Depression, dementia and immune dysregulation

Major depression is a prevalent illness that increases the risk of several neurological conditions. These include stroke, cardiovascular disease, and dementia including Alzheimer's disease. In this review we ask whether certain types of depression and associated loneliness may be a harbinger of cognitive decline and possibly even dementia. We propose that chronic stress and inflammation combine to compromise vascular and brain function. The resulting increases in proinflammatory cytokines and microglial activation drive brain pathology leading to depression and mild cognitive impairment, which may progress to dementia. We present evidence that by treating the inflammatory changes, depression can be reversed in many cases. Importantly, there is evidence that anti-inflammatory and antidepressant treatments may reduce or prevent dementia in people with depression. Thus, we propose a model in which chronic stress and inflammation combine to increase brain permeability and cytokine production. This leads to microglial activation, white matter damage, neuronal and glial cell loss. This is first manifest as depression and mild cognitive impairment, but can eventually evolve into dementia. Further research may identify clinical subgroups with inflammatory depression at risk for dementia. It would then be possible to address in clinical trials whether effective treatment of the depression can delay the onset of dementia.

Automated summary

Major depression may be a precursor to cognitive decline and dementia, with chronic stress and inflammation compromising brain function and leading to depression and mild cognitive impairment. Treating inflammatory changes in depression can reverse the condition, and anti-inflammatory and antidepressant treatments may reduce or prevent dementia in individuals with depression. Chronic stress and inflammation may increase brain permeability and cytokine production, eventually manifesting as depression, cognitive impairment, and potentially dementia.