Research reportDecrease in parietal cerebral hemoglobin oxygenation during performance of a verbal fluency task in patients with Alzheimer's disease monitored by means of near-infrared spectroscopy (NIRS) — correlation with simultaneous rCBF-PET measurements
Introduction
Optical methods are able to detect signals related to neuronal activity. For instance, functional cortical maps with high spatial and temporal resolution have been obtained from the cat occipital cortex using optical imaging based on intrinsic signals [19]. As these procedures require a cranial window, they are not suitable for neuroimaging in live humans. Near-infrared spectroscopy (NIRS) uses the relative transparency of tissue to light in the near-infrared (700–900 nm). This `optical window' permits the noninvasive measurement of endogenous chromophore concentrations (e.g. hemoglobin or cytochrome aa3) through the inctact skull and has been applied in animal models, neonatology and neurosurgery (for review see [5]). Although at the moment inferior to PET as well as to functional magnetic resonance imaging (fMRI) with regard to spatial resolution, NIRS has an interesting potential: the method requires neither large expensive equipment, unlike PET or MRI, nor an exogenous contrast medium, unlike PET. The apparatus itself is easy to handle and portable. As no radioactive compounds are necessary, the measurements may be repeated as many times as one likes/needs.
The NIRS variables to date are oxygenated hemoglobin [HbO2], deoxygenated hemoglobin [HbR] and total hemoglobin [HbT] (=[HbO2]+[HbR]). Assuming that hematocrit is constant the changes in [HbT] are used as an indicator of alterations in cerebral blood volume [7]. In healthy subjects, changes in [HbO2] and [HbT] are correlated with changes in regional cerebral blood flow (rCBF) as shown by simultaneous NIRS and PET measurements 23, 44.
We and others have recently been able to demonstrate that NIRS, applied in a reflection mode, is able to detect changes in cerebral hemoglobin oxygenation during brain activation in adult healthy human subjects through the intact skull 6, 23, 27, 42, 32, 21. The typical findings were regional increases in [HbO2] and [HbT] as well as a slight decrease in [HbR] during the performance of either cognitive tasks 23, 42, 21or visual [27]and motor stimulation [32]. In addition, we showed that the activation-induced increases in [HbO2] and [HbT] decline gradually with aging [21]. We speculated that regional cerebral hemoglobin oxygenation may be altered even more pronounced in patients with neurodegenerative disorders. Therefore we compared activation-induced changes in cerebral hemoglobin oxygenation in Alzheimer's disease patients to age-matched normal controls.
In order to cross-validate the NIRS method, we performed simultaneous NIRS and rCBF-PET measurements during brain activation.
Section snippets
Materials and methods
We examined 27 elderly healthy subjects. First experiment: 19 elderly healthy volunteers (age (mean±SD): 67±10 years, 14 females, 5 males), second experiment: 8 elderly healthy volunteers (age 60±16 years, 5 females, 3 males). We examined 29 patients with probable moderate AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria [29]. First experiment: 19 patients with AD (mean age
Results
Fig. 1a shows the typical time course of the NIRS variables ([HbO2], [HbR] and [HbT]) measured with optodes placed over the left superior parietal cortex while an elderly healthy volunteer (70 years, female) performed a verbal fluency task. Shortly after the beginning of the activation period the healthy subject showed an increase in [HbO2] and [HbT] and a slight decrease in [HbR]. [HbO2] and [HbT] normally tend to decrease again during the stimulation period. Fig. 1b shows the typical time
Discussion
Using PET, so far, reduced increases of metabolic parameters, such as the regional cerebral metabolic rate of glucose, during the performance of cognitive tasks were observed in various brain regions in AD patients compared to age-matched controls 37, 20. Based on the PET findings and, in addition, on our finding of an age-dependent decline in activation-induced increases in [HbO2] and [HbT] [21], a smaller increase of these variables was expected in patients with AD during brain activation.
Acknowledgements
A.V. and U.D. are supported by the Deutsche Forschungsgemeinschaft. The authors would like to thank L. Schleinkofer, Hamamatsu Photonics, Germany, for continuous support. C.H. and F.M-S. are supported by the Schweizerischer Nationalfonds, Grant 3200-043588.95/1. S. S-H. and H.H. did parts of this work as their medical doctoral thesis at the Ludwigs-Maximilians-Universität München.
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