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Current Alzheimer Research, 2013, 10, 907-930 907

Military Risk Factors for Cognitive Decline, Dementia and Alzheimer’s

Disease

Dallas P. Veitcha, Karl E. Friedlb and Michael W. Weinerc,*

a
Center for Imaging of Neurodegenerative Diseases, Veterans Medical Center, San Francisco, CA, USA; bTelemedicine
and Advanced Technology Research Center, US Army Medical Research and Materiel Command, Fort Detrick, MD,
USA; cCenter for Imaging of Neurodegenerative Diseases, Veterans Medical Center and Departments of Radiology,
Medicine, Psychiatry and Neurology, University of California, San Francisco, San Francisco, CA, USA

Abstract: Delayed neurological health consequences of environmental exposures during military service have been gen-
erally underappreciated. The rapidly expanding understanding of Alzheimer’s disease (AD) pathogenesis now makes it
possible to quantitate some of the likely long-term health risks associated with military service. Military risk factors for
AD include both factors elevated in military personnel such as tobacco use, traumatic brain injury (TBI), depression, and
post-traumatic stress disorder (PTSD) and other nonspecific risk factors for AD including, vascular risk factors such as
obesity and obesity-related diseases (e.g., metabolic syndrome), education and physical fitness. The degree of combat ex-
posure, Vietnam era Agent Orange exposure and Gulf War Illness may also influence risk for AD. Using available data on
the association of AD and specific exposures and risk factors, the authors have conservatively estimated 423,000 new
cases of AD in veterans by 2020, including 140,000 excess cases associated with specific military exposures. The cost as-
sociated with these excess cases is approximately $5.8 billion to $7.8 billion. Mitigation of the potential impact of military
exposures on the cognitive function of veterans and management of modifiable risk factors through specifically designed
programs will be instrumental in minimizing the impact of AD in veterans in the future decades.
Keywords: Alzheimer’s disease, armed forces, combat, depression, gulf war illness, post-traumatic stress disorder, risk factors,
traumatic brain injury.

INTRODUCTION
There has been a great deal of attention in recent years
regarding how best to support the health of our active mili-
tary personnel and veterans, especially following their in-
volvement in military conflicts. Many studies have focused
on health issues directly related to military deployment such
as physical injuries (including traumatic brain injury and
limb loss) and mental health problems (including anxiety
disorder, PTSD and depression), and more have examined
issues common to aging veterans, especially those under the
medical care of Veterans Administration facilities. However,
an area that has not been studied is how military service
might affect risk for cognitive decline and dementia. Demen-
tia affects around 14% of Americans over the age of 71 [1].
The most common forms of dementia are AD, which ac-
counts for 60-80% of dementia cases, and vascular dementia
(VaD) which is largely associated with stroke. The preva-
lence of dementia is increasing in the US as the population
ages, and according to the 2010 World Alzheimer report, the
number of AD cases may double in 20 years. This represents
a huge cost to society. Hurd et al. [2] recently calculated that
the total yearly cost of dementia, including both formal and
informal care, was in the range of $41,000 to $56,000 per
person, or a total cost of between $157 billion to $215 billion
in the US.
This review will primarily focus on military risk factors
for cognitive decline and AD, and will note other dementias
where applicable. The biological basis of dementia is in-
creasingly understood and at the same time, risk factors for
cognitive decline and AD have been identified and validated.
In the process, it has become abundantly clear that dementia
risks include a variety of genetic factors, modifiable lifestyle
factors and mental health morbidities [3]. This review aims
to evaluate these risks as they pertain to the military and to
discuss particular issues that may affect dementia risk in
veterans as they age. The risks include effects of combat ex-
posure, Agent Orange exposure in Vietnam veterans, multi-
symptom diseases in Persian Gulf War veterans and traumatic
brain injury in forces deployed to Iraq and Afghanistan. We
report estimated numbers of veterans likely to be affected by
each risk factor by 2020 in the hope of providing a possible
structural framework for medical care resource planning.

*Address correspondence to this author at the Center for Imaging of Neu-
rodegenerative Diseases, Veterans Medical Center and Departments of
Radiology, Medicine, Psychiatry and Neurology, University of California,
San Francisco, San Francisco, CA, USA; Tel: 415-221-4810 x3642; Fax:
415-668-2864; E-mail: michael.weiner@ucsf.edu
Populations Examined
This review focuses on both current military personnel
and veterans of the US military. It is important to note that
many health studies of veterans use populations drawn from
the Department of Veterans Affairs (VA) Health Care sys-

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908 Current Alzheimer Research, 2013, Vol. 10, No. 9
tem that differ substantially from the non-VA user veteran
population [4]. Approximately 8.34 million (37%) veterans
are enrolled in the VA healthcare system based on a congres-
sionally mandated eligibility system which gives priority to
veterans with service-connected injuries or conditions, low
income or net worth, or other circumstances [5]. This results
in demographically and socioeconomically dissimilar popu-
lations [4, 6]; VA users are older, more likely to be in a ra-
cial or ethnic minority [4, 6], less educated, have lower in-
comes, and are less likely to be employed than non-VA vet-
erans [4, 6]. With the exception of being predominantly
male, veterans who are not enrolled in the VA Health Care
system are demographically and socioeconomically more
similar to the general population [4, 6].
Another important distinction between veterans is
whether or not they have experienced combat exposure. This
is a critical distinction as military service alone, military de-
ployment to a combat zone but within protected areas,and
actual combat engagement (“outside the wire”) each signify
very different exposures. The majority of studies of veterans’
health do not even distinguish between the deployed and
non-deployed groups. In this review available data are noted
where applicable and a separate section details the effects of
combat exposure on risk factors for dementia.
Prevalence of Dementia in Veterans
In 2011 veterans numbered over 22 million, or around 7%
of the total US population. Of the population aged 60 years
and over, 22% were veterans, and moreover, nearly 50% of
men in this age group were veterans [7]. In addition, the US-
military comprised 1, 160, 611 enlisted personnel, 226, 023
officers [8] and 470, 000 National Guard [7], a combined total
of around 8% of the total US population. Prevalence estimates
for AD in the general US population range from 11.7% of
those 65 years and older [9] to 14.7% of those 70 years and
older [2]. AD affects an estimated 5.4 million people in the
US, 5.2 million older than 65 [7, 10, 11]. Estimates of the
prevalence of dementia in military or veterans populations
vary. The prevalence of dementia among VA Health System
users over the age of 65 was estimated at 7.3% in 2005, with
AD the predominant form of dementia [12]. An earlier study
reported the prevalence of dementia in veterans using VA
medical care between 1996-2001 to be 4%, 9% and 18% in
age groups 65-74, 75-84 and 85 and older, respectively [13].
During that same time period, the American Association of
Geriatric Psychiatry estimates that 30% of older patients in
veterans’ nursing home facilities have some sort of dementia.
However, recent studies of dementia prevalence in veterans
are lacking and current prevalence may be substantially higher
if this population reflects trends in the general population.
However, to our knowledge, no rigorous comparison has been
made between veterans and non-veterans, no studies have fo-
cused on effects of combat exposures, and very few studies
have examined the relationship between various risk factors
(discussed below) on development of cognitive decline, AD,
and dementia in aging US veterans.
Risk factors
Introduction
A number of risk factors for AD have been identified for
which there are currently substantial bodies of evidence from
Veitch et al.
meta-analyses and systematic reviews. These are summa-
rized in 1) 2011 Alzheimer’s Association Report and 2) Re-
itz et al. [14] and include age, APOE 4 allele status, trau-
matic brain injury (TBI), major depression, post-traumatic
stress disorder, physical inactivity and a variety of vascular
risk factors (smoking, hypertension, type 2 diabetes, body
mass index, coronary artery disease, stroke, hyperhomocys-
teinemia, dyslipidemia, chronic kidney disease and the meta-
bolic syndrome). In April 2010, an NIH State-of-the-Science
statement [15] presented an analysis of current studies of
modifiable AD risk factors and concluded that, due to the
overall low quality of evidence for each factor, “insufficient
evidence exists to draw firm conclusions on the association
of any modifiable factors with the risk of AD”. In the inter-
vening three years further studies have provided support for
various risk factors and, while the caveats of the NIH must
be acknowledged, this review will consider previously re-
ported potential risk factors that appear more prevalent in
veterans than in civilian populations or militarily unique.
The heritability of AD is estimated to be 74% with re-
maining variance attributable to environmental factors [16].
Environmental factors may epigenetically regulate genes
involved in dementia as proposed by the Latent Early Life
Associated Regulation model [17, 18]. While we recognize
the potential role of epigenetics in dementia, particularly in
regard to chemical exposures, there is insufficient data per-
taining to military populations to draw conclusions at this
time.
The following sections will describe the effects of each
risk factor on cognitive decline and/or AD, the mechanisms
by which the risk factor may act and the prevalence or inci-
dence of each risk factor in the civilian and military/veteran
populations. Finally, estimates of the potential numbers of
veterans who may develop AD as a result of each risk factor
will be presented.
Age As a Risk Factor in Military Populations
Age is the greatest risk factor for AD, with the risk of
developing the disease doubling every 5 years after the age
of 65 [19]. The prevalence of AD increases dramatically
over age 75 and reaches a peak in the oldest old with more
than 1 in 3 people over the age of 85 affected [19].
The veteran population is substantially older than the
general population: nearly half (48.8%) of veterans are over
the age of 60 compared to only 18.5% of civilians who have
a median age of 37 [7]. Currently, over 9 million veterans are
aged 65 and older [7] with roughly 2.5 million younger than
70, a further 3.8 million aged between 70 and 80 and 2.9
million over the age of 80. In addition, 3.3 million veterans
who served predominantly in the Vietnam era, are aged be-
tween 60 and 64 with a further 2 million aged between 55
and 60. These demographics suggest that, as the bulk of
Vietnam veterans enter the age at which risk for AD in-
creases dramatically over the next decade, there is a likeli-
hood of a greatly increased burden on the VA Health Care
system with respect to the treatment of AD. In the longer
term, veterans involved in conflicts in the Persian Gulf and
Afghanistan will begin to reach an age of increased risk for
AD in about 20 years (Table 1).
Military Risk Factors for Alzheimer’s Disease Current Alzheimer Research, 2013, Vol. 10, No. 9 909

Table 1. Number of Veterans [in thousands] Living by Period of Service, Age and Sex: 2010

Age Total veterans Wartime veterans Peacetime veterans

Total1 Gulf War2 Vietnam era Korean conflict World War II

Total 22,658 16,866 5,737 7,526 2,448 1,981 5,792

Under 20 years old 8 8 8 _ _ _ _

20 to 24 years old 301 301 301 _ _ _ _

25 to 29 years old 768 768 768 _ _ _ _

30 to 34 years old 887 887 887 _ _ _ _

35 to 39 years old 1,023 996 996 _ _ _ 26

40 to 44 years old 1,461 1,033 1,033 _ _ _ 429

45 to 49 years old 1,790 692 692 _ _ _ 1,098

50 to 54 years old 1,922 648 477 189 _ _ 1,274

55 to 59 years old 2,005 1,589 312 1,415 _ _ 416

60 to 64 years old 3,327 3,208 184 3,153 _ _ 119

65 to 69 years old 2,470 1,944 56 1,935 _ _ 525

70 to 74 years old 1,904 640 16 509 151 _ 1,264

75 to 79 years old 1,877 1,350 4 188 1,270 6 527

80 to 84 years old 1,522 1,431 1 98 891 637 91

85 years & over 1,393 1,370 _ 40 137 1,338 23

Female, total 1,840 1,295 918 251 61 98 545

_ Represents or rounds to zero. 

1
Veterans who served in more than one wartime period are counted only once in the total.
2
Service from August 2, 1990 to the present.
Source: U.S. Department of Veterans Affairs, VA Office of the Actuary, Vetpop 2007, <http://www1.va.gov/vetdata/>

Given the current demographics of the veteran popula-
tion, we can expect approximately 5.8 million veterans to
reach the age of 70 at which there is a substantial risk of AD
by 2020. Assuming a conservative prevalence of 7.3% [12],
this translates to an estimated 423,000 new cases of AD in
the veteran population by the end of the decade.
RISK FACTORS ELEVATED IN MILITARY AND/OR
VETERAN POPULATIONS
Mechanisms of Action of Smoking as a Risk Factor
Smoking may act through myriad mechanisms as it is
itself a risk factor for cardiovascular and cerebrovascular
disease, stroke, inflammation, and increased oxidative stress
leading to neuronal damage, all of which may contribute to
cognitive decline [24, 25]. Smoking may also accelerate re-
ductions in cerebral blood flow, cerebral atrophy and the
formation of white matter lesions [26].

1. Smoking Prevalence of Smoking in Military and Veteran Popula-

Effect of Smoking on Risk of AD
Smoking in late life appears to approximately double the
risk of developing AD. A comprehensive systematic review
by Peters et al. concluded that in cohorts aged 65 and older,
current, but not former smoking increased the risk of AD
[20] and from this analysis, Barnes and Yaffe calculated a
relative risk (RR) for AD among smokers of 1.59 (95% CI:
1.15-2.20) [21]. A more recent systematic review by Lee et
al. [22] reported a RR for AD among smokers of 2.2 (95%
CI: 1.3-3.6). An additional meta-analysis that rejected stud-
ies in which there were tobacco industry affiliations also
estimated a RR in the same range [23].
tions
The military has long been known for its high rates of
smoking although smoking rates have decreased steadily
over the last 30 years [27]. A study of recently discharged
Operation Enduring Freedom (OEF) and Operation Iraqi
Freedom (OIF) veterans with an average age of 35.5 years
found 27% of the cohort to be smokers [28]. A national sur-
vey of adult males in 2000 found that 31.5% of veterans
were current smokers compared to 22.5% of non-veterans
[29] and the prevalence of smoking in veterans remained
higher after corrections for age, race, education and house-
hold income with an adjusted OR of 1.55 reported for veter-
ans compared to non-veterans as current smokers. In a sur-
910 Current Alzheimer Research, 2013, Vol. 10, No. 9
vey of VA service users, 18.5% of those aged 65-74, 19.4%
of those 75-84 and 4.9% of those 85 and older were current
smokers [30]. Similarly, the Behavioral Risk Factor Surveil-
lance System which surveyed over 224,000 veterans from
2003-2007 found that that 26% of veterans born between
1945 and 1954 [31] were current smokers, as were 23% of
respondents in the Veterans Quality of Life study (average
age 64.5) [32]. Finally, in a small sub-cohort of the Veterans
Again Cohort study, 47.1% of VA veterans (average age
50.8) were current smokers [33]. Just as in the civilian popu-
lation, smoking in the military has been associated with ad-
verse health outcomes. In a cohort of over 12,000 military
personnel, it was found that smoking status was a strong and
consistent predictor of mental and physical health, with an
inverse relationship between amount of smoking and level of
health [34] and similar results were obtained in a study of
personnel in the Naval Service [35].
In comparison, in 2010, 19.3% of the US general popula-
tion were current smokers, which included 21.3% of those
aged 18-44, 21% of those aged 65-74 and 5% of those older
than 75 [36]. Although the rate of smoking in veterans is
trending down in tandem with the general population, it re-
mains significantly higher than the general population and
this cannot be fully explained by demographic or socioeco-
nomic factors.
Effect of Smoking in Veterans on Prevalence of Dementia
How many of the approximately 423,000 new cases of
AD in veterans expected by 2020 can be attributed to the
elevated rate of smoking in this population? Barnes and
Yaffe performed similar calculations in their study of modi-
fiable risk factors for AD and used the Population Attribut-
able Risk (PAR) to represent the ‘proportion of people with a
disease in a population than can be attributed to a given risk
factor assuming there is a causal relationship’ [21]. We have
used similar calculations which are outlined in Appendix 1.
Assuming a prevalence of smoking of 25.3% in veterans and
RRs ranging from 1.59 [21] to 2.2 [22], we could expect
approximately between 55,000 and 97,000 new AD cases in
veterans by 2020 attributable to smoking. Furthermore, as-
suming that the prevalence of smoking in veterans is 6%
higher than the general population, then of these new cases,
between 13,000 and 17,000 can be attributed specifically to
the increased prevalence of smoking in the military. Clearly,
cigarette smoking is a significant risk factor for AD in the
military population, elevated significantly beyond use in the
general population. As a modifiable risk factor, the potential
exists to reduce these numbers with a continuation of the US
Military’s Stance Against Tobacco and the intention of the
Department of Defense to eventually go tobacco free.
2. TRAUMATIC BRAIN INJURY
Effect of TBI on Risk of Cognitive Decline, Dementia and
AD
Despite the assessment of the NIH state-of-the-science
statement that ‘good quality studies [of TBI as a risk factor
for AD] are lacking’[15], there is considerable evidence from
epidemiological studies linking chronic and acute TBI to
cognitive decline and the development of dementia clinically
diagnosed as AD (reviewed in [37-43] (Fig. 1). However, at
Veitch et al.
present, it is unknown whether the pathophysiology underly-
ing dementia following TBI resembles that of AD or some
other condition such as chronic traumatic encephalopathy
[44]. The degree of risk of AD development may be propor-
tional to the severity of injury [39, 40, 45]. One study that
used a cohort of World War II and Korea veterans hospital-
ized during service due to non-penetrating head injury or
other conditions (controls) found that those who had suffered
moderate TBI had a more than two-fold risk, and those who
had suffered severe TBI had a four and a half fold risk of
developing AD compared to controls [45]. A systematic re-
view of case control studies supported an association be-
tween a history of head injury and the risk of developing AD
in men and reported an Odds Ratio (OR) of 2.29 (95% CI =
1.47 – 3.58) [46]. TBI has been labeled the signature injury
of OIF and OEF due to the large number of blast injuries
from improvised explosive devices [47-49]. Direct evidence
for their effect on cognition in the military comes from sev-
eral studies. Soldiers who reported active symptomatology a
week post-deployment were significantly more likely to
demonstrate cognitive decline from baseline compared to
either soldiers who sustained non-TBI injuries or soldiers
who suffered a TBI but who had no unresolved symptoms
[50] (Fig. 2). However, a history of self-reported mild TBI
with or without current post-concussive symptoms was not
associated with a decrease in cognitive performance up to 2
years following injury in a similar sized sample of OIF/OEF
service members [51]. Larger studies are required to deter-
mine the exact effect on cognition of mild TBI suffered by
OIF and OEF troops.
Mechanisms of Action of TBI as a Risk Factor
TBI appears to be a provocative event for the develop-
ment of AD [41] as trauma to the central nervous system is
one of the most consistent candidates for initiating molecular
cascades culminating in the development of AD pathology.
AD and acute TBI share many pathological features: -
amyloid (A) deposition, tau phosphorylation, neurite de-
generation, synapse loss and microgliosis [52]. A plaques
and intra-axonal A deposits were found in approximately
one third of TBI subjects who died sometime after the TBI
insult (who did not have preexisting AD, Down syndrome,
or clinical dementia) [53-62]. Both A plaques [52, 63] and
neurofibrillary tangles [64] have been identified in the brains
of patients following a single TBI. Furthermore, increased
levels of A42 and deposition of amyloid plaques have been
observed as early as 2 hours after severe TBI [52]. Repetitive
mild TBI such as that identified in boxers or football or
hockey players [64], is associated with the development of
chronic traumatic encephalopathy (CTE), a progressive
tauopathy and TDP-43 proteinopathy that may also result in
a late-life dementia [65, 66]. CTE is distinguished from AD
by the relative lack of Aß containing neuritic plaques [65]
(Fig. 1). CTE is frequently associated with other neurode-
generative diseases suggesting that mild TBI–induced
tauopathy promotes abnormal aggregation of other dementia
proteins [67]. Recently, an autopsy of a 27 year old Marine
Corps Iraq veteran who had been exposed to close range IED
and mortar blasts and who had subsequently suffered PTSD
found neurofibrillary tangles and neuritic threads typical of
CTE [68]. The authors suggest that PTSD symptoms may in
fact represent a part of a spectrum of diseases related to brain
Military Risk Factors for Alzheimer’s Disease Current Alzheimer Research, 2013, Vol. 10, No. 9 911

Fig. (1). Relationship between traumatic brain injury and cognitive decline and dementia. From [66].

(A) (B)

Fig. (2). Change in neuropsychological assessment at baseline and after reporting a TBI. A) Automated Neuropsychological Assessment
Metrics for controls, and individuals self-reporting TBI with (srTBI+) or without (srTBI-) active symptoms. B) Automated Neuropsychologi-
cal Assessment Metrics for controls, individuals self-reporting TBI with active symptoms (srTBI+) and individuals with active symptoms of
physical injury (non-TBI+). From [50].
912 Current Alzheimer Research, 2013, Vol. 10, No. 9
Traumatic
brain injury
Aberrant
amyloid
precursor
processing due
to axonal injury
Activated
microglia
Higher J-
secretase
Higher risk of
Alzheimer’s and
dementia
Fig. (3). Mechanisms for TBI-related risk of AD and dementia. Adapted from [70].
trauma exposures that include CTE. Recent animal studies
suggest a connection between blast exposure and consequent
tau pathology consistent with CTE [69].
As a result of diffuse axonal injury occurring after TBI
[66], glial activation induces a series of neuroinflammatory
responses including alterations in the expression of a number
of genes (APP, BACE, tau, APOE4,
-synuclein) which are
ultimately involved in formation of AD neuropathology [66,
70]. APOE 4 status may worsen patient outcome after TBI
[71, 72][73-76] and has been associated with the deposition
of A-amyloid after fatal head injury [77]. After acute TBI,
hypoxia upregulates BACE1 gene transcription and expres-
sion, resulting in increased -secretase cleavage of amyloid
precursor protein (APP) and increased deposition of insolu-
ble A production (Fig. 3) [70].
An additional mechanism by which TBI might increase
risk for AD is through the effects of vasospasm. There is an
increased risk of vasospasm following severe head injury
and there may be special risks of vasospasm associated with
TBI following blast exposure in military settings [78-80].
Vasospasm is monitored by transcranial doppler studies in
blast injured soldiers with moderate and severe TBI [80].
Vasospasm has prognostic value in head injury but the sig-
nificance of vasospasm to ischemic damage and other secon-
dary vascular brain injury is still unknown [81].
Incidence of TBI in Military and Veteran Populations
Given the extensive evidence to support the view that
TBI is a risk factor for AD, the degree of susceptibility of the
military population to TBI is of great interest. The incidence
of TBI in the general US population is 0.5%. Each year ap-
proximately 1.7 million people per year suffer some form of
TBI and 255,000 require hospitalization [82]. The prevalence
Veitch et al.
ApoE4
negatively
modulates TBI
outcome relative
of long-term disability associated with TBI in civilians is
estimated to be 1.1% [83]. In contrast, it is estimated that
between 12 and 14% of Vietnam troops suffered TBI [47,
49, 84]. However, whereas in Vietnam mortality from head
wounds was 75% or greater, in recent conflicts mortality has
decreased to 8-25% of blast injuries primarily due to im-
provements in protective equipment such as Kevlar armor
and helmets [48, 49]. Across all military services, 4% of
personnel reported being exposed to a blast accident or suf-
fering a head wound with concomitant memory loss suggest-
ing possible TBI in a 2008 survey [27] (Fig. 4), but the rates
among deployed troops with combat exposure in OIF and
OEF have been reported to be as high as 22% [48, 49, 85].
Two recent studies of service members deployed in the
OIF/OEF conflicts found that around 7% of veterans [86] or
soldiers [50] self-reported or were diagnosed with a TBI
sustained during deployment.
Effect of TBI in Veterans on Prevalence of Dementia
TBI is a major health issue affecting a significant portion
of military and veteran population. The Department of De-
fense reported 266,810 medical diagnoses of TBI from 2000
to February 2013 of which 10.8% were penetrating, severe or
moderate and 82.4% were mild [87]. As abundant evidence
supports TBI as a risk factor for AD, the elevated incidence
of TBI in the military population may increase the incidence
of AD in veterans relative to the general population, espe-
cially as veterans of the Gulf and Afghanistan conflicts age.
Assuming a RR of 2.29 [46] and assuming 12% of Vietnam
veterans were affected by TBI, we can expect approximately
57,000 new cases of AD attributable to TBI in veterans be-
fore 2020. Subtracting the prevalence of TBI in the general
population (1.1%), approximately 51,000-60,000 of these
cases could be attributable to military service (Appendix 1).
Military Risk Factors for Alzheimer’s Disease
100
90
80
70
Percentage
60
50 40
37 36
36
40 31 31
30 21
20
10
0
Never Deployed Deployed But Exposed,But No Exposed, Was
Not Exposed
Army Navy Marine Corps
Fig. (4). Deployment Experience and Possible TBI by Service, 2008. Adapted from [27].
As service members involved in the OIF/OEF conflicts age,
there is an even greater potential for new cases of AD caused
by in-theater TBI injuries.
3. MENTAL HEALTH RISK FACTORS
Most studies of mental health inveterans show a greater
prevalence of mental health disorders than in the general
non-veteran population, even after adjusting for demographic
and socioeconomic factors [32, 88-90]. The most commonly
reported mental health problems in these studies are depres-
sion and PTSD, both common sequelae of traumatic brain
injury (TBI) [91]. Therefore, it is useful to consider this triad
of conditions as both independent and combined risk factors
for cognitive decline and AD.
DEPRESSION
Effect of Depression on Risk of Cognitive Decline, De-
mentia and AD
Depression has been consistently found to be associated
with cognitive decline [15]. Numerous epidemiological stud-
ies have provided support for major depression as a risk fac-
tor for dementia, as recently reported by Byers et al. [92] in a
VA veteran population and reviewed by Enache et al. [93].
A diagnosis of both dysthymia and depression were associ-
ated with the development of dementia with hazard ratios
(HRs) of 1.96 and 2.18, respectively [92]. Early life depres-
sion has been consistently associated with a doubling of the
risk for dementia later in life, and studies also supported the
hypothesis that depression is a prodrome of dementia [92,
93]. Depression in later life also appears to be a risk factor
for dementia. A recent study reported a nearly 4-fold likeli-
hood of developing mild cognitive impairment and a 3-fold
likelihood of developing dementia in oldest-old women with
depressive symptoms [94]. There is a continuous relationship
between the severity of depression and the likelihood of de-
veloping cognitive impairment and, moreover, multiple epi-
sodes of depression increase the risk of developing AD [95].
Current Alzheimer Research, 2013, Vol. 10, No. 9 913
72
58
51 49
39
19
15 13
11 8
5 7 4 5 4
2 1 4 1 0 1 1 1
Exposed, Had
Symptoms Dazed But No Memory Loss
Memory Loss (Possible TBI)
(Possible TBI)
Air Force Coast Guard All Services.
Mechanisms of Action of Depression as a Risk Factor
The relationship between depression and dementia is
complex, as depression is both a risk factor, prodrome and
common complication of dementia at all stages, occurring in
20-30% of all patients [93]. The underlying mechanism by
which depression predisposes an individual to AD is un-
known. The two diseases share common risk factors for vas-
cular disease [95, 96] and are also linked by hypothalamus-
pituitary-adrenal (HPA) axis dysfunction, chronic inflamma-
tion, and a deficit in neurotrophin signaling. These combine
to cause increased neurodegeneration and reduced neuropro-
tection and neuronal repair in both diseases leading to an
enhanced vulnerability of depressed patients to neurodegen-
erative changes later in life [96-99]. Activation of the HPA
axis resulting in the excessive release of glucocorticoids can
damage the hippocampus [93, 96, 100]. The release of proin-
flammatory cytokines such as interleukin-1, interleukin-6
and tumor necrosis factor-
from microglial cells produce
downstream apoptotic signals and accelerate the deposition
of A by upregulating the expression of APP and
- and -
secretase [98, 101, 102]. In both depression and AD, a spe-
cific impairment in the signaling of neurotrophins such as
transforming-growth factor 1 (TGF-1) and brain-derived
neurotrophic factor (BDNF) has been observed [102]. Some
evidence also exists for common genetic elements in depres-
sion and AD and for mechanisms involving neurotransmitter
changes [93].
Prevalence of Depression in Military and Veteran Popu-
lations
Given that an estimated 10-15% of AD cases are attribut-
able to depression [93], it is pertinent to consider the preva-
lence of depression in the US armed forces and veterans. In
the general US population, the 12 month prevalence of a
DSM-IV major depressive disorder has been estimated at
between 5.3% and 6.7% [103-105] with lower prevalence in
men and older people (4.6% in males, versus 8.1% in fe-
males and of 4.5% in those aged over 50). The prevalence of
914 Current Alzheimer Research, 2013, Vol. 10, No. 9
depression in the military is a more complex story. On one
hand, the Department of Defense requires that applicants for
military service are screened at entry for disqualifying men-
tal disorders [106] and this screening is repeated before de-
ployment, thereby ensuring an initial population with a low
prevalence of major depression. On the other hand, post-
deployment depression is a common health problem in vet-
erans and appears to be exacerbated by combat exposure (see
later section). Depression is also a common sequela of TBI
and other injuries and these two factors raise the prevalence
of depression beyond levels in civilian populations. Preva-
lence estimates from different conflicts range from 4.5% to
around 30% [107, 108]. In a 2008 DOD survey, 21% of mili-
tary personnel met screening criteria suggesting that further
evaluation for depression was warranted and this rate was
significantly higher among personnel who had been de-
ployed with combat exposure [27] (Fig. 5). This rate appears
to be elevated beyond that in the general population and may
represent a significant health problem to military personnel.
Furthermore, the prevalence of depression in the veteran
population appears to be significantly higher than those in
active service. One study found that 31% of male veterans
enrolled in the Veterans’ Health Study [88] as outpatients in
VA facilities in the Boston area suffered depression [48,
109]. A recent study by Byers et al. [92] found that in their
cohort of nearly 300,000 veterans aged 55 and older receiv-
ing treatment through the VA health services, 9.8% had de-
pression and a further 0.8% has dysthymia. A survey of VA
Medical Center users from 1999 to 2001 found a similar
prevalence of depression of 12% in veterans with an average
age of 60 [110].
Effect of Depression in Veterans on Prevalence of De-
mentia
Assuming a prevalence of depression of 10% in veterans
and a RR of 2.18, by the end of the decade there could be
around 46,000 new cases of AD attributable to depression,
approximately double the load that would be expected in the
civilian population (Appendix 1). The direct and potentially
devastating effect of combat on depression was starkly illus-
trated by the observation that 30% of Gulf War veterans who
100
80
Percentage
60
40
21 26 25 24 23 19 25
20
0
Army Navy
Never Combat Deployed
Deployed 1+Times Since Sept 11, 2011 (Other than OIF/OEF)
Combat Deployed 1+ Times Since Sept 11,2001 (OIF/OEF)
Fig. (5). Need for further depression evaluation by combat deployment status, theater and service, 2008. OIF = Operation Iraqi Free-
dom; OEF = Operation Enduring Freedom. Adapted from [27].
Veitch et al.
deployed to the Persian Gulf region suffered depression
compared to only 18% of Gulf War personnel who did not
deploy to this conflict [107], implying that 12% of depres-
sion cases observed in those populations were attributable to
combat exposure. Nearly 700,000 troops were deployed dur-
ing Operation Desert Shield and Operation Desert Storm [8],
suggesting that when this population reaches the age of 70 in
10-30 years, an additional 50,000 AD cases might be ex-
pected. Of these, around 6000 could be attributable to com-
bat – induced depression. It is clear that depression among
veterans is of great concern and cognitive assessment of
these patients will be crucial.
POST-TRAUMATIC STRESS DISORDER
Effect of PTSD on Risk of Cognitive Decline, Dementia
and AD
Recent evidence from two studies of older veterans found
an increased risk of developing dementia in veterans with
PTSD compared to those without [111, 112]. After account-
ing for the effects of combat-related trauma, other comorbid-
ities, differences in health care use and sex, both studies
found that PTSD engendered an approximate doubling of
risk for dementia with Yaffe et al. [111] reporting a hazard
ratio of 2.31 (95% CI: 2.24-2.39). Additional evidence for
the association of PTSD with dementia has recently come
from the study of 93 Holocaust survivors suffering from
PTSD [113] of whom 14% were also diagnosed with demen-
tia, predominantly of vascular origin.
Mechanisms of Action of PTSD as a Risk Factor
There are several lines of evidence to suggest how PTSD
might be associated with increased risk for AD. First, PTSD
is associated with cognitive impairments, especially mem-
ory. Therefore, there may be reduced “cognitive reserve” in
PTSD subjects making them more vulnerable to the effects
of AD pathology [114]. Alternatively, PTSD and dementia
share both common risk factors and neuroanatomical
changes and cognitive changes in PTSD may be early mark-
ers of dementia [112]. Neuroanatomical changes in AD typi-
cally initially manifest as atrophy of the hippocampus, the
32 27
25
19 20 23 21
14 13 14 18
Marine Air Force Coast All
Corps Guard Services
Military Risk Factors for Alzheimer’s Disease
20
18
16
16
14
Percentage
12
10
10 9 9
8
6 5
4
2
0
Army Navy
Not Combat Deployed Since Sept 11, 2001
Combat Deployed 1+ Time Since Sept 11, 2001
Fig. (6). PTSD symptoms by combat deployment status and service, 2008. Adapted from [27].
brain structure involved in the consolidation of information
from short-term memory to long-term memory [3]. Patients
with combat-related PTSD have been shown to have smaller
hippocampal volumes by magnetic resonance imaging [115,
116] and ongoing PTSD is associated with greater hippo-
campal atrophy [117, 118] while improvement of symptoms
is associated with less progressive atrophy [117].
Second, PTSD is associated with brain alterations pri-
marily in the hippocampus [117-121]), including reduced
hippocampal N-acetyl aspartate [119-121], a neuronal
marker. Atrophy has also been observed in the anterior cin-
gulate [121], prefrontal structures (reviewed in [122]) and in
the CA3/dentate gyrus subfield [118] of PTSD patients. In
older subjects with PTSD this could represent either evi-
dence of early AD pathology, evidence of damage that could
increase risk for development of AD pathology and/or re-
duced synaptic mass indicating reduced cognitive reserve,
leaving the subject more susceptible to the effects of AD.
Third, PTSD is also associated with other independent
risk factors for dementia and AD including smoking, hyper-
tension, hyperlipidemia, diabetes, obesity and hyperhomo-
cysteinemia (reviewed in [123]). Veterans of OIF and OEF
who were treated at VA medical facilities for PTSD had ad-
justed odds ratios of 2.88 [95% CI 2.79-2.97] and 2.70 [95%
CI 2.63-2.78] of having hypertension or dyslipidemia, re-
spectively, compared to veterans without PTSD [124]. Like-
wise, considerable observational research indicated that
PTSD may result in an increased risk of coronary heart dis-
ease morbidity and mortality [125-127]. PTSD has also been
associated with an increased risk of stroke. For example,
female veterans with PTSD who received care at the VA
Puget Sound Health Care System had an adjusted odds ratio
of 2.9 [95% CI: 1.4-6.0] of stroke compared to those who did
not report PTSD symptomatology [128]. Several studies
examined combat veterans with PTSD and found that MetS
was comorbid with PTSD in 31.9 - 43% of patients [129-
132].
Current Alzheimer Research, 2013, Vol. 10, No. 9 915
15 15
12
11
9
6 6
Marine Air Force Coast All
Corps Guard Services
A PTSD diagnosis with current symptoms was associated
with lower scores in the physical component summary score
in the Millennium Cohort [133]. In particular, PTSD has
been associated in clinical and epidemiologic studies with a
number of other factors that are independent risk factors for
AD [125, 134]. Both obesity and hypertension were also
found to be substantially more prevalent in Persian Gulf war
veterans with PTSD than in veterans with no recent history
of mental illness [107, 135]. PTSD has also been associated
with lower levels of vigorous activity [136], obesity and
smoking [137]. Due to the numerous potential clinical seque-
lae of these conditions and behaviors, veterans with PTSD
are at much higher risk for cardiovascular disease, and there-
fore possibly cognitive decline.
Prevalence of PTSD in Military and Veteran Populations
In the military populations PTSD is but ‘a new name for
an old story’[138]. War has always had severe and lasting
psychological impact on soldiers, and among AD risk fac-
tors, PTSD is an enduring and fundamental wartime risk that
has only relatively recently been defined and acknowledged.
According to the National Center for PTSD, in the gen-
eral US population PTSD has a lifetime prevalence of 6.8%
(3.6% men, 9.7% women). In WWII, 37.5% of the approxi-
mately 800,000 US soldiers exposed to direct combat were
ultimately permanently discharged with serious psychiatric
illnesses. As PTSD became more fully recognized and de-
fined during Vietnam, many subsequent studies of this and
later conflicts have reported on PTSD prevalence in veterans,
reviewed by Richardson et al. [139]. The point prevalence of
combat-related PTSD in US samples ranged from 2-17.1%:
from 2.2-15.2% in Vietnam veterans, from 1.9-13.2% in
Persian Gulf war veterans and from 4-17.1% in veterans of
OIF/OEF. The overall lifetime prevalence of PTSD in US
combat veterans is estimated at 6-31% which translates to a
2-4 fold increase in prevalence compared to US civilians [48,
139].
916 Current Alzheimer Research, 2013, Vol. 10, No. 9
PTSD is often a chronic condition, and while symptoms
abate, they can persist for years or even decades [111]. A 94
year old veteran of WWI was reported to have suffered
PTSD symptoms for 75 years which were exacerbated by the
onset of dementia [140]. As many as 12% of older WWII
and Korean veterans were found to experience PTSD symp-
toms up to 45 years after combat [141]. Between 10% and
15% of Vietnam veterans reported PTSD symptoms 15 years
or more after their return from Vietnam [142]. Two studies
of older veterans (mean age = 62) found the prevalence in
male veterans in the Veterans’ Health Study to be 20% [109]
and 12% at a later date [143]. Symptoms may even increase
with time as reported. In a study of Persian Gulf War veter-
ans, PTSD symptoms increased over 10 years from the 1995
baseline in both deployed and non-deployed personnel [144].
Effect of PTSD in Veterans on Prevalence of Dementia
Taking the prevalence of PTSD in Vietnam veterans to
be 15% and assuming a RR of 2.31, we might expect around
70,000 new cases of AD attributable to PTSD by 2020. Sub-
tracting a baseline prevalence of 4.5%, around 51,000 of
these are likely related to combat exposure (Appendix 1).
These calculations assume a direct causal relationship be-
tween PTSD and AD and as PTSD clearly influences a wide
variety of other independent risk factors for cognitive decline
and dementia, the full impact of PTSD on the development
of dementia in veterans may in fact be underestimated.
Clearly, PTSD remains a major health issue in military and
veteran populations, especially those exposed to combat.
THE EFFECT OF TBI, PTSD AND MAJOR DEPRES-
SION CO-MORBIDITIES ON THE RISK OF COGNI-
TIVE DECLINE
The triad of PTSD, TBI and depression are intercon-
nected in many ways (Fig. 7). There is abundant evidence
that survivors of TBI are more likely to report other neuro-
psychiatric symptoms that those without history of TBI [47,
84] and two of the most common comorbidities are major
depression and PTSD. When the TBI has involved a loss of
consciousness, it is more likely to be comorbid with PTSD
[47, 91, 145, 146]. This is perhaps not surprising considering
that deployment-related TBI is often sustained in the context
of potentially traumatizing events within the war zone. The
prevalence of PTSD in returning OIF/OEF soldiers who re-
ported loss of consciousness was 43.9% compared to 16.2%
in personnel with other injuries and 9.1% in those with no
injuries [47]. In a longitudinal cohort study of National
Guard troops deployed to Iraq, about 30% of mild TBI pa-
tients had PTSD [145]. These studies are in agreement with a
systematic review of the co-occurrence of PTSD and TBI
that reported the frequencies of probable PTSD among
OIF/OEF veterans with probable mild TBI average around
36% [147] and with a study of over 300,000 OEF/OIF veter-
ans using VHA services in 2009 that found PTSD was co-
morbid in 54% of TBI patients [86].
Major depression is also often associated with PTSD [47,
148, 149] and TBI [150, 151]. Depression in TBI patients
appears to be mediated by PTSD [145, 152, 153] and in one
study [154] PTSD affected 37% of patients with comorbid
TBI and depression, and no patients with TBI alone without
Veitch et al.
depression. The central role of PTSD was indicated again by
one study of OIF soldiers which concluded that adverse neu-
ropsychological outcomes a year post-deployment were bet-
ter predicted by PTSD than by depression or TBI [155]. The
Veterans’ Health Study showed that 51% of veterans who
screened positively for depression also met screening criteria
for PTSD and conversely, among veterans testing positive
for PTSD, 82% met screening criteria for depression [109].
Likewise, a study of hospitalized physical trauma survivors
found that 19% had comorbid PTSD and depression at 12
months [156]. Whelan-Robinson et al. [157] assessed rates
of psychiatric illness pre- and post- mild to severe TBI and
found that, of all illnesses examined, the largest increase was
for the major depressive disorder which rose from 17% to
45% of patients (the prevalence of PTSD also rose). Major
depressive disorder was observed in 33% of patients during
the first year after sustaining TBI [150] and a systematic
review found that the prevalence of depression after TBI
found in a range of studies was approximately 30% [154].
Moreover, depressive symptoms following TBI are persis-
tent. World War II veterans who had suffered head injury
had a lifetime prevalence of 18.5% for depression compared
to 13.4% in veterans hospitalized with other injuries and the
lifetime risk of depression increased with severity of head
injury [158].
IndependentADriskfactors
associatedwithdisorder
TBI 
Obesity
30


30% 55
%
Obesity
Hypertension
PTSD
 Hyperlipidemia
Elevatedhomocysteine
Smoking
Physicalinactivity
Coronaryheartdisease
 Stroke
80% 2050%

Obesity
TypeIIdiabetes
Hypertension
Depression Smoking
Physicalinactivity
Coronaryheartdisease
Stroke
Fig. (7). Relationships between the traumatic brain injury –
post-traumatic stress disorder-depression triad and their asso-
ciations with other independent AD risk factors. Numbers repre-
sent the estimated percentage of patients with one disorder who are
comorbid with the second. The development of depression in TBI
patients may be mediated by PTSD (dotted line).
As cognitive impairment associated with TBI [159] is
likely detrimental to the resilience required to overcome
PTSD [160, 161] and as PTSD is pernicious condition that
tends to worsen with time, along with comorbid depression
[160], the health consequences of this triad of conditions in
terms of risk for cognitive impairment and AD are undoubt-
edly a serious concern in military populations.
Military Risk Factors for Alzheimer’s Disease
OTHER MILITARY-SPECIFIC FACTORS THAT
MAY AFFECT RISK FOR DEMENTIA OR AD
Combat Exposure
A history of deployment to a theater of conflict has been
associated with higher proportion of medical and psychiatric
illnesses in active military and veterans populations [48, 162-
165]. One study of Gulf War veterans reported that veterans
who had not been deployed reported excellent health more
often than those who had been deployed (31% versus 21%)
[164]. Veterans have been shown to have poorer general
health than civilian populations, after adjustment for demo-
graphic and socioeconomic factors with the difference
largely attributed to service-connected disabilities (OR for
poor health of 3.5 [95% CI: 2.4-5.2] and for having more
than 5 conditions, 5.6 [95% CI: 4.1-7.7]) [4, 32].
Impact of Combat-related Medical Morbidities on the
Physical Health of Veterans
Physical limitations due to medical morbidities and pain
have been given as a primary reason for post-deployment
changes in exercise habits with 39% of veterans citing health
problems and 52% citing chronic pain as barriers to physical
activity [166]. Similarly, limitation of physical activity by
disability was reported in 45.7% of veterans using VA medi-
cal health services, compared to 24.1% of veterans outside
the VA medical system and 19.1% of civilians in a study of
nearly a quarter million US adults [166]. Furthermore,
around 15% of veterans over the age of 18 have a VA serv-
ice-connected disability rating and around 21% of veterans
have applied for disability compensation benefits [8, 11].
Given the links between physical inactivity and vascular risk
factors such as obesity, heart disease and hypertension, the
impact of combat on the physical health of veterans likely
increases risk of future cognitive decline and dementia.
However, the ramifications of these health issues may not be
fully recognized. According to Buis et al. [28] given the
number of wounded veterans returning from OIF and OEF
suffering often chronic pain, “the lack of lifestyle and behav-
ior-focused preventive programs…is a major gap in the VAs
suite of healthcare programs for veterans”.
IMPACT OF COMBAT-RELATED STRESS ON
MENTAL AND PHYSICAL HEALTH OF VETERANS
An area of concern for the military population is the im-
pact of chronic and acute stress associated with military de-
ployment. After deployment to Iraq, more than 90% of sol-
diers surveyed in one study had experienced being attacked
or ambushed, or receiving incoming artillery, rocket, mortar,
or small arms fire and more than 80% had seen dead or seri-
ously injured compatriots, or had known someone seriously
injured or killed [167]. Exposure to stresses such as these
may be reflected in higher prevalence of mental health prob-
lems such as depression or PTSD [108], may manifest as
maladaptive coping mechanisms such as smoking [48] or
may affect physical health.
Depression
It is well established that combat exposure increases risk
for depression across multiple theaters of conflict including
Current Alzheimer Research, 2013, Vol. 10, No. 9 917
Vietnam [168-170], the Gulf War [171, 172], Bosnia [171],
OIF and OEF [103, 108], both in the US military and forces
elsewhere in world. One recent report stated that around 30%
of Gulf War veterans suffered depression compared to
around 18% of Gulf era personnel. A meta-analysis of 11
studies of troops deployed to the Persian Gulf war reported
an overall odds ratio of depression of 2.04 (95% CI: 1.94-
2.14) compared to troops not deployed to the area [173].
Deployment-related depression appears to persist with Gulf
War veterans reported to have a 12 month prevalence of ma-
jor depression of 15% 10 years post-conflict compared to a
prevalence of 7.8% in Gulf era veterans [174, 107]. More
rigorous studies of the OIF/OEF conflict are now emerging
from the Millennium Cohort Study [175, 176]. In Millen-
nium Cohort troops deployed to Iraq, where an estimated
65% of troops experienced combat exposure, 4.5% of return-
ing soldiers reported new onset depression in a mental health
assessment compared to 2.5% of troops returning from OEF
where the estimated combat exposure was lower (46% of
troops)[108, 177]. Of deployed troops with combat exposure,
5.7% of males and 15.7% of females reported new onset
depression, the most frequently reported mental health out-
come in the Millennium Cohort [48, 103]. This equated to an
adjusted odds ratio 1.32 (95% CI = 1.13-1.54 in men) for
new onset depression following deployment with combat
exposure compared to deployment without combat exposure
[103], and a similar result was reported amongst Canadian
military personnel (adjusted odds ratio 1.32, 95% CI = 1.09-
1.72) [178]. The risk of new depression was elevated further
if soldiers had witnessed atrocities or massacres (adjusted
odds ratio 1.82, 95% CI: 1.33-2.48).
PTSD
Exposure to combat has been shown to be a major risk
factor for PTSD in the military and the degree of combat
exposure has been shown to manifest in the prevalence and
severity of PTSD [179]. A study of twins discordant for
service in Vietnam revealed that 16.8% of twins who had
served had PTSD compared to 5% of twins who had not
served in Vietnam. Moreover, the prevalence of PTSD in
twins exposed to high rates of combat experience was 9
times higher than non-combat siblings [180]. Likewise, the
prevalence of PTSD in Vietnam veterans who were exposed
to high levels of war-zone stress was quadruple that in veter-
ans with low combat exposure [181]. Deployed Persian Gulf
War veterans had a three-fold higher prevalence of PTSD
than non-deployed veterans and this disparity was still evi-
dent 10 years after the baseline assessment [144]. Similarly,
a meta-analysis of studies of PTSD in Gulf War veterans
reported an overall odds ratio of 3.17 (95% CI = 2.16-4.65)
for increased risk of PTSD with combat [173] (Fig. 6). In the
current Iraq and Afghanistan conflicts, new onset PTSD was
identified by self-report questionnaires in 7.6-8.7% of those
deployed reporting combat exposures compared to less than
3.0% in those not deployed or deployed without combat ex-
posure in the Millennium Cohort [176, 182]. A 2008 DOD
survey found that the prevalence of PTSD in all services was
higher in personnel deployed with combat exposure (12%)
than in those without combat exposure (9%) and that the
highest rates were seen in services exposed to the most com-
bat: 16% in the Army and 15% in the Marine Corps [27].
918 Current Alzheimer Research, 2013, Vol. 10, No. 9
The elevated rate of PTSD after deployment with combat
exposure persists for many years [144, 174, 181] and there-
fore increases the risk of cognitive decline and dementia in
affected veterans.
Smoking
Combat stress has been associated with an increase in
tobacco use in the military. Roughly 1 in 7 active duty per-
sonnel started smoking after joining the military, about 30%
of all smokers in this population [27]. Moreover, 28% of
males and 21% of females cited lighting up a cigarette as a
coping behavior for stress and higher rates of smoking were
seen in personnel deployed with combat exposure than those
with no combat exposure across all services [27] (Fig. 10). In
a longitudinal study of Persian Gulf War veterans, 33% of
deployed versus 26% of non-deployed personnel reported
smoking within the last year in 1995 and while these num-
bers dropped over the subsequent decade, veterans with
combat history were still more likely to be smokers (26% of
deployers and 20% of non-deployers) [144]. Studies of the
Millennium Cohort reported that at baseline in 2001—2003,
15.7% of non-deployed troops and 20% of troops deployed
with multiple combat exposures were current smokers [183].
A follow-up study in 2004-2006 reported that the smoking
rate increased during deployment, mainly due to recidivism
of former smokers, and that this increase was greatest in per-
sonnel who had been deployed multiple times [184]. In ac-
cordance with the increase in smoking rates being due to
stress, a further study of the Millennium Cohort found that
46.7% of personnel diagnosed with PTSD were current
smokers compared to 5.8% of cohort members with no
PTSD symptoms [176].
Hypertension
Of particular relevance to military populations is the ef-
fect of combat exposure on hypertension. Studies of Persian
Gulf war and Persian Gulf era veterans found that the inci-
dence of newly reported hypertension roughly doubled in
troops with combat exposure compared to those with no
combat experiences but that this difference was much
smaller after 10 years during which time hypertension had
risen to levels more typical of the average age of the cohort
[144, 185, 186]. A more recent study of the Millennium Co-
hort found newly reported hypertension in 6.9% of troops at
a follow-up evaluation compared to baseline [183]. Interest-
ingly, non-deployed troops generally had a higher prevalence
of hypertension, possibly due to their inferior physical condi-
tion, but the incidence of newly reported hypertension was
greatest in deployed troops who had experienced combat
exposures, especially witnessing death due to war. The long
term effects of combat exposures on hypertension in the Mil-
lennium Cohort are yet to be determined.
Conclusions
Combat exposure clearly can have a major impact on
both the mental and physical health of soldiers and veterans.
The often co-morbid mental health conditions of TBI, major
depression and PTSD with their myriad effects on vascular
health, together with physical injuries that result in chronic
pain and a sedentary lifestyle are common consequences of
Veitch et al.
combat exposure and can increase the risk of cognitive de-
cline and dementia.
AGENT ORANGE EXPOSURE
One area of concern specific to Vietnam veterans is the
long term health effects of exposure to Agent Orange due to
increased risk for diabetes, hypertension, ischemic heart dis-
ease and possibly the metabolic syndrome from 2,3,7,8-
tetrachlorodibenzo-p-dioxin (TCDD).
Type 2 Diabetes
Type 2 diabetes (T2D), a well-established independent
risk factor for dementia and AD [25, 187-191], has been
recognized by the VA as a presumptive disease associated
with exposure to Agent Orange or other herbicides during
military service. Veterans of Operation Ranch Hand, the unit
responsible for aerial herbicide spraying in Vietnam were
found to be at increased risk of glucose abnormalities and
T2D [192]. Among these veterans, the odds ratio of
developing T2D compared to non-Vietnam veterans was
1.50 [95%CI = 1.15-1.95] [193]. An increased frequency of
T2D was also observed in Korean veterans of the Vietnam
war who had an adjusted odds ratio of 2.69 [95% CI= 1.09-
6.67] [194]. Army Chemical Corps veterans who were
occupationally exposed to herbicides in Vietnam had a 79%
excess risk of diabetes mortality compared to veterans who
did not serve in Vietnam [RR 1.70, 95% CI = 0.73-
4.39][195]. TCDD has also been shown to promote an
insulin-resistant state, a precursor to T2D, in exposed
Vietnam veterans [196] and in people who lived near or
worked at manufacturing plants that produced large
quantities of Agent Orange dioxin [197]. The Institute of
Medicine of the National Academy of Sciences concluded in
its report ‘Veterans and Agent Orange: Update 2010’ that
‘mechanisms associated with insulin signaling and glucose
uptake may contribute to the diabetogenic effects of TCDD
observed in humans’. Recent evidence suggests that these
effects may be mediated by its induction of mitochondrial
dysfunction [198, 199].
Hypertension
Epidemiological evidence suggests that exposure to
Agent Orange in Vietnam significantly increased risk of hy-
pertension in veterans, with odds ratios ranging from 1.32 to
2.29 [193, 194]. Animal studies have suggested that TCDD
exerts its effect on hypertension via the production of in-
creased levels of superoxide anions resulting from the induc-
tion of cytochrome CYP1A1 by the aryl hydrocarbon recep-
tor (AHR) [200, 201].
Heart Disease
In October of 2011, the VA recognized ischemic heart
disease as a presumptive disease associated with Agent Or-
ange and other herbicides. Vietnam veterans assigned to
chemical operations jobs had an odds ratio for the develop-
ment of heart disease of 1.52 (95% CI – 1.18-1.94) compared
to non-Vietnam veterans [193] and higher levels of exposure
to Agent Orange were associated with an increased fre-
quency of ischemic heart disease in Korean Vietnam veter-
ans [194]. The link between TCDD exposure and heart dis-
ease had been previously established in studies of workers in
Military Risk Factors for Alzheimer’s Disease
German chemical plants and moreover, the relationship was
shown to be dose-dependent [202, 203]. A meta-analysis of
epidemiological studies investigating the relationship be-
tween TCDD exposure and cardiovascular disease concluded
exposure is strongly associated with ischemic heart disease
[204]. Once again, TCDD appears to exert its affect through
binding of the AHR receptor and subsequent induction of the
CYP1 family of cytochrome P450s resulting in significant
changes to many metabolic pathways and in cardiac gene
expression [205].
Metabolic Syndrome
MetS is a multifactorial disorder comprising a constella-
tion of risk factors for cardiovascular disease and T2D, in-
cluding central obesity, hypertension and high cholesterol
[206-208] and is a recognized risk factor for AD [209]. Rec-
ognition that metabolic syndrome (MetS) can be related to
TCDD exposure has come only recently. A case study of a
veteran exposed to Agent Orange during the Vietnam war
reported that several components of MetS, including hyper-
tension, obesity and abnormal glucose metabolism, were
among the multiple medical problems suffered by the patient
[210]. Several epidemiological studies of populations ex-
posed to dioxins have supported a link with metabolic syn-
drome and reported that exposure and disease are related in a
dose dependent manner [211-213]. Of MetS components,
central obesity, high blood pressure, elevated triglycerides,
and glucose intolerance were most closely associated with
these pollutants [211, 213]. The central component of MetS
is abdominal obesity and TCDD accumulates in the adipose
tissue, most likely acting via the binding of the AHR recep-
tor to modulate metabolic pathways such as those involved
in inflammation that accompanies the pathogenesis of meta-
bolic diseases [214, 198, 199].
GULF WAR ILLNESS AND CHRONIC MULTI-
SYMPTOM ILLNESS
The Persian Gulf War, fought in 1991 to liberate Kuwait
from the control of Iraqi forces, was a short conflict associ-
ated with minimal casualties. In the ensuing years, however,
multiple reports emerged of unexplained disparate health
symptoms in Gulf War veterans, most commonly fatigue,
headache, sleep disturbance, low mood and memory loss.
Cognitive decline has often been reported in studies of Gulf
War veterans, even prior to the recognition of these symp-
toms as a syndrome [171, 215-217]. Many veterans attrib-
uted these symptoms to their service in the Gulf which may
have subjected them to a number of physical exposures
[218]. This eventually led to this group of medically unex-
plained symptoms being grouped together under the term
‘Gulf War Syndrome’ [219]. However, the difficulty in de-
fining this syndrome has led the VA to consider this constel-
lation of symptoms a “medically unexplained chronic multi-
symptom illness” (CMI) and take the stance that this is a
presumptive illness when these symptoms appeared during
active duty to the Gulf. Deployment to the Gulf has been
associated with mental disorders including PTSD and de-
pression that have remained elevated over time [220, 221] as
well as with chronic fatigue syndrome, irritable bowel syn-
drome and multiple chemical sensitivity [217]. A linear dose
response between the severity of the CMI and combat has
Current Alzheimer Research, 2013, Vol. 10, No. 9 919
been reported, but only at mild to moderate levels of stress
[222], suggesting the possibility that this cluster of non-
specific illnesses is partially attributable to combat stress in
addition to exposure to some environmental factor [220, 223,
224]. A magnetic resonance spectroscopy study by Haley et
al. [225] found elevated ratios of N-acetyl aspartate to
creatine in the basal ganglia and pons of soldiers suffering
GWI, indicative of lower neuronal volume. The authors
found lower levels of a paraoxanase involved in organo-
phosphate metabolism in symptomatic individuals suggest-
ing that neuronal mass may be decreased following sarin
exposure. A subsequent more extensive study [224] failed to
find support for these specific brain changes underlying GWI
but observed elevated rates of PTSD in GWI individuals.
Exposure to sarin, however, has been shown to impede neu-
robehavioral functioning [226] in specific domains, and has
been associated with subtle brain volumetric changes [227]
such as reduced total grey matter and hippocampal volumes.
Furthermore, reduced grey matter and white matter volumes
were found in sarin and cyclosarin-exposed individuals with
GWI [228, 229]. Some studies have suggested that no single
factor specific to the Gulf conflict was causative and indi-
cated that deployment exacerbates what appears to be an
identical CMI syndrome that already exists in the general
population [219, 220, 230]. Scientifically, the physical and
mental ill effects of the conflict remain to be explained satis-
factorily.
Regardless of definition or cause, several studies have
demonstrated higher prevalence of both mental and physical
health risk factors for cognitive decline and dementia in vet-
erans who were deployed to combat operations in the Persian
Gulf War and who later reported some form of multi-
symptom illness.
Mental Illness Risk Factors
The association of mental illness with deployment to the
Persian Gulf is well-established, but fewer studies have ex-
amined the relationship between CMI and mental illness in
Gulf War veterans. An early study linked the severity of
CMI with the prevalence of depression in this population,
reporting that 54% of veterans with severe CMI and 13% of
those with mild to moderate CMI suffered comorbid depres-
sion compared to only 2% of veterans who did not report
CMI symptoms [231]. More recently, a study of Australian
male Gulf War veterans reported that 25% suffered CMI,
and of these, 15.0% suffered PTSD compared to only 1.7%
of veterans without CMI, and 22.9% suffered major depres-
sion compared to 4.2% with no CMI. Moreover, personnel
deployed elsewhere who suffered CMI had higher rates of
PTSD and depression than compared to those who did not
suffer CMI [221]. A similar pattern was observed in US
troops and appeared to be persistent as differences were ob-
served a decade after the conflict with a prevalence of PTSD
of 6.1% reported in CMI veterans compared to a prevalence
of 2% in Gulf veterans without CMI [220]. Elevated rates of
PTSD and major depression were also noted in non-deployed
veterans with CMI, suggesting that the phenomenon was not
limited to Persian Gulf deployment. It is a matter of conten-
tion whether combat stress resulting in PTSD is partially
causative of CMI or whether elevated rates of PTSD arise
from the non-specific illness which then, presumably, has an
920 Current Alzheimer Research, 2013, Vol. 10, No. 9
alternative etiogenesis [223, 232]. Whatever the relationship
between mental illness, combat exposure and unexplained
illnesses following the Persian Gulf War, both PTSD and
major depression are elevated in patients suffering from CMI
(from any conflict or even if non-deployed) and therefore
these patients are at higher risk of cognitive decline and de-
mentia.
Vascular Risk Factors
A study of Persian Gulf war veterans a decade after the
conflict found elevated rates of a number of vascular risk
factors for cognitive decline and dementia in veterans with
CMI compared to veterans who did not. The prevalence of
hypertension, metabolic syndrome and nicotine dependence
were 14.1%, 25.1%, and 18.5%, respectively, in deployed
veterans with CMI, and 9.1%, 13.1% and 8.1%, respectively,
in deployed veterans without CMI [220]. Similarly, in com-
parison with Australian Gulf War veterans without CMI,
those who suffered CMI were less likely to be fit to perform
a fitness test (OR 0.48) and more likely to stop the fitness
test prematurely (OR 2.10), indicating a diminished physical
fitness in veterans with CMI [221]. Moreover, the likelihood
of these veterans with CMI of having other vascular risk
factors such as liver disease and components of MetS (obe-
sity and elevated plasma glucose levels) was elevated rela-
tive to veterans asymptomatic for CMI. As with PTSD and
major depression, the prevalence of these vascular risk fac-
tors was also elevated in veterans with CMI who had not
been deployed to the Gulf War, suggesting that CMI in any
veteran may result in an increased risk of cognitive decline
and dementia due to its mental and physical comorbidities.
POST-SERVICE WEIGHT GAIN AND SEDENTARY
LIFESTYLE
Active military personnel are expected to maintain height
and weight standards and certain levels of fitness throughout
their service but enforcement of these standards do not ap-
pear to translate to better cardiovascular health than the aver-
age US citizen in later life in part due to other health issues
such as PTSD, depression or chronic pain from wounds suf-
fered in active service [233, 234]. A recent study of post-
deployment OEF/OIF veterans compared levels of physical
activity during service compared to post-deployment [28].
The number of physical activities per day decreased from
2.08 ± 1.08 during deployment to 1.59 ± 1.20 post-
deployment, and moreover, there was a drop in the intensity
of exercise with the transition to civilian life as the most
popular form of exercise changed from running to walking.
Increasing evidence suggests that the transition from active
duty to veteran status is often accompanied by a ‘burst’ of
weight gain, followed by a gradual convergence with civilian
norms [235]. Obesity at mid-life appears to be the driving
force behind many of the vascular risk factors for AD [236].
Mid-life obesity and sedentary lifestyle have relative risks
for the development of AD of 1.60 [21] to 1.80 [3], and 1.82
[21], respectively. A reported prevalence of physical inactiv-
ity of 14.7% in non-VA veterans and of 20.8% in VA veter-
ans [166] suggests a possible 28,000 and 23,000 new cases
of AD in non-VA and VA veterans, respectively (Appendix
1). The prevalence of obesity in a large sample of veterans at
mid-life was reported to be 29% [237], indicating that there
Veitch et al.
may be between 63,000 and 80,000 new cases attributable to
obesity by 2020 (Appendix 1). If the long term impact of
these risk factors on the cognitive status of veterans is to be
mitigated, even more emphasis will need to be placed on
such educational programs designed to promote weight loss,
healthy eating and exercise such as the VA Managing Over-
weight and Obesity in Veterans Everywhere (MOVE!) Pro-
gram(http://www.move.va.gov/). This is of particular impor-
tance for VA veterans who have been shown to have the
highest utilization of services for chronic conditions of any
healthcare system in the US [238] and who have higher rates
of obesity, T2D and hypertension than non-VA veterans or
the general US population [239].
CONCLUSIONS
With over a quarter of all veterans over the age of 70, and
another quarter over the age of 60 [7], the issue of the
development of dementia in this population in the coming
decades represents a potentially huge challenge in terms of
planning logistics and the allocation of resources to treat the
disease in VA Health Care facilities. Beyond age, the
primary risk factor for dementia [3], it is useful to understand
the relevance of other risk factors for cognitive decline and
dementia to veterans and to assess their potential impact on
this population.
Active military service exposes personnel to certain risk
factors for cognitive decline and AD at levels substantially
elevated beyond what is experienced by the general popula-
tion. Deployment to current and past war zones may result in
exposure to combat, to chemicals such as Agent Orange in
Vietnam, or possibly to neurotoxins in the Persian Gulf War.
Combat exposure has been well-documented to result in ele-
vated levels of PTSD and depression in troops, conditions
that are known to commonly persist for many years, result-
ing in a significantly higher prevalence of these disorders
than in the general population [108]. Both have been
strongly associated with a higher risk for cognitive decline
and dementia [92, 111, 112] and are often co-morbid [47].
Exposure to Agent Orange has been associated with a greater
prevalence of T2D, heart disease, hypertension and MetS
(among many other conditions) which are all independent
vascular risk factors for cognitive decline, and the medically
unspecified chronic multi-symptom illnesses experienced by
veterans of the Persian Gulf War have been linked to both
mental (depression and PTSD) and physical (hypertension,
MetS, nicotine dependence) risk factors [220, 221, 231].
TBI, experienced by a higher percentage of military person-
nel in OIF/OEF than in previous conflicts, is a strong risk
factor for cognitive decline and has symptoms that can per-
sist in the long term [39, 40]. TBI is often comorbid with
PTSD and depression [47, 145] and this triad of conditions
may be especially relevant to resource planning as this gen-
eration of military personnel ages. As a direct consequence
of military service, the additional risk experienced by veter-
ans’ populations for cognitive decline due to the elevated
prevalence of TBI, PTSD, depression and smoking may re-
sult in as many as 140,000 new cases of AD by 2020.
Chronic multisymptom illness developed as a result of serv-
ice, combat exposure, Agent Orange exposure and changes
in weight and activity on discharge from active service may
further contribute to the risk of AD and dementia in veterans.
Military Risk Factors for Alzheimer’s Disease Current Alzheimer Research, 2013, Vol. 10, No. 9 921

Very few studies have looked at prevalence of dementia l. Janssen

in veteran population, especially those veterans outside the
2012
VA healthcare system, and none have attempted to correlate
dementia with health history of veterans. The true prevalence m. Harvard University
of cognitive decline and dementia in veterans remains un- n. KLJ Associates
known, but given the elevated prevalence of risk factors as-
sociated with their military service, there is a strong possibil- III) Funding for Travel
ity that dementia rates will surpass those found in the general 2010:
population as veterans age. Our calculations conservatively
estimate that approximately 423,000 new cases of AD could a. NeuroVigil, Inc.
be expected in veterans by 2020 including 140,000 cases b. CHRU-Hopital Roger Salengro
directly attributable to military service (Appendix 1). The c. Siemens
cost of caring for this latter group may be between $5.8 bil-
lion and $7.9 billion. More studies will be required to deter- d. AstraZeneca
mine the extent of the effect of military service on the preva- e. Geneva University Hospitals
lence of dementia in veterans, and the potential cost to soci-
ety. f. Lilly
g. University of California, San Diego - ADNI
CONFLICTS OF INTEREST AND DISCLOSURES
h. Paris University
Karl E. Friedl is a patent holder on US Patent 7,837,472 i. InstitutCatala de NeurocienciesAplicades
"Neurocognitive and Psychomotor Performance and Reha-
bilitation System. The opinions and assertions in this paper j. University of New Mexico School of Medicine
are those of the authors and do not necessarily represent the k. Ipsen
official views or policy of the U.S. Department of the Army
or Department of Defense. l. CTAD (Clinical Trials on Alzheimer’s Disease)
Michael W. Weiner has the following discolsures: 2011
I) Scientific Advisory Boards a. Pfizer
b. AD PD meeting
2010:
c. Paul Sabatier University
a. Lilly d. Novartis
b. Araclon and InstitutCatala de NeurocienciesAplicades e. Tohoku University
c. Gulf War Veterans Illnesses Advisory Committee, VACO 2012
d. Biogen Idec f. Fundacio ACE
2011 g. Travel eDreams, Inc.
e. Pfizer IV) Editorial Advisory Board
2012 a. Alzheimer’s & Dementia
f. Pfizer b. MRI

II) Consulting V) Honoraria

2010: 2010:
a. NeuroVigil, Inc.
a. Astra Zeneca
b. Araclon b. InsitutCatala de NeurocienciesAplicades
c. Medivation/Pfizer 2011:
d. Ipsen a. PMDA /Japanese Ministry of Health, Labour, and Welfare
e. TauRx Therapeutics LTD b. Tohoku University
f. Bayer Healthcare 2012
g. Biogen Idec a. Alzheimer’s Drug Discovery Foundation
h. Exonhit Therapeutics, SA VI) Commercial Entities Research Support
i. Servier a. Merck
j. Synarc b. Avid
2011 VII) Government Entities Research Support
k. Pfizer a. DOD
922 Current Alzheimer Research, 2013, Vol. 10, No. 9 Veitch et al.

b. VA Gene Network Sciences

VIII) Stock options Genentech
a. Synarc GE Healthcare
b. Elan GlaxoSmithKline
IX) Organizations contributing to the Foundation for NIH Innogenetics
and thus to the NIA funded Alzheimer’s Disease Neuroimag-
ing Initiative. Johnson & Johnson
Abbott Eli Lilly & Company
Alzheimer's Association Medpace
Alzheimer's Drug Discovery Foundation Merck
Anonymous Foundation Novartis
AstraZeneca Pfizer Inc
Bayer Healthcare Roche
BioClinica, Inc. (ADNI 2) Schering Plough
Bristol-Myers Squibb
ACKNOWLEDGEMENTS
Cure Alzheimer's Fund
Declared none.
Eisai
Elan

APPENDIX 1: CALCULATIONS OF PROJECTED POTENTIAL FOR COGNITIVE DECLINE OR DEMENTIA IN

VETERANS DUE TO RISK FACTORS

AD Prevalence in Veterans
For the purposes of calculations, we used a prevalence of AD of 7.3%, reported by Krishnan et al. in a study of VA veterans
aged 65 and over [12].

Expected Number of Cases of AD in Veterans by 2020

In 2010, 3.327 million and 2.470 million veterans were aged 60-64 and 65-70, respectively (Statistical Abstract, 2012).
Therefore by 2020, we can expect approximately 5.797 million veterans to be aged between 70 and 80 and at highest risk for
the development of AD. using 7.3% prevalence, we could expect 423,000 new cases of AD in veterans by 2020.

Population Attributable Risk

The population attributable risk (PAR) represents the proportion of people with a disease in a population that can be attrib-
uted to a given risk factor [21]. This assumes a causal relationship between the risk factor and disease and does not take into
account risk factors that may not be completely independent of each other. PAR is given by the following equation:
PAR = PRF x (RR-1)
1+ PRF x (RR-1)
where PRF = population prevalence of a risk factor
RR = relative risk
PRF was estimated by averaging figures reported in major studies which focused on Vietnam veterans, if possible, as they com-
prise the majority of this population in this age group.

Expected Number of New Cases of AD in Veterans Caused by a Particular Risk Factor by 2020
To estimate the expected number of new cases of AD in veterans caused by each risk factor in the next decade, we multi-
plied the calculated PAR by the estimated number of new AD cases (423,000) by 2020.
Estimates for some risk factors were not made due to lack of published relative risks or other data.
Military Risk Factors for Alzheimer’s Disease Current Alzheimer Research, 2013, Vol. 10, No. 9 923

Risk Factors Elevated in Military and Veteran Populations

AD risk factor Relative Military and Veteran populations General US population Estimated number
risk of AD cases due to
PRF reported in PRFused in PAR Estimated PR PAR Estimated
(RR) increased preva-
literature calculations number of AD number of
lence of risk factor
cases due to risk cases of AD
attributable to
factor by 2020 caused by
military service by
baseline
2020
prevalence
of risk
factor

Smoking 1.59 [21] 31.5% [29] 25.3% 13-23% 55,000-97,000 19% (2012 10- 42,000 – 13,000-55,000
2.2 [22] 26% [31] Statistical 19% 80,000
18.5% [30] Abstract)

Traumatic 2.29 [46] 12% (Defense and 12% 13.5% 57,000 1.1% [83] 1.4% 6000 51,000
Brain Injury Veterans Brain
Injury Center,
Department of
Defense)

Posttraumatic 2.31 [111] 15%[163] 15% 16.5% 70,000 3.6% 4.5% 19,000 51,000
stress disorder 10% [185] (males)
18.7% [142] 16.8% (National
[180] Center for
PTSD)

Depression 2.18 [92] 9.8% [92] 9.8% 11% 46,000 4.6% 5.1% 22,000 24,000
(males)
(National
Institute of
Mental
Health)
Special case: Effect of depression on risk of AD in Gulf War veterans.

Gulf War veterans were reported to have a prevalence of depression 12% higher than Gulf era veterans (30% vs 18%) [107]. According to the
Department of Defense, 697,000 troops were deployed to the Gulf War, of whom approximately 50,000 may develop AD (using 7.3% preva-
lence). Using a RR of 2.18 [92] we calculated a PAR of 12.4% and therefore approximately 6300 new AD cases in this veterans could be
attributable to depression suffered as a consequence of deployment to the Persian Gulf.

Risk Factors Not Elevated in Military Personnel and Veterans

AD risk factor PRF reported in literature PRF Relative risk PAR Estimated number of AD
(RR) cases due to risk factor in
veterans by 2020

Chronic kidney disease 39% [240] 35% 2.0 [243] 25.8% 109,000
34% - Black vets
50% - White vets [241]
16% [242]

Midlife obesity 25.3 [244] 29% 1.60 [21] 14.8% - 63,000 – 80,000
27.7 [239] 1.80 [3] 18.8%
32.9 [245]
29.6 [107]
32 [28]

Hypertension 30.1% [186] 35.3% 1.61 [21] 17.7% 75,000

34.6% [32]
41.2% [88]
924 Current Alzheimer Research, 2013, Vol. 10, No. 9 Veitch et al.

Dyslipidemia 21% (VA Pfizer facts) 32.5% 1.4-3.1 [3] 11.5%-18% 49,000 – 76,000
36.1% [246]
45.1% [33]
35% -obese
31% overweight
26% normal weight[247]

Sedentary VA vets 20.8% [166] 20.8% 1.82 [21] 14.6% 23,000 (of 157,000)
lifestyle (37%)

Non-VA 14.7% [166] 14.7% 10.7% 28,000 (of 266,000)

vets
(63%)

Type 2 VA vets 16% [248] 18.6% 1.39 [21] 6.3% - 9.4% 10,000 – 15,000
Diabetes (37% of 18% [110] 1.60 [250]
all vets) 16.7% [249]

All vets 12% [248] 12% 4.5% - 6.7% 19,000 – 28,000

Stroke 5.8% [33] 5.8% 2.0 [3] * 5.5% 23, 265

Coronary heart disease 11.3% [251] 13% 1.3 [253] 3.8% 16,000
14.6% [33]
16.8% [252]
9.5% [37]
*‘overall doubling of the incidence’.

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