Cortical pathophysiology and plasticity in Alzheimer’s disease investigated by fMRI

Projektdetails:

Projektbeschreibung

 At an early stage, different forms of dementia often cannot be distinguished clinically. Dr. Dierks wants to use functional magnetic resonance imaging (fMRI), a non-invasive method for the assessment of regional brain activity. With the use of fMRI he hopes to get a clear view of characteristic differences between forms of dementia. Using the same technique, he will enlarge the knowledge about the pattern of brain activity during cognitive tasks. This would aid in a better understanding of the pathological mechanisms involved in dementive disorders.

The third major aim of this project will be to assess the effects of cognitive training on patients’ short-term memory. One of the main questions will be whether, after training, the degenerated brain areas are used more efficiently, yielding a better and faster performance, or whether other areas, which are less affected by the disease process, take over part of the function.

This study will contribute to the understanding and differential diagnosis of Alzheimer’s disease and to the design and evaluation of future therapeutic strategies using cognitive training programs.

Abschlussbericht

 Alzheimer's disease (AD) is the most common cause of dementia in the elderly and the most frequent single cause of disability in aging. lt has become one of the major health and social issues of  our century. Despite extensive research, the causes and pathophysiological mechanism of AD are still largely unknown.

We have used functional magnetic resonance imaging (fMRl), a novel method for the non-invasive assessment of regional brain activity to elucidate the specific pattern of brain activity in AD and various other types of dementia such as dementia resulting from damage to the cerebral blood vessels. At an early stage, these types of dementia often cannot be distinguished clinically. The establishment of characteristic differences between these diseases would be of great importance for the early differential diagnosis of dementia. Secondly, knowledge about the pattern of brain activity during cognitive tasks would help towards a better understanding of the pathological mechanisms involved in dementia.

lt is commonly thought that the pattern of atrophy of the cerebral cortex predicts the pattern of cognitive decline, i.e. which brain functions are more affected and which less. However, clinical observations show that the picture is often more complex. In these cases our method allowed to assess whether the preserved cognitive ability can be explained by residual functionality of degenerated areas or by a mechanism that recruits new (and less affected) cortical areas for the respective functions. Our data suggest that the pattern of cerebral activations assessed by functional magnetic resonance imaging (fMRl) reflects the pattern of affected areas in the brain of AD patients. Furthermore our data indicated that local atrophy is an important factor when assessing brain activation images. Our third major aim, based on an improved knowledge about brain function in AD, was to assess the effects of cognitive training on patients ability to perform visuospatial tasks, such as clock reading, and the underlying pattern of brain activation. Again one of the main question was whether, after training, the degenerated brain  areas were used more efficiently, yielding a better and faster performance, or whether other areas, which are morphologically less affected by the disease process take over part of the function. Here only a few subjects managed to complete cognitive training,  and preliminary results indicate that the plasticity of brain function declines with age, and within the same age group, from healthy individuals to AD patients.

The potential clinical value of this study could be in the monitoring of subclinical treatment effects of anti-dementive drugs. We also demonstrated the value of the consideration of local atrophy for the interpretation of functional imaging data in AD patients and regard our study as one step towards a better understanding of the development of AD. This is important for the development of non drug-related therapeutic strategies which can accompany interventions on the level of signal conducting substances neurotransmitters and so improve the daily living of the patients and reduce the social and economic burden on both relatives and the society in general.

Wissenschaftliche Publikationen auf Basis des geförderten Projekts

Formisano, E., Linden, D.E.J., Di Salle, F., Trojano, L., Esposito, F., Sack, A.T., Grossi, D., Zanella, F.E., Goebel, R.  (2002). Tracking the mind’s image in the brain I: time-resolved fMRI during visuospatial mental imagery. Neuron, 35(1):185-194.

Prvulovic, D., Hubl, D., Sack, A. T., Melillo, L., Maurer, K., Frölich, L., Lanfermann, H., Zanella, F. E., Goebel, R., Linden, D. E. J., and Dierks, T. (2002). Functional imaging of visuospatial processing in alzheimer's disease. NeuroImage, 17(3):1403-1414.

Sack, A.T., Hubl, D., Prvulovic, D., Formisano, E., Jandl, E., Zanella, F.E., Maurer, K., Goebel, R., Dierks, T., Linden, D.E.J.(2002). The experimental combination of rTMS and fMRI reveals the functional relevance of parietal cortex in visuospatial functions. Cognitive Brain Research 13(1):85-93.

Sack, A. T., Sperling, J. M., Prvulovic, D., Formisano, E., Goebel, R., Di Salle, F., Dierks, T., and Linden, D. E. J. (2002). Tracking the mind's image in the brain iitranscranial magnetic stimulation reveals parietal asymmetry in visuospatial imagery. Neuron, 35(1):195-204.

Linden, D.E.J., Prvulovic, D., Formisano, E., Völlinger, M., Zanella, F.E., Goebel, R., Dierks, T. (1999). The functional neuroanatomy of target detection: An fMRI study of visual and auditory oddball tasks. Cerebral Cortex, 9:515-523.