Associations of Subsyndromal Symptomatic Depression with Cognitive Decline and Brain Atrophy in Elderly Individuals without Dementia: A Longitudinal Study

Background: Subsyndromal symptomatic depression (SSD) is prevalent in older adults. However, it remains unclear whether there are e ffects of SSD on brain aging outcomes (cognition and brain structures), especially in the presence of Alzheimer's Disease (AD) pathology. Methods: A total of 1,188 adults without dementia were recruited from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants with SSD were measured using the 15-item Geriatric Depression Scale (GDS-15). In multivariable models, the cross-sectional and longitudinal associations of SSD with brain aging outcomes were explored. We further evaluated whether baseline amyloid-beta (A beta) load modi fies the relations between SSD and brain aging outcomes. Results: SSD at baseline was associated with signi ficantly longitudinal decline in cognition and displayed sig- ni ficantly accelerated atrophy in hippocampus (beta =-29.53, p = 0.001) and middle temporal gyrus (beta =- 77.82, p = 0.006) among all participants and A beta-Positive individuals. SSD interacted with baseline A beta load in predicting longitudinal decline in Mini Mental State Examination (MMSE) (beta =- 0.327, p = 0.023), episodic memory (beta =-0.065, p = 0.004) and increase in Alzheimer's Disease Assessment Scale Cognition 13-item scale (ADAS-cog13) (beta = 0.754, p = 0.026). Limitations: Our study didn't look at AD diagnosis but A beta status. Conclusions: Our findings suggested that older people without dementia with both SSD and a high level of A beta load may have higher risk of cognitive deterioration and brain atrophy. Therapeutic mitigation of depressive symptoms, especially in those with abnormal A beta levels, may help delay progressive decline in cognition.