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

Stephanie Perin, Karra D. Harrington, Yen Ying Lim, Kathryn Ellis, David Ames, Robert H. Pietrzak, Adrian Schembri, Stephanie Rainey-Smith, Olivier Salvado, Simon M. Laws, Ralph N. Martins, Victor L. Villemagne, Christopher C. Rowe, Colin L. Masters, Paul Maruff, for the AIBL research group

Relationships between depression and Alzheimer's disease (AD) may become clearer if studied in preclinical AD where dementia is not present. The aim of this study was to evaluate prospectively, relationships between brain amyloid-β (Aβ), 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 (Aβ+; n = 136) or low (Aβ-; n = 449) Aβ according to positron emission tomography at 18-month intervals over 72 months. Incident cases of screen positive depression were not increased in Aβ+ 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. 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 Aβ and depression in preclinical AD. 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 Aβ. New depressive disorders presenting in CN older adults could therefore be investigated for aetiologies beyond AD.