J Head Trauma Rehabil

Vol. 39, No. 2, pp. E48–E58

Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Associations of Prior Head Injury With

Mild Behavioral Impairment Domains
Lisa N. Richey, BA; Nicholas O. Daneshvari, MD; Lisa Young, BS;
Michael J. C. Bray, MD, MS; Rebecca F. Gottesman, MD, PhD; Thomas Mosley, PhD;
Keenan A. Walker, PhD; Matthew E. Peters, MD; Andrea L. C. Schneider, MD, PhD

Objective: This study investigated associations of prior head injury and number of prior head injuries with
mild behavioral impairment (MBI) domains. Setting: The Atherosclerosis Risk in Communities (ARIC) Study.
Participants: A total of 2534 community-dwelling older adults who took part in the ARIC Neurocognitive Study
stage 2 examination were included. Design: This was a prospective cohort study. Head injury was defined using
self-reported and International Classification of Diseases, Ninth Revision (ICD-9) code data. MBI domains were defined
using the Neuropsychiatric Inventory Questionnaire (NPI-Q) via an established algorithm mapping noncognitive
neuropsychiatric symptoms to the 6 domains of decreased motivation, affective dysregulation, impulse dyscontrol,
social inappropriateness, and abnormal perception/thought content. Main Measures: The primary outcome was
the presence of impairment in MBI domains. Results: Participants were a mean age of 76 years, with a median time
from first head injury to NPI-Q administration of 32 years. The age-adjusted prevalence of symptoms in any 1+
MBI domains was significantly higher among individuals with versus without prior head injury (31.3% vs 26.0%, P
= .027). In adjusted models, a history of 2+ head injuries, but not 1 prior head injury, was associated with increased
odds of impairment in affective dysregulation and impulse dyscontrol domains, compared with no history of head
injury (odds ratio [OR] = 1.83, 95% CI = 1.13-2.98, and OR = 1.74, 95% CI = 1.08-2.78, respectively). Prior head
injury was not associated with symptoms in MBI domains of decreased motivation, social inappropriateness, and
abnormal perception/thought content (all P > .05). Conclusion: Prior head injury in older adults was associated
with greater MBI domain symptoms, specifically affective dysregulation and impulse dyscontrol. Our results suggest
that the construct of MBI can be used to systematically examine the noncognitive neuropsychiatric sequelae of
head injury; further studies are needed to examine whether the systematic identification and rapid treatment of
neuropsychiatric symptoms after head injury is associated with improved outcomes. Key words: mild behavioral
impairment, neuropsychiatric symptoms, older adults, traumatic brain injury

Author Affiliations: Department of Psychiatry and Behavioral Sciences,

Johns Hopkins University School of Medicine, Baltimore, Maryland (Mss
Richey and Young, Drs Daneshvari, Bray, and Peters); National Institute
of Neurological Disorders and Stroke Intramural Research Program,
National Institutes of Health, Bethesda, Maryland (Dr Gottesman);
University of Mississippi Medical Center, Jackson, Mississippi (Dr
Mosley); National Institute on Aging, National Institutes of Health,
Baltimore, Maryland (Dr Walker); andDivision of Neurocritical Care,
Department of Neurology, and Department of Biostatistics, Epidemiology,
and Informatics, University of Pennsylvania Perelman School of Medicine,
Philadelphia (Dr Schneider).
The authors thank the staff and participants of the ARIC Study for their
important contributions.
The Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by the NHLBI contracts (HHSN2682017
00001I, HHSN268201700002I, HHSN268201700003I, HHSN26
8201700004I, and HHSN268201700005I). Neurocognitive data are
collected by U01 2U01HL096812, 2U01HL096814, 2U01HL096899,
2U01HL096902, and 2U01HL096917 from the NIH (NHLBI,
NINDS, NIA, and NIDCD). Dr Schneider is supported by grant
K23NS123340 from the NINDS. Dr Gottesman is supported by the
NINDS Intramural Research Program. Dr Walker is supported by the NIA
Intramural Research Program. This research was supported, in part, by the
NIA Intramural Research Program.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions
of this article on the journal’s website (www.headtraumarehab.com).
T RAUMATIC BRAIN INJURY has been associated
with cognitive impairment, cognitive decline,1 and
increased risk of dementia.2,3 However, post-head injury
neuropsychiatric disruption encompasses more than
just cognition and also includes mood and behavioral
symptoms, among others. There has been less research
examining the chronic, noncognitive neuropsychiatric
symptoms after head injury, especially among older
community-dwelling adults.
There have been several smaller studies in older adults
with a history of head injury showing increased preva-
lence of specific neuropsychiatric symptoms, namely,
agitation/aggression, disinhibition, irritability/lability,
anxiety, apathy, and aberrant motor behavior compared
The authors declare no conflicts of interest.
Corresponding Author: Lisa N. Richey, BA, Department of Psychiatry and
Behavioral Sciences, Johns Hopkins University School of Medicine, 5300
Alpha Commons Dr, Room 446, Baltimore, MD 21224 (LNR6@case.edu,
Lrichey2@jh.edu).
DOI: 10.1097/HTR.0000000000000880

E48

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 Head Injury, NPS, and MBI E49

with those without a history of head injury.4,5 Another METHODS

study suggested that a history of head injury is associated
with earlier onset of neuropsychiatric symptoms prior Study design and participants
to the development of dementia.6 In light of this prior
The Atherosclerosis Risk in Communities (ARIC)
work, there is potential utility in adapting a systematic
Study is a community-based prospective cohort of 15
approach to characterizing the noncognitive neuropsy-
792 participants aged 44 to 66 years at study baseline in
chological sequelae of head injury in older adults to
1987 to 1989.15 The study recruited participants from
better understand the neurobehavioral sequelae of head
4 US communities (Washington County, Maryland;
injury.
Forsyth County, North Carolina; selected suburbs of
Following head injury, noncognitive, neuropsy-
Minneapolis, Minnesota; and Jackson, Mississippi). The
chiatric symptoms often do not fully satisfy existing
ARIC Study was approved by the institutional review
criteria for idiopathic psychiatric diagnoses (eg, major
boards of all participating institutions. All participants
depressive disorder as defined by the Diagnostic and
(or legally authorized proxies) gave written informed
Statistical Manual of Mental Disorders).7 Although some
consent at each study visit. Participants were followed at
diagnostic criteria for these diagnoses may be present
subsequent in-person visits (visit 2 [1990-1992, partici-
(eg, depressed mood), the entirety of the syndrome often
pants aged 46-70 years], visit 3 [1993-1995, participants
is not. The mild behavioral impairment (MBI) construct
aged 49-73 years], and visit 4 [1996-1998, participants
was developed by the International Society to Advance
aged 52-75 years]) and annually by telephone. The ARIC
Alzheimer’s Research and Treatment (ISTAART) and is
Neurocognitive Study (ARIC-NCS) began at in-person
officially defined as persistent neuropsychiatric symp-
ARIC visit 5 (2011-2013, participants aged 66-90 years),
toms emerging later in life (that are not better explained
which is the focus of the present analyses because that
by a common psychiatric disorder), which predate a
is when neuropsychiatric symptoms were assessed in
dementia diagnosis.8 In this context, MBI serves as a
a subset of participants who attended the ARIC-NCS
behavioral analog to supplement the more widely used
stage 2 examination. A subset of ARIC visit 5 partic-
concept of mild cognitive impairment. In contrast to
ipants meeting at least one of the following selection
diagnostic, criteria-based syndromes, the MBI construct
criteria attended the ARIC-NCS stage 2 examination:
links individual noncognitive, neuropsychiatric
(1) participants with evidence of cognitive impairment
symptoms into “domains” felt to signify underlying
or dementia, (2) individuals who previously participated
neural circuit disruption: decreased motivation,
in the 2004-2006 ARIC Brain MRI study,16 and/or (3)
affective dysregulation, impulse dyscontrol, social
age-stratified (<80 years and ≥80 years) random sample
inappropriateness, and abnormal perception/thought
of cognitively normal participants.
content.9,10 We hypothesize this domain-based
Of the 6538 participants who attended ARIC visit 5,
approach may also have utility when looking at
3000 completed the ARIC-NCS stage 2 examination.
noncognitive, neuropsychiatric symptoms following
We further excluded 21 participants of non-White and
head injury regardless of cognitive status. Indeed, there
non-Black race or of Black race at the Minnesota or
is evidence that the presence of behavioral neuropsy-
Maryland field centers in accordance with ARIC Study
chiatric symptoms after head injury is associated with
analysis recommendations due to race/field center alias-
worse rehabilitation and long-term outcomes.11,12 Being
ing (whereby mostly White participants were recruited
able to systematically identify and swiftly treat head
in Minnesota/Maryland, only Black participants were
injury-related behavioral symptoms has the potential
recruited in Mississippi, and mostly White and Black
to contribute to improved rehabilitation and long-term
participants were recruited in North Carolina), 332 par-
outcomes.
ticipants who were missing Neuropsychiatric Inventory
In this study, we utilized MBI domains to system-
Questionnaire (NPI-Q) data, and 113 who were missing
atically examine associations of head injury with later
data on covariates included in statistical models, leaving
noncognitive neuropsychiatric symptoms in a large
2534 participants included in the present analysis (see
population-based sample of older adults. Specifically,
Figure 1).
we aimed to investigate associations of prior head injury
(including number of prior head injuries) with MBI do-
Head injury
mains. We hypothesized that prior head injury would be
associated with impairment in all of the MBI domains, Head injury was defined using a combination of self-
with stronger associations seen with increasing number reported data (from visits 3, 4, 5, and the brain MRI
of prior head injuries. We additionally hypothesized that visit) and International Classification of Diseases, Ninth Re-
associations would be stronger among older (vs younger) vision (ICD-9) code data from hospitalizations (ARIC
individuals and among women compared with among hospitalization surveillance; Centers for Medicare &
men.13,14 Medicaid Services fee-for-service data hospitalization
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E50 Journal of Head Trauma Rehabilitation/MARCH–APRIL 2024
Figure 1. Study flow diagram and application of inclusion/
exclusion criteria. ∗ Stage 2 visit selection criteria: (1) all partici-
pants with evidence of cognitive impairment, (2) age-stratified
(<80 and ≥80 years) random sample of cognitively normal
participants, and (3) all participants who participated in the
2004-2006 ARIC Brain MRI study.
and emergency department visits) (see Supplemental
Digital Content eTable 1, available at: http://links.lww.
com/JHTR/A694). ICD-9 codes for head injury were
defined according to the Centers for Disease Control
and Prevention (CDC) traumatic brain injury surveil-
lance definition.17,18 The definition of head injury in
this study encompasses injury that resulted in physi-
cian or hospital/emergency department care and/or was
associated with loss of consciousness. In addition to
dichotomous yes/no head injury occurring before ARIC
visit 5, we categorized head injury by the number of
prior head injuries occurring by the time of ARIC visit
5 (0; 1; 2+).
Neuropsychiatric inventory and mild behavioral
impairment domains
Noncognitive neuropsychiatric symptoms were
assessed using the NPI-Q administered by a trained
staff member at each field site. This instrument asks
an informant about the presence and severity of
12 symptoms (delusions, hallucinations, agitation/
Copyright © 2024 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
aggression, depression/dysphoria, anxiety,
elation/euphoria, apathy/indifference, disinhibition,
irritability/lability, motor disturbance, nighttime
behaviors, and appetite/eating).19 The Mild Behavioral
Impairment Checklist (MBI-C) is a rating scale
for the 5 domains of MBI (decreased motivation,
affective dysregulation, impulse dyscontrol, social
inappropriateness, and abnormal perception or thought
content) operationalized by the ISTAART-AA as
research diagnostic criteria.8,9 Because the MBI-C is a
relatively new scale and the NPI-Q is widely used, the
authors of the MBI-C have developed a standardized,
published algorithm, which approximates MBI status
through a transformation of NPI-Q items to MBI
domains (see Table 1).20 For our analyses, we created
binary variables for yes versus no impairment in each of
the 5 MBI domains separately (defined as the presence
of any 1+ NPI-Q symptoms mapping to each MBI
domain) and also created a binary variable for yes versus
no impairment in any one or more MBI domains. In
sensitivity analyses, we also looked at associations of
prior head injury with each of the 12 neuropsychiatric
symptoms separately.
Covariates
All covariates included in statistical models were
identified a priori from the literature as potential
confounders of the association between head injury and
neuropsychiatric symptoms. Covariates included age
(years; continuous), sex (male; female), race/field center
(Minnesota Whites, Maryland Whites, North Carolina
Whites, North Carolina Blacks, and Mississippi
Blacks), education (less than high school, high
school/GED/vocational school, and college/graduate
school/professional school), alcohol consumption
(never, former, current, and not reported), smoking
(never, former, current, and not reported), military
veteran (yes, no), apolipoprotein (APOE) ɛ4 genotype
(0 ɛ4 alleles, 1 or 2 ɛ4 alleles), and cognitive status
(normal, mild cognitive impairment, and dementia).16
Statistical analysis
Since participants who took part in the ARIC-NCS
stage 2 examination were selected based on age and
cognitive status, we incorporated sampling weights in all
analyses so that all results presented herein are represen-
tative of the entire ARIC visit 5 population. Weighted
baseline characteristics are presented overall and strat-
ified by head injury status (yes vs no history of head
injury and by number of prior head injuries). Differences
in participant characteristics between head injury groups
and between individuals included versus excluded from
our analytic population were assessed using t tests or
 Head Injury, NPS, and MBI E51

analyses of variance (for continuous variables) and χ 2

thought content
tests (for categorical variables).

perception or

hallucinations
Abnormal
We calculated weighted age-adjusted prevalence and
(95% CI for impairment in each MBI domain by head

Delusions
injury status. We used weighted logistic regression to
estimate the adjusted odds ratios (ORs) and 95% CIs
for the associations between head injury status and MBI
domain impairment. Statistical models were adjusted for
Definition of mild behavioral impairment domains using neuropsychiatric inventory symptoms

age, sex, race center, education, alcohol consumption,

smoking, military veteran status, APOE ɛ4 genotype,
and cognitive status. We formally evaluated for mul-
inappropriateness

tiplicative interaction by age (at the time of NPI-Q

administration) and sex. In sensitivity analyses, we re-
Social

peated analyses of associations between head injury and

Disinhibition

MBI domain impairment, excluding individuals with a

not include the Neuropsychiatric Inventory Questionnaire domains of motor disturbance, nighttime behaviors, and appetite/eating.

diagnosis of dementia (in accordance with the standard

Mild behavioral impairment domainsa

ISTAART-AA use of MBI domains among individuals

without dementia). We also separately considered asso-
ciations of self-reported and ICD code-diagnosed head
injury with MBI domain impairment and among the
subset of head injuries defined by ICD-9 codes, we
Impulse dyscontrol

evaluated the association of head injury severity (defined

Agitation/aggression

according to Department of Defense criteria21,22 ) with

Irritability/lability
Aberrant motor

MBI domain impairment. Given the nonspecificity of

ICD-9 code 959.01 (“head injury, unspecified”), we ad-
behavior

ditionally performed a sensitivity analysis excluding this

ICD code from our head injury definition (n = 67 head
injuries were identified by 959.01 alone). In secondary
analyses, we used weighted logistic regression to estimate
the adjusted ORs (95% CIs) for the associations between
head injury status and each neuropsychiatric symptom
separately.
dysregulation

Elation/euphoria

Stata SE version 17 (College Station, Texas) for Mac-

Affective

Depression/
dysphoria

intosh was used for all analyses. The threshold for

statistical significance for all tests was set a priori as a
Anxiety

2-sided α = .05.

RESULTS
Participant characteristics are shown in Table 2. Over-
indifference
motivation
Decreased

all, participants were a mean age of 75.8 years, 58.9%

were women, 22.1% were of Black race, and 31.8% had
Apathy/

a history of head injury. Compared with individuals

with no history of head injury, participants with head
injury were more likely to be men (49.6% vs 37.2%,
P < .001), of White race (83.1% vs 75.4%, P = .002),
current consumers of alcohol (54.1% vs 46.8%, P <
.001), current or former smokers (68.3% vs 85.6%, P
< .001), be a military veteran (33.5% vs 19.8%, P <
Neuropsychiatric

.001), and were less likely to have 1 or 2 APOE ɛ4 alleles

symptoms

(24.8% vs 30.9%, P = .014). Similar patterns were seen

inventory
TABLE 1

when characteristics were shown by number of prior

head injuries. Compared with individuals excluded to
a Does

the analytic population, those included were of similar

age and sex and had a similar prevalence of head injury
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 TABLE 2 Weighted participant characteristics (ARIC visit 5, 2011-2013) E52

No history of History of No history of 1 prior head 2+ prior head

head injury head injury head injury injury injuries
(unweighted (unweighted (unweighted (unweighted (unweighted
n = 1717) n = 817a ) P value n = 1717) n = 632) n = 185) P value
Age, mean (SE), y 75.7 (0.2) 76.1 (0.2) .10 75.7 (0.2) 76.0 (0.2) 76.4 (0.4) .21
Female (SE), % 62.8 (1.5) 50.4 (2.3) <.001 62.8 (1.5) 50.2 (2.6) 51.1 (4.7) <.001
Race/center (SE), % .002 .002
Minnesota Whites 29.6 (1.4) 35.2 (2.2) 29.6 (1.4) 37.8 (2.5) 26.3 (4.2)
Maryland Whites 28.5 (1.3) 25.6 (1.7) 28.5 (1.3) 23.9 (1.9) 31.8 (4.0)
North Carolina Whites 17.2 (1.2) 22.3 (2.0) 17.2 (1.2) 20.6 (2.2) 28.0 (4.5)
North Carolina Blacks 1.4 (0.4) 1.6 (0.7) 1.4 (0.4) 1.4 (0.7) 2.2 (1.7)
Mississippi Blacks 23.2 (1.5) 15.3 (1.7) 23.2 (1.5) 16.4 (2.0) 11.6 (3.3)
Education (SE), % .22 .47
Less than high school 14.6 (1.1) 13.5 (1.5) 14.6 (1.1) 14.0 (1.8) 11.8 (3.0)
High school, GED, or vocational school 42.1 (1.5) 38.6 (2.2) 42.1 (1.5) 38.7 (2.5) 37.9 (4.5)
At least some college 43.3 (1.6) 48.0 (2.3) 43.3 (1.6) 47.3 (2.6) 50.3 (4.7)
Alcohol consumption (SE), % <.001 .006
Never 22.1 (1.3) 13.8 (1.4) 22.1 (1.3) 13.3 (1.6) 15.4 (3.7)
Former 26.2 (1.4) 25.9 (1.9) 26.2 (1.4) 27.1 (2.3) 21.9 (3.6)
Current 46.8 (1.6) 54.1 (2.2) 46.8 (1.6) 53.4 (2.6) 56.4 (4.6)
Not reported 5.0 (0.7) 6.2 (1.0) 5.0 (0.7) 6.1 (1.2) 6.3 (2.1)
Smoking (SE), % <.001 .003
Never 41.4 (1.5) 31.7 (2.1) 41.4 (1.5) 31.0 (2.4) 34.2 (4.5)
Former 44.2 (1.6) 55.6 (2.2) 44.2 (1.6) 56.0 (2.6) 54.3 (4.7)
Current 5.1 (0.7) 3.7 (0.9) 5.1 (0.7) 3.3 (1.0) 5.2 (2.3)
Not reported 9.3 (1.0) 9.0 (1.3) 9.3 (1.0) 9.7 (1.5) 6.3 (2.1)
Military veteran (SE), % 19.8 (1.1) 33.5 (2.1) <.001 19.8 (1.1) 33.0 (2.4) 35.4 (4.6) <.001
APOE ɛ4 genotype (SE), % .01 .04
0 ɛ4 alleles 69.1 (1.5) 75.2 (1.9) 69.1 (1.5) 75.9 (2.1) 72.7 (4.1)
Journal of Head Trauma Rehabilitation/MARCH–APRIL 2024

1 or 2 ɛ4 alleles 30.9 (1.5) 24.8 (1.9) 30.9 (1.5) 24.1 (2.1) 27.3 (4.1)
Cognitive status (SE), % .08 .03
Normal 72.2 (1.2) 69.0 (1.8) 72.2 (1.2) 68.1 (2.0) 71.8 (3.6)
Mild cognitive impairment 22.4 (1.1) 23.5 (1.5) 22.4 (1.1) 25.1 (1.8) 17.9 (2.5)
Dementia 5.4 (0.5) 7.6 (0.9) 5.4 (0.5) 6.8 (1.0) 10.3 (2.6)
Impairment in mild behavioral impairment
(MBI) domain (SE), %
Decreased motivation 5.4 (0.6) 7.4 (1.1) .10 5.4 (0.6) 6.7 (1.2) 9.8 (2.7) .12
Affective dysregulation 14.7 (1.0) 17.9 (1.6) .07 14.7 (1.0) 15.5 (1.7) 26.3 (4.1) .003
Impulse dyscontrol 16.6 (1.1) 20.9 (1.8) .03 16.6 (1.1) 18.4 (1.9) 29.7 (4.3) .002
Social inappropriateness 3.3 (0.5) 5.7 (0.9) .02 3.3 (0.5) 5.5 (1.1) 6.4 (2.0) .04
Abnormal perception or thought content 2.3 (0.3) 3.9 (0.7) .02 2.3 (0.3) 3.9 (0.8) 3.8 (1.1) .04
Impairment in 1+ MBI domains 25.9 (1.3) 31.5 (2.0) .02 25.9 (1.3) 28.9 (2.2) 40.3 (4.6) .004

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Abbreviations: APOE, apolipoprotein; SE, standard error.
a Only self-reported head injury (n = 584), only head injury identified by ICD-9 codes (n = 223), both self-reported head injury and head injury identified by ICD-9 codes (n = 10).

but were less likely to have mild cognitive impairment or
dementia (see Supplemental Digital Content eTable 2,
available at: http://links.lww.com/JHTR/A695).
The median time from first head injury to ad-
ministration of the NPI-Q for participants with prior
head injury was 31.5 years (25th percentile: 12.1 years,
75th percentile: 59.4 years). Age-adjusted prevalence of
impairment in MBI domains by head injury status is dis-
played in Figure 2. Compared with no head injury, prior
head injury was associated with greater age-adjusted
prevalence of impairment in impulse dyscontrol (20.8%
vs 16.7%, P = .044), social inappropriateness (5.6% vs
3.4%, P = .026), and abnormal perception or thought
content (3.7% vs 2.3%, P = .029) domains. The age-
adjusted prevalence of impairment in any one or more
MBI domains was higher among individuals with versus
without prior head injury (31.3% vs 26.0%, P = .027).
Compared with no head injury, a history of 1 head
injury was associated with greater age-adjusted preva-
lence of impairment in the abnormal perception or
thought content domain (3.8% vs 2.3%, P = .044), and
a history of 2+ prior head injuries was associated with
greater age-adjusted prevalence of impairment in the
affective dysregulation (25.9% vs 14.7%, P = .002) and
impulse dyscontrol (29.4% vs 16.7%, P = .001) domains.
The age-adjusted prevalence of impairment in any one
or more MBI domains was higher among individuals
with 2+ prior head injuries compared with individuals
without prior head injury (39.8% vs 26.0%, P = .002).
In fully adjusted models, a history of 2+ head injuries,
but not 1 prior head injury, was associated with increased
odds of impairment in the affective dysregulation and
impulse dyscontrol domains, compared with no history
of head injury (OR = 1.83, 95% CI = 1.13-2.98 for
the affective dysregulation domain, and OR = 1.74,
95% CI = 1.08-2.78 for the impulse dyscontrol domain)
(see Table 3). We observed evidence for interaction by
age and sex in associations of head injury status with
impairment in the impulse dyscontrol domain where
associations were stronger among younger (median age
of less than 77 years, OR = 1.30, 95% CI = 0.84-2.00)
compared with older individuals (≥77 years, OR = 0.91,
95% CI = 0.64-1.28) (P-interaction-by-age = .021) and
were stronger among women (OR = 1.59, 95% CI =
1.05-2.40) compared with men (OR = 0.82, 95% CI =
0.56-1.19) (P-interaction-by-sex = .011). Similar patterns
by age and sex were observed for the association of
number of prior head injuries with impairment in the
impulse dyscontrol domain (P-interaction-by-age = .018
and P-interaction-by-sex = .024). We also found evi-
dence for stronger associations of 2+ head injuries with
impairment in any 1+ MBI domain among younger
(<77 years, OR = 2.29, 95% CI = 1.16-4.53) compared
with older individuals (≥77 years, OR = 0.97, 95% CI
Copyright © 2024 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Head Injury, NPS, and MBI E53
= 0.69-1.32) (P-interaction-by-age = .035). Associations
of head injury with impairment in any 1+ MBI domain
were also stronger among women (OR = 1.48, 95% CI
= 1.04-2.09) compared with men (OR = 0.85, 95% CI =
0.60-1.21) (P-interaction-by-sex = .023). Similar patterns
by sex were observed for the association of number of
prior head injuries with impairment in any 1+ MBI
domain (P-interaction-by-sex = .048).
In sensitivity analyses, excluding 264 individuals with
a dementia diagnosis, associations between head in-
jury and impairment in MBI domains were similar,
but slightly stronger compared with our main analysis,
with a history of 2+ head injuries being significantly
associated with greater odds of impairment in the
decreased motivation, affective dysregulation, impulse
dyscontrol, and in any 1+ MBI domains compared
with no head injury (see Supplemental Digital Con-
tent eTable 3, available at: http://links.lww.com/JHTR/
A696). Associations of self-reported head injury and
of ICD code-defined head injury with impairment in
MBI domains were similar to our main analysis, but
self-reported head injury was significantly associated
with abnormal perception or thought content (OR
= 2.07, 95% CI = 1.13-3.81) and ICD code-defined
head injury was significantly associated with social in-
appropriateness (OR = 2.13, 95% CI = 1.18-3.85) (see
Supplemental Digital Content eTable 4, available at:
http://links.lww.com/JHTR/A697). Among the subset
with ICD code-identified head injury, mild head injury
was also associated with social inappropriateness, but
associations of moderate/severe head injury with im-
pairment in MBI domains were limited by low power
(unweighted n = 37 with moderate/severe head injury)
(see Supplemental Digital Content eTable 5, available at:
http://links.lww.com/JHTR/A698). In sensitivity analy-
ses excluding head injury cases identified by the ICD-9
code 959.01 alone (unweighted n = 67), associations of
head injury and head injury number with impairment
in MBI domains were similar to our main analysis (see
Supplemental Digital Content eTable 6, available at:
http://links.lww.com/JHTR/A699).
In secondary analyses evaluating the associations be-
tween head injury status and each neuropsychiatric
symptom individually (see Supplemental Digital Con-
tent eTable 7, available at: http://links.lww.com/JHTR/
A700), head injury, compared with no head injury, was
not significantly associated with any individual neu-
ropsychiatric symptom (all P > .05 in fully adjusted
models). Compared with no prior head injuries, a his-
tory of 2+ prior head injuries was associated with
2.23 times (95% CI = 1.33-3.75) increased odds of
depression/dysphoria and with 1.77 times (95% CI =
1.04-3.00) increased odds of irritability/lability in fully
adjusted models.
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E54 Journal of Head Trauma Rehabilitation/MARCH–APRIL 2024

Figure 2. Weighted age-adjusted prevalence (95% CI) of mild behavioral impairment domains and impairment in 1 or more
domains by prior head injury and number of prior head injuries. ∗ P < .05 compared with no history of head injury group.

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 TABLE 3 Weighted adjusteda odds ratios (95% CI) for the association of prior head injury and number of prior head
injuries with mild behavioral impairment domains
No history of head History of head No history of head 1 prior head injury 2+ prior head
injury (unweighted injury (unweighted injury (unweighted (unweighted injuries (unweighted
n = 1717) n = 817) n = 1717) n = 632) n = 185)
OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI)
Decreased motivation 1 (reference) 1.21 (0.79-1.85) 1 (reference) 1.10 (0.70-1.73) 1.58 (0.72-3.44)
Affective dysregulation 1 (reference) 1.17 (0.88-1.57) 1 (reference) 1.00 (0.73-1.36) 1.83 (1.13-2.98)
Impulse dyscontrolb 1 (reference) 1.13 (0.85-1.51) 1 (reference) 0.97 (0.70-1.34) 1.74 (1.08-2.78)
Social inappropriateness 1 (reference) 1.58 (1.00-2.49) 1 (reference) 1.55 (0.96-2.52) 1.66 (0.75-3.67)
Abnormal perception or thought 1 (reference) 1.59 (0.95-2.65) 1 (reference) 1.64 (0.92-2.93) 1.41 (0.70-2.88)
content
Impairment in 1+ MBI domainsb 1 (Reference) 1.12 (0.88-1.45) 1 (reference) 1.01 (0.77-1.34) 1.56 (0.99-2.45)

Abbreviations: MBI, mild behavioral impairment; OR, odds ratio.

a Model adjusted for age, sex, race center, education, alcohol consumption, smoking, military veteran status, APOE ɛ4 genotype, and cognitive status.
b P value for interaction by age was .021 for the association of prior head injury with impulse dyscontrol domain impairment and was .018 for the association of number of prior head injuries

with impulse dyscontrol domain impairment. P value for interaction by age for the association of number of prior head injuries with impairment in 1+ MBI domains was .035. P value
for interaction by sex was .011 for the association of prior head injury with impulse dyscontrol domain impairment and was .024 for the association of number of prior head injuries with
impulse dyscontrol domain impairment. P value for interaction by sex for the association of head injury with impairment in 1+ MBI domains was .023 and P value for interaction by sex for
the association of number of prior head injuries with impairment in 1+ MBI domains was .048. All other P values for interaction by age and sex performed were >.05 for all domains.
Head Injury, NPS, and MBI

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E56 Journal of Head Trauma Rehabilitation/MARCH–APRIL 2024

DISCUSSION no head injury history.6,30–32 In terms of sex differences,

this study found that associations of head injury status
This investigation analyzed data from a large
with impairment in the impulse dyscontrol domain
community-based sample of older adults with mixed
were stronger among females than among males. This is
cognitive status to determine the relationship between
consistent with a prior study from the subacute period
head injury and neuropsychiatric symptoms grouped
after head injury, which found that women were more
into MBI domains. We found that the association of
vulnerable than men to persistent mild head injury-
head injury with neuropsychiatric symptoms, specifi-
related cognitive and somatic symptoms.14 Further, we
cally within the domains of affective dysregulation and
found that the association of head injury with symptoms
impulse dyscontrol, was strongest among individuals
in any one or more MBI domain (in particular, impulse
who have sustained 2 or more head injuries, which
dyscontrol) was stronger among younger compared with
required physician/hospital care and/or were associ-
older individuals, which may be due to the higher
ated with loss of consciousness. Most heavily driving
baseline prevalence of impulse dyscontrol in younger
these significant MBI domains were the specific neu-
compared with older individuals, such that head injury
ropsychiatric symptoms of depression/dysphoria and
does not confer as much added impact among older
irritability/lability. These findings have implications for
individuals as it does among younger individuals.
the utility of the MBI construct as a tool to sys-
The literature also supports the significant association
tematically investigate noncognitive, neuropsychiatric
that we found between the MBI domain of affective
symptoms following head injury.
dysregulation and head injury. The neuropsychiatric
This study demonstrates a threshold association of
symptoms that map onto the MBI domain of affective
head injury with MBI, finding that neuropsychiatric
dysregulation are depression/dysphoria, anxiety, and
symptoms are most common in individuals who have
elation/euphoria. Jorge et al33 found major depressive
sustained multiple (2+) head injuries, which required
disorder to be significantly more frequent among pa-
physician/hospital care and/or were associated with
tients with head injury than among the controls, and
loss of consciousness. Supporting this finding, com-
the majority of these patients with major depression
pared with single head injury, repetitive head injury
exhibited comorbid anxiety and aggressive behavior.
has been found to portend worse outcomes in depres-
The mean prevalence of depression after head injury has
sion and suicide risk.23 Intrinsically related to repetitive
been reported at 30%, which is approximately 7.5 times
head injury, chronic traumatic encephalopathy has
greater than in the general population.34,35 Sustaining a
been clinically associated with aspects of neuropsy-
head injury significantly increases the risk of depression
chiatric dysregulation including irritability, impulsivity,
among older adults and has persisting adverse effects
aggression, explosivity, depression, and suicidality.24,25
on outcome, including higher degrees of psychological
The cumulative effect of repetitive head injury is far-
distress, increased psychosocial dysfunction, and poorer
reaching, with subsequent head injuries being linked to
performance in instrumental activities of daily living
higher levels of impairment in delayed memory and
than those without depression.36,37 Additionally, it has
executive functioning,26 higher endorsement of post-
been found that older adults sustaining a head injury
concussive symptoms including irritability,27 and more
before onset of dementia lead to higher rates of depres-
sleep disturbances.28 In the context of the prior litera-
sion and irritability than without head injury history.32
ture, our study provides further evidence that multiple
The present study did not find a significant association
head injuries, particularly those which require physi-
between head injury and anxiety, although this relation-
cian/hospital care and/or are associated with loss of
ship is suggested in the literature.6,32,38 Differences may
consciousness, have a cumulative negative consequence
be due to differences in study populations, most sig-
on neuropsychiatric outcomes.
nificantly, that we included individuals with dementia.
There is literature supportive of our findings on neu-
However, when we excluded individuals with demen-
ropsychiatric symptoms related to the MBI construct of
tia, observed associations were generally strengthened.
impulse dyscontrol in head injury. The neuropsychiatric
Excluding those with dementia may have preferentially
symptoms that map onto the MBI domain of impulse
removed some of the MBI presenting independent of
dyscontrol are agitation/aggression, irritability/lability,
head injury, which could instead be related to brain
and aberrant motor behavior. In a hospital-based sam-
pathology of dementia syndromes.
ple, the prevalence of acute/subacute posthead injury
There are several limitations of the present study
aggression has been estimated to be 28.4%, and is often
that should be considered. First, the MBI-C was not
associated with new-onset major depression.29 Addition-
collected in the ARIC Study, but we used an estab-
ally, it has been found that sustaining a head injury
lished algorithm for converting NPI-Q data to MBI
before onset of dementia leads to higher rates of irritabil-
domains.20 Further, the MBI-C was designed to be
ity, disinhibition, and motor disorders compared with
used prior to dementia onset. We chose to include

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participants regardless of cognitive status to investigate
associations of head injury with behavioral impairment,
though we included a sensitivity analysis excluding in-
dividuals with diagnosed dementia. Additionally, head
injury was self-reported and defined by ICD code; how-
ever, self-report has previously been shown to be reliable
for assessing head injury and the standardized CDC
definition was used to identify hospitalizations with an
ICD-9 code for head injury.17,18,39 Given that the ma-
jority of head injury cases were identified by self-report
in our population, we were limited regarding detailed
information on injury characteristics and our analyses
investigating associations of head injury severity with
MBI domains were limited by low power because they
were limited to head injury cases identified by ICD-9
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