Near-infrared spectroscopy (NIRS) and vagus somatosensory evoked potentials (VSEP) in the early diagnosis of Alzheimer's disease: rationale, design, methods, and first baseline data of the Vogel study.

Functional near-infrared spectroscopy (fNIRS) and vagus somatosensory evoked potentials (VSEP) show deviant patterns in subjects with Alzheimer's disease (AD) compared to healthy controls. We now aimed at testing the predictive value of these methods in the early diagnosis of AD. The Vogel study is a prospective, observational, long-term follow-up study with three time points of investigation within 6 years. Residents of the city of Würzburg born between 1936 and 1941 were recruited. Every participant underwent physical, psychiatric, and laboratory examinations, and performed an intense neuropsychological testing as well as VSEP and NIRS according to the published procedures. 604 subjects were included. Mean age of the participants was 73.9 ± 1.55 years. The most frequent pathological physical and laboratory examination results were observed for blood pressure (62%), body weight (54%), HbA1c (16%), cholesterol (42%), and homocysteine (69%). Comprehensive analysis of cognitive testing showed mild cognitive impairment (MCI) in 12.3% of the patients. Concurrent major depression was found in 6.6% of the patients. We observed a high rate of MCI and somatic comorbidity in our cohort. The high rate of vascular risk factors and depressive symptoms, all of which are known risk factors of AD, is consistent with the notion that there are multiple options to prevent or postpone the onset of AD in a geriatric population like the one of the Vogel studies.

Vagus somatosensory evoked potentials are delayed in Alzheimer's disease, but not in major depression.

In Alzheimer's disease (AD), the degeneration of brainstem nuclei is different from major depression (MD). Thus, vagus somatosensory evoked potentials (VSEP) proposed for the functional assessment of brainstem nuclei should show prolonged latencies in AD but not in MD. In 55 AD patients, 57 MD patients and two age-matched control groups evoked potentials were recorded upon stimulation of the auricular branch of the vagus nerve. In the AD, not in the MD group, latencies were significantly longer as compared to controls. Thus, the method of VSEP could contribute to the important differential diagnosis of AD and MD in elderly patients.

Altered parietal brain oxygenation in Alzheimer's disease as assessed with near-infrared spectroscopy.

OBJECTIVE: Visuospatial deficits are among the first symptoms of Alzheimer disease (AD) and linked to lower activation in the superior parietal cortex as assessed with functional imaging. Near-infrared spectroscopy (NIRS) is an optical method to measure changes in the concentration of oxygenated hemoglobin and deoxygenated hemoglobin in the microvascular system of the cortex. Because of its advantages in measurement situation, NIRS has proven to be especially suited for investigating psychiatric patients. The aim of this study was to probe the activation of parietal regions in patients with AD, performing a visuospatial task by means of functional NIRS (fNIRS). METHODS: Thirteen patients with suspected mild AD and 13 healthy subjects comparable in age and gender were investigated while working on a modified version of the Benton Line Orientation Task. RESULTS: During the spatial task, healthy subjects showed explicit parietal activation, whereas patients displayed only activation during the control task. Interestingly, there was no difference in visuospatial performance between the two groups. CONCLUSION: The results indicate that fNIRS is able to measure parietal activation deficits in patients with AD, which could be developed into an early detection method in the future.

Reduced spontaneous low frequency oscillations as measured with functional near-infrared spectroscopy in mild cognitive impairment.

Spontaneous low frequency oscillations (LFO) in functional imaging data have gained increased interest in the study of cognitive decline. Persons diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD) display alterations in their amount of LFO in various brain regions. This is commonly interpreted as disruptions in the autoregulation of the cerebral microvascular system. In the present study LFO (0,07-0,11 Hz) were measured with 52-channel near-infrared spectroscopy (NIRS) in 61 healthy elderly persons (70-76 years), 54 MCI subjects (70-76 years) and 25 healthy young controls (21-48 years) during rest over the frontal and the parietal cortex. Both MCI and healthy elderly controls showed less LFO in the frontal cortex as compared to young subjects. For the parietal cortex a decrease in LFO could be observed for the MCI group in comparison to healthy elderly subjects. Correlations of more LFO with worse performance in neuropsychological tests point to compensatory processes. LFO measured with NIRS might be especially suited for longitudinal studies aiming at predicting cognitive decline.

Decreased hemodynamic response in inferior frontotemporal regions in elderly with mild cognitive impairment.

The verbal fluency task (VFT) is a well-established cognitive marker for mild cognitive impairment (MCI) in the prodromal stage of Alzheimer´s dementia (AD). The behavioral VFT performance of patients allows the prediction of dementia two years later. But effective compensatory mechanism might cover or reduce the predictive value of the VFT. Therefore the aim of this study is to measure the hemodynamic response during VFT in patients with mild cognitive impairment (MCI) to establish the hemodynamic response during the VFT as a screening instrument for the prediction of dementia. One method which allows measuring the hemodynamic response during speech production without severe problems with moving artifacts like in functional magnetic resonance imaging (fMRI) is the functional near-infrared spectroscopy (fNIRS). It is optimal as a screening instrument, as it is easy to apply and without any contraindications. In this study we assessed the hemodynamic response in prefrontal and temporal regions in patients with MCI as well as matched healthy controls with fNIRS. We found a decreased hemodynamic response in the inferior frontotemporal cortex for the MCI group. Our results indicate that a frontotemporal decreased hemodynamic response could serve as a diagnostic biomarker for dementia.

Reduced Activity in the Right Inferior Frontal Gyrus in Elderly APOE-E4 Carriers during a Verbal Fluency Task.

Apolipoprotein-E4 (APOE-E4) is a major genetic risk factor for developing Alzheimer's disease (AD). The verbal fluency task (VFT), especially the subtask category fluency, has shown to provide a good discrimination between cognitively normal controls and subjects with AD. Interestingly, APOE-E4 seems to have no effect on the behavioral performance during a VFT in healthy elderly. Thus, the purpose of the present study was to reveal possible compensation mechanisms by investigating the effect of APOE-E4 on the hemodynamic response in non-demented elderly during a VFT by using functional near-infrared spectroscopy (fNIRS). We compared performance and hemodynamic response of high risk APOE-E4/E4, -E3/E4 carriers with neutral APOE-E3/E3 non-demented subjects (N = 288; 70-77 years). No difference in performance was found. APOE-E4/E4, -E3/E4 carriers had a decreased hemodynamic response in the right inferior frontal junction (IFJ) with a corresponding higher response in the left middle frontal gyrus (MFG) during category fluency. Performance was correlated with the hemodynamic response in the MFG. We assume a compensation of decreased IFJ brain activation by utilizing the MFG during category fluency and thus resulting in no behavioral differences between APOE-groups during the performance of a VFT.

Neural correlates of a standardized version of the trail making test in young and elderly adults: a functional near-infrared spectroscopy study.

The trail making test (TMT) is a widely applied diagnostic tool measuring executive functioning in order to discriminate between healthy and pathological aging processes. However, due to its paper-and-pencil nature it is difficult to adapt for functional brain imaging. Related neural underpinnings even in healthy aging are mostly unknown since no consistent administration for imaging is available. In this study a standardized implementation of the TMT for functional near-infrared spectroscopy (fNIRS) is proposed to investigate associated frontal cortex activation in healthy young (mean age 25.7 ± 3.02 years) and elderly adults (mean age 70.95 ± 3.55 years). The TMT consisted of a number condition (TMT-A), an alternating number and letter condition (TMT-B) as well as a control task. Behavioral results demonstrated that elderly participants performed slower but committed a similar number of errors compared to younger adults. The fNIRS results showed that particularly the TMT-B provoked bilateral activation in the ventro- and dorsolateral prefrontal cortex (vlPFC and dlPFC) as well as in premotor regions. Elderly participants displayed more significantly activated channels and a different activation pattern compared to younger participants especially manifesting in more bilateral dlPFC activation. In line with the hemispheric asymmetry reduction in elderly adults (HAROLD) model, the results were interpreted as an additional need for cognitive control resources in elderly participants. This study succeeded in implementing an appropriate version of the TMT for fNIRS and helps elucidating neural aging effects associated with this task.