The method of vagus somatosensory evoked potentials (VSEP) was introduced to easily measure the activity of vagus brain stem nuclei. In Alzheimer's disease, this measure was characterized by longer latencies as compared to controls while amplitudes did not show statistical significant differences at frontal and central recording sites. Therefore, the influence of stimulation and recording parameters on amplitudes of VSEP were systematically examined. In 20 healthy participants, VSEP measurement was done by electrical stimulation of the cutaneous representation of the vagus nerve in the external auditory channel and recording of VSEP over the scalp. The optimum stimulation intensity is 8 mA without perception of pain. There is no effect of stimulation side or gender. Maximum VSEP amplitudes are detected at bipolar recordings comprising the electrode T4 without statistically significant differences of latencies, wave shape and polarity. Thus, recordings of future examinations should be performed at 8 mA including this temporal electrode position. The reason for focussing on brain stem evoked potentials is that recent work has accumulated evidence for this area being involved in early phases of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Improved methodological knowledge may facilitate the assessment of this non-invasive and cost-effective method in the early diagnosis of neurodegenerative disorders.

Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. We investigated the profiles of 33 genes, previously found by our group to have altered expression in postmortem brains of AD. The gene profiles were studied via quantitative-real-time-reverse-transcription-polymerase-chain-reaction, in whole blood samples (collected with the PAXgene blood RNA system) isolated from a population clinically diagnosed with AD and healthy controls (1-year period/ up to 4 samples). Five genes showed significant correlation to the dementia score, Mini-Mental State Examination (MMSE). Focusing on the two genes with the smallest p-value, H3-histone and cannabinoid-receptor-2, notable increases in these genes were found in peripheral blood mRNA in subjects with lower MMSE scores. Seasonal variations in gene expression were not significant due to sample size, but did seem to vary due to time of sample withdrawal. In conclusion, gene expression profiling might be a promising method to investigating a large population with the aim of developing an early diagnosis of AD.

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In Alzheimer's disease (AD), mild functional disturbances should precede gross structural damage and even more clinical symptoms, possibly by decades. Moreover, alterations in the brainstem are supposed to occur earlier as cortical affections. Based on these considerations, we developed a new method aiming at the measurement of vagal brainstem functioning by means of evoked potentials after electrical stimulation of the cutaneous representation of the vagus nerve in the external auditory channel. In the current study, a first sample of patients with Alzheimer's disease (n = 7) and mild cognitive impairment (n = 3) were investigated (6m, 4f, range from 57 to 78 y, mean age 68.6 years). Vagus somatosensory evoked potentials (VSEP) were characterized by significantly longer latencies as compared to healthy age- and gender-matched controls (p < 0.05). Future large scale studies - also including preclinical stages of AD - have to assess the value of this non-invasive, fast and cheap method in the early diagnosis of neurodegenerative disorders.

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