No evidence of decreased perfusion or blood‐brain barrier leakiness in later life depression

Abstract

Depression and dementia are both common diseases. Although new cases of depression are more common in younger adults there is a second peak at the age of 50 years suggesting a different pathological process. Late-life depression (LLD) is associated with dementia. However, it remains unclear whether depression represents a dementia prodrome or is a true risk factor for its development. LLD is thought to have a vascular component and this may be a possible link between depression and dementia. We hypothesised that later-life depression is a prodromal manifestation of dementia and would therefore be associated with more AD, and/or ischaemic brain abnormalities than are present in earlier-life depression or in age- and sex-matched controls.We assessed post-mortem orbitofrontal cortex and dorsolateral pre-frontal cortex from 145 individuals in 4 groups: 28 18-50-year-olds with depression, 30 older individuals (ages 51-90) with depression, 28 with early AD (Braak tangle stages III-IV) and 57 matched controls (17 early-life, 42 later-life). Levels of Aβ, phospho-tau and α-synuclein were assessed by immunohistochemistry and ELISA. To quantify chronic ischaemia, VEGF, MAG and PLP1 were measured by ELISA. To assess pericyte damage, PDGFRB was measured by ELISA. For blood-brain barrier leakiness, JAM-A, claudin 5 and fibrinogen were measured by ELISA and the ratio of ICAM1:collagen IV assessed by immunohistochemistry.There was no evidence of chronic cerebral hypoperfusion or increased Aβ in either depression group. There was also no indication of pericyte damage or increased blood-brain barrier leakiness in the OFC in the depression groups CONCLUSION: Contrary to some previous findings, we have not found evidence of impaired vascular function or increased Aβ in LLD. These results suggest that it is a risk factor for dementia rather than an early manifestation of AD or a consequence of cerebral vascular insufficiency.