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Original Article |

Posttraumatic Stress Disorder and Risk of Dementia Among US Veterans FREE

Kristine Yaffe, MD; Eric Vittinghoff, PhD; Karla Lindquist, MS; Deborah Barnes, PhD; Kenneth E. Covinsky, MD, MPH; Thomas Neylan, MD; Molly Kluse, BA; Charles Marmar, MD
[+] Author Affiliations

Author Affiliations: Departments of Psychiatry (Drs Yaffe, Barnes, Neylan, and Marmar and Ms Kluse), Neurology (Dr Yaffe), Epidemiology and Biostatistics (Drs Yaffe and Vittinghoff), and Medicine (Ms Lindquist and Dr Covinsky), School of Medicine, University of California, San Francisco, and San Francisco Veterans Affairs Medical Center (Drs Yaffe, Covinsky, Neylan, and Marmar).


Arch Gen Psychiatry. 2010;67(6):608-613. doi:10.1001/archgenpsychiatry.2010.61.
Text Size: A A A
Published online

Context  Posttraumatic stress disorder (PTSD) is highly prevalent among US veterans because of combat and may impair cognition.

Objective  To determine whether PTSD is associated with the risk of developing dementia among older US veterans receiving treatment in the Department of Veterans Affairs medical centers.

Design  A stratified, retrospective cohort study conducted using the Department of Veterans Affairs National Patient Care Database.

Setting  Department of Veterans Affairs medical centers in the United States.

Participants  A total of 181 093 veterans 55 years or older without dementia from fiscal years 1997 through 2000 (53 155 veterans with and 127 938 veterans without PTSD).

Main Outcome Measures  During the follow-up period between October 1, 2000, and December 31, 2007, 31 107 (17.2%) veterans were ascertained to have newly diagnosed dementia according to International Classification of Diseases, Ninth Revision, Clinical Modification codes.

Results  The mean baseline age of the veterans was 68.8 years, and 174 806 (96.5%) were men. Veterans with PTSD had a 7-year cumulative incident dementia rate of 10.6%, whereas those without had a rate of 6.6% (P < .001). With age as the time scale, Cox proportional hazards models indicated that patients with PTSD were more than twice as likely to develop incident dementia compared with those without PTSD (hazard ratio, 2.31; 95% confidence interval, 2.24-2.39). After multivariable adjustment, patients with PTSD were still more likely to develop dementia (hazard ratio, 1.77; 95% confidence interval, 1.70-1.85). Results were similar when we excluded those with a history of head injury, substance abuse, or clinical depression.

Conclusions  In a predominantly male veteran cohort, those diagnosed as having PTSD were at a nearly 2-fold-higher risk of developing dementia compared with those without PTSD. Mechanisms linking these important disorders need to be identified with the hope of finding ways to reduce the increased risk of dementia associated with PTSD.

Figures in this Article

Posttraumatic stress disorder (PTSD) is a common psychiatric syndrome associated with high rates of morbidity and mortality and is one of the most common sequelae in veterans returning from combat. Among veterans returning from Iraq and Afghanistan, the prevalence of PTSD has been estimated as 17%.1 In addition, PTSD can be a chronic condition. Vietnam veterans have been found to have a 20% to 30% lifetime prevalence of combat-related PTSD, and 10% to 15% had the disorder 15 years or longer after returning from Vietnam.2,3 A study of older World War II and Korean veterans found that the PTSD prevalence remained as high as 12% even 45 years after combat.4

Previous studies59 have found that PTSD is associated with greater health care use and an increased risk of developing a wide range of medical conditions in younger and middle-aged veterans. Despite evidence that PTSD may impair cognitive performance10,11 and that older individuals with PTSD have greater decline in cognitive performance relative to control patients,12 little is known about PTSD as a risk factor for developing dementia. Given that PTSD symptoms often continue until late in life and that alterations in the hypothalamic-pituitary-adrenal axis often accompany PTSD13 and these in turn may be associated with dementia,14 there is reason to believe that PTSD might be associated with accelerated brain aging. Another possible mechanism that may link PTSD to higher rates of dementia is the co-occurrence of depression, head injury, or medical comorbidities, conditions all associated with both PTSD and dementia.1517 No studies to date have determined whether PTSD is independently associated with an increased risk of developing dementia.

The goal of our study was to determine whether PTSD was associated with an increased risk of being diagnosed as having dementia among veterans using Department of Veterans Affairs (VA) health care services in the United States. In addition, we were interested in whether such an association might be explained by medical comorbidities, clinical depression, or head injury.

DATA AND STUDY PARTICIPANTS

Data for this retrospective cohort study were obtained from the VA National Patient Care Database, which captures all inpatient and outpatient services within the VA each fiscal year (October 1 through September 30). Records were extracted for veterans 55 years and older who had been treated at a VA health care facility and did not have a diagnosis of dementia during our baseline period, fiscal years 1997 through 2000, and who also had at least 1 visit during our follow-up period from fiscal year 2001 (October 1, 2000) to the end of the calendar year 2007.

There were 3 120 213 veterans seen at a VA facility at least once during the 1997 through 2000 fiscal years who were 55 to 100 years of age at the time of their first encounter. We excluded the 170 378 (5.5%) who had received a dementia diagnosis at the VA during this period. Among the remaining 2 949 835 veterans, we identified 59 633 (2.0%) as having received a PTSD diagnosis at least twice during the baseline period, all of whom were included in our potential cohort. The rest of the potential cohort was a group of 178 899 randomly selected veterans (3 per patient with PTSD) without a PTSD diagnosis.

Among the 238 532 patients with and without PTSD selected as potential participants, we excluded 26 311 (11.0%) who died during the baseline period and 31 128 (13.1%) who were not seen at a VA health care facility during the follow-up period because we did not have the ability to determine whether they had developed incident dementia. Thus, our final cohort of 181 093 veterans consisted of 53 155 patients with and 127 938 without PTSD.

OUTCOME MEASURES
Posttraumatic Stress Disorder

Veterans with PTSD were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)18 codes recorded in the VA database. To be conservative, those with a diagnosis code of 309.81 (PTSD) on at least 2 different visits during the baseline period were classified as having PTSD. Veterans with 1 diagnosis of PTSD were not included in our primary analyses (combined total = 88 568 veterans).

Dementia

Veterans with dementia were identified using ICD-9-CM codes during the baseline period to exclude prevalent cases and during the follow-up to identify incident cases. Patients with diagnosis codes 290.0, 290.2, 290.3, 331.2 (senile dementias, n = 3450), 290.4 (vascular dementia, n = 2698), 294.8 (dementia not otherwise specified, n = 10 291), 331.0 (Alzheimer disease, n = 3882), 331.1 (frontotemporal dementia, n = 139), and 331.82 (Lewy body dementia, n = 356) were considered to have dementia diagnoses.

Evaluation of incident dementia diagnosis occurred from October 1, 2000, through December 31, 2007. If dementia was not diagnosed before the patient's death or the end of the follow-up period, the patient's data was censored at whichever event occurred first. Dates of death were obtained through the VA Vital Status File, which combines death data from the VA, the Center for Medicare and Medicaid Services, and the Social Security Administration.19

Baseline Characteristics

Baseline age (in years) was calculated on October 1, 2000. Sex and race/ethnicity information was also determined based on VA database records. We classified veterans as living in broad educational and income strata according to zip code tabulation areas by linking our data to 2000 US Census data. For educational level, veterans were categorized according to whether they were living in a zip code tabulation area where 25% or less vs greater than 25% of the adult population had completed a college education (bachelor's degree or higher). This cutoff was chosen because the average zip code tabulation area in 2000 had a 24.4% college-educated adult population.20 For income, veterans were categorized in tertiles of median zip code tabulation area income for adults younger than 75 years or 75 years or older.

Indicators of prevalent medical comorbidity during the baseline period were obtained using ICD-9-CM diagnosis codes for hypertension, diabetes mellitus, myocardial infarction, cancer, and cerebrovascular disease. Psychiatric comorbidities were also determined using ICD-9-CM codes, including history of tobacco use, alcohol abuse, other substance abuse, major clinical depression, and head injury, including concussion, contusion, skull fracture, and other head injury (ICD-9-CM codes 310.2, 800-804.xx, 850.x, 851.x, 854.0, 854.1, and 959.01). The Committee on Human Research at the University of California, San Francisco, the Committee for Research and Development at the San Francisco VA, and the Human Research Protection Office of the US Army Medical Research and Material Command approved the study.

STATISTICAL ANALYSES

Baseline characteristics were summarized with means and standard deviations or percentages for the veterans with and without PTSD. The characteristics of the 2 groups were compared using t tests for continuous variables and χ2 tests for categorical variables.

Cumulative incidence of dementia was plotted by patient age (in years) for each group. These curves show estimates of the cumulative incidence by age in the presence of death as a competing risk; with complete follow-up, this could be estimated by the simple proportion with a dementia diagnosis by any given age. This is in contrast to Kaplan-Meier curves, which estimate the incidence that would be observed if the competing risk could be “removed.” To determine whether the relative rates of incident dementia over time would be different for those without other major neuropsychiatric diagnoses, we also constructed cumulative incidence curves excluding those with diagnoses of major clinical depression, substance abuse, or head injury during the baseline period.

Cox proportional hazards models were used to compare the age of incident dementia in patients with and without PTSD. With age as the time scale, the effects of age on incidence are flexibly modeled by the baseline hazard, which is nonparametric in the Cox model and need not even be estimated to obtain estimates of covariate effects. Several different adjusted Cox models were run to assess the influence of confounding by different types of baseline characteristics. First, models were adjusted for the demographic characteristics of race/ethnicity, sex, and educational and income strata. Second, the models were adjusted for indicators of medical comorbidity at baseline, including hypertension, diabetes, myocardial infarction, and cerebrovascular disease, followed by adjustments for neuropsychiatric comorbidities, such as clinical depression, substance abuse, and head injury. To assess the impact of differential opportunity for receiving dementia diagnoses by presence or absence of PTSD, we also ran models adjusting for a time-varying covariate for the number of inpatient or outpatient visits to a VA clinic per month. Proportional hazards assumptions were tested graphically and statistically and were met for all models. All analyses were conducted with Stata statistical software, version 10.1 (StataCorp LP, College Station, Texas), and SAS statistical software, version 9.1 (SAS Institute Inc, Cary, North Carolina).

PARTICIPANT CHARACTERISTICS

The mean (SD) baseline age of the 181 093 veterans in our cohort was 68.8 (8.6) years; 174 806 (96.5%) were men. Baseline characteristics of veterans are presented in Table 1. Compared with the patients without PTSD, those with PTSD were younger, had greater comorbidities, and lived in zip codes with more college-educated and higher-income individuals, although the absolute differences were small. Substance abuse (P = .004), tobacco use (P = .009), major clinical depression (P = .001), and head injury (P = .009) were also statistically significantly more common among patients with than in those without PTSD.

Table Graphic Jump LocationTable 1. Baseline Characteristics of the Veterans With and Without PTSD
INCIDENT DEMENTIA

The median follow-up time for veterans with and without PTSD was 7.2 (range, 0.1-7.4) years. Cumulative incidence rates of dementia were significantly higher for veterans with than those without PTSD. Those with PTSD had a 7-year cumulative incidence rate of 10.6% with incident dementia, whereas veterans without PTSD had a 7-year rate of 6.6% (P < .001). Incident dementia rates were higher for patients with PTSD throughout the follow-up period (Figure).

Place holder to copy figure label and caption
Figure.

Cumulative incidence of dementia by age for all veterans. PTSD indicates posttraumatic stress disorder.

Graphic Jump Location

Cox proportional hazards models using age as the time scale also show that patients with PTSD were more than twice as likely to develop incident dementia compared with those without PTSD (hazard ratio [HR], 2.31; 95% confidence interval [CI], 2.24-2.39) (Table 2). After adjusting for the demographic variables of sex, race/ethnicity, educational level, and income, results were similar (HR, 2.28; 95% CI, 2.21-2.36). Adjustment for medical comorbidities at baseline also was not greatly influential but reduced the risk slightly (HR, 2.21; 95% CI, 2.13-2.28). Adjustment for other neuropsychiatric diagnoses reduced the strength of the association between PTSD and dementia, although those with PTSD were still more likely to develop incident dementia than those without (HR, 1.84; 95% CI, 1.76-1.91). In the final multivariable-adjusted model adjusting for demographics and medical and neuropsychiatric comorbidities, patients with PTSD were still nearly twice as likely to develop incident dementia as those without (HR, 1.77; 95% CI, 1.70-1.85).

Table Graphic Jump LocationTable 2. Association Between PTSD and Risk of Dementia in Multivariable-Adjusted Models

We next determined whether the association between PTSD and risk of dementia differed by dementia diagnosis subtype. The unadjusted HR ranged from 1.94 to 3.13, and the multivariable-adjusted HR ranged from 1.71 to 2.19 (Table 3). There was no consistent pattern other than that PTSD was associated with a higher risk of dementia among all dementia subtypes.

Table Graphic Jump LocationTable 3. Association Between PTSD and Risk of Subtypes of Dementiaa

We conducted several sensitivity analyses. To determine whether those with PTSD were more likely to receive a diagnosis of dementia because of more frequent care at the VA (inpatient or outpatient), we adjusted for the number of visits to inpatient and outpatient clinics. The addition of adjustment for clinic visits did not appreciably change the model results, but those with PTSD had more clinic visits (P < .001). To determine whether veterans with PTSD remained at an increased risk of developing dementia even in the absence of psychiatric comorbidities, we excluded veterans with a diagnosis of major clinical depression, substance abuse, or head injury (n = 48 241) during the baseline period and found almost identical results. We also repeated our analyses excluding women veterans and including veterans with a diagnosis of PTSD at 1 or more visits (n = 88 568), and our results were similar in both analyses. Finally, we determined whether veterans with PTSD had a greater risk of developing dementia compared with veterans without PTSD psychiatric disorders and found an increased risk (adjusted HR, 1.47; 95% CI, 1.37-1.56).

We found that among primarily male veterans, those diagnosed as having PTSD had nearly a 2-fold increased risk of dementia compared with those without PTSD. This association remained after adjustment for important differences between those with and without PTSD, such as demographics and medical and neuropsychiatric comorbidities.

There are several reasons why patients with PTSD may have an increased risk of developing dementia. One possibility is that PTSD is causally related to the development of dementia. There is some evidence, albeit controversial, that veterans with PTSD perform more poorly on cognitive tests.1012,21 This poorer performance on cognitive testing compared with those without PTSD could be a risk factor for development of dementia because those with worse function may have less cognitive reserve and be at higher risk for cognitive impairment.22

Another mechanism possibly linking PTSD to dementia is chronic stress. Stress may damage the hippocampus, a brain structure crucial for memory and learning. Indeed, others, including some of us,23 have previously found that PTSD is associated with decreased concentrations of the neuronal marker, N-acetyl aspartate, in the hippocampus. Others24 have found that veterans with PTSD have smaller hippocampal volumes, which are correlated with deficits in short-term memory performance. Smaller hippocampal volumes have been associated with poor cognitive function and increased risk of dementia in healthy elderly people.25 It is possible then that PTSD leads to hippocampal atrophy, which in turn increases risk of cognitive deficits and dementia, especially during short-term follow-up, or that a smaller hippocampus is a predisposition factor for both PTSD and dementia.

As a stress-related disorder, PTSD also is associated with alterations in the hypothalamic-pituitary-adrenal axis and proinflammatory cytokines. Acute stress produces increases in cortisol levels, and a study26 has found that hypercortisolemia is associated with increased risk of dementia. Veterans with chronic PTSD typically have reduced cortisol levels, which may reflect an allostatic downregulation of the glucocorticoid system and may facilitate chronic inflammation.13 Several studies have demonstrated that PTSD is associated with proinflammatory immune alterations, including increased levels of cytokines,27 enhanced cellular immune responses,28 and increased levels of C-reactive protein.29,30 It was found previously that inflammation is associated with increased risk of cognitive decline.31 Several other related possible mechanisms include alterations in homocysteine level and other vascular risk factors, possibly because of medications, in the setting of PTSD.32,33

Another explanation for the association is that dementia and PTSD co-occur more frequently together or that one condition may “unmask” the other. Indeed, there have been several case series and case reports that PTSD symptoms may worsen in veterans as they develop dementia or cognitive impairment.3436 We doubt this explains our findings because we excluded those veterans with PTSD and a diagnosis of dementia at baseline. In addition, we required a documented PTSD diagnosis on at least 2 visits to ensure a robust clinical diagnosis. Finally, it may be that having PTSD, or other chronic brain disorders, may predispose patients to developing dementia because of an increased nonspecific vulnerability, for example, genetic vulnerabilities shared by both disorders or childhood environmental factors.37 It is possible that having PTSD, especially in patients followed up by mental health care professionals, may bring more attention to other neuropsychiatric diagnoses, such as dementia. We attempted to control for this possible detection bias by adjusting for the number of VA visits, and our results were not appreciably different.

We believe our study has several important strengths, including a large number of veterans with and without PTSD who received care at a VA facility, allowing for documentation of dementia diagnosis for several years. In addition, we have attempted to carefully adjust for possible confounding from medical and neuropsychiatric comorbidities. Finally, this study is the first, to our knowledge, to report that PTSD may increase the risk of developing dementia. Several limitations of our study are also important to mention. The diagnoses of PTSD, dementia, and medical and neuropsychiatric comorbidities were made on the basis of clinician ICD-9-CM codes, an insensitive assessment of symptoms compared with structured research diagnostic interviews and with some differences compared with Diagnostic and Statistical Manual of Mental Disorders–based criteria. Because of this, we were also unable to assess the possibility of any subclinical cases of PTSD or dementia, and our data cannot be used to estimate the prevalence of PTSD in the older veteran population. In addition, our population included primarily male veterans followed up by the VA system; therefore, we need to determine whether our findings generalize to women and to those patients not cared for at VA medical centers.

The finding that PTSD is associated with a near doubling of the risk of dementia has important public health, policy, and biological implications. Posttraumatic stress disorder has emerged as a common sequela of combat and other trauma exposure, and its course is often chronic, leading to increased mortality and morbidity. As patients with PTSD age, these adverse health conditions usually increase in frequency, and some have suggested that PTSD may accelerate the “aging process” in general.38 It is important that those with PTSD are treated, and further investigation is needed to see whether successful treatment of PTSD may reduce the risk of adverse health outcomes, including dementia. In addition, it is critical to follow up patients with PTSD, especially if they are of an advanced age, to screen for cognitive impairment. Finally, mechanisms linking PTSD and dementia must be identified in hope of finding ways to improve the care and outcomes of patients with PTSD.

Correspondence: Kristine Yaffe, MD, San Francisco Veterans Affairs Medical Center, 4150 Clement St, Box 181, San Francisco, CA 94121 (kristine.yaffe@ucsf.edu).

Submitted for Publication: June 17, 2009; final revision received December 4, 2009; accepted December 11, 2009.

Financial Disclosure: Dr Yaffe reports having served as a consultant to Novartis Inc for reasons not related to the current project. Dr Vittinghoff reports having received grant support from Zelos Therapeutics, Tethys Bioscience Inc, and NPS Pharmaceuticals. Dr Neylan reports having served as a consultant for Actelion Pharmaceuticals Ltd and Takeda Pharmaceutical Company Limited and receiving lecture fees from speaking at the invitation of The Chatham Institute and the Pri-Med Institute. Dr Marmar reports having served as a consultant for Sanofi Aventis LLC and Actelion Pharmaceuticals Ltd.

Funding/Support: This study was funded by US Department of Defense grant W81XWH-05-2-0094 (principal investigator: Dr Yaffe). Dr Yaffe was supported in part by the National Institute on Aging (grant AG031155) and an anonymous foundation.

Role of the Sponsor: Representatives of the US Department of Defense approved the study design and human subjects review.

Hoge  CWCastro  CAMesser  SC McGurk  DCotting  DIKoffman  RL Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med 2004;351 (1) 13- 22
PubMed Link to Article
Dohrenwend  BPTurner  JBTurse  NAAdams  BGKoenen  KCMarshall  R The psychological risks of Vietnam for US veterans: a revisit with new data and methods. Science 2006;313 (5789) 979- 982
PubMed Link to Article
Kulka  RSchlenger  WEFairbank  JAHough  RLJordan  BKMarmar  CRWeiss  DS Trauma and the Vietnam War Generation: Report of Findings From the National Vietnam Veterans Readjustment Study.  New York, NY: Brunner/Mazel Publishers Inc; 1990
Spiro  A  IIISchnurr  PPAldwin  CM Combat-related posttraumatic stress disorder symptoms in older men. Psychol Aging 1994;9 (1) 17- 26
PubMed Link to Article
Boscarino  JA Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies. Ann N Y Acad Sci 2004;1032141- 153
PubMed Link to Article
Drescher  KDRosen  CSBurling  TAFoy  DW Causes of death among male veterans who received residential treatment for PTSD. J Trauma Stress 2003;16 (6) 535- 543
PubMed
Hearst  NNewman  TBHulley  SB Delayed effects of the military draft on mortality: a randomized natural experiment. N Engl J Med 1986;314 (10) 620- 624
PubMed Link to Article
Schnurr  PPSpiro  A  IIIParis  AH Physician-diagnosed medical disorders in relation to PTSD symptoms in older male military veterans. Health Psychol 2000;19 (1) 91- 97
PubMed Link to Article
Zatzick  DFMarmar  CRWeiss  DSBrowner  WSMetzler  TJGolding  JMStewart  ASchlenger  WEWells  KB Posttraumatic stress disorder and functioning and quality of life outcomes in a nationally representative sample of male Vietnam veterans. Am J Psychiatry 1997;154 (12) 1690- 1695
PubMed
Samuelson  KWNeylan  TCMetzler  TJRothlind  JHenn  Haase  CChoucroun  GWeiner  MWMarmar  CR Neuropsychological functioning in posttraumatic stress disorder and alcohol abuse. Neuropsychology 2006;20 (6) 716- 726
PubMed Link to Article
Vasterling  JJProctor  SPAmoroso  PKane  RHeeren  TWhite  RF Neuropsychological outcomes of Army personnel following deployment to the Iraq war. JAMA 2006;296 (5) 519- 529
PubMed Link to Article
Yehuda  RTischler  LGolier  JAGrossman  RBrand  SRKaufman  SHarvey  PD Longitudinal assessment of cognitive performance in Holocaust survivors with and without PTSD. Biol Psychiatry 2006;60 (7) 714- 721
PubMed Link to Article
Yehuda  R Post-traumatic stress disorder. N Engl J Med 2002;346 (2) 108- 114
PubMed Link to Article
Herbert  JGoodyer  IMGrossman  ABHastings  MHde Kloet  ERLightman  SLLupien  SJRoozendaal  BSeckl  JR Do corticosteroids damage the brain? J Neuroendocrinol 2006;18 (6) 393- 411
PubMed Link to Article
Hoge  CW McGurk  DThomas  JLCox  ALEngel  CCCastro  CA Mild traumatic brain injury in US soldiers returning from Iraq. N Engl J Med 2008;358 (5) 453- 463
PubMed Link to Article
Keane  TMKaloupek  DG Comorbid psychiatric disorders in PTSD: implications for research. Ann N Y Acad Sci 1997;82124- 34
PubMed Link to Article
Yaffe  KBlackwell  TGore  RSands  LReus  VBrowner  WS Depressive symptoms and cognitive decline in nondemented elderly women: a prospective study. Arch Gen Psychiatry 1999;56 (5) 425- 430
PubMed Link to Article
World Health Organization International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM).  Geneva, Switzerland: World Health Organization; 1992
United States Department of Veterans Affairs VA vital status files. http://www.virec.research.va.gov/DataSourcesName/VitalStatus/VitalStatus.htm. Accessed December 9, 2008
Bauman  KJGraf  NL Educational Attainment: 2000: US Census 2000 Brief.  Washington, DC: US Census Bureau; 2003: 1-11
Bremner  JDScott  TMDelaney  RCSouthwick  SMMason  JWJohnson  DRInnis  RB McCarthy  GCharney  DS Deficits in short-term memory in posttraumatic stress disorder. Am J Psychiatry 1993;150 (7) 1015- 1019
PubMed
Stern  Y Cognitive reserve and Alzheimer disease. Alzheimer Dis Assoc Disord 2006;20 (3) (suppl 2)S69- S74
PubMed Link to Article
Schuff  NNeylan  TCLenoci  MADu  A-TWeiss  DSMarmar  CRWeiner  MW Decreased hippocampal N-acetylaspartate in the absence of atrophy in posttraumatic stress disorder. Biol Psychiatry 2001;50 (12) 952- 959
PubMed Link to Article
Bremner  JDRandall  PScott  TMBronen  RASeibyl  JPSouthwick  SMDelaney  RC McCarthy  GCharney  DSInnis  RB MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry 1995;152 (7) 973- 981
PubMed
Grundman  MSencakova  DJack  CR  JrPetersen  RCKim  HTSchultz  AWeiner  MFDeCarli  CDeKosky  STvan Dyck  CThomas  RGThal  LJAlzheimer's Disease Cooperative Study, Brain MRI hippocampal volume and prediction of clinical status in a mild cognitive impairment trial. J Mol Neurosci 2002;19 (1-2) 23- 27
PubMed Link to Article
Swaab  DFRaadsheer  FCEndert  EHofman  MAKamphorst  WRavid  R Increased cortisol levels in aging and Alzheimer's disease in postmortem cerebrospinal fluid. J Neuroendocrinol 1994;6 (6) 681- 687
PubMed Link to Article
Sutherland  AGAlexander  DAHutchison  JD Disturbance of pro-inflammatory cytokines in post-traumatic psychopathology. Cytokine 2003;24 (5) 219- 225
PubMed Link to Article
Altemus  MCloitre  MDhabhar  FS Enhanced cellular immune response in women with PTSD related to childhood abuse. Am J Psychiatry 2003;160 (9) 1705- 1707
PubMed Link to Article
Miller  RJSutherland  AGHutchison  JDAlexander  DA C-reactive protein and interleukin 6 receptor in post-traumatic stress disorder: a pilot study. Cytokine 2001;13 (4) 253- 255
PubMed Link to Article
Spitzer  CBarnow  SVölzke  HWallaschofski  HJohn  UFreyberger  HJLöwe  BGrabe  HJ Association of posttraumatic stress disorder with low-grade elevation of C-reactive protein: evidence from the general population. J Psychiatr Res 2010;44 (1) 15- 21
PubMed Link to Article
Yaffe  KLindquist  KPenninx  BWSimonsick  EMPahor  MKritchevsky  SLauner  LKuller  LRubin  SHarris  T Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology 2003;61 (1) 76- 80
PubMed Link to Article
Jendričko  TVidović  AGrubišić-Illić  MRomić  ZKovačić  ZKozarić-Kovačić  D Homocysteine and serum lipids concentration in male war veterans with posttraumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry 2009;33 (1) 134- 140
PubMed Link to Article
Seshadri  SBeiser  ASelhub  JJacques  PFRosenberg  IHD’Agostino  RBWilson  PWFWolf  PA Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 2002;346 (7) 476- 483
PubMed Link to Article
Hamilton  JDWorkman  RH  Jr Persistence of combat-related posttraumatic stress symptoms for 75 years. J Trauma Stress 1998;11 (4) 763- 768
PubMed Link to Article
Johnston  D A series of cases of dementia presenting with PTSD symptoms in World War II combat veterans. J Am Geriatr Soc 2000;48 (1) 70- 72
PubMed
Mittal  DTorres  RAbashidze  AJimerson  N Worsening of post-traumatic stress disorder symptoms with cognitive decline: case series. J Geriatr Psychiatry Neurol 2001;14 (1) 17- 20
PubMed Link to Article
Gilbertson  MWPaulus  LAWilliston  SKGurvits  TVLasko  NBPitman  RKOrr  SP Neurocognitive function in monozygotic twins discordant for combat exposure: relationship to posttraumatic stress disorder. J Abnorm Psychol 2006;115 (3) 484- 495
PubMed Link to Article
Yehuda  RGolier  JAHarvey  PDStavitsky  KKaufman  SGrossman  RATischler  L Relationship between cortisol and age-related memory impairments in Holocaust survivors with PTSD. Psychoneuroendocrinology 2005;30 (7) 678- 687
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Cumulative incidence of dementia by age for all veterans. PTSD indicates posttraumatic stress disorder.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Baseline Characteristics of the Veterans With and Without PTSD
Table Graphic Jump LocationTable 2. Association Between PTSD and Risk of Dementia in Multivariable-Adjusted Models
Table Graphic Jump LocationTable 3. Association Between PTSD and Risk of Subtypes of Dementiaa

References

Hoge  CWCastro  CAMesser  SC McGurk  DCotting  DIKoffman  RL Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med 2004;351 (1) 13- 22
PubMed Link to Article
Dohrenwend  BPTurner  JBTurse  NAAdams  BGKoenen  KCMarshall  R The psychological risks of Vietnam for US veterans: a revisit with new data and methods. Science 2006;313 (5789) 979- 982
PubMed Link to Article
Kulka  RSchlenger  WEFairbank  JAHough  RLJordan  BKMarmar  CRWeiss  DS Trauma and the Vietnam War Generation: Report of Findings From the National Vietnam Veterans Readjustment Study.  New York, NY: Brunner/Mazel Publishers Inc; 1990
Spiro  A  IIISchnurr  PPAldwin  CM Combat-related posttraumatic stress disorder symptoms in older men. Psychol Aging 1994;9 (1) 17- 26
PubMed Link to Article
Boscarino  JA Posttraumatic stress disorder and physical illness: results from clinical and epidemiologic studies. Ann N Y Acad Sci 2004;1032141- 153
PubMed Link to Article
Drescher  KDRosen  CSBurling  TAFoy  DW Causes of death among male veterans who received residential treatment for PTSD. J Trauma Stress 2003;16 (6) 535- 543
PubMed
Hearst  NNewman  TBHulley  SB Delayed effects of the military draft on mortality: a randomized natural experiment. N Engl J Med 1986;314 (10) 620- 624
PubMed Link to Article
Schnurr  PPSpiro  A  IIIParis  AH Physician-diagnosed medical disorders in relation to PTSD symptoms in older male military veterans. Health Psychol 2000;19 (1) 91- 97
PubMed Link to Article
Zatzick  DFMarmar  CRWeiss  DSBrowner  WSMetzler  TJGolding  JMStewart  ASchlenger  WEWells  KB Posttraumatic stress disorder and functioning and quality of life outcomes in a nationally representative sample of male Vietnam veterans. Am J Psychiatry 1997;154 (12) 1690- 1695
PubMed
Samuelson  KWNeylan  TCMetzler  TJRothlind  JHenn  Haase  CChoucroun  GWeiner  MWMarmar  CR Neuropsychological functioning in posttraumatic stress disorder and alcohol abuse. Neuropsychology 2006;20 (6) 716- 726
PubMed Link to Article
Vasterling  JJProctor  SPAmoroso  PKane  RHeeren  TWhite  RF Neuropsychological outcomes of Army personnel following deployment to the Iraq war. JAMA 2006;296 (5) 519- 529
PubMed Link to Article
Yehuda  RTischler  LGolier  JAGrossman  RBrand  SRKaufman  SHarvey  PD Longitudinal assessment of cognitive performance in Holocaust survivors with and without PTSD. Biol Psychiatry 2006;60 (7) 714- 721
PubMed Link to Article
Yehuda  R Post-traumatic stress disorder. N Engl J Med 2002;346 (2) 108- 114
PubMed Link to Article
Herbert  JGoodyer  IMGrossman  ABHastings  MHde Kloet  ERLightman  SLLupien  SJRoozendaal  BSeckl  JR Do corticosteroids damage the brain? J Neuroendocrinol 2006;18 (6) 393- 411
PubMed Link to Article
Hoge  CW McGurk  DThomas  JLCox  ALEngel  CCCastro  CA Mild traumatic brain injury in US soldiers returning from Iraq. N Engl J Med 2008;358 (5) 453- 463
PubMed Link to Article
Keane  TMKaloupek  DG Comorbid psychiatric disorders in PTSD: implications for research. Ann N Y Acad Sci 1997;82124- 34
PubMed Link to Article
Yaffe  KBlackwell  TGore  RSands  LReus  VBrowner  WS Depressive symptoms and cognitive decline in nondemented elderly women: a prospective study. Arch Gen Psychiatry 1999;56 (5) 425- 430
PubMed Link to Article
World Health Organization International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM).  Geneva, Switzerland: World Health Organization; 1992
United States Department of Veterans Affairs VA vital status files. http://www.virec.research.va.gov/DataSourcesName/VitalStatus/VitalStatus.htm. Accessed December 9, 2008
Bauman  KJGraf  NL Educational Attainment: 2000: US Census 2000 Brief.  Washington, DC: US Census Bureau; 2003: 1-11
Bremner  JDScott  TMDelaney  RCSouthwick  SMMason  JWJohnson  DRInnis  RB McCarthy  GCharney  DS Deficits in short-term memory in posttraumatic stress disorder. Am J Psychiatry 1993;150 (7) 1015- 1019
PubMed
Stern  Y Cognitive reserve and Alzheimer disease. Alzheimer Dis Assoc Disord 2006;20 (3) (suppl 2)S69- S74
PubMed Link to Article
Schuff  NNeylan  TCLenoci  MADu  A-TWeiss  DSMarmar  CRWeiner  MW Decreased hippocampal N-acetylaspartate in the absence of atrophy in posttraumatic stress disorder. Biol Psychiatry 2001;50 (12) 952- 959
PubMed Link to Article
Bremner  JDRandall  PScott  TMBronen  RASeibyl  JPSouthwick  SMDelaney  RC McCarthy  GCharney  DSInnis  RB MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry 1995;152 (7) 973- 981
PubMed
Grundman  MSencakova  DJack  CR  JrPetersen  RCKim  HTSchultz  AWeiner  MFDeCarli  CDeKosky  STvan Dyck  CThomas  RGThal  LJAlzheimer's Disease Cooperative Study, Brain MRI hippocampal volume and prediction of clinical status in a mild cognitive impairment trial. J Mol Neurosci 2002;19 (1-2) 23- 27
PubMed Link to Article
Swaab  DFRaadsheer  FCEndert  EHofman  MAKamphorst  WRavid  R Increased cortisol levels in aging and Alzheimer's disease in postmortem cerebrospinal fluid. J Neuroendocrinol 1994;6 (6) 681- 687
PubMed Link to Article
Sutherland  AGAlexander  DAHutchison  JD Disturbance of pro-inflammatory cytokines in post-traumatic psychopathology. Cytokine 2003;24 (5) 219- 225
PubMed Link to Article
Altemus  MCloitre  MDhabhar  FS Enhanced cellular immune response in women with PTSD related to childhood abuse. Am J Psychiatry 2003;160 (9) 1705- 1707
PubMed Link to Article
Miller  RJSutherland  AGHutchison  JDAlexander  DA C-reactive protein and interleukin 6 receptor in post-traumatic stress disorder: a pilot study. Cytokine 2001;13 (4) 253- 255
PubMed Link to Article
Spitzer  CBarnow  SVölzke  HWallaschofski  HJohn  UFreyberger  HJLöwe  BGrabe  HJ Association of posttraumatic stress disorder with low-grade elevation of C-reactive protein: evidence from the general population. J Psychiatr Res 2010;44 (1) 15- 21
PubMed Link to Article
Yaffe  KLindquist  KPenninx  BWSimonsick  EMPahor  MKritchevsky  SLauner  LKuller  LRubin  SHarris  T Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology 2003;61 (1) 76- 80
PubMed Link to Article
Jendričko  TVidović  AGrubišić-Illić  MRomić  ZKovačić  ZKozarić-Kovačić  D Homocysteine and serum lipids concentration in male war veterans with posttraumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry 2009;33 (1) 134- 140
PubMed Link to Article
Seshadri  SBeiser  ASelhub  JJacques  PFRosenberg  IHD’Agostino  RBWilson  PWFWolf  PA Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 2002;346 (7) 476- 483
PubMed Link to Article
Hamilton  JDWorkman  RH  Jr Persistence of combat-related posttraumatic stress symptoms for 75 years. J Trauma Stress 1998;11 (4) 763- 768
PubMed Link to Article
Johnston  D A series of cases of dementia presenting with PTSD symptoms in World War II combat veterans. J Am Geriatr Soc 2000;48 (1) 70- 72
PubMed
Mittal  DTorres  RAbashidze  AJimerson  N Worsening of post-traumatic stress disorder symptoms with cognitive decline: case series. J Geriatr Psychiatry Neurol 2001;14 (1) 17- 20
PubMed Link to Article
Gilbertson  MWPaulus  LAWilliston  SKGurvits  TVLasko  NBPitman  RKOrr  SP Neurocognitive function in monozygotic twins discordant for combat exposure: relationship to posttraumatic stress disorder. J Abnorm Psychol 2006;115 (3) 484- 495
PubMed Link to Article
Yehuda  RGolier  JAHarvey  PDStavitsky  KKaufman  SGrossman  RATischler  L Relationship between cortisol and age-related memory impairments in Holocaust survivors with PTSD. Psychoneuroendocrinology 2005;30 (7) 678- 687
PubMed Link to Article

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PTSD and dementia in Holocaust survivors
Posted on July 19, 2010
Teresa Biermann, M.D.; Dr. med.
Department of Psychiatry and Psychotherapy, University Hospital of Erlangen, Germany,
Conflict of Interest: None Declared
Yaffe et al.1 reported on the markedly increased risk of dementia from all origins in veterans suffering from posttraumatic stress disorder (PTSD). In this predominantly male and impressively large veteran cohort, those diagnosed with a PTSD were at a nearly 2-fold higher risk of developing dementia compared to those without. Reasons for this finding include poorer performance in cognitive testing as a risk factor, chronic stress damaging the hippocampus, alterations in the hypothalamic-pituitary -adrenal axis and proinflammatory cytokines, some kind of over reporting bias, or an increased non-specific vulnerability to several neuro psychiatric disorders caused by PTSD. A large body of research has been undertaken to prove the association between PTSD and altered brain structures such as decreases in hippocampus volume. In veterans as well as in Holocaust survivors, PTSD is associated with substantial impairments in learning, free and cued recall, and recognition memory compared to respective non-exposed subjects though findings on hippocampus volume loss have been contradictory.2
Within the context of internal research 93 Holocaust survivors suffering from PTSD have been examined who were found to be strongly at risk for late-onset schizophrenia mainly explained by the stress diathesis model 3: All of these patients surviving the Holocaust suffered from PTSD, 70% had an anxiety disorder, and 50.5% had major depression and personality changes following extreme exposure to traumatisation. They were diagnosed with somatic diseases as well: gastrointestinal (47.3%), cardiovascular (17%) and chronic infectious diseases (22.6%). Patients suffered on average from 4.5 (Standard Deviation SD ± 1.8) somatic diagnoses as well as 1.8 (SD ± 0.5) psychiatric diagnoses. In 14% a diagnosis of dementia was ascertained according to ICD-10 criteria. Vascular dementia (66%) dominated in comparison to Alzheimer’s dementia (23%) and other subtypes (11%). The preference for vascular dementia in this group of 93 survivors of the Holocaust with PTSD differs from the results of the exhaustive analysis of veterans with PTSD. Explanations for the phenomena of an increased dementia rate are manifold. It might be speculated that different causes of traumatisation might lead to different subtypes of psychiatric disease. Even if veterans seem to be a relatively homogenous collective of patients having suffered from comparable experiences during a defined time frame, possibly their traumas differ in some way. This difference might account for different explanations of different pathophysiologic explanations for the genesis of dementia or other neurodegenerative diseases.
Yours sincerely, Dr. med. Teresa Biermann Prof. Wolfgang Sperling
References:
1. Yaffe K, Vittinghoff E, Lindquist K, et al. Posttraumatic stress disorder and risk of dementia among US veterans. Arch Gen Psychiatry. Jun;67(6):608-613.
2. Golier JA, Harvey PD, Legge J, Yehuda R. Memory performance in older trauma survivors: implications for the longitudinal course of PTSD. Ann N Y Acad Sci. Jul 2006;1071:54-66.
3. Reulbach U, Bleich S, Biermann T, Pfahlberg A, Sperling W. Late- onset schizophrenia in child survivors of the holocaust. J Nerv Ment Dis. Apr 2007;195(4):315-319.

Conflict of Interest: None declared
Enkephalin may be a contributing factor in developing Alzheimer's disease in PTSD patients
Posted on July 15, 2010
Xing-Xing Sun, M.D.
School of Stomatology, Fourth Military Medical University,
Conflict of Interest: None Declared
In a recent paper, Yaffe et al reported that older veterans who suffered from posttraumatic stress disorder (PTSD) were almost twice as likely to develop Alzheimer's disease and other age-related dementias as veterans without PTSD.(1) How to reduce the increased risk of dementia associated with PTSD would be an important problem for doctors to address. The enkephalin pathway could illustrate the relationship between PTSD and dementias. Reduction of the production of enkephalin in exposure to traumatic stress and enkepahlin signaling may be a new target for curing dementias.(2)
PTSD is a severe anxiety disorder that can be caused by exposure to traumatic stress. Under the traumatic stress, enkephalin can be elevated or the enkephalinergic neurons can be activated in certain brain areas such as hypothalamus and hippocampus in rats.(3) On the other hand, enkephalin is involved in many functions that are affected by Alzheimer's disease and other neurodegenerative diseases. It was found that there are increased levels of preproenkephalin mRNA and enkephalin in brain regions important for memory that are affected in early stages of Alzheimer's disease, and modulating the activity of enkephalin peptides in the brain could relieve the symptoms of Alzheimer's disease in mice.(4) We propose that the enkephalin generated under the traumatic stress may be a contributing factor in the development of Alzheimer’s disease.
The enkephalin pathway may be a tentative point to prevent patients with PTSD from developing Alzheimer’s disease. Neprilysin, which could dissolve generated enkephalin in the central nervous system, was proven to be useful and has been widely used in clinical treatment for reducing the syndrome of Alzheimer’s disease. However, reduction of enkephalin and inhibition of the enkephalin pathway may also be harmful to veterans under traumatic stress (such as in battle, or when wounded), for enkephalin generated in the brain, especially in the hypothalamus and thalamus, seems to be associated with analgesia.(5) Considering this side effect, patients can be given agonists of µ-receptor at the same time to relieve pain, for there is no conclusive evidence that activation of µ- receptor increases the possibility of developing Alzheimer’s disease in patients with PTSD. This letter just provides a tentative point illustrating a relationship between PTSD and Alzheimer’s disease and a possible treatment to slow or stop the process, which requires further studies for proof.
No relevant conflicts of interest.
Xing-Xing Sun, MD* Hao Xu, MD* Ting-Ting Du, MD# Jing Chen, MD, PhD candidate** Sheng-Xi Wu, MD, PhD, professor Li-Xian Xu, MD, PhD, Professor
*Department of Anesthesiology, School of Stomatology **Department of Anatomy and K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an, PR China. #Tongji medical college of huazhong university of science & technology, Wuhan, PR China.
Correspondence: Sheng-Xi Wu MD, PhD, Unit for Evidence-Based Medicine, Department of Anatomy and K. K. Leung Brain Research Centre, Fourth Military Medical University;
Li-Xian Xu, MD, PhD, Department of Anesthesiology, School of Stomatology, Fourth Military Medical University
REFERENCES
1.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.
2.Meilandt WJ, Yu G-Q, Chin J, et al. Enkephalin elevations contribute to neuronal and behavioral impairments in a transgenic mouse model of Alzheimer’s disease. J Neurosci. 2008;28(19):5007-5017.
3.Dumont EC, Kinkead R, Trottier JF, Gosselin I, Drolet G. Effect of chronic psychogenic stress exposure on enkephalin neuronal activity and expression in the rat hypothalamic paraventricular nucleus. J Neurochem. 2000;75(5):2200-11.
4.Meilandt WJ, Yu GQ, Chin J, Roberson ED, Palop JJ, Wu T, Scearce- Levie K, Mucke L.Enkephalin elevations contribute to neuronal and behavioral impairments in a transgenic mouse model of Alzheimer's disease. J Neurosci. 2008;28(19):5007-17.
5. Kurumaji A, Takashima M, Shibuya H. Cold and immobilization stress -induced changes in pain responsiveness and brain Met-enkephalin-like immunoreactivity in the rat. Peptides. 1987;8(2):355-9.

Conflict of Interest: None declared
PTSD and Dementia
Posted on April 15, 2011
Sebastian K. Kreil, MD
University of Erlangen-Nuremberg, Psychiatric Clinic, Schwabachanlage 6, 91054 Erlangen, Germany,
Conflict of Interest: None Declared
Yaffe et al. came to the result that veterans with PTSD had a 7-year cumulative incident dementia rate of 10.6%, whereas those without had a rate of 6.6% (P < .001). In a predominantly male veteran cohort, those diagnosed as having PTSD were at a nearly 2-fold-higher risk of developing dementia compared with those without PTSD. No consistent pattern was seen, other than that PTSD was associated with a higher risk of dementia among all dementia subtypes (Patients with PTSD: Alzheimer hazard ratio 1.71 [confidence interval 95%], Frontotemporal dementia 2.19, Senile dementia 2.03, vascular dementia 1.69, Lewy body dementia 2.05). In another study with Holocoaust survivors with PTSD older age and smaller left hippocampal volume were more strongly associated in the PTSD+ group than in the PTSD- groups (Yehuda et al., 2007). Within the context of internal research, 93 Holocaust survivors suffering from posttraumatic stress disorder have been examined in our own sample. Patients suffered on average from 4.5 (standard deviation 1.8) somatic diagnoses as well as 1.8 (standard deviation 0.5) psychiatric diagnoses. A diagnosis of dementia was ascertained according to ICD-10 criteria in 14%. Vascular dementia (66%) dominated over Alzheimer`s dementia (23%) and other subtypes (11%). Patients with PTSD and dementia in our group showed an increase in hypertension, chronic gastrointestinal, and infectious diseases in comparison with other PTSD-patients (Sperling, Kreil, & Biermann, 2011). In veterans, hypertension was found in 65.3% of PTSD subjects, while chronic gastrointestinal and infectious diseases have not been described (Yaffe et al., 2010). The high rate of vascular dementia in our group in comparison to veterans with similarly increased rates of hypertension might therefore be explained by the interaction of chronic infectious diseases, hypertension, and the atherogenic risk in PTSD victims of the Holocaust (Sperling, et al.,2011). It can be supposed that hyperactivity of the sympathoadrenal axis might contribute to vascular disease through the effects of the catecholamines in this group (Bedi & Arora,2007).
References:
Bedi, U. S., & Arora, R. (2007). Cardiovascular manifestations of posttraumatic stress disorder. J Natl Med Assoc, 99(6), 642-649.
Sperling, W., Kreil, S. K., & Biermann, T. (2011). Posttraumatic stress disorder and dementia in holocaust survivors. J Nerv Ment Dis, 199(3), 196-198.
Yaffe, K., Vittinghoff, E., Lindquist, K., Barnes, D., Covinsky, K. E., Neylan, T., et al.(2010). Posttraumatic stress disorder and risk of dementia among US veterans. Arch Gen Psychiatry, 67(6), 608-613.
Yehuda, R., Golier, J. A., Tischler, L., Harvey, P. D., Newmark, R., Yang, R. K., et al.(2007). Hippocampal volume in aging combat veterans with and without posttraumatic stress disorder: relation to risk and resilience factors. J Psychiatr Res, 41(5), 435-445.

Conflict of Interest: None declared
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