Brain perfusion correlates of the apathy inventory dimensions of Alzheimer's disease

BACKGROUND: Apathy is defined as a lack of motivation in behavior, cognition and affect. This syndrome is frequent in various neuropsychiatric diseases but little is known about its pathophysiology. OBJECTIVES: The aim of this study was to investigate the metabolic correlates of the behavioral, cognitive and emotional, aspects of apathy in Alzheimer's disease (AD). METHOD: Thirty AD patients were included. Lack of initiative, lack of interest and of emotional blunting were assessed with the Apathy Inventory (IA), a tool designed to provide a separate assessment of the behavioral, cognitive and emotional, aspects of apathy. Brain perfusion was measured by (99m)Tc-labeled bicisate (ECD) single photon emission tomography. RESULTS: The Statistical Parametric Mapping software provides negative correlation between IA total score and brain perfusion in left and right superior orbito-frontal gyrus, and to a lesser extent in left middle frontal gyrus (BA10). Lack of initiative score was negatively correlated with perfusion in right anterior cingulate cortex. Lack of interest score was negatively correlated with perfusion in right middle orbitofrontal gyrus). Emotional blunting score correlated negatively with in left superior dorsolateral prefrontal cortex activity. CONCLUSION: These results underline that the cognitive, behavioral and affective components of motivation are mediated by different fronto-sub-cortical circuits and are differently lateralized. In particular, left prefrontal hypoperfusion is involved in emotional blunting, as it was often demonstrated in depressive disorders. These distinct components of apathy may be targeted by different therapeutic means, in which dopaminergic enhancement might play a major role.