New review suggests that PTSD may be a modifiable risk factor for dementia

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Dementia is a huge public health concern within the ageing populating. Around 50 million people in the world live with dementia, and that number is expected to triple by 2050 (Livingston et al, 2017). In the UK one in 14 people over the age of 65 have dementia, with the prevalence rising to 1 in 6 people in the over 80 population (NHS, 2020). Dementia can be caused by a number of diseases, the most common being Alzheimer’s Disease.

There is currently no cure for dementia, but we are now starting to build a picture of its contributing risk factors. One such potential risk factor that has recently been identified is PTSD (post traumatic stress disorder). PTSD is a disorder that can develop after an individual is exposed to a traumatic stressor such as abuse, serious injury or the threat of death. Symptoms of PTSD include flashbacks of the traumatic event, avoidant behaviour and hypervigilance, and it can severely impact the daily functioning of the affected person (Bryant, 2019). Some studies suggest that there is a bidirectional association between PTSD and impaired cognition (Patel et al, 2012).

The present study by Günak et al (2020) aims to examine the association between dementia and PTSD by running a meta-analysis and review of the quality of the existing evidence.

PTSD has been identified as a potential risk factor for dementia. This study aims to provide a synthesis of research to date which explores this relationship.

PTSD has been identified as a potential risk factor for dementia. This study aims to provide a synthesis of research to date which explores this relationship.

Methods

Nine databases were searched up to 25th October 2019 combined with additional hand-searching through reference lists of relevant reviews.

Both prospective and retrospective longitudinal studies were included if they investigated the association between PTSD and dementia. The population was specified as adults aged 18 years or older. Studies were included where a diagnosis of PTSD was based on a) clinical diagnostic criteria or b) a validated self-report scale. Studies were excluded if they did not diagnose dementia on the basis of clinical criteria.

Two reviewers then independently extracted the data from each study and risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale.

Pooled risk estimates for studies reporting hazard ratios and odds ratios were obtained and heterogeneity was measured. Where heterogeneity was detected, prediction intervals were calculated. The impact of each study and the effect of study quality was then examined and publication bias was assessed. Meta-analyses were then performed.

Results

A total of 12 studies met the inclusion criteria; with all of them being longitudinal cohort studies. Most of the studies were retrospective, deriving from medical records. A total of 1,693,678 participants were accounted for across all studies. Nine studies scored highly for methodological quality and four studies were judged to be of poor quality. Pooled data from 10 studies were used in the meta-analyses.

The primary meta-analysis pooled data from studies reporting hazard ratios and studies reporting odds ratios separately. The eight studies reporting hazard ratios showed that PTSD increased the risk of all-cause dementia when pooled. The two studies reporting odds ratios also showed that PTSD increased the risk of dementia when pooled. Studies that were not included in the meta-analysis reported similar findings.

Subgroup analyses indicated that people with PTSD in the general population had an increased risk of dementia compared to veterans with PTSD. The effect was slightly lower in studies conducted in the USA compared to studies conducted outside the USA. The subgroup analyses further found an increased risk of dementia onset in studies where 50% or more of the participants were female compared to studies where under 50% were female. The risk was also higher in studies where the maximum follow up was below 10 years in comparison to studies with a follow up of 10 years or more.

The strength of the results remained significant after omitting any single study, even one study which had a high risk of bias. When considering confounding factors, the authors pooled studies that adjusted for a history of traumatic brain injury (a known risk factor for dementia) and found that this slightly increased the overall effect estimate.

The meta-analyses found that PTSD was associated with an increased risk of all-cause dementia.

The meta-analyses found that PTSD was associated with an increased risk of all-cause dementia.

Conclusions

This review concludes that PTSD is a significant and potentially modifiable risk factor for dementia. The meta-analyses demonstrated that those diagnosed with PTSD have a 1.61 to 1.99 times greater risk of being diagnosed with dementia, when compared to those not diagnosed with PTSD. This association remained significant even after controlling for confounding factors like traumatic brain injury.

Interestingly, the subgroup analyses showed a different effect in veterans versus the general population. The lower risk seen in the veteran population may possibly be because veterans are more likely to receive treatment for PTSD than the general population. This could potentially indicate that the onset of PTSD-associated dementia may be modifiable through treatment for the PTSD. This is supported by the findings that young to middle-aged veterans were more likely to have health insurance and to receive counselling or psychotherapy compared with non-veterans in the same age-group (Fortney et al, 2016).

Possible mechanisms of the association between PTSD and dementia are relatively unknown. Some studies propose that some neural pathways in the brain, which are potentiated by PTSD, may also increase the risk of dementia onset (Miller, 2018). Additionally, as the symptoms of PTSD develop, withdrawal from daily and social life may result in reduced cognitive stimulation which could reduce resilience to the neuropathological changes associated with dementia (Stern, 2012). It is also possible that PTSD and dementia may share a common genetic vulnerability (Bryant, 2019; Desmarais et al, 2020).

PTSD is potentially a modifiable risk factor for dementia, though we still don’t know what the mechanisms of this relationship are.

PTSD is potentially a modifiable risk factor for dementia, though we still don’t know what the mechanisms of this relationship are.

Strengths and limitations

This study is notable as being the first to quantify the association between PTSD and all-cause dementia. The search strategy used for the review was comprehensive and thorough, and the included studies were longitudinal, where PTSD was present before the onset of dementia, allowing for long follow-up periods. Worldwide studies were included across a range of populations and countries, drawing on data from just under two million participants in total.

However, by the authors own admission, there are some limitations to this study. There was substantial statistical heterogeneity between studies, and even though several subgroup and sensitivity analyses were run, heterogeneity remained high and its sources could not be detected. Additionally, the second meta-analysis was only based on two studies, leaving a very limited sample.

It is also notable that most of the papers included were retrospective designs which can be flawed themselves, as they may rely on healthcare professionals to diagnose PTSD and dementia. This, coupled with the varying and ever-changing definitions and classifications of PTSD across studies, means that measurements will be inconsistent and less accurate compared to a prospective design.

This study is a notable step towards assessing the association between PTSD and all-cause dementia, but could be strengthened through the inclusion of prospective study designs.

This study is a notable step towards assessing the association between PTSD and all-cause dementia, but could be strengthened through the inclusion of prospective study designs.

Implications for practice

This study represents an important step in determining the association between PTSD and dementia. However, more research is needed to examine the specific contribution of different mechanisms, both environmental and neurocognitive, towards increasing the cognitive impairment vulnerability over time.

Future studies may address how the varying classifications of PTSD and dementia may influence the association with dementia. This study also raises the question of whether access to treatment for PTSD could reduce the risk of developing dementia. The authors suggest that future studies might examine PTSD interventions as a preventative factor against the onset of dementia.

The authors further recommended strengthening future meta-analyses by conducting harmonisation of potential modifiers across studies, including for example, the use of antipsychotics.

This study ultimately identifies PTSD as a potentially strong and modifiable risk factor for dementia, which has huge implications for the treatment of all-cause dementia in the context of global public health.

Future research should examine PTSD interventions as a preventative factor against the onset of dementia.

Future research should examine PTSD interventions as a preventative factor against the onset of dementia.

Statement of interests

No known conflicts of interest.

Links

Primary paper

Günak, M. M., Billings, J., Carratu, E., Marchant, N. L., Favarato, G., & Orgeta, V. (2020). Post-traumatic stress disorder as a risk factor for dementia: systematic review and meta-analysisThe British journal of psychiatry: the journal of mental science217(5), 600–608.

Other references

Bryant, R. A. (2019). “Post-traumatic stress disorder: a state-of-the-art review of evidence and challenges.” World Psychiatry 18(3): 259-269.

Desmarais, P., D. Weidman, A. Wassef, M.-A. Bruneau, J. Friedland, P. Bajsarowicz, M.-P. Thibodeau, N. Herrmann and Q. D. Nguyen (2020). “The Interplay Between Post-traumatic Stress Disorder and Dementia: A Systematic Review.” The American Journal of Geriatric Psychiatry 28(1): 48-60.

Fortney, J. C., G. M. Curran, J. B. Hunt, A. M. Cheney, L. Lu, M. Valenstein and D. Eisenberg (2016). “Prevalence of probable mental disorders and help-seeking behaviors among veteran and non-veteran community college students.” Gen Hosp Psychiatry 38: 99-104.

Livingston, G., A. Sommerlad, V. Orgeta, S. G. Costafreda, J. Huntley, D. Ames, C. Ballard, S. Banerjee, A. Burns, J. Cohen-Mansfield, C. Cooper, N. Fox, L. N. Gitlin, R. Howard, H. C. Kales, E. B. Larson, K. Ritchie, K. Rockwood, E. L. Sampson, Q. Samus, L. S. Schneider, G. Selbæk, L. Teri and N. Mukadam (2017). “Dementia prevention, intervention, and care.” The Lancet 390(10113): 2673-2734.

Miller, M. W., A. P. Lin, E. J. Wolf and D. R. Miller (2018). “Oxidative Stress, Inflammation, and Neuroprogression in Chronic PTSD.” Harv Rev Psychiatry 26(2): 57-69.

NHS. (2020). About dementia. Dementia guide. Retrieved from https://www.nhs.uk/conditions/dementia/about/

Patel, R., R. N. Spreng, L. M. Shin and T. A. Girard (2012). “Neurocircuitry models of posttraumatic stress disorder and beyond: a meta-analysis of functional neuroimaging studies.” Neurosci Biobehav Rev 36(9): 2130-2142.

Stern, Y. (2012). “Cognitive reserve in ageing and Alzheimer’s disease.” Lancet Neurol 11(11): 1006-1012.

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