Aging Clinical Trial
The purpose of this study is :
- to look for changes induced by aging in a population of old subjects, during silent
word generation tasks studied by fMRI.
- to look for a possible link between these changes and alterations in language
Introduction : Several factors may influence cerebral organization of language, age being
one of the most important. We previously showed that activations were different in old
subjects compared to young for a silent word generation task : In Old subjects, activations
appeared less important and more parceled but involved the same regions of the left
hemisphere than for young subjects. Several small clusters of activation were present on the
right hemisphere of old subjects and more or less mirrored left activations in the same
group, leading to a less lateralized pattern than in young subjects. Moreover, during the
same task, activations decreased for about of 1/3 subject whereas is increased or was stable
for young. These changes may be a preclinical indicator of cognitive decline.
Objective: In this study, we propose to rescan the same subjects 2 years after the first
protocol using the same paradigm, and to look for possible changes in location, extend and
time course of activations. These results will be compared to neuropsychological examination
in order to find a possible correlation between possible changes and cognitive impairment.
Subjects : the 22 old right-handed subjects (age>76y, 11M, 11F) enrolled in the preliminary
study will be included.
Method :
- fMRI : Data will be collected on a 1.5 T General Electric Signa MR scanner. Functional
images will cover the whole brain and will be scanned using a single-shot echoplanar
imaging sequence (FOV : 24 cm ¡thickness : 5 mm - 64 x 64 matrix - TE : 60 ms ¡ TR : 3s
¡ flip angle : 90°). The paradigm will follow a box car design and 3 periods of
activation (30 s duration) will alternate with 3 periods of fixation (30s duration).
During the active conditions subjects will have to mentally generate words
corresponding to a visually presented semantic category (condition 1), or beginning by
a visually presented letter (condition 2). During the control condition, they will be
requested to concentrate on their breathing. Data will be analyzed using the FSFAST
package. MR data will be motion corrected using AFNI and then smoothed with a FWHM of 5
mm. The voxel intensities will be rescaled such that the in-brain grand mean will be
1000 for all subjects. The hemodynamic response will be modeled as a gamma function
(delay : 2.25 s - dispersion :1.25 s). The offset and linear drift in the BOLD signal
will be removed by estimating those components simultaneously with the amplitude of the
hemodynamic response. A t-test will then be performed on the amplitude of the
hemodynamic response to determine which voxels has significant paradigm-related
activity. Time course of the signal will be separately studied for each condition
- anatomical MR : Results will be displayed on the inflated cortical surface for each
subject. A group analysis will be performed for each contrast using a surface
coordinate system and random model effect and General linear model using age an
neuropsychological scores as regressors.
- Neuropsychological examination : subjects will be interviewed by a psychologist 4-6
weeks after scanning session. Semantic and lexical verbal fluency will be evaluated, as
will general cognitive function (MMS, lokk for Alzheimer's disease, IADL, BEC96), and
episodic memory (Grober & Buschke).
;
Observational Model: Defined Population, Time Perspective: Cross-Sectional
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