The biological basis of cognitive impairment Deposits of tau and amyloid in the brain are the two main hallmarks of the pathology of Alzheimer’s disease, the most common cause of dementia. Researchers at the University of Geneva are using advanced imaging and analysis techniques to investigate pathways to the development of neurodegenerative disease and its progression, as Dr Valentina Garibotto explains. The onset of
dementia is marked by a decline in brain functioning, causing then a progressive cognitive deterioration which affects memory, language and attention, and subsequently leads to reduced autonomy in daily activities. Cognitive impairment is defined in terms of certain age-related norms, to differentiate a ‘pathological’ decline from the decline which occurs normally as we age. “Patients are diagnosed as having cognitive impairment or dementia when they have impairments in memory or other domains that are more marked than expected for their age,” explains Dr Valentina Garibotto, head of the Laboratory of Neuroimaging and Innovative Molecular Tracers at the University of Geneva. In her research Dr Garibotto is investigating the biological basis of cognitive impairment, looking at people over the age of 50 and comparing those patients who have mild The Biological Basis of Cognitive Impairment due to Suspected NonAlzheimer’s Pathology (SNAP): Studying the interplay between amyloidosis and tau-related neurodegeneration Valentina Garibotto Department of Radiology and Medical Informatics, HUG 4 rue Gabrielle-Perret-Gentil CH-1211 Genève 14 T: +41 22 372 72 52 E: Valentina.Garibotto@unige.ch W: https://www.unige.ch/ medecine/radio/en/researchgroups/984garibotto/
Valentina Garibotto is a Group Leader in the Department of Radiology and Medical Informatics at the University of Geneva. She uses molecular neuroimaging to evaluate neurological and psychiatric diseases.
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An example of a subject showing the PET signal of tau pathology in the temporal cortex, indicating an early stage of Alzheimer’s Disease.
cognitive impairment with those who do not. Among the subjects who have mild cognitive impairment, researchers are also investigating those who are stable and those who worsen over time. “We are also interested in individuals who have a cognitive complaint, the perception that something is not going well. Even if it is not always a sign that there is a ‘real’, objective cognitive impairment, this could possibly be a preclinical index of subtle cognitive and brain alterations” says Dr Garibotto.
and amyloid in different regions of the brain. “We’ve observed that the areas in which tau is deposited are linked to a specific individual’s clinical expression. For example, a subject with marked memory problems will have a higher level of tau deposition in those brain regions linked to memory,” she continues. A clearer picture of where tau and amyloid have been deposited in the brain could lead to a deeper understanding of each individual case, which is a major motivating factor behind Dr Garibotto’s research. A lot of attention in the project is currently focused on developing and improving imaging tools, with a view to potentially using them in diagnosis. “We want to understand the factors that influence the results, in order to then use them subject-bysubject to provide diagnostic information. Where does the subject have the pathology? How is the disease likely to evolve over the following years?” asks Dr Garibotto. This latter point is an issue of great interest to Dr Garibotto, with plans for a follow-up project.
We’ve observed that the areas in which tau is deposited are linked to a specific individual’s clinical expression. For example, a subject with marked memory problems will have a higher level of tau deposition in those
brain regions linked to memory.
Imaging and analysis This research involves the use of sophisticated imaging and analytical techniques, including positron emission tomography (PET), to observe neurological differences between different groups of subjects. Techniques like PET tracers allow researchers to monitor the presence and distribution of specific substances in the brain, among which are tau and amyloid, the two main hallmarks of the pathology of Alzheimer’s disease, the most common cause of dementia. “With PET tracers, we essentially inject a radioactive dye that is as specific as possible for amyloid or tau. We effectively end up with a map that quantifies the amount of tau or amyloid overall in the brain,” says Dr Garibotto. From this point, Dr Garibotto and her colleagues in the project can then look to study levels of tau
“The participants in our current project will be re-contacted to enter into a longitudinal study in which we aim to repeat the procedures, in order to see how and where tau and amyloid deposition has changed,” she explains. This research could also lead to new insights into the cognitive reserve, essentially the capacity of the brain to tolerate the pathology without it causing damage. Taking regular physical exercise, doing mental puzzles and in general remaining active are thought to protect people against dementia, but the precise mechanisms are not fully understood. “It’s not clear if these types of activities provide some sort of resistance to the pathology, or if the pathology is ultimately there anyway, but the extent of their cognitive reserve means an individual is able to cope with it better. This is something that we’re going to look at,” continues Dr Garibotto.
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