Prospective Study to Evaluate the Predictive Value of Vagus Somatosensory Evoked Potentials (VSEP) and Near-infrared Spectroscopy (NIRS) in the Early Diagnosis of Alzheimer´s Disease

With the increasing life span of our population, the prevalence of dementia syndromes is increasing. The most frequent cause of dementia is Alzheimer´s disease (AD), and still, it is not curable. Thus, AD is of increasing medical, social and economic importance.

Intensive scientific work within the past 30 years has identified a range of different factors contributing to the pathogenesis of AD. These complex processes result in specific therapeutic options which are currently investigated in clinical trials. Regardless of the considered risk factor or the specific therapeutic intervention, treatment should be started as early in the excessive preclinical process of AD as possible since it can interfere with the formation of amyloid plaques or neurofibrils. Especially neuroprotective interventions are more effective the less neurons are irreversibly damaged.Therefore, an early diagnosis of developing or incipient AD should be of utmost importance. Likewise, in the light of therapeutic options specific for AD, its differential diagnosis from other forms of dementia seems important.

Therefore, an ideal examination method should not only be easy to conduct, cost effective, repeatable, non-invasive and without discomfort for patients, but it should in particular detect early stages of disease and it should, if possible, consider the development of AD-specific changes. Obviously, today´s routine examination methods in the diagnosis of AD or MCI such as magnetic resonance imaging, cerebrospinal fluid analysis or positron emission tomography do not fulfil all of these requirements. Thus, in the absence of a single diagnostic test and realizing the necessity to combine biomarkers to increase the diagnostic accuracy there is still need for methods that circumvent all those disadvantages.

Since early cellular changes of the disease are expected to impact brain function long before severe morphological alterations occur, these changes should primarily be investigated using functional examination which can be conducted with neurocognitive methods such as intensive neuropsychological rating or with electrophysiological or functional brain imaging methods.

Neuropsychological rating Prior studies investigated the predictive validity of different cognitive measures for the development of AD such as associative learning, verbal fluency and constructive praxis. As such, verbal and non-verbal memory, visual-spatial and executive functions and verbal fluency with executive component seem to be suited for following the deterioration of cognition. In subjects who later develop AD or MCI as compared to a healthy controls, worse performance in episodic memory according (Delayed Verbal and Visual Memory und Associative Learning) and in semantic verbal fluency are known to be characteristic. An extended neuropsychologic testing to measure these cognitive processes thus seems reasonable in particular to evaluate the additional benefit of other diagnostic methods.