurable with neurophysiological imaging methods, is one of the earliest markers of AD pathology (Terry et al., 1991, Annals of Neurology, 30(4), 572–580). Noninvasive neurophysiological recordings of synaptic functioning using magnetoencephalography (MEG) could thus provide valuable tools for early detection of AD. To enable patient MEG studies, we need robust tasks able to differentiate AD-related deterioration from normal aging-related effects. Language processing serves as an ideal domain to study cortical aging effects, as it remains relatively well preserved in normal aging (Shafto & Tyler, 2014, Science, 346(6209), 583–588). Here, our goal is to develop a language task that is sensitive to the effects of normal and abnormal aging and feasible for later patient studies. To do so, we investigated age-related neurophysiological changes in a semantic priming task using MEG in healthy volunteers of different age groups. The N400 effect in semantic priming tasks typically gets weaker and slower in older subjects (Kutas & Iragui, 1998, Electroencephalography and Clinical Neurophysiology 108, 456–471), and the process is further affected in patients with Alzheimer's disease (Iragui et al., 1996, Electroencephalography and Clinical Neurophysiology 100, 392–406). We will measure 25 young (age 22–32) and 25 elderly (age 63–70) Finnish-speaking adults. In order to assess test-retest reliability, each participant is measured on two separate days. Structural MRIs are available from all subjects. According to our preliminary results (10 old and 13 young participants), there were notable differences between the age groups both in MEG activations and behavioral measures. A significant (p<0.05) N400 effect was observed in both subject groups on both measurement days. As expected, the N400 latency was longer for old than young participants: the difference was significant in the second measurement (p=0.008) and approached significance on the first measurement day (p=0.06). Surprisingly, despite the greater N400 latency, behavioral reaction times were considerably faster for older participants. This finding speaks for a difference in cognitive strategies between age groups. Task-related increase in frontal activation was observed in the older participants, possibly indicating more prominent use of compensatory top-down cognitive strategies (Wlotko et al., 2010, Linguistics and Language Compass, 4(8), 623–638). Our preliminary results suggest that the semantic priming task produces a reproducible N400 effect in both age groups and may provide a MEG biomarker for aging in the language domain. The results also establish a strong foundation for further developing the methodology toward clinical studies.

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