The growing population of older adults and increasing rates of dementia highlight the critical need for measures that may attenuate the risk of dementia in vulnerable populations. Emerging study results suggest that individuals with posttraumatic stress disorder (PTSD) may have a greater chance of developing dementia compared to the general population, highlighting the need to explore this association as a potential target for early intervention.1-3

In the November 2020 issue of the British Journal of Psychiatry, Vasiliki Orgeta, PhD, associate professor in the division of psychiatry at the University College London in the United Kingdom, and colleagues, along with Mia Maria Günak, MSc, a PhD student in the department of psychology at Ludwig-Maximilian University of Munich in Germany, published the first meta-analysis to explore the PTSD-dementia connection.1

They found significant associations between PTSD and the risk of all-cause dementia, with a pooled hazard ratio (HR) of 1.61 in veterans (95% CI, 1.46-1.78; I2 = 80.9%; P <.001; n = 905,896; 5 studies) and 2.11 in the general population (95% CI, 1.03-4.33, I2 = 91.2%; P <.001; n = 787,782; 3 studies).


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These results indicate that PTSD may represent a strong and modifiable risk factor for the development of all-cause dementia. However, given the high level of heterogeneity and retrospective design of most studies examined, substantial research needs remain to further clarify the connection between PTSD and dementia risk.

For an in-depth discussion regarding additional evidence in this area and related implications for screening and treatment, we interviewed Günak and Orgeta as well as the following experts: Helen Lavretsky, MD, MS, professor-in-residence in the department of psychiatry at the David Geffen School of Medicine at the University of California, Los Angeles, and director of UCLA’s Late-life Mood, Stress, and Wellness Research Program, and Christopher Nguyen, PhD, neuropsychologist and clinical assistant professor at The Ohio State University Wexner Medical Center.

In addition to the meta-analysis by Günak and colleagues, what are some of the most notable findings thus far regarding associations between PTSD and dementia risk?

Nguyen: Epidemiological studies in military and civilian populations over the past decade have provided evidence on the link between PTSD and increased risk of developing dementia.  In a study consisting of more than 180,000 male veterans aged 55 and older, those diagnosed with PTSD had nearly 2-fold the risk of developing dementia syndromes such as Alzheimer disease, frontotemporal dementia, Lewy Body dementia, vascular dementia, and senile dementia compared to those without PTSD.4

In another study consisting of nearly 500,000 civilians, the risk of dementia in older adults with PTSD was approximately 70% higher, with males having a 2-fold increase in risk and females having a 60% higher risk, compared with those without PTSD.5 Notably, adjusting for vascular risk factors such as stroke, diabetes, and heart disease, as well as adjusting for a history of TBI [Traumatic Brain Injury], did not affect this association, while there was nearly a 2-fold increase in risk for both females and males with PTSD and depression. 5

In one comprehensive review, the elevated risk for dementia from PTSD remained even after accounting for demographics, and medical and psychiatric comorbidities.3

Christopher Nguyen, PhD
Credit: OSU WMC

What are the proposed mechanisms by which PTSD may increase dementia risk?

Dr Lavretsky: Unlike for depression and anxiety, there is not a clear relationship between PTSD and dementia, mostly because of the long gap between the time of developing PTSD and developing dementia, and it is also less clear what type of dementia may result from PTSD.

However, there is growing evidence of PTSD accelerating cellular aging based on DNA methylation, increased oxidative stress, chronic inflammation, decreased synaptic plasticity, and also some brain and cognitive measures including hippocampal atrophy and degraded neural integrity on diffusion tensor MRI imaging that are typical.

Helen Lavretsky, MD, MS
Credit: UCLA

Günak and Vasiliki: Certain neurobiological pathways may be potentiated by PTSD and thereby increase the risk of developing dementia. Among others, these include altered activity of the hypothalamic-pituitary-adrenal axis, with potential implications for an individual’s response to stress, and a reduction in the volume of the hippocampus which could affect learning and memory.1

The PTSD symptoms of hypervigilance and recurrent re-experiencing of the traumatic event may continuously activate threat- and stress-related neurobiological pathways. The avoidance and withdrawal from daily and social life observed in PTSD may result in reduced cognitive stimulation and thereby diminish an individual’s cognitive reserve and resilience.1

All of these proposed mechanisms may make the brain more vulnerable to the neuropathology underlying dementia.

Additionally, while the underlying mechanisms remain largely unknown, the pathways may also be bidirectional, with case studies having described a delayed onset of PTSD in individuals with dementia.3 Another interesting finding, according to a few studies, is that PTSD may be most strongly associated with the subtype frontotemporal dementia.6

Mia Maria Günak, MSc Credit: LMU
Vasiliki Orgeta
Credit: UCL

What are the relevant recommendations for clinicians regarding screening, diagnosis, and treatment for at-risk patients?

Günak and Vasiliki: While we cannot yet say how to best modify this potential risk of dementia related to PTSD, treating PTSD is likely to be very important7 not only to alleviate the symptoms of PTSD but to potentially prevent the development of dementia. 

Dr Lavretsky: It is important to screen for and treat underlying PTSD to prevent a chronic course and comorbid depression, suicidality, and the deleterious health consequences of chronic stress. It is important to identify individuals at risk for cognitive decline and those with a family history, TBI, cerebrovascular disease, and subjective memory concerns, and follow them more closely with cognitive assessment and some preventative approaches like stress reduction, mind-body therapies, improvement in sleep, physical exercise, and cognitive training that would add to the tools they can use to improve PTSD and prevent cognitive decline.

Nguyen: The presence of PTSD symptoms such as nightmares, trauma history, or agitation in response to certain cues can be signs that evaluation of PTSD is warranted in patients with co-occurring neurocognitive disorders.7 While assessment measures for PTSD among individuals with dementia have not been validated, several self-reported measures validated among older adults can be considered for screening tools such as the PTSD Checklist for DSM-5, the Impact of Event Scale-Revised, the Symptoms Checklist-90 PTSD Scale, and the Self-Rating Inventory for PTSD.

While the primary treatments for PTSD are psychotherapy and pharmacotherapy, limited evidence has indicated that evidence-based treatments for PTSD are appropriate for patients with mild dementia whereas the efficacy among patients with moderate-to-severe dementia remains unclear.7 Specifically, cognitive-behavioral therapy, prolonged exposure, and cognitive processing therapy have demonstrated effectiveness among patients with PTSD and co-occurring mild neurocognitive disorders. 

What should be the focus of future research pertaining to the connection between PTSD and dementia?  

Günak and Vasiliki: Future studies are needed to better understand the contributing factors and underlying mechanisms in the association between PTSD and dementia. This would enable the development of specific recommendations regarding screening, diagnosing, and treating individuals with PTSD, and could reduce the risk of developing dementia in the long run. While it may be intuitive, an important question is whether access to effective and timely treatment for PTSD indeed reduces the risk of developing dementia.

Dr Lavretsky: We need prospective studies of individuals with PTSD into older ages in order to identify risk factors, trajectories of decline, and the type of dementia that tends to be the results of chronic stress disorders, and to develop strategies for preventing cognitive decline in this population.

In the age of the COVID-19 pandemic and climate change disasters, with the entire world population subject to developing PTSD, this indicates the urgency for understanding the effects of PTSD on aging-related disorders and accelerated aging in order to develop meaningful ways of treating the disorder and preventing cognitive decline and aging-related disorders including dementias.

Nguyen: Based on the literature, future studies are needed to elucidate the mechanisms and neurobiological underpinnings of the association between PTSD and dementia, explore whether the association is dose-dependent, investigate the prophylactic potential of PTSD treatments in preventing or delaying onset of dementia, and improve screening and treatment outcomes for PTSD in elderly populations and individuals with neurocognitive disorders.

References

1.  Günak MM, Billings J, Carratu E, Marchant NL, Favarato G, Orgeta V. Post-traumatic stress disorder as a risk factor for dementia: systematic review and meta-analysis. Br J Psychiatry. 2020;217(5):600-608. doi:10.1192/bjp.2020.150. Erratum in: Br J Psychiatry. 2021;218(3):174.

2.  Desmarais P, Weidman D, Wassef A, et al. The interplay between post-traumatic stress disorder and dementia: a systematic review. Am J Geriatr Psychiatry. 2020;28(1):48-60. doi:10.1016/j.jagp.2019.08.006

3.  Kang B, Xu H, McConnell ES. Neurocognitive and psychiatric comorbidities of posttraumatic stress disorder among older veterans: A systematic review. Int J Geriatr Psychiatry. 2019;34(4):522-538. doi:10.1002/gps.5055

4.  Yaffe K, Vittinghoff E, Lindquist K, et al. Posttraumatic stress disorder and risk of dementia among US veterans. Arch Gen Psychiatry. 2010;67(6):608-613. doi:10.1001/archgenpsychiatry.2010.61

5.  Flatt JD, Gilsanz P, Quesenberry CP Jr, Albers KB, Whitmer RA. Post-traumatic stress disorder and risk of dementia among members of a health care delivery system. Alzheimers Dement. 2018;14(1):28-34. doi:10.1016/j.jalz.2017.04.014

6.  Bonanni L, Franciotti R, Martinotti G, et al. Post-traumatic stress disorder heralding the onset of semantic frontotemporal dementia. J Alzheimers Dis. 2018;63(1):203-215. doi:10.3233/JAD-171134

7.  Yoder M, Norman S, Friedman MJ. Assessment and treatment for PTSD with co-occurring neurocognitive disorder (NCD). US Department of Veteran Affairs. Accessed September 8, 2021. https://www.ptsd.va.gov/professional/treat/cooccurring/ncd_assess_cooccur.asp