Depressive Symptoms and Biomarkers of Alzheimer's Disease in Cognitively Normal Older Adults

Abstract

Even low levels of depressive symptoms are associated with an increased risk of cognitive decline in older adults without overt cognitive impairment (CN). Our objective was to examine whether very low, "subthreshold symptoms of depression" are associated with Alzheimer's disease (AD) biomarkers of neurodegeneration in CN adults and whether these associations are specific to particular depressive symptoms. We analyzed data from 248 community-dwelling CN older adults, including measurements of cortical amyloid burden, neurodegeneration markers of hippocampal volume (HV) and cerebral 18F-fluorodeoxyglucose (FDG) metabolism in a composite of AD-related regions and the 30-item Geriatric Depression Scale (GDS). Participants with GDS >10 were excluded. General linear regression models evaluated the cross-sectional relations of GDS to HV or FDG in separate backward elimination models. Predictors included GDS total score, age, gender, premorbid intelligence, a binary amyloid variable and its interaction with GDS. Principal component analyses of GDS item scores revealed three factors (the Dysphoria, Apathy-Anhedonia, and Anxiety-Concentration Factors). In secondary analyses, GDS total score was replaced with the three factor scores in repeated models. Higher GDS score (p = 0.03) was significantly associated with lower HV and was marginally related (p = 0.06) to FDG hypometabolism. In secondary models, higher Dysphoria (p = 0.02) and Apathy-Anhedonia (p = 0.05) were related to lower HV while higher Apathy-Anhedonia (p = 0.003) was the sole factor related to FDG hypometabolism. Amyloid was not a significant predictor in any model. In conclusion, very low-level dysphoria, apathy and anhedonia may point to neurodegeneration in AD-related regions but this association appears to be independent of amyloid burden.

Keywords: Alzheimer’s disease; biomarkers; neurodegeneration; normal cognition; preclinical; subthreshold depressivesymptoms.

Figure 1. GDS Factors and their Endorsement: the Apathy-Anhedonia Factor, Dysphoria Factor and Anxiety-Concentration Factor

Numbers of individuals endorsing GDS items corresponding to the Apathy-Anhedonia Factor (unfilled bars), Dysphoria Factor (solid bars) and Anxiety-Concentration Factor (grey bars) are shown. Four of the 30 GDS items were not included in the factor analysis due to low endorsement (n=0–1) by the sample. In addition, the GDS items pertaining to social avoidance (n=16), boredom (n=19), decision-making (n=30) and to subjective memory symptoms (n=23) did not load onto any of the 3 factors and were not included in analyses. Abbreviation: GDS (Geriatric Depression Scale- 30 item version)

Figure 2. The relation of GDS to Hippocampal Volume (A) and FDG Metabolism (B)

Multiple regression models with backward elimination were employed. In each model the pool of predictors included GDS, age, sex, premorbid intelligence, prior depression, antidepressant medication use, amyloid status and the interaction of GDS with amyloid. Hippocampal volume was adjusted for intracranial volume. Abbreviation: GDS (Geriatric Depression Scale-30 item) FDG (18F-fluorodeoxyglucose)