P1‐333: Brain metabolism study in frail elderly (2011)

Alzheimer's disease (AD) is a neurodegenerative disease which should be diagnosed at an early stage. Mild Cognitive Impairment diagnosis seems to be too late in evolution of AD and frailty appears very interesting to detect these subjects before they were symptomatic with cognitive decline. Cohort studies of elderly frail subjects were able to show a link between the existence of frailty and Alzheimer's disease occurrence. From anatomical point of view, cerebral amyloid uptake in the frail elderly seems higher than in normal elderly subjects. Aim of this study is to describe brain metabolism of 20 frail elderly compared to 20 normal subjects in PET-FDG and to correlate their neuropsychological performance to their brain metabolism. 20 subjects in Multidomain Alzheimer Prevention Trial NeuroImaging study (MAPT-NI) were compared to 20 normal subjects from the ADNI (Alzheimer's Disease Neuroimaging Initiative) study, matched for age and sex. MAPT-NI subjects are issued of MAPT Study at inclusion and have benefited of PET-FDG every six months during one year, and MRI at inclusion and at one year. The MAPT Study is a 3-year, french, randomized, controlled and multicentric trial. The study enrolled 1680 frail elderly subjects on the basis of at least one of the following criteria: subjective memory complaint spontaneously expressed to a general practitioner, limitation in one instrumental activity of daily living (IADL), and slow walking speed. To demonstrate the protective effect of interventions, subjects are randomized into one of the following four groups: omega 3 alone, multidomain intervention alone, omega 3 plus multidomain intervention, or placebo (n = 420 each). The principal outcome measure is a change in cognitive function at 3 years, as determined by Gröber and Buschke Test. During MAPT study participants are monitored every six months and receive memory clinic in investigator centre (memory and functional assessment). MAPT study's subjects and normal ADNI study's subjects were paired with Stata® statistic software (Khi2 and T-Student) and imaging statistic analyse was performed with SPM® software. In frail elderly MAPT Study's subjects SPM® software allowed us to highlight on the one hand, temporal bilateral (Z-Score 4.79 to 5.76, < 0.05), anterior cingulated (Z-Score 4.9, < 0.05), and right frontal hypometabolism (Z-Score 4.81 to 5.67, < 0.05), and on the other hand, left inferior temporal (Z-Score 5.27, < 0.05), right middle temporal (Z-Score 5.31, < 0.05), and bilateral frontal (Z-Score 5.2 to 5.6, < 0.05) hypermetabolism, comparatively to normal ADNI study's subjects. Poor performance in gait speed, memory (RLRI-16), and executive function (TMT-A and Test Code) are significantly correlated with right inferior parietal (Z-Score 3.57, < 0.05), left temporal and right middle frontal (Z-Score 3.56 to 4.03, < 0.05) and bilateral frontotemporal (Z-Score 3.24 to 4.4, < 0.05) hypermetabolism, respectively. This original study has highlighted presence of cerebral metabolic abnormalities in frail elderly even before cognitive decline is symptomatic. This could fortify Jack and colleagues hypothesis which consist of thinking that metabolic cerebral modified should precede cognitive impairment in evolution of Alzheimer's disease (2010). Furthermore these are the same metabolism, particularly temporal hypometabolism, as in Alzheimer's disease. This work is preliminary to a more comprehensive analysis, including structural MRI data and evolution of cerebral metabolic profile over time.