Amyloid burden and incident depressive symptoms in preclinical Alzheimer's disease

Background: Relationships between depression and Alzheimer's disease (AD) may become clearer if studied in preclinical AD where dementia is not present. Method: The aim of this study was to evaluate prospectively, relationships between brain amyloid-beta (A beta), depressive symptoms and screen positive depression in cognitively normal (CN) older adults. Depressive symptoms were measured with the Geriatric Depression Inventory (GDS-15) in CN adults from the Australian Imaging Biomarkers and Lifestyle (AIBL) study without depression at baseline and classified as having abnormally high (A beta+; n = 136) or low (A beta-; n = 449) A beta according to positron emission tomography at 18-month intervals over 72 months. Results: Incident cases of screen positive depression were not increased in A beta+CN adults although small increases in overall depressive symptoms severity (d = - 0.25; 95% CI, - 0.45, - 0.05) and apathy-anxiety symptoms (d = - 0.28; 95% CI - 0.48, - 0.08) were. Limitations: As the AIBL sample is an experimental sample, no individuals had severe medical illnesses or significant psychiatric disorders. Additionally, individuals who had evidence of screen-positive depression at screening were excluded from enrolment in the AIBL study. Thus, the current data can be considered only as providing a foundation for understanding relationships between A beta and depression in preclinical AD. Conclusions: These results suggest that the presence of a depressive disorder or even increased depressive symptoms are themselves unlikely to be a direct consequence of increasing A beta. New depressive disorders presenting in CN older adults could therefore be investigated for aetiologies beyond AD.