No Association of Lower Hippocampal Volume With Alzheimer’s Disease Pathology in Late-Life Depression

Objective:Hippocampal volume is commonly decreased in late-life depression. According to the depression-as-late-life-neuropsychiatric-disorder model, lower hippocampal volume in late-life depression is associated with neurodegenerative changes. The purpose of this prospective study was to examine whether lower hippocampal volume in late-life depression is associated with Alzheimer’s disease pathology.Method:Of 108 subjects who participated, complete, good-quality data sets were available for 100: 48 currently depressed older adults and 52 age- and gender-matched healthy comparison subjects who underwent structural MRI, [18F]flutemetamol amyloid positron emission tomography imaging, apolipoprotein E genotyping, and neuropsychological assessment. Hippocampal volumes were defined manually and normalized for total intracranial volume. Amyloid binding was quantified using the standardized uptake value ratio in one cortical composite volume of interest. The authors investigated group differences in hippocampal volume (both including and excluding amyloid-positive participants), group differences in amyloid uptake and in the proportion of positive amyloid scans, and the association between hippocampal volume and cortical amyloid uptake.Results:A significant difference was observed in mean normalized total hippocampal volume between patients and comparison subjects, but there were no group differences in cortical amyloid uptake or proportion of amyloid-positive subjects. The difference in hippocampal volume remained significant after the amyloid-positive subjects were excluded. There was no association between hippocampal volume and amyloid uptake in either patients or comparison subjects.Conclusions:Lower hippocampal volume was not related to amyloid pathology in this sample of patients with late-life depression. These data counter the common belief that changes in hippocampal volume in late-life depression are due to prodromal Alzheimer’s disease.