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alpha trace medical systems

The human electroencephalogram (EEG) delivers a standardised view of cortical brain activity with high temporal resolution; but the signal is difficult to decipher, and only EEG specialists with extensive training are able to ‘read’ the EEG signature. Even with extensive experience in reading EEGs, many details remain hidden within the complex traces recorded from minute voltage differences derived with electrodes positioned in a standardised manner (10/20 system) on the scalp. For this reason, computer programs are essential for a more detailed analysis of the EEG signature. Degenerative processes within the brain, leading to dementia and maybe Alzheimer’s disease (AD), are bound to affect the EEG signature in subtle to more pronounced ways. Computer programs (e.g. Sigla) have been designed that differentiate EEG recordings from MCI (mild cognitive impairment), dementia with vascular origin, AD and others from EEG recordings derived from age-matched, normal controls. Due to the lack of EEG specialists endorsing these programs, EEG-based diagnostics of dementia have not yet found their way into the mainstream. This is unfortunate since these methods are readily available, inexpensive and without adverse effects.

I would like to draw the focus for those interested in the matter of dementia diagnostics and monitoring to another electrophysiological method showing great promise: event-related potential (ERP) testing. This method records the brain’s EEG response to standardised provocations such as auditory, visual, somatosensory stimuli. An effective ERP experiment thought to test for post-stimulus information processing and executive function is the auditory oddball test. In this diagnostic setup, one to three EEG electrodes (compared to 19 electrodes for standard EEG) at central positions (Fz, Cz, Pz) are typically used to record the brain’s electrical response to auditory stimuli supplied via headphones to the subject. The task given to the tested person is to actively (press a button or mental count) differentiate a rare tone (typically higher pitch) supplied with about 20% occurrence, from a lower pitch, frequent tone supplied at about 80% occurrence randomly mixed with the rare events. The EEG response to the frequent and rare tones is very minute (µV range), hidden within the background EEG activity and cannot easily be derived from the EEG traces.

A method called ‘averaging’ resolves this obstacle by independently averaging the EEG recorded data just before and 500-1,000ms (sweeps) after the tone stimulus for the frequent and rare events. The background EEG assumed not to be trigger related will tend towards zero, whereas the trigger-related ERP will become more pronounced (improved signal/noise ratio) and reproducible after several averages (35-60 for the rare events). The result of this auditory oddball test is a pronounced deflection of the averaged sweeps about 300ms post-stimulus for the rare tone averages not showing in the frequent tone averages. A first report providing evidence for the clinical utility of the so-called ‘P300’ component in dementia appeared in 1978 (Goodin, Squires and Starr).

A meta-analysis by Aaron S Howe, Ali Bani-Fatemi and Vincenzo De Luca in Brain and Cognition (2014) reports on the clinical utility of the auditory P300 latency subcomponent ERP in preclinical diagnosis of patients with MCI and AD. In the conclusion of the meta-analysis, the authors summarise: “This meta-analysis supports the use of the auditory P300 latency subcomponent as a biological marker of prodromal AD. It has been shown to consistently discriminate between patients with AD (and even mild AD), patients with MCI and unaffected controls.”

Considering other studies on P300 and dementia, it seems reasonable to adopt this simple and readily applicable test – especially in early age (before 70 years) – to test for cognitive decline and possibly to monitor the success of therapy efforts.

Dieter Grossegger, PhD
CEO
alpha trace medical systems