Depressive symptoms accelerate cognitive decline in amyloid-positive MCI patients

Purpose Late-life depression even in subsyndromal stages is strongly associated with Alzheimer's disease (AD). Furthermore, brain amyloidosis is an early biomarker in subjects who subsequently suffer from All and can be sensitively detected by amyloid PET. Therefore, we aimed to compare amyloid load and glucose metabolism in subsyndromally depressed subjects with mild cognitive impairment (MCI). Methods [F-18]AV45 PET, [F-18]FDG PET and MRI were performed in 371 MCI subjects from the Alzheimer's Disease Neuroimaging Initiative Subjects were judged beta-amyloid-positive (A beta+; 206 patients) or beta-amyloid-negative (A beta-; 165 patients) according to [F-18]AV45 PET. Depressive symptoms were assessed by the Neuropsychiatric Inventory Questionnaire depression item 4. Subjects with depressive symptoms (65 A beta+, 41 A beta) were compared with their nondepressed counterparts. Conversion rates to AD were analysed (mean follow-up time 21.5 +/- 9.1 months) with regard to coexisting depressive symptoms and brain amyloid load. Results. A beta+ depressed subjects showed large clusters with a higher amyloid load in the frontotemporal and insular cortices (p<0.001) with coincident hypermetabolism (p<0.001) in the frontal cortices than nondepressed subjects. Faster progression to AD was observed in subjects with depressive symptoms (p<0.005) and in A beta+ subjects (p<0.001). Coincident depressive symptoms additionally shortened the conveision time in all A beta+ subjects (p<0.005) and to a greater extent in those with a high amyloid load (p<0.001). Conclusion Our results clearly indicate that A beta+ MCI subjects with depressive symptoms have an elevated amyloid load together with relative hypeimetabolism of connected brain areas compared with cognitively matched nondepressed individuals. MCI subjects with high amyloid load and coexistent depressive symptoms are at high risk of faster conversion to AD.