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Bernard Mazoyer"Brain imaging for understanding of Alzheimer's disease physiopathology: the role of structural neuroimaging "

Abstract :

Increase in the incidence of age-related neurological diseases makes the identification of brain aging mechanisms a major issue.
Several studies have demonstrated that cerebral morphology and its evolution is a predictive marker of clinical ageing. Age is indeed associated with structural changes of brain anatomy at the macroscopic level that can be detected with brain imaging over a time period as short as one year. These changes affect the three components of the intracranial volume, namely the grey and white matters, and the cerebrospinal fluid, each with specific amplitude and chronometry, and are regionally modulated.
The loss of brain substance, i.e. atrophy, is by and large the most obvious marker of the aging process in the brain. It is a global process that affects the entire brain and results in an increase in CSF and a parallel reduction in grey and white matter volumes. Recent studies conducted in large cohorts have shown that some cortical areas, including the hippocampus but also the primary cortices, seem to be the seats of an earlier and enhanced atrophy process, as shown for example by a preliminary analysis of the 3C-MRI Dijon cohort. Such findings are important since structural changes in AD start in the entorhinal cortex and that monitoring the macro-structural changes of the temporal lobe structures may therefore be a powerful tool for early diagnosis and/or clinical trials in the future.
The presence of anomalies in the cerebral white matter of healthy elderly subjects has also been a constant finding since the advent of MRI. These anomalies, appearing as white matter hyperintensities (WMH) on T2/FLAIR MRI scans, seem to be a marker of chronic parenchyma ischemia due to the degeneration of small diameter arteries. As such, WMH’s constitute a potential biomarker of the vascular component of cerebral aging. WMH are associated with cognitive decline in subjects over 65 years old but also appears to be a biomarker of various age-related clinical phenotypes such, memory complaints, depression and gait troubles.
In summary, atrophy and WMH can be viewed as biomarkers of two processes at work during aging, namely neurodegeneration and vascular changes that were recently demonstrated to co-occur, independently of vascular risk factors, in the brain of non-demented elderly subjects.

Selected publications

Sex-dependent modulation of activity in the neural networks engaged during emotional speech comprehension.
Beaucousin V, Zago L, Hervé PY, Strelnikov K, Crivello F, Mazoyer B, Tzourio-Mazoyer N.
Brain Res. 2011 Mar 22. [Epub ahead of print]
Brain activity at rest: A multi-scale hierarchical functional organization.
Doucet G, Naveau M, Petit L, Delcroix N, Zago L, Crivello F, Jobard G, Tzourio-Mazoyer N, Mazoyer B, Mellet E, Joliot M.J Neurophysiol. 2011 Mar 23. [Epub ahead of print]
Longitudinal neuroimaging correlates of subjective memory impairment: 4-year prospective community study.
Stewart R, Godin O, Crivello F, Maillard P, Mazoyer B, Tzourio C, Dufouil C.
Br J Psychiatry. 2011 Mar;198(3):199-205.

Reproducibility of fMRI activations during a story listening task in patients with schizophrenia.
Maïza O, Mazoyer B, Hervé PY, Razafimandimby A, Dollfus S, Tzourio-Mazoyer N.
Schizophr Res. 2011 Feb 22.

Bertrand Bloch et François Tison de l'IMN