Subjective cognitive decline-related worries modulate the relationship between global amyloid load and gray matter volume in preclinical Alzheimer’s disease

Subjective cognitive decline (SCD)-related worries are indicative of an increased risk for developing Alzheimer’s disease (AD) dementia. However, the influence of SCD-related worries on the relationship between amyloid and gray matter (GM) atrophy remains unknown. A total of 93 SCD participants underwent 18F-florbetapir PET and T1-weighted MRI scans. SCD individuals were classified into amyloid-positive or amyloid-negative groups based on global amyloid uptake. Three-step statistical analyses were performed: (1) partial correlation analysis was conducted to determine whether global amyloid relates to GM volume in amyloid-positive and amyloid-negative groups; (2) linear regression analysis was conducted to determine whether the interaction term (worries × global amyloid) predicts GM volume; and (3) post hoc subgroup linear regression analysis was conducted to determine the association between amyloid and GM volume in the subgroups with and without worries. Age, sex, education and total intracranial volume were adjusted in all models. We found a negative relationship between global amyloid load and GM volume in the right hemisphere (r = 0.441, p = 0.012) and right temporal cortex (r = 0.506, p = 0.003) in the amyloid-positive group. Moreover, in the amyloid-positive group, a significant worries × amyloid interaction effect on GM volume was found in the bilateral hemisphere (right: pinteraction=0.037; left: pinteraction=0.036), left temporal cortex (pinteraction=0.044) and bilateral frontal cortex (right: pinteraction=0.010; left: pinteraction=0.011). Subsequent post hoc analysis revealed a significant amyloid-GM association only in the subgroup with worries but not in the subgroup without worries. In preclinical AD cases, SCD-related worries may occur as a symptom in those cases where amyloid affects GM to a greater extent and may thus represent a high-risk population for future cognitive decline.