Investigation of brain beta amyloid deposition and plasma beta amyloid level in late life onset depression

Abstract

Introduction: Previous researches on the late life onset depression (LLOD) have revealed its association with vascular risk factors, supporting vascular depression hypothesis. However, several recent studies suggested the possibility of the role for cerebral amyloidosis in LLOD. The aim of this study is to investigate the association of cerebral amyloidosis with the experience of LLOD and related structural brain changes using both 11C-labelled Pittsburgh compound B (PiB) PET imaging and assessment of plasma beta-amyloid (Aβ) protein level.

Methods: Twenty-nine non-demented subjects who first experienced a major depressive episode at the age of 60 years or older, were recruited as LLOD patients. Twenty-seven non-demented elderly individuals, who had no experience of major depressive episode and who scored 16 or lower on the Korean version of the Geriatric Depression Scale, were included as normal controls (NC). All participants received a comprehensive clinical assessment including vascular risk evaluation, 11C-labeled Pittsburgh Compound B (PiB) positron emission tomography (PET), and magnetic resonance imaging (MRI). Blood was sampled for Apolipoprotein E (APOE) genotyping and assessment of plasma beta-amyloid (Aβ) protein levels.

Results: There were no differences in age, gender, educational level, and frequency of APOE ε4 carrier between LLOD and NC groups. In terms of regional or global PiB retention and plasma Aβ levels, no significant differences were found between LLOD and NC groups. A univariate group comparison demonstrated significantly higher systolic blood pressure (SBP) in LLOD group than in NC group. A multiple logistic regression analysis with age, gender, education, and SBP as covariates indicated that PiB positivity was not significantly associated with diagnostic status of LLOD, whereas SBP was associated with diagnostic status of LLOD in the same regression model. In a subgroup analysis, LLOD subjects with mild cognitive impairment (MCI) had significantly elevated PiB retention and plasma Aβ levels, whereas those without MCI did not differ relative to the NC group. Structural imaging analysis demonstrated that LLOD subjects had reduced gray matter volume and white matter integrity mainly in bilateral prefrontal regions.

Conclusions: In this study, no significant differences were found in brain PiB retention and plasma Aβ protein levels between the LLOD and NC groups, although a subset of LLOD subjects with MCI had increased levels of both. These findings suggest that cerebral amyloidosis per se is probably not a major contributor to LLOD, but may be involved in the underlying pathophysiology of a subset of LLOD patients with MCI.