Katja Hagen

Aging-related cortical reorganization of verbal fluency processing: a functional near-infrared spectroscopy study

While progressive neurocognitive impairments are associated with aging and Alzheimers disease (AD), cortical reorganization might delay difficulties in effortful word retrieval, which represent one of the earliest cognitive signs of AD. Using functional near-infrared spectroscopy (fNIRS), we investigated cortical hemodynamic responses elicited by phonological and semantic verbal fluency in non-demented, healthy subjects (n = 325; age: 51-82 years). Age predicted bilaterally reduced inferior frontal junction (IFJ) and increased middle frontal and supramarginal gyri activity in both task conditions using multiple regressions. Compared with age the years of education as well as sex (IFJ activation in females > males) partly predicted opposite effects on activation, while task performance was not significant predictor. All predictors showed small effect sizes. IFJ activation was more pronounced during phonological compared with semantic fluency, and higher in the left hemisphere. Age only marginally predicted relative lateralization. Middle frontal and supramarginal gyri activity may compensate for an aging-related decrease in IFJ recruitment during verbal fluency. Longitudinal observations will further investigate these neural changes regarding an early AD prediction, while individuals are still cognitively healthy.

Evolutionary transformations of myoseptal tendons in gnathostomes

Axial undulations in fishes are powered by a series of three–dimensionally folded myomeres separated by sheets of connective tissue, the myosepta. Myosepta have been hypothesized to function as transmitters of muscular forces to axial structures during swimming, but the difficulty of studying these delicate complex structures has precluded a more complete understanding of myoseptal mechanics. We have developed a new combination of techniques for visualizing the three–dimensional morphology of myosepta, and here we present their collagen–fibre architecture based on examination of 62 species representing all of the major clades of notochordates. In all gnathostome fishes, each myoseptum bears a set of six specifically arranged tendons. Because these tendons are not present outside the gnathostomes (i.e. they are absent from lampreys, hagfishes and lancelets), they represent evolutionary novelties of the gnathostome ancestor. This arrangement has remained unchanged throughout 400 Myr of gnathostome evolution, changing only on the transition to land. The high uniformity of myoseptal architecture in gnathostome fishes indicates functional significance and may be a key to understanding general principles of fish swimming mechanics. In the design of future experiments or biomechanical models, myosepta have to be regarded as tendons that can distribute forces in specific directions.

Activation during the Trail Making Test measured with functional near-infrared spectroscopy in healthy elderly subjects

Cognitive decline is very common in age and particularly in subjects with neurodegenerative conditions. Besides memory and language, executive functions are very often affected in elderly and patients with Alzheimers disease or Parkinsons disease. However, the neural alterations associated with these executive deficits are still not fully understood. Therefore, we measured cortical activation using functional near-infrared spectroscopy (fNIRS) in 16 healthy elderly subjects (50-75 years) performing the Trail Making Test (TMT), a widely used neuropsychological instrument measuring executive function. In line with previous studies focusing on younger subjects, the results showed frontal activation during the TMT A and the TMT B in the dorsolateral prefrontal cortex, the frontopolar area and also Brocas area. Furthermore, significant activation in the left motor, somatosensory cortices and somatosensory association cortices was demonstrated. Additionally, after a median split the differences between younger (<58 years) and older (>58 years) subjects were analyzed with the older subjects showing a less focused prefrontal activation. Altogether, fNIRS was found to be suitable to detect cortical activation in elderly subjects during performance of the TMT as well as aging-related differences in prefrontal activation topography. These neural correlates of executive functions should be further investigated as a potential prodromal neural marker of executive deficits and neurodegenerative processes.

Decreased α-Synuclein Serum Levels in Patients with Lewy Body Dementia Compared to Alzheimer’s Disease Patients and Control Subjects

Background/Aims: Detection and differentiation of neurodegenerative dementias, such as dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD), with blood-based biomarkers would facilitate diagnosis and treatment. Methods: By use of a commercially available ELISA kit, we measured α-synuclein levels in the serum of 40 DLB patients and controls, and of 80 AD patients. Results: We found significantly reduced α-synuclein serum levels in DLB compared to both AD (p = 0.006) and control subjects (p = 0.001), reaching an area under the curve of >0.70. Conclusion: Although these results do not justify a definition of serum α-synuclein as a potential single biomarker, results may contribute to a multimarker strategy in DLB diagnosis.

Vagus somatosensory evoked potentials--a possibility for diagnostic improvement in patients with mild cognitive impairment?.

Objective: Vagus somatosensory evoked potentials (VSEP) are far-field potentials probably generated in nuclei of then. vagus in the lower brainstem. They represent a putative, easily applicable method for discrimination between patients with Alzheimer’s disease (AD), patients with mild cognitive impairment (MCI), and healthy controls (HC). Methods: Thirteen patients with AD, 12 with MCI, and 27 age- and gender-matched HC were investigated by stimulating the cutaneous branch of the n. vagus; 8, 6, and 20, respectively, were included in the main part of the analysis. Results: In fronto-central recordings (electrode positions Fz-F4) a grading from HC over MCI to AD could be found, with a significant linear trend over the three groups and significantly increased latencies of the cognitively impaired patients but no significant difference between MCI and AD. Conclusion: The results indicate that the method of VSEP is able to discriminate between cognitively declined patients and HC, whereas no clear-cut differences were detected between MCI and AD.

Influence of different stimulation parameters on the somatosensory evoked potentials of the nervus vagus--how varied stimulation parameters affect VSEP.

Summary: Vagus somatosensory evoked potentials are a method for assessing the function of the vagus nerve, which were shown to be altered in neurodegenerative diseases like Alzheimers and Parkinsons disease. Various parameters of the stimulation such as the electrode position and the stimulus intensity have already been investigated. In this study, the focus is on the systematic examination of the other parameters of the stimulation of the vagus somatosensory evoked potentials: stimulus duration, interstimulus interval, and, again, the stimulation intensity. Thirty young and healthy subjects were examined using five different sets of stimulation parameters, and 24 were included in the further analysis. The results show that a reduction of the stimulus duration and a decrease in stimulus intensity have a significant effect on the amplitudes. A shortening of the interstimulus interval does not seem to have such an effect, but this stimulation is rated more painful and unpleasant than the standard stimulation. Overall, the standard stimulation used so far seems to be the most preferable condition.

The relation of SMI and the VSEP in a risk sample for neurodegenerative disorders.

Vagus somatosensory evoked potentials (VSEP) have been shown to have higher latencies with aging, which are even more increased in patients with Alzheimer’s disease and subjects with mild cognitive impairment compared to age-matched healthy controls. In this study, the association of VSEP with subjective memory impairment (SMI), a potential risk or prodromal marker for Alzheimer’s disease, was examined. The association of VSEP latencies and SMI was studied in a healthy risk cohort, including 358 elderly subjects, who are in a longitudinal study of risk factors for neurodegenerative disorders. The results show increased VSEP latencies for peak P2 at Fz–F4 in subjects who report SMI and are worried about it as compared to subjects who report memory impairment, but are not concerned and subjects without complaints. The results support a potential role of VSEP for the detection of very early neurodegenerative processes which may precede Alzheimer’s disease.

Stem cell factor plasma levels are decreased in Alzheimer's disease patients with fast cognitive decline after one-year follow-up period: the Pythia-study.

Alzheimers disease (AD) is the most common cause of cognitive decline in the elderly and is characterized by massive neuronal loss in the brain. Stem cell factor (SCF) is a hematopoietic growth factor that promotes neuroprotective effects and supports neurogenesis in the brain. Decreased SCF plasma levels have been described in AD patients. Whether SCF plasma levels are also associated with the rate of cognitive decline in AD patients has not been reported so far. In the present study, we demonstrate that SCF plasma levels are significantly decreased in AD patients with fast cognitive decline (decrease of Mini-Mental State Examination [MMSE] score > 4 after one year; n = 12) compared to AD patients with slow cognitive decline (decrease of MMSE score ≤ 4 after one year; n = 28) (fast versus slow cognitive decline: mean ± SD: 1051.1 ± 178.7 versus 1237.9 ± 274.2 pg/ml; p = 0.037). Moreover, SCF plasma levels correlated with the rate of cognitive decline after one year follow-up period (r = 0.315; p = 0.048). In a multiple linear regression analysis, independent predictors of the rate of cognitive decline in our study cohort were age, MMSE scores at baseline, SCF plasma levels, as well as brain-derived neurotrophic factor and activated glycoprotein (GP) IIb/IIIa. These results suggest that lower SCF plasma levels are associated with a higher rate of cognitive decline in AD patients. Thus, treatment strategies increasing SCF plasma levels could be useful for delaying the progression of AD. Further prospective studies are needed to elucidate the value of plasma SCF in a multimarker approach determining AD prognosis.