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 effects 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-β (Aβ) load modifies the relations between SSD and brain aging outcomes.

Results: SSD at baseline was associated with significantly longitudinal decline in cognition and displayed significantly accelerated atrophy in hippocampus (β = -29.53, p = 0.001) and middle temporal gyrus (β = - 77.82, p = 0.006) among all participants and Aβ-Positive individuals. SSD interacted with baseline Aβ load in predicting longitudinal decline in Mini Mental State Examination (MMSE) (β = - 0.327, p = 0.023), episodic memory (β = -0.065, p = 0.004) and increase in Alzheimer's Disease Assessment Scale Cognition 13-item scale (ADAS-cog13) (β = 0.754, p = 0.026).

Limitations: Our study didn't look at AD diagnosis but Aβ status.

Conclusions: Our findings suggested that older people without dementia with both SSD and a high level of Aβ load may have higher risk of cognitive deterioration and brain atrophy. Therapeutic mitigation of depressive symptoms, especially in those with abnormal Aβ levels, may help delay progressive decline in cognition.