Inflammatory markers in persons with clinically-significant depression, anxiety or PTSD: A systematic review and meta-analysis.

BACKGROUND: Depression, anxiety and PTSD appear to be risk factors for dementia, but it is unclear whether they are causal or prodromal. The inflammatory-mediated neurodegeneration hypothesis suggests a causal link, proposing that mental illness is associated with an inflammatory response which, in turn, triggers neurodegenerative changes that lead to dementia. Existing meta-analyses have yet to examine inflammatory markers in depression, anxiety or PTSD with the view to exploring the inflammatory-mediated neurodegeneration hypothesis. The current meta-analysis therefore examined whether: a) depression, anxiety and PTSD are individually associated with inflammation, independently of comorbid mental illnesses and physical health problems with known inflammatory responses, and b) there are any similarities in the inflammatory profiles of these disorders in order to provide a basis for exploring inflammation in people with dementia who have a history of clinically-significant anxiety, depression or PTSD. METHODS: PubMed, EMBASE, PsycINFO and CINAHL searches identified 64 eligible studies. RESULTS: Depression is associated with an inflammatory response, with tentative evidence to suggest anxiety and PTSD are also associated with inflammation. However, the specific response may differ across these disorders. LIMITATIONS: The data for anxiety, PTSD and multiple inflammatory markers were limited. CONCLUSIONS: Depression, anxiety, and PTSD each appear to be associated with an inflammatory response in persons who do not have comorbid mental or physical health problems that are known to be associated with inflammation. Whether this inflammatory response underlies the increased risk of dementia in persons with a history of depression and anxiety, and possibly PTSD, remains to be determined.

Risk of Dementia in persons who have previously experienced clinically-significant Depression, Anxiety, or PTSD: A Systematic Review and Meta-Analysis.

BACKGROUND: Depression, anxiety and PTSD appear to be linked to dementia, but it is unclear whether they are risk factors (causal or prodromal) for, comorbid with, or sequelae to (secondary effect of) dementia. Existing meta-analyses have examined depression or anxiety in all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VaD), but have not considered post-traumatic stress disorder (PTSD), dementia with Lewy bodies (DLB), or frontotemporal dementia (FTD). The current meta-analysis examined the risk of developing dementia (AD, VaD, DLB, FTD, all-cause) in people with and without a history of clinically-significant depression, anxiety or PTSD in order to better understand the link between mental illness and dementia (PROSPERO number: CRD42018099872). METHODS: PubMed, EMBASE, PsycINFO and CINAHL searches identified 36 eligible studies. RESULTS: There is a higher risk of developing all-cause dementia and AD in people with previous depression, and a higher risk of all-cause dementia in people with prior anxiety, than in persons without this history. Prior PTSD was not associated with a higher risk of later being diagnosed with dementia. LIMITATIONS: The data for anxiety, PTSD, DLB and FTD were limited. CONCLUSIONS: Depression and anxiety appear to be risk factors for dementia, but longitudinal studies across adulthood (young adult/mid-life/older adult) are needed to evaluate the likely causal or prodromal nature of this risk. The link between PTSD and dementia remains unclear. Regular screening for new onset mental illness and for cognitive changes in older adults with a history of mental illness may assist with earlier identification of dementia.

Prevalence of Depression, Anxiety and PTSD in People with Dementia: a Systematic Review and Meta-Analysis.

There appears to be a link between depression/anxiety/PTSD and dementia, although the evidence is incomplete and the reason is unclear. Mental illness may cause dementia or may be prodromal or comorbid with dementia, or dementia may trigger a relapse of symptoms in individuals with a history of mental illness. This study examined the link between depression/anxiety/PTSD and dementia by evaluating the prevalence of these disorders in people with dementia, relative to their healthy peers. Existing meta-analyses have examined the prevalence of clinically-significant depression and anxiety in Alzheimer's disease (AD), and depression in frontotemporal dementia (FTD), but have not considered vascular dementia (VaD), dementia with Lewy bodies (DLB), PTSD, or anxiety in FTD. The current meta-analysis compared the prevalence of clinically-significant depression, anxiety and PTSD in the four most common types of dementia (AD, VaD, DLB, FTD) and in unspecified dementia to that of healthy controls (PROSPERO number: CRD42017082086). PubMed, EMBASE, PsycINFO and CINAHL database searches identified 120 eligible studies. Prevalence rates were calculated for depression and anxiety in AD, VaD, DLB, FTD, unspecified dementia, and controls. PTSD data were only available for unspecified dementia. Subgroup analyses indicated that depression, but not anxiety, was more prevalent in people with dementia compared to controls; however, the anxiety analyses were probably under-powered. The results support a link between depression and dementia; however, the link between anxiety or PTSD and dementia remains unclear due to insufficient data. Longitudinal data is now needed to clarify whether depression/anxiety/PTSD may be risk factors for dementia.