Baseline FDG-PET and volumetric MRI predicts Alzheimer's disease conversion from mild cognitive impairment: An ADNI study

Abstract

Background: Cerebral white matter hyperintensities (WMH), detected in vivo with magnetic resonance imaging (MRI), are commonly used to assess cerebrovascular burden in cognitive impairment. However, the association between WMH and cognition is not consistent across the literature. We hypothesized that some determinants including cognitive reserve (CR) and age could modulate the effects of WMH on the risk of Mild Cognitive Impairment (MCI) or dementia. Methods: We followed 500 healthy subjects from a cohort of community-dwelling persons aged 65 years and over (ESPRIT Project). At baseline, WMH volume was measured using a semi-automatic method on T2-weighted MRI. Standardized cognitive and neurological evaluations were repeated after 2, 4 7, and 10 years. Stratified Cox proportional hazards models were run to predict incident dementia and Mild Cognitive impairment. Results: After adjustment for potential confounders, we found that CR and age have an impact on the relationship between WML and progression to dementia and MCI. 1) the association between severe WMH and increased MCI/dementia risk was significant in the low CR group (education 8 years) (p1⁄40.02, HR1⁄4 3.77 [1.29-10.99]), but not in the high CR group (education >8 years) (p1⁄40.82, HR1⁄41.07 [0.61-1.87]). 2) the association between WMH volume and the risk of developing severe cognitive deterioration was significant in the younger group ( 73 years) (p 73 years) (p1⁄40.70, HR1⁄41.01 [0.98-1.04]). Conclusions: These findings suggest that 1) the association between increasing WMH volume and cognitive deterioration becomes weaker with advancing age. These results have implications in clinical trials using WML as surrogate marker, in raising the question of relevance of such a marker in the old-old. 2) Subjects with higher CR level were seen to be more likely to be resilient to the deleterious effects of severe WMH. The CR hypothesis suggests several avenues for dementia prevention.