Factors associated with progression of brain atrophy during ageing: 6 year follow-up from the Austrian stroke prevention study

Neuroimaging techniques are increasingly used to study mechanisms leading to cognitive impairment. In particular, brain atrophy has been proposed as a surrogate marker of dementia. However, little is known regarding confounding factors which might modulate the evolution of brain atrophy during ageing. We therefore determined the rate of atrophy over 6 years for 201 participants (F/M=96/105; 59.8±5.9 yrs) in the Austrian Stroke Prevention Study and probed the impact of baseline variables on its progression. The mean annual brain volume change was -0.40±0.29%. The rate of brain atrophy was significantly higher in subjects of greater age and those with higher HbA1c, higher body-mass-index, high alcohol intake, severe white matter hyperintensities, and in APOEε4-carriers. Multivariate analysis suggested that baseline brain volume, HbA1c and the extent of white matter hyperintensities explain a major proportion of variance in the rates of brain atrophy. These results indicate that neurologically asymptomatic elderly experience continuing brain volume loss, which appears to accelerate with age. HbA1c was identified as a risk factor for a greater rate of brain atrophy. Clustering of factors associated with the so-called "metabolic syndrome" in subjects with high HbA1c suggests a link between this syndrome and late-life brain tissue loss. Together, this underscores the need to control for confounding factors in future Clinical trials and indicates possible new directions for intervention