Epidemiology • Volume 33, Number 4, July 2022
Education and Risk
Downloaded from http://journals.lww.com/epidem by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1
AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 04/28/2023
Letters
was mild cognitive impairment. Trained
of Mild Cognitive
Impairment in Older
Adults Displaced by
Violence in Colombia
To the Editor:
E ducation may play an important role in
building cognitive reserve and reducing
the risk of dementia.1 However, exposure
to traumatic events may have a “scarring”
effect and increase the risk of mental ill-
ness across the life course.1,2 Education
is associated with reduced risk of mild
cognitive impairment in the general popu-
lation,3 but more research is required to
determine whether education reduces the
risk of mild cognitive impairment in peo-
ple who have been displaced by violence.2
Six million people are thought to have
been displaced by violence in Colombia in
the past 50 years.4 We used data from the
National Survey of Health, Wellbeing and
Aging in Colombia to investigate associa-
tions between education and mild cogni-
tive impairment in people who had been
displaced by violence.
The National Survey of Health,
Wellbeing and Aging in Colombia is
described elsewhere.5 The methods used
in the present analysis are also described
elsewhere.6 Briefly, participants were
community-dwelling adults with age 60
years or older. The dependent variable
The authors report no funding and conflicts of
interest.
Requests to access the data should be directed to
the Colombian Ministry of Health (reposi-
torio@minsalud.gov.co). The original name
of the study is in Spanish: Salud, Bienestar &
Envejecimiento (SABE Colombia). The analysis
plan is available from the corresponding author.
Supplemental digital content is available
through direct URL citations in the HTML
and PDF versions of this article (www.epi-
dem.com).
Correspondence: Gary O’Donovan, Facultad de
Medicina, Universidad de los Andes, Carrera 1,
18A-12, Bogotá 111711, Colombia. E-mail:
g.odonovan@uniandes.edu.co.
Copyright © 2022 Wolters Kluwer Health, Inc. All
rights reserved.
ISSN: 1044-3983/22/334-e13
DOI: 10.1097/EDE.0000000000001459
© 2022 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
interviewers administered a shorter ver-
sion of the mini-mental state examina-
tion, and mild cognitive impairment was
defined as a score of 12 or less out of
19. The independent variable was dis-
placement by violence. Participants were
asked if they had ever been displaced by
armed conflict or violence. The covari-
ates included age, height, education,
current income, civil status, smoking,
alcohol drinking, and physical activity.
Participants were asked about the high-
est level of education they had achieved,
and three groups were created: no educa-
tion; some primary education; and, some
secondary education or more. Logistic
regression was used to model associa-
tions between education and cognitive
impairment (Stata MP version 15.1,
StataCorp, TX). We modeled age as a
continuous variable and all other covari-
ates as categorical variables. We used
the estimated coefficients from the fitted
logistic regression models to calculate
risk differences, with marginal standard-
ization for handling of the covariates.
eTable 1 (http://links.lww.com/
EDE/B895) shows participants’ char-
acteristics. The prevalence of mild cog-
nitive impairment was 19% in 19,276
adults who had not been displaced by
violence and 21% in 4,413 adults who
had been displaced by violence [contrast
of risks of mild cognitive impairment
adjusting for age and sex (95% confi-
dence interval): 0.04 (0.03, 0.05)]. There
were some missing values, as shown
in the table, and the analytic sample
included 1,901 males and 1,866 females
who had been displaced by violence. The
risk (95% confidence interval) of mild
cognitive impairment was 0.25 (0.22,
0.29) in males with no education, 0.11
(0.09, 0.12) in males with some primary
education, and 0.08 (0.04, 0.12) in males
with some secondary education or more.
The risk of mild cognitive impairment
was 0.36 (0.32, 0.39) in females with no
education, 0.13 (0.11, 0.15) in females
with some primary education, and 0.07
(0.03, 0.11) in females with some sec-
ondary education or more. eTable 2
(http://links.lww.com/EDE/B895) shows
the age when participants were first dis-
placed by violence and the number of
times they were displaced.
The 2016 peace deal between the
Colombian government and the FARC
guerrillas was intended to end a war that
is thought to have displaced millions of
people.4 Nonetheless, displacement by
violence is an ongoing problem7 and the
United Nations has urged the Colombian
government to do more to implement the
peace deal.8 Given that education may
build cognitive reserve and may reduce
the risk of dementia,1 it is concerning that
many schools are closed in the rural areas
of Colombia most affected by violence.
Although this analysis suggests that educa-
tion is associated with reduced risk of mild
cognitive impairment even in older adults
who have been displaced by violence, more
should be done to end the cycle of low edu-
cation and violence in Colombia. The ques-
tionnaire used in the present study is a valid
screening tool,9 but it is not a clinical diag-
nosis of cognitive impairment. Longitudinal
studies with clinical measurements are
needed to confirm associations between
education and cognitive impairment in peo-
ple who have been displaced by violence.
Gary O’Donovan
Olga L. Sarmiento
Facultad de Medicina
Universidad de los Andes
Bogotá, Colombia
Philipp Hessel
Escuela de Gobierno Alberto Lleras
Camargo, Universidad de los Andes
Bogotá, Colombia
REFERENCES
1. Patel V, Saxena S, Lund C, et al. The Lancet
Commission on global mental health and sustain-
able development. Lancet. 2018;392:1553–1598.
2. Zimmer Z, Fraser K, Korinek K, Akbulut-
Yuksel M, Young YM, Toan TK. War across the
life course: examining the impact of exposure to
conflict on a comprehensive inventory of health
measures in an aging Vietnamese population.
Int J Epidemiol. 2021;50:866–879.
3. Livingston G, Sommerlad A, Orgeta V, et al.
Dementia prevention, intervention, and care.
Lancet. 2017;390:2673–2734.
4. NobelPrize.org. The Nobel Peace Prize. 2016.
Available at: https://www.nobelprize.org/prizes/
peace/2016/summary/. Accessed 14 July 2021.
5. Gomez F, Corchuelo J, Curcio CL, Calzada MT,
Mendez F. SABE Colombia: Survey on health,
well-being, and aging in Colombia-study design
www.epidem.com | e13
 Letters
and protocol. Curr Gerontol Geriatr Res.
2016;2016:7910205.
6. O’Donovan G, Hamer M, Sarmiento OL, Hessel
P. Education in early life markedly reduces the
probability of cognitive impairment in later life
in Colombia. Sci Rep. 2020;10:17685.
7. Defensoría del Pueblo Colombia. Defensoría
Downloaded from http://journals.lww.com/epidem by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1
alerta ante el aumento de eventos de desplaza-
miento masivo y confinamiento de comunidades
[Ombudsman raises alert about the increasing
number of massive displacements and community
confinements]. 2021. Available at: https://www.
AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 04/28/2023
defensoria.gov.co/es/nube/comunicados/10268/
Defensor%C3%ADa-alerta-ante-el-aumento-
de-eventos-de-desplazamiento-masivo-y-
confinamiento-de-comunidades-desplazamiento-
conf inamiento-Defensor%C3%ADa.htm
Accessed 15 July 2021.
8. United Nations. Colombia peace process at criti-
cal juncture: UN envoy. 2021. Available at: https://
news.un.org/en/story/2021/07/10957322021).
Accessed 15 July 2021.
9. Organización Panamericana de la Salud. Salud,
bienestar y envejecimiento en Santiago, Chile
[Health, wellbeing and ageing in Santiago,
Chile]. 2005. Available at: https://iris.paho.org/
bitstream/handle/10665.2/741/9275316090.
pdf?sequence=1 Accessed 27 June 2020.
The Case–Crossover
Design Under
Changing Baseline
Outcome Risk:
A Simulation of
Ambient Temperature
and Preterm Birth
To the Editor:
T he case–crossover design is widely
used in epidemiology. Case–cross-
over studies are case-only, within-person
This work was supported by NIH grant P30
ES023515. D.C. was funded by NIH T32
HD049311.
The authors report no conflicts of interest.
All data and analytical code to reproduce results
are available on GitHub: https://github.com/
justlab/casecrossover_preterm_simulation.
Supplemental digital content is available
through direct URL citations in the HTML
and PDF versions of this article (www.epi-
dem.com).
Correspondence: Daniel Carrión, P.O. Box 208034,
New Haven, CT 06520-8034. E-mail: daniel.
carrion@yale.edu.
Copyright © 2022 Wolters Kluwer Health, Inc. All
rights reserved.
ISSN: 1044-3983/22/334-e15
DOI: 10.1097/EDE.0000000000001477
e14 | www.epidem.com
Copyright © 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Epidemiology • Volume 33, Number 4, July 2022
comparisons, therefore not confounded
by time-invariant characteristics.1 Proper
inference with case–crossover studies
relies on appropriate selection of control
times, and time-stratified designs are a
preferred strategy for control selection.2
However, these studies assume stable
baseline outcome risks.3 Multiple studies
have used the case–crossover approach
linking ambient temperature and pre-
term birth,4 but since preterm birth risk
increases secularly from baseline over
gestation, the validity of the case–cross-
over design for studying preterm birth is
unclear.5 We assessed the appropriate-
ness of the case–crossover design using
simulated associations between ambient
daily temperature and preterm birth.
We conducted simulations using
2018 data for New York State. Data were
acquired from National Weather Service
records for LaGuardia Airport (daily
maximum temperature) and the Centers
for Disease Control’s WONDER data-
base (preterm birth data).6 Daily births
by gestational age are unavailable, so we
estimated them using marginal distribu-
tions of births by month and day of week
(within month) (eFigure 1; http://links.
lww.com/EDE/B922).
Estimated daily births per gesta-
tional age (20–36 weeks) served as the
basis for baseline risk. We combined
baseline risks with simulated tempera-
ture effects to create expected counts
per day. Relative risks (RR) were set
from 0.9 to 1.25 per 10°F increase on
lag day 0. We created 1,000 datasets
per simulated RR using Poisson ran-
dom number generation, exploiting the
equivalence of conditional logistic and
Poisson regression under a common
exposure time series.7 We disaggregated
counts into individual records for case–
crossover analyses, estimated via condi-
tional logistic regression with 2-week,
28-day, and calendar-month stratified
control period selection matched on the
day of week. Analyses only included
warm months, May through September.4
Sensitivity analysis included modeling
2007 (eFigure 2; http://links.lww.com/
EDE/B922).
© 2022 Wolters Kluwer Health, Inc. All rights reserved.
We summarized results accord-
ing to bias and coverage. We calculated
bias according to the absolute difference
ln(β ) − ln(β ); β is the estimated effect
and β is the simulated effect. Coverage
is the proportion of simulations where
the 95% confidence intervals include the
simulated effect. Reproducible analyses
were conducted in R 4.1.0 and using the
targets package.8
Each control-selection strategy
exhibited little bias (Figure part A).
Median bias, across all simulated effects,
was 0 for the 2-week and 28-day strati-
fied results. The month results exhibited
a median bias of –0.001. The 2-week
results exhibited the largest variability
as measured by the interquartile range
(0.023), compared with the other two
models, which both had interquartile
ranges of 0.016.
Coverage of 95% confidence
intervals was consistent for all control
selection strategies; between 94%–96%,
94%–97%, and 94%–96% of all intervals
included the simulated effect for 2-week,
28-day, and month-stratified results,
respectively (Figure part B). Sensitivity
analyses simulating data from 2007 were
consistent in bias and coverage (eFigure 3;
http://links.lww.com/EDE/B922).
Case–crossover studies may suffer
systematic bias if control times are non-
exchangeable within person.1 Although
temperature varies seasonally and the risk
of preterm birth changes quickly over
pregnancy, our simulations show that
the case–crossover study design yields
negligible bias and appropriate coverage
of confidence intervals. We employed
time-stratified control selection, result-
ing in the opportunity for control times
before or after the case time within stra-
tum. Including control times after the case
time likely improves exchangeability by
accounting for exposure trends; in envi-
ronmental epidemiology this holds for
ambient exposures where reverse causa-
tion is not a concern.1 We did not assess
other control-selection strategies. Results
from calendar-month, 28-day, and 2-week
strata were consistent, but 2-week strata
yielded a wider range of estimates. Two-
week strata were attempted as an alternate