Single-domain amnestic mild cognitive impairment identified by cluster analysis predicts Alzheimer's disease in the european prospective DESCRIPA study.

BACKGROUND/AIMS: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). METHODS: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e.g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE ≥28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. RESULTS: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (Aß42, t-tau, APOE ε4, and medial temporal atrophy), compared to SCI or naMCI. CONCLUSION: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings.

Changes in cortical blood oxygenation during arithmetical tasks measured by near-infrared spectroscopy.

Solving arithmetical problems is a core skill which is learned starting early in childhood and has been shown to involve a temporo-parietal network. In this study, we investigated hemodynamic concentration changes in oxygenated (O(2)Hb) and deoxygenated hemoglobin (HHb) within cortical brain regions by means of near-infrared spectroscopy (NIRS). Ten healthy subjects had to calculate or just read two-digit addition tasks that were either presented as numeric formulas or embedded in text. We found higher increases for O(2)Hb in parietal brain regions of both hemispheres for the calculation compared to the reading-only condition. Furthermore, these increases were more pronounced during text-embedded tasks than during numeric tasks. Corresponding decreases of HHb could also be detected. These first NIRS findings on that topic confirm that parietal regions are involved in the processing of arithmetic tasks while the amount of activation seems to depend on task modalities like difficulty or complexity.

Arithmetic tasks in different formats and their influence on behavior and brain oxygenation as assessed with near-infrared spectroscopy (NIRS): a study involving primary and secondary school children.

This study investigated whether near-infrared spectroscopy (NIRS) can be used to measure the processing of arithmetic problems in school children. Another aim was to assess whether distinct formats of such problems would lead to different neural processing. Two large samples of school children from different age groups were examined while calculating or reading arithmetic problems that were either presented in numeric or in word format. As expected, we found that, compared to reading, calculation resulted in greater average oxygenation in parietal and posterior frontal regions. Neither format nor age had a significant effect on brain oxygenation. We were able to demonstrate that NIRS measurements can readily be conducted with children and in school settings, which is an indication for the ecological validity of this measurement technique.

Cortical excitability in adult patients with attention-deficit/hyperactivity disorder (ADHD).

Attention-deficit/hyperactivity disorder (ADHD) is more and more focused on, and the awareness of adult patients with ADHD increases. Deficits in inhibitory processes in cortical brain areas are discussed as possible causes for ADHD. An easy measurement of these processes is provided by transcranial magnetic stimulation (TMS). We applied single- and double-pulse TMS to the left motor cortex while an electromyogram (EMG) was taken at the abductor pollicis brevis muscle (APB) of the right hand. Intracortical inhibition (SICI) and facilitation (ICF) were measured in ten adult ADHD patients and ten healthy participants using inter-pulse intervals of 2 and 3ms (SICI), and 8 and 15ms (ICF). Furthermore, resting motor threshold (RMT) and latency of the motor evoked potential (MEP) following magnetic stimulation were compared. t-Tests were calculated for statistical analysis. TMS measurements resulted in impaired inhibition in ADHD patients, whereas there were no differences in facilitation, RMT and MEP-latency between groups. Large variability in the patient group was found. This study expands the findings of deficits in inhibition described in earlier studies in children to an adult population, which could be a hint for similar neurophysiological mechanisms underlying ADHD symptomatology in children and adults.

Brain activation in elderly people with and without dementia: Influences of gender and medication.

Patients suffering from dementia show altered functional brain activation patterns especially in prefrontal brain regions, as research suggests. The present study follows three aims: to replicate these findings, to investigate treatment effects when administering galantamine, and to put gender differences in focus. We compared 12 patients with dementia to 12 age- and gender-matched healthy subjects regarding changes in haemoglobin concentration in brain tissue while performing a verbal fluency task (VFT). Concentration changes of oxygenated (O(2)Hb) and deoxygenated (HHb) haemoglobin were measured by multi-channel near-infrared spectroscopy (NIRS), an easily applicable and non-invasive method of optical topography. In the patient group, measurement was repeated 4 and 8 weeks after starting treatment with galantamine. The results showed a reduced increase in O(2)Hb during task performance for patients compared to healthy controls. Furthermore, female subjects showed more pronounced activation in O(2)Hb as well as HHb compared to male subjects. Regarding treatment effects, no clear results could be obtained. In HHb, evidence for an entrainment effect was found. In the light of existing literature, the present study suggests an interaction of gender and age regarding brain activation patterns which should be aimed at in future investigations.

Panic disorder and a possible treatment approach by means of high-frequency rTMS: a case report.

Panic disorder still remains a pervasive, life quality impairing disorder requiring adequate treatment options. In this case report we present the data of a patient with panic disorder and comorbid depression who was treated with high-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the left prefrontal cortex over a course of 3 weeks. Measurements of the cerebral oxygenation with near-infrared spectroscopy (NIRS) during an emotional Stroop task before and after the rTMS treatment suggests that rTMS may modulate panic-related prefrontal brain dysfunctions in panic patients and that it may serve as a possible treatment option for anxiety disorders.