Cognitive decline after hospitalization in a community population of older persons.
ABSTRACT To test the hypothesis that hospitalization in old age is associated with subsequent cognitive decline.
As part of a longitudinal population-based cohort study, 1,870 older residents of an urban community were interviewed at 3-year intervals for up to 12 years. The interview included a set of brief cognitive tests from which measures of global cognition, episodic memory, and executive function were derived. Information about hospitalization during the observation period was obtained from Medicare records.
During a mean of 9.3 years, 1,335 of 1,870 persons (71.4%) were hospitalized at least once. In a mixed-effects model adjusted for age, sex, race, and education, the global cognitive score declined a mean of 0.031 unit per year before the first hospitalization compared with 0.075 unit per year thereafter, a more than 2.4-fold increase. The posthospital acceleration in cognitive decline was also evident on measures of episodic memory (3.3-fold increase) and executive function (1.7-fold increase). The rate of cognitive decline after hospitalization was not related to the level of cognitive function at study entry (r = 0.01, p = 0.88) but was moderately correlated with rate of cognitive decline before hospitalization (r = 0.55, p = 0.021). More severe illness, longer hospital stay, and older age were each associated with faster cognitive decline after hospitalization but did not eliminate the effect of hospitalization.
In old age, cognitive functioning tends to decline substantially after hospitalization even after controlling for illness severity and prehospital cognitive decline.
- SourceAvailable from: Daniel H.j. DavisThe American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 07/2013; · 3.35 Impact Factor
- Journal of general internal medicine. 06/2014;
- Journal of General Internal Medicine 01/2013; · 3.28 Impact Factor
Cognitive decline after hospitalization in a
community population of older persons
R.S. Wilson, PhD
L.E. Hebert, ScD
P.A. Scherr, ScD, PhD
X. Dong, MD
S.E. Leurgens, PhD
D.A. Evans, MD
Objective: To test the hypothesis that hospitalization in old age is associated with subsequent
Methods: As part of a longitudinal population-based cohort study, 1,870 older residents of an
set of brief cognitive tests from which measures of global cognition, episodic memory, and exec-
utive function were derived. Information about hospitalization during the observation period was
obtained from Medicare records.
Results: During a mean of 9.3 years, 1,335 of 1,870 persons (71.4%) were hospitalized at least
once. In a mixed-effects model adjusted for age, sex, race, and education, the global cognitive
score declined a mean of 0.031 unit per year before the first hospitalization compared with
0.075 unit per year thereafter, a more than 2.4-fold increase. The posthospital acceleration in
cognitive decline was also evident on measures of episodic memory (3.3-fold increase) and exec-
utive function (1.7-fold increase). The rate of cognitive decline after hospitalization was not re-
lated to the level of cognitive function at study entry (r ? 0.01, p ? 0.88) but was moderately
correlated with rate of cognitive decline before hospitalization (r ? 0.55, p ? 0.021). More severe
illness, longer hospital stay, and older age were each associated with faster cognitive decline
after hospitalization but did not eliminate the effect of hospitalization.
Conclusion: In old age, cognitive functioning tends to decline substantially after hospitalization even
Cognitive decline in old age is common and is associated with increased risk of disability,
dementia, and death. With the aging of the US population, this problem is expected to increase
in the coming decades, underscoring the need to identify factors contributing to cognitive
decline and strategies to reduce its impact. One common occurrence in old age that may be
related to cognitive decline is hospitalization. Two observations suggest an association. First,
hospitalization of older persons increases risk of loss of independence in daily living activi-
ties,1–3and this effect has been associated with impairment in cognitive functioning.4–8Second,
some common medical conditions, such as diabetes9,10and chronic obstructive pulmonary
disease,11,12and general indicators of physical health, such as frailty13,14and body mass in-
dex,15,16have been associated with late life cognitive decline. However, few studies have exam-
ined the relationship between hospitalization and change in cognitive function,17,18and their
ability to reliably estimate the association has been limited by insufficient longitudinal cogni-
tive data before and after hospitalization.
In the present study, we used data from the Chicago Health and Aging Project19to test the
hypothesis that hospitalization of older people is associated with subsequent cognitive decline.
Participants are 1,870 older residents of a geographically defined neighborhood in Chicago,
From the Rush Alzheimer’s Disease Center (R.S.W., S.E.L.), Rush Institute for Health Aging (L.E.H., P.A.S., X.D., D.A.E.), and Departments of
Neurological Sciences (R.S.W., S.E.L.), Behavioral Sciences (R.S.W.), and Internal Medicine (L.E.H., X.D., D.A.E.), Rush University Medical
Center, Chicago, IL.
Study funding: This research was supported by NIH/NIA grant R01-AG11101. The funding organization had no role in the design or conduct of the
study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.
Disclosure: Author disclosures are provided at the end of the article.
Correspondence & reprint
requests to Dr. Wilson:
Copyright © 2012 by AAN Enterprises, Inc.
Illinois. During a mean of more than 9 years
of observation, cognitive function was as-
sessed 3–5 times at 3-year intervals, and
Medicare records of hospitalizations were ob-
tained. We used mixed-effects regression
models to test the hypothesis that cognitive
decline accelerates after hospitalization.
METHODS Participants. As part of the Chicago Health
and Aging Project,19,20a census of a geographically defined sec-
tion of the city was taken beginning in 1993. Those aged 65
years or older were invited to participate in an interview, which
included brief tests of cognitive function. The interview was sub-
sequently repeated at intervals of approximately 3 years, with 5
waves of interviews completed at the time of these analyses.
Eligibility for analyses required Medicare data to assess hos-
pitalization and completion of at least 3 interviews (including at
least one before hospitalization) to make it possible to observe a
shift in the rate of cognitive change over time. As of December
31, 2007, the baseline interview had been completed by 10,052
people. Medicare records were not available for 3,894 persons
(enrolled in a health maintenance organization [n ? 1,902];
Medicare number not provided [n ? 349], not yet submitted
[n ? 561], or did not match data from the Centers for Medicare
and Medicaid Services [n ? 891]; and age less than 65 years at
baseline [n ? 191]). This left 6,158 persons eligible at baseline.
They were similar in age to those without Medicare data (mean
of 73.2 vs 73.3 years, t[7,706] ? 1.03, p ? 0.304), more apt to
be men (42% vs 35%, ?2 ? 54.9, p ? 0.001) and white
(41% vs 29%, ?2 ? 138.9, p ? 0.001), and had more years of
schooling (mean of 12.3 vs 12.0, t[9,992] ? 3.95, p ? 0.001)
and better cognitive function at baseline (mean Mini-Mental
State Examination of 26.2 vs 25.5, ?2 ? 30.7, p ? 0.001). Of
those with Medicare data, 2,101 died within 6 years of baseline
(the time needed to complete 2 follow-up interviews) and 1,869
had been in the study less than 6 years, leaving 2,188 eligible for
follow-up. Of these, 1,870 (85.5%) completed 2 or more
follow-up visits. Analyses are based on this group. Compared
with the 4,288 ineligible persons (i.e., 2,101 ? 1,869 ? 318),
they were younger at baseline (mean of 72.7 vs 73.4, t[4,578.8] ?
3.66, p ? 0.001), more educated (mean of 12.9 vs 12.0,
t[6,139] ? 9.42, p ? 0.001), less apt to be men (39% vs 43%,
?2 ? 9.3, p ? 0.002) and black (51% vs 62%, ?2 ? 68.0,
p ? 0.001), and had better baseline cognitive function (mean
Mini-Mental State Examination of 27.2 vs 25.7, ?2 ? 131.8,
p ? 0.001).
Standard protocol approvals, registrations, and patient
consents. After a thorough description of the study, written
informed consent was obtained from all subjects. The study was
approved by the institutional review board of Rush University
Assessment of cognitive function. Each interview included
administration of 4 cognitive tests.20–22Episodic memory was
assessed by immediate and delayed recall of the East Boston
Story. The oral version of the Symbol Digits Modalities Test was
used to assess perceptual speed, a component of executive func-
tion. The Mini-Mental State Examination assessed global cogni-
tion. A composite of all 4 measures was the primary outcome.
Raw scores on each measure were converted to z scores, using the
baseline mean and SD of the population, and z scores were aver-
aged to yield a composite measure of global cognition. In sec-
ondary analyses, we used the Symbol Digit Modalities Test score
as a measure of executive function and a composite of immediate
and delayed recall as a measure of episodic memory.23
Assessment of hospitalization and other covariates.
Data on hospital use from January 1993 through December
2007 were obtained from Part A Medicare beneficiary records.
Analyses are based on the first hospitalization that occurred be-
tween the baseline interview and the last assessment of cognitive
function for a given individual.
Severity of illness during hospitalization was assessed with
the Charlson comorbidity index,24a weighted measure that re-
flects the number and seriousness of diseases, and length of hos-
pital stay. The definition of critical illness hospitalization was
based on codes from the International Classification of Diseases,
Ninth Revision, as specified in the Adult Changes in Thought
Depressive symptoms were assessed at baseline with a 10-
item version of the Center for Epidemiologic Studies Depression
Scale.25Disability was assessed at baseline with the Katz scale,26a
self-report measure of the ability to perform 6 basic activities of
daily living (e.g., dressing and bathing).
Statistical analysis. Mixed-effects regression models27were
used to characterize change in cognitive function. Each model
allowed rate of cognitive change to shift after the first hospitaliza-
tion. Random effects were included for the intercept, slope be-
fore hospitalization, and slope after hospitalization to allow for
individual differences in initial level of cognitive function and
rates of prehospital and posthospital change. Each model also
included fixed effects for time before hospitalization (in years
since baseline); time after hospitalization; and age, sex, race, ed-
ucation and their interactions with time before hospitalization.
We examined the interactions of age, sex, race, and education
with time after hospitalization and retained the only significant
interaction (with age) in subsequent models. We repeated the
initial analysis excluding persons hospitalized in the year before
baseline cognitive assessment, excluding individuals first hospi-
talized after their last cognitive assessment, with terms for the
interaction of time after hospitalization with Charlson score dur-
ing hospitalization and length of hospital stay, and with a term
for the interaction of time after hospitalization with an indicator
for whether a critical illness was involved. We tested the effects of
depressive symptoms and disability (in separate models) includ-
ing terms for baseline level of the covariate and its interactions
with time before and after hospitalization. Programming was
done in SAS.28
RESULTS During a mean of more than 9 years of
observation, 1,335 of 1,870 persons (71.4%) were hos-
pitalized at least once. The initial hospitalization oc-
and lasted for a median of 5 days (interquartile range
3–8 days) with a median Charlson comorbidity Index
score of 1 (interquartile range 0–2). There was a mean
of 5.7 years of follow-up (SD ? 3.1) after the initial
and less educated and had higher baseline levels of cog-
who were not hospitalized (table 1).
Hospitalization and cognitive decline. At study entry,
scores on the composite measure of global cognition
Neurology 78 March 27, 2012
ranged from ?3.03 to 1.54 (mean ? 0.36, SD ?
0.66). To characterize change on this measure, we
used a mixed-effects regression model that allowed
the rate of cognitive change to shift after the initial
hospitalization and controlled for the potentially
confounding effects of age, sex, race, and education.
As shown in table 2, the composite measure of
global cognition declined a mean of 0.031 unit per
year before hospitalization and in those never hospi-
talized. After hospitalization, the rate accelerated by
0.044 unit to a mean loss of 0.075 unit per year, a
more than 2.4-fold increase relative to the decline
preceding hospitalization. This effect is shown in fig-
ure 1 for a person hospitalized in year 4 (red line)
compared with a person not hospitalized (solid line).
We considered the possibility that findings were
biased by hospitalizations that occurred outside the
cognitive data collection period. Results were essen-
tially unchanged, however, in analyses that excluded
the 222 individuals hospitalized in the year before
their baseline cognitive assessment (estimate for time
before hospitalization ? ?0.029, SE ? 0.004, p ?
0.001; estimate for time after hospitalization ?
?0.075, SE ? 0.006, p ? 0.001) or the 189 individ-
uals who were hospitalized after their last cognitive
assessment (estimate for time before hospitaliza-
tion ? ?0.027, SE ? 0.004, p ? 0.001; estimate for
time after hospitalization ? ?0.075, SE ? 0.005,
p ? 0.001).
To see whether hospitalization was related to de-
cline in some cognitive domains but not others, we
repeated the analysis separately with episodic mem-
ory (mean ? 0.33, SD ? 0.76) and executive func-
tion (mean ? 0.48, SD ? 0.91) as outcome
measures. There was a 3.3-fold increase in the rate of
episodic memory decline, from a loss of 0.014 unit
per year before hospitalization (SE ? 0.005, p ?
0.005) to 0.046 unit per year after hospitalization
(SE ? 0.006, p ? 0.001) (top panel of figure e-1 on
the Neurology®Web site at www.neurology.org). De-
cline on the executive function measure increased
1.7-fold, from a loss of 0.053 unit per year before
hospitalization (SE ? 0.004, p ? 0.001) to 0.091
unit per year after hospitalization (SE ? 0.005, p ?
0.001) (bottom panel of figure e-1).
Modifying factors. To examine individual differences
in paths of cognitive change after hospitalization, we
plotted the model-estimated paths for a 7.5% ran-
dom sample of the cohort (figure 2). Much variabil-
ity is evident, with posthospital cognitive function
stable in some individuals but declining at rates rang-
ing from gradual to rapid in others.
To determine whether prehospital cognitive func-
tioning affected results, we examined the correlations
among the person-specific deviations from the inter-
cept and slopes estimated in the initial mixed-effects
model. Posthospital rate of cognitive decline was not
associated with baseline level of cognition (r ? 0.01,
p ? 0.88) but was associated with prehospital cogni-
tive decline (r ? 0.56, p ? 0.021). To further exam-
ine this effect, we plotted the predicted 10-year paths
of cognitive change for 2 individuals hospitalized in
year 4, one with average prehospitalization cognitive
decline (50th percentile, black line) and the other
with moderate decline (10th percentile, red line).
Table 1Cohort description: Characteristics of participants who were
hospitalized during the study and those who were not
(n ? 535)
(n ? 1,335)p Value
Age, y, mean (SD)
71.0 (4.1) 73.1 (5.8)
Education, y, mean (SD)
13.4 (3.4)12.8 (3.6)0.012
African American, %
Global cognitive score,
0.54 (0.55) 0.32 (0.67)
27.9 (2.4) 27.1 (3.8)
Episodic memory score
0.43 (0.73) 0.29 (0.77)
Executive function score
0.58 (0.87)0.43 (0.92)0.002
CES-D scale score, mean (SD)
0.99 (1.55) 1.41 (1.87)
Katz scale score, mean (SD)
0.05 (0.38)0.22 (0.84)
Observation time, y, mean (SD)
8.9 (2.6)9.5 (2.5)
Prehospitalization time, y,
Posthospitalization time, y,
Charlson comorbidity index
score, mean (SD)
Length of hospital stay, d,
Abbreviations: CES-D ? Center for Epidemiological Studies–Depression; MMSE ? Mini-
Mental State Examination.
Table 2Annual rate of change in global cognitiona
Model termEstimate SEp Value
Time after hospitalization
Time ? age
Time ? sex
Time ? education
Time ? race
Time after hospitalization ? age
aEstimated from a mixed-effects regression model.
Neurology 78March 27, 2012
Figure e-2 suggests that posthospital cognitive de-
cline partly reflects an exacerbation of prehospital
The Charlson comorbidity index score for the
hospitalized participants ranged from a low of 0 to a
high of 5 (median ? 1, interquartile range ? 0–2)
and duration of hospitalization ranged from 1 to 92
days (median ? 5, interquartile range ? 3–8). To
see whether these indicators of illness severity modi-
fied the relation of hospitalization to cognitive func-
tioning, we repeated the initial analysis with terms
for the interactions of time after hospitalization with
illness severity and with duration of hospitalization.
A higher Charlson score (estimate of interaction ?
?0.016, SE ? 0.005, p ? 0.001) and longer hospital
tive decline after hospitalization. The overall impact of
these variables on cognitive decline was modest, how-
ever, as shown by the predicted paths of cognitive
panel of figure 3) and durations of hospitalization (bot-
tom panel of figure 3).
To see whether hospitalization involving a critical
illness disproportionately contributed to results,18we
tested for an interaction between a critical illness at
first hospitalization (n ? 43) and time after hospitaliza-
tion. There was no interaction (estimate ? ?0.009,
SE ? 0.020, p ? 0.67).
Older age was associated with lower level of cog-
nition at baseline and more rapid decline before and
after hospitalization (table 2). This effect is shown in
figure e-3 for a younger participant (baseline age 67,
10th percentile, solid line) compared with an older
one (baseline age 81, 90th percentile, dotted line).
Sex, education, and race were related to level of cog-
nitive function but not to change before or after hos-
pitalization (data not shown).
Because depression has been associated with both
hospitalization29and cognitive decline,30,31we con-
ducted an additional analysis with terms added for
baseline score on the Center for Epidemiologic Stud-
ies Depression scale and its interactions with time. In
this analysis, depressive symptoms were robustly re-
lated to baseline cognition (estimate ? ?0.032,
SE ? 0.007, p ? 0.001), marginally related to
prehospital cognitive decline (estimate ? ?0.003, SE ?
0.002, p ? 0.053) and unrelated to posthospital
cognitive decline (estimate ? ?0.003, SE ?
0.003, p ? 0.26). Disability has also been linked
to hospitalization1–3and cognitive decline.32,33In a
subsequent analysis, baseline disability on the Katz
scale was associated with cognition at baseline (es-
timate ? ?0.175, SE ? 0.016, p ? 0.001) but not
with rate of cognitive decline before (estimate ?
0.001, SE ? 0.005, p ? 0.90) or after (estimate ?
0.002, SE ? 0.008, p ? 0.84) hospitalization.
DISCUSSION As part of a longitudinal population-
based study, change in cognitive function was as-
sessed in more than 1,800 older people and Medicare
records of hospitalization were obtained. During a
mean of more than 9 years of observation, 71.4% of
the participants were hospitalized at least once, and
there was a more than 2.4-fold increase in the rate of
cognitive decline after hospitalization. This finding
Figure 1Typical path of posthospital change in global cognitive function
Predicted 10-year paths of change in composite measure of global cognition for typical
participants hospitalized in year 4 (red line) or not hospitalized (black line) from a mixed-
effects model adjusted for age, sex, race, and education.
Figure 2 Individual differences in posthospital change in global
Person-specific paths of change in composite measure of global cognition estimated for a
7.5% random sample of participants from a mixed-effects model adjusted for age, sex,
race, and education.
Neurology 78March 27, 2012
persisted after controlling for severity of illness and
prehospital cognitive decline. The results support the
hypothesis that hospitalization in old age is associ-
ated with accelerated cognitive decline.
The association between hospitalization and cog-
nitive decline has not been extensively investigated.
One population-based study of older persons found
that hospitalization was associated with increased de-
cline on a brief mental status test during a 3-year
period,17consistent with the results of the present
study. Yet decline was not observed on other out-
come measures and was estimated from 2 measure-
ment points, making it difficult to distinguish from
level of function or to know whether it preceded or
followed hospitalization. Another population-based
study found that hospitalization of older people was
associated with a lower level of cognitive function
but not with cognitive decline.18However, the power
to detect an association between hospitalization and
cognitive change was limited, possibly because of in-
sufficient posthospitalization data (i.e., mean of 1.9
years of posthospital observation with cognitive test-
ing at 2-year intervals). Thus, these studies may not
have had enough longitudinal cognitive data to se-
curely estimate the relation of hospitalization to cog-
The bases of the association of hospitalization
with accelerated cognitive decline are uncertain.
Cognitive dysfunction has been identified as a com-
plication of critical illnesses34and surgical proce-
dures.35Delirium is common in older patients with
these conditions, affecting about 75% of those with a
critical illness36and 25%–65% of those undergoing
surgery,37and it has been associated with chronic
cognitive impairment.38In the present study, only
3% of hospitalizations involved a critical illness, but
15%–20% of older general medical inpatients are es-
timated to meet the criteria for delirium,39and it is
likely that many more exhibit subsyndromal signs of
delirium.40These data suggest that confusion and in-
attention due to acute brain dysfunction during hos-
pitalization contributed to posthospital cognitive
Individuals differed in the rate of posthospital
cognitive decline. Those who were sicker and had
longer hospital stays experienced more rapid decline
after hospitalization, suggesting that the severity of
the medical conditions that necessitated hospitaliza-
tion may have contributed to accelerated cognitive
decline. That these illness severity effects were rela-
tively weak, however, suggests that other factors were
also involved. Posthospital cognitive decline was also
related to older age and more rapid prehospital rate
of cognitive decline. Thus, individuals at elevated
risk for cognitive decline or already experiencing it
tended to experience a relatively greater posthospital
increase in cognitive decline, suggesting that hos-
pitalization may unmask cognitive symptoms in
vulnerable older persons and perhaps that hospi-
talization is associated with declining cognitive
competence. That more severe illness, older age,
and prehospital cognitive impairment are also risk
factors for delirium supports the idea that delirium
partially mediates the association of hospitaliza-
tion with subsequent cognitive decline.
Research on hospitalization and cognitive decline
has focused mainly on global cognition, but one pre-
vious study found no association between hospital-
ization and change on 2 measures of episodic
memory,17suggesting that hospitalization might af-
fect some cognitive functions and spare others. In the
present study, however, hospitalization was robustly
related to decline on a measure of executive function
Figure 3Modification of posthospital change in global cognitive function
Predicted 10-year paths of change in composite measure of global cognition for typical
participants hospitalized in year 4 with a Charlson score of 0 (black line) vs 2 (red line) (A) or
a hospital stay of 2 days (black line) vs 13 days (red line) (B), from mixed-effects models
adjusted for age, sex, race, and education.
Neurology 78 March 27, 2012