Daytime Napping, Nighttime Sleeping, and Parkinson Disease

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
American journal of epidemiology (Impact Factor: 5.23). 03/2011; 173(9):1032-8. DOI: 10.1093/aje/kwq478
Source: PubMed
ABSTRACT
Preliminary evidence suggests that daytime sleepiness may predate clinical diagnosis of Parkinson disease. The authors examined daytime napping and nighttime sleeping durations, reported in 1996-1997 by 220,934 US NIH-AARP Diet and Health Study participants, in relation to Parkinson disease diagnoses at 3 clinical stages: established (cases diagnosed before 1995, n = 267), recent (1995-1999, n = 396), and prediagnostic (2000 and after, n = 770). Odds ratios and 95% confidence intervals were derived from multivariate logistic regression models. Longer daytime napping was associated with higher odds of Parkinson disease at all 3 clinical stages: the odds ratios comparing long nappers (>1 hour/day) with nonnappers were 3.9 (95% confidence interval: 2.8, 5.6) for established cases, 2.2 (95% confidence interval: 1.7, 3.0) for recent cases, and 1.5 (95% confidence interval: 1.2, 1.9) for prediagnostic cases. Further control for health status or nighttime sleeping duration attenuated the association for established cases but made little difference for recent or prediagnostic cases. In the nighttime sleeping analysis, a clear U-shaped association with Parkinson disease was observed for established cases; however, this association was attenuated markedly for recent cases and disappeared for prediagnostic cases. This study supports the notion that daytime sleepiness, but not nighttime sleeping duration, is one of the early nonmotor symptoms of Parkinson disease.

Full-text

Available from: Aaron Blair
American Journal of Epidemiology
Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2011.
Vol. 173, No. 9
DOI: 10.1093/aje/kwq478
Advance Access publication:
March 14, 2011
Original Contribution
Daytime Napping, Nighttime Sleeping, and Parkinson Disease
Jianjun Gao, Xuemei Huang, Yikyung Park, Albert Hollenbeck, Aaron Blair, Arthur Schatzkin, and
Honglei Chen*
* Correspondence to Dr. Honglei Chen, Epidemiology Branch, National Institute of Environmental Health Sciences, 111 T. W.
Alexander Drive, P. O. Box 12233, Mail Drop A3-05, Research Triangle Park, NC 27709 (e-mail: chenh2@niehs.nih.gov).
Initially submitted August 31, 2010; accepted for publication December 7, 2010.
Preliminary evidence suggests that daytime sleepiness may predate clinical diagnosis of Parkinson disease.
The authors examined daytime napping and nighttime sleeping durations, reported in 1996–1997 by 220,934 US
NIH-AARP Diet and Health Study participants, in relation to Parkinson disease diagnoses at 3 clinical stages:
established (cases diagnosed before 1995, n ¼ 267), recent (1995–1999, n ¼ 396), and prediagnostic (2000 and
after, n ¼ 770). Odds ratios and 95% confidence intervals were derived from multivariate logistic regression
models. Longer daytime napping was associated with higher odds of Parkinson disease at all 3 clinical stages:
the odds ratios comparing long nappers (>1 hour/day) with nonnappers were 3.9 (95% confidence interval: 2.8,
5.6) for established cases, 2.2 (95% confidence interval: 1.7, 3.0) for recent cases, and 1.5 (95% confidence
interval: 1.2, 1.9) for prediagnostic cases. Further control for health status or nighttime sleeping duration attenuated
the association for established cases but made little difference for recent or prediagnostic cases. In the nighttime
sleeping analysis, a clear U-shaped association with Parkinson disease was observed for established cases;
however, this association was attenuated markedly for recent cases and disappeared for prediagnostic cases.
This study supports the notion that daytime sleepiness, but not nighttime sleeping duration, is one of the early
nonmotor symptoms of Parkinson disease.
Parkinson disease; prospective studies; sleep
Parkinson disease is clinically diagnosed by the presence
of motor dysfunctions including tremor at rest, rigidity, and
bradykinesia. However, Parkinson disease patients also suf-
fer from a variety of nonmotor symptoms, some of which
may predate clinical onset of the disease and may be an
integral part of the underlying pathogenesis (1–3). Recog-
nizing and characterizing these nonmotor symptoms at dif-
ferent stages of the disease may eventually lead to earlier
Parkinson disease diagnosis, better clinical management,
and improvement of our understanding of the pathoetiology
and progression of the disease (4). Atypical sleep habits
such as excessive daytime sleepiness are common among
Parkinson disease patients, which may be partially ex-
plained by usage of dopaminergic medications (5). It is un-
clear, however, whether Parkinson disease patients have
atypical or altered sleep habits prior to their clinical diag-
nosis. Therefore, we examined the associations between
durations of daytime napping or nighttime sleeping and
Parkinson disease occurrence during 3 clinical periods
(i.e., before, peri-, or after Parkinson disease diagnosis) in
a large cohort of older men and women in the National
Institutes of Health (NIH)-AARP Diet and Health Study.
MATERIALS AND METHODS
Study population and case identification
The cohort was established in the mid-1990s by the Na-
tional Cancer Institute and recruited 566,402 members of
AARP (formerly the American Association of Retired Per-
sons), aged 50–71 years, from 6 states and 2 metropolitan
areas of the United States (6). The baseline survey was
conducted in 1995–1996, focusing on dietary habits (6).
Between 1996 and 1997, 334,908 participants of the original
cohort also answered a risk factor questionnaire to provide
more details on their health behaviors, including numbers of
hours of daytime napping and nighttime sleeping.
In 2004–2006, a follow-up questionnaire was mailed to all
surviving participants of the original cohort to update their
health status and to ascertain the occurrence of cancers and
1032 Am J Epidemiol. 2011;173(9):1032–1038
Page 1
other major chronic diseases, including Parkinson disease. On
the follow-up questionnaire, participants were asked whether
they had ever been diagnosed by a physician as having
Parkinson disease and the year of first diagnosis (before
1985, 1985–1994, 1995–1999, or 2000 and after). A total of
318,261 participants answered the follow-up questionnaire.
The base population of the current study therefore in-
cluded 220,934 participants who answered both the risk
factor survey in 1996–1997 and the follow-up survey in
2004–2006. Of these participants, 1,681 reported physi-
cian-diagnosed Parkinson disease on the 2004–2006 fol-
low-up survey. We excluded 242 self-reports that were
later found to be erroneous by the validation procedure de-
scribed below and 6 additional cases for whom data on sleep
habits were missing. Of the eligible participants who did not
report a Parkinson disease diagnosis, we excluded 4,916
missing data on Parkinson disease status and 452 missing
data on sleep habits. The nal analyses included 1,433
Parkinson disease cases and 213,885 individuals without
Parkinson disease. In reference to the exposure assessment
in 1996–1997, these cases included 267 that were estab-
lished (diagnosed before 1995), 396 that were recent
(diagnosed between 1995 and 1999), and 770 that were
prediagnostic (diagnosed in 2000 and after).
Participants consented to the study by returning survey
questionnaires. The study protocol was approved by the
institutional review board of the National Institute of Envi-
ronmental Health Sciences and the Special Studies Institu-
tional Review Board of the National Cancer Institute.
We started to validate the diagnoses of surviving Parkinson
disease cases in this cohort in 2007. With permission from
cases who self-reported Parkinson disease, we asked their
treating neurologists to complete a Parkinson disease diag-
nostic form and to send us a copy of the patients’ medical
records. The medical records were subsequently reviewed by
a movement disorder specialist, and a self-report of clinical
Parkinson disease diagnosis was accepted if the treating neu-
rologist confirmed the diagnosis or if medical record review
by the movement disorder specialist showed at least 2 of the 4
cardinal Parkinson disease signs (with one being rest tremor
or bradykinesia), a progressive course, and the absence of
unresponsiveness to dopaminergic treatment or other features
suggesting an alternative diagnosis. This protocol has been
successfully implemented in other large cohorts (7, 8). Of the
1,069 responses from physicians and medical record review
we received to date, 940 (87.9%) Parkinson disease diagnoses
were confirmed. The confirmation rate was similar across all
3 groups of patients: 91.3% for established cases, 88.0% for
recent cases, and 87.2% for prediagnostic cases.
Exposure assessment
At the risk factor survey in 1996–1997, participants were
asked how many hours were spent napping during daytime
or sleeping at nighttime in a typical 24-hour period over the
past 12 months. Five choices were available for the daytime
napping question (hours): none, <1, 1–2, 3–4, and 5. For
nighttime sleeping, 4 categories were provided (hours): <5,
5–6, 7–8, and 9. The risk factor survey also asked partic-
ipants to report how often they participated in moderate to
vigorous physical activities in the past 10 years, providing 6
categories (never, rarely, <1, 1–3, 4–7, and >7 hours/week).
At the dietary survey in 1995–1996, participants were asked
whether they had ever smoked more than 100 cigarettes
during their lifetime and, for ever smokers, the typical
amount of smoking, current smoking status, and number
of years since last smoking. The dietary survey also col-
lected information on date of birth, sex, race, self-evaluated
general health status, and consumption of coffee and other
caffeinated drinks (6). Unlike other covariates, information
on depression was not collected until the follow-up survey
in 2004–2006, where physician-diagnosed depression was
asked about in the same format as Parkinson disease (none;
year of first diagnosis: before 1985, 1985–1994, 1995–1999,
2000 and after).
Statistical analysis
We used multivariate logistic regression models to calculate
odds ratios and 95% confidence intervals. Because sleep habits
were asked about in 1996–1997, the exposure information was
collected after diagnosis for established cases, within 2 years
before or after the diagnosis for recent cases, and at least 3–4
years prior to the diagnosis for prediagnostic cases.
Using participants reporting no napping as the reference,
we examined the relation between daytime napping and
Parkinson disease occurrence for all 3 case groups. In these
analyses, we combined participants with 1 hour of nap-
ping because few participants reported more than 2 hours of
napping. In the analysis for nighttime sleeping, we used 7–8
hours of sleeping as the reference. Covariates included age
(in 5-year age groups), sex, race (non-Hispanic Caucasian
vs. others), smoking status (never smoker, past smoker
(years since last smoking: 35, 30–34, 20–29, 10–19,
5–9, and 1–4), and current smoker (cigarettes per day:
1–10, 11–20, >20)), daily caffeine intake (mg/day, quin-
tiles), and moderate to vigorous physical activity (never,
rarely, <1, 1–3, 4–7, and 7 hours/week). We additionally
adjusted for self-reported health status (excellent, very good,
good, fair, or poor) to examine the potential impact of gen-
eral health status on the analyses. Depression is associated
with both sleeping behaviors (9) and the occurrence of Par-
kinson disease (10, 11). However, we did not have informa-
tion on depression at the time that sleeping and napping
durations were asked about. We therefore conducted addi-
tional sensitivity analyses to further adjust for ever presence
of depression until the follow-up survey.
The primary analyses were first conducted by including
all participants and then by sex, age (years: 62 vs. >62),
smoking status (never vs. ever smoker), and caffeine intake
(above or below the median). In the analysis of napping, we
tested the statistical significance for a linear trend by assign-
ing a value to each category of the variable napping (0 for no
napping, 0.5 for <1 hour, and 1.5 for 1 hour) and includ-
ing it as a continuous variable in the regression model. To
further examine whether the relation between napping and
Parkinson disease was influenced by atypical nighttime
sleeping, we conducted analysis by further controlling for
nighttime sleeping duration or limited the analysis to par-
ticipants who reported the typical 7–8 hours of sleeping. All
Napping, Sleeping, and Parkinson Disease 1033
Am J Epidemiol. 2011;173(9):1032–1038
Page 2
statistical analysis was conducted by using SAS software
(version 9.2; SAS Institute, Inc., Cary, North Carolina),
and the significance tests were 2-tailed with a ¼ 0.05.
RESULTS
Table 1 shows population characteristics of Parkinson
disease patients diagnosed at different time periods and of
those without the disease. As expected, Parkinson disease
patients were older than those without Parkinson disease;
they also were more likely to be men and Caucasians but
were less likely to be current smokers, consumed less caf-
feine, and were less physically active. Parkinson disease
patients were more likely to report daytime napping and less
optimal (excellent or very good) health. They were also
more likely to report an ever diagnosis of depression at
the follow-up survey. Refer to Web Table 1 (posted on the
Journals Web site (http://aje.oupjournals.org/)) for popula-
tion characteristics by hours of daytime napping and night-
time sleeping.
Longer daytime napping was associated with higher odds
of having a Parkinson disease diagnosis at all 3 time periods
(Figure 1). The association was strongest for established
cases diagnosed before 1995 (multivariate odds ratio compar-
ing 1hourwithnonapping¼ 3.9, 95% confidence interval:
2.8, 5.6; P for trend <0.0001), followed by recent cases
diagnosed in 1995–1999 (corresponding odds ratio ¼ 2.2,
95% confidence interval: 1.7, 3.0; P for trend <0.0001) and
prediagnostic cases diagnosed in 2000 and after (correspond-
ing odds ratio ¼ 1.5, 95% confidence interval: 1.2, 1.9; P for
trend ¼ 0.0003). Additionally adjusting for self-reported
health status (Figure 1) or hours of nighttime sleeping (Table
2), or limiting the analysis to participants who reported 7–8
hours of sleep (Table 2), modestly attenuated the association
for established cases but made little difference for recent or
prediagnostic cases. Further adjusting for depression up to the
follow-up survey barely changed the results. For example, on
the basis of the fully adjusted model shown in Figure 1, the
odds ratios comparing 1 hour with no napping with addi-
tional adjustment for depression were 2.4 (95% confidence
interval: 1.6, 3.4; P for trend <0.0001) for established cases,
1.9 (95% confidence interval: 1.4, 2.6; P for trend <0.0001)
for recent cases, and 1.4 (95% confidence interval: 1.1, 1.8;
P for trend ¼ 0.0043) for prediagnostic cases. Stratified anal-
yses according to subgroups of age, sex, smoking, and caf-
feine intake generally produced similar results despite lower
statistical power (data not shown).
In the analysis for nighttime sleeping, both shorter and
longer sleeping seemed to be associated with higher odds of
reporting established Parkinson disease diagnosed prior to
1995 (Figure 2). Compared with that for participants who
slept 7–8 hours per night, the multivariate odds ratios for
having established Parkinson disease were 4.9 (95% confi-
dence interval: 3.0, 7.9) for participants reporting <5 hours
of nighttime sleeping, 2.0 (95% confidence interval: 1.5,
2.6) for 5–6 hours, and 1.6 (95% confidence interval: 0.9,
3.0) for 9 hours. However, this association was much at-
tenuated after further adjustment for self-reported health
status (Figure 2). In contrast to prevalent cases, this U-
shaped relation was less apparent for recent cases and
disappeared for prediagnostic cases (Figure 2). Similar to
the napping analysis, further adjustment for depression
or stratifying analyses by age, sex, smoking, and
caffeine intake generally showed similar results (data not
shown).
DISCUSSION
In this large population of older adults in the United States,
we demonstrated that, in addition to strong associations for
established and recent cases, longer daytime napping was
also associated with future Parkinson disease occurrence.
Compared with nonnappers, participants who napped 1
hour per day in 1996–1997 had an approximately 50% higher
chance of reporting a Parkinson disease diagnosis in 2000 and
after. This association with prediagnostic cases could not be
explained by Parkinson disease medications or by inadequate
nighttime sleeping and deteriorating health status, as shown
in our sensitivity analyses. In contrast to napping, although
atypical sleeping durations were more common among estab-
lished Parkinson disease cases, they showed no relation with
future Parkinson disease diagnosis.
It is well known that most Parkinson disease patients
experience sleep abnormalities, ranging from difficulty in
sleep maintenance, to sleep fragmentation, to conditions
such as excessive daytime sleepiness and rapid eye move-
ment sleep behavior disorder (5, 12). This disorder is rare in
the general population but affects up to 27% of Parkinson
disease patients over time (13) and has been suggested to
precede the clinical onset of Parkinson disease (13–17). Not
surprisingly, the current study supports the association of
atypical sleep habits with Parkinson disease. As expected,
the strongest associations were found for established
Parkinson disease cases, which could be partially explained
by their poor health status.
Excessive daytime sleepiness is the well-documented
sleep disturbance that affects 16%–50% of Parkinson dis-
ease patients (18). Longitudinal data among Parkinson
disease patients show that the prevalence of excessive day-
time sleepiness increases as the disease progresses, and
Parkinson disease medications such as dopamine agonists
may, at least partially, contribute to this problem (18). How-
ever, most studies did not clarify whether the presence of
excessive daytime sleepiness is secondary to inadequate
sleep at night and/or side effects of Parkinson disease treat-
ments, or whether it actually develops prior to Parkinson
disease diagnosis. To our knowledge, only one prospective
study has investigated whether daytime sleepiness appears
before Parkinson disease diagnosis (2). The analysis was
conducted in the Honolulu Asia Aging Study with 43 inci-
dent cases and 7 years of follow-up of 3,078 Japanese-Amer-
ican men. The study showed that men who felt sleepy most
of the day were about 3 times more likely to develop Par-
kinson disease than men who did not. Another study found
an association for nurses who slept longer hours in a 24-hour
period, compared with shorter sleepers, with higher future
Parkinson disease occurrence (19). However, this study did
not differentiate between daytime and nighttime sleeping
1034 Gao et al.
Am J Epidemiol. 2011;173(9):1032–1038
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Table 1. Population Characteristics
a
of Parkinson Disease Cases and Individuals Without Parkinson Disease, NIH-AARP Diet and Health Study
Parkinson Disease Case
b
No Parkinson
Disease
(n 5 213,885)
Established
(n 5 267)
Recent
(n 5 396)
Prediagnostic
(n 5 770)
% Mean (SD) % Mean (SD) % Mean (SD) % Mean (SD)
Age, years 64.4 (4.8) 64.9 (5.0) 65.1 (4.7) 62.6 (5.3)
Male sex 77.5 74.5 73.9 57.7
Race
Caucasian 95.5 96.5 94.8 93.2
Others 3.4 2.8 4.3 5.8
Missing 1.1 0.8 0.9 1.0
Cigarette smoking
Never smoker 44.6 46.0 40.1 38.6
Past smoker 49.1 48.5 53.8 51.0
Current smoker 3.8 4.8 4.7 9.3
Missing 2.6 0.8 1.4 1.1
Daily caffeine intake, mg 234.1 (309.7) 311.9 (345.9) 315.5 (336.2) 358.9 (367.6)
Physical activity, hours/week
Never or rare 15.0 11.4 14.8 12.9
<1 12.0 8.6 11.7 10.1
1–3 30.3 31.1 25.3 25.2
4–7 25.8 31.6 26.9 26.4
>7 16.1 16.4 20.4 24.4
Missing 0.8 1.0 0.9 1.1
General health status
Excellent 4.5 15.7 14.8 19.6
Very good 14.6 31.8 37.4 37.8
Good 38.6 38.6 33.3 32.8
Fair 33.0 9.9 11.6 7.9
Poor 6.0 2.3 1.2 0.8
Missing 3.4 1.8 1.8 1.2
Depression
No 71.2 71.5 78.2 82.0
Yes 12.7 14.7 11.6 9.5
Missing 16.1 13.9 10.3 8.6
Hours of daytime napping/day
0 28.8 41.7 41.8 52.0
<1 50.6 41.4 45.7 39.7
1 20.2 16.4 12.2 8.0
Missing 0.4 0.5 0.3 0.3
Hours of nighttime sleeping/day
<5 7.5 2.0 1.6 2.5
5–6 41.6 22.7 30.0 30.9
7–8 46.8 69.7 64.2 63.2
9 4.1 5.6 4.2 3.3
Missing 0.0 0.0 0.1 0.1
Abbreviations: NIH, National Institutes of Health; SD, standard deviation.
a
Sex, race, smoking status, daily caffeine intake, and general health status were derived from the dietary survey (1995–1996); age, physical
activity, and napping/sleeping duration were obtained from the risk factor survey (1996–1997); and depression was ascertained from the follow-up
survey (2004–2006).
b
Established cases: diagnosed before 1995; recent cases: diagnosed in 1995–1999; prediagnostic cases: diagnosed in 2000 and after.
Napping, Sleeping, and Parkinson Disease 1035
Am J Epidemiol. 2011;173(9):1032–1038
Page 4
and might have been affected by the fact that nurses had
altered sleep habits due to shift-work schedules.
The current study is substantially larger than the previous
ones, included both men and women, and simultaneously
examined daytime napping and nighttime sleeping. The re-
sults of our study show that longer daytime napping, but not
atypical nighttime sleeping durations, is associated with fu-
ture Parkinson disease occurrence. Furthermore, our sensi-
tivity analyses of participants with a typical night sleeping
duration (7–8 hours) suggest that the association of longer
day napping and future Parkinson disease occurrence could
not be explained simply by short night sleeping.
The lack of an association between nighttime sleeping and
future Parkinson disease occurrence may need to be ap-
proached cautiously. Although these data may suggest that
indeed nighttime sleeping is not disturbed during the premo-
tor stage of Parkinson disease, this finding may be due to
measurement errors regarding nighttime sleeping duration.
Self-reported night sleeping duration is both approximate
and subjective, and it may not reflect the quality of nighttime
sleeping and the various sleep cycles. Objective, yet relatively
expensive polysonographic assessment provides much better
data on the quality and quantity of nighttime sleeping but is
not suitable for use in large populations. Because daytime
napping generally involves less than one sleep cycle, people
tend to arise if they awake from a daytime nap; thus, reports
of daytime napping time may be more accurate.
Although this study has several strengths, as mentioned
earlier, it also has some limitations. Daytime napping is only
a surrogate for excessive daytime sleepiness, because
whether or not one can actually nap depends on several
factors in addition to his or her tendency to sleep. Therefore,
our result may not be directly comparable to those from
Abbott et al. (2), who aimed to directly ask about daytime
sleepiness. In the current study, we adjusted for and strati-
fied by some known Parkinson disease risk factors and con-
ducted several sensitivity analyses to examine the
robustness of our findings; however, we did not have data
on some other potential confounders such as head injury that
may be associated with both sleep duration and Parkinson
disease (20, 21). Therefore, we were unable to exclude the
possibility of unmeasured confounding.
We relied on self-reports for case identification because it
was necessary in such a large population-based cohort. It is
likely that some cases were not identified and some non-
cases were misclassified as cases. On the other hand, the
ongoing validation study suggests that most self-reports can
be confirmed by the treating neurologists or by expert med-
ical record review. Furthermore, we previously reported the
well-known association of smoking with Parkinson disease
in this cohort, which indirectly supports our case identifica-
tion strategy (22). We did not have information on the co-
hort’s use of dopaminergic medicines, which may alter
sleeping/napping habits; therefore, we were unable to exam-
ine how the use of dopaminergic medicines might have
affected our analyses for prevalent and recent cases.
As in many other epidemiologic studies (23, 24), hours of
napping was self-reported; therefore, misclassification of
Odds Ratio, 95% CI
Hours of Daytime Napping per Day
8.0
4.0
2.0
1.0
0 <1 ≥1 0 <1 ≥1 0 <1 ≥1
Figure 1. Numbers of hours of daytime napping in relation to Parkinson disease diagnosis at different clinical stages for NIH-AARP Diet and
Health Study participants, 1996–2006. Black lines: adjusted for age, sex, race, physical activity, smoking status, and caffeine intake; grey lines:
also adjusted for self-reported health status. All P for trend < 0.0001 except for prediagnostic cases in the basic model (P ¼ 0.0003) and with
additional adjustment for self-reported health status (P ¼ 0.0022). Established cases: diagnosed before 1995; recent cases, diagnosed in 1995–
1999; prediagnostic cases: diagnosed in 2000 and after. Actual values for odds ratios and 95% confidence intervals are provided in Web Table 2
(which is posted on the Journal’s Web site (http://aje.oupjournals.org/)). CI, confidence interval; NIH, National Institutes of Health.
1036 Gao et al.
Am J Epidemiol. 2011;173(9):1032–1038
Page 5
exposure is also possible. For incident cases diagnosed in
2000 and after, however, these misclassifications were likely
nondifferential and therefore might have underestimated the
strength of the association between napping and future
Parkinson disease. The analyses were limited to participants
of the follow-up survey in 2004–2006, which included
approximately only 66.0% of the risk factor survey partic-
ipants. A selection bias could have been introduced if deaths
Odds Ratio, 95% CI
Hours of Nighttime Sleeping per Day
16.0
8.0
4.0
2.0
1.0
0.5
0.25
0.12
<5 5–6 7–8 ≥9 <5 5–6 7–8 ≥9 <5 5–6 7–8 ≥9
Figure 2. Numbers of hours of nighttime sleeping in relation to Parkinson disease diagnosis at different clinical stages for NIH-AARP Diet and
Health Study participants, 1996–2006. Black lines: adjusted for age, sex, race, physical activity, smoking status, and caffeine intake; grey lines:
also adjusted for self-reported health status. Established cases: diagnosed before 1995; recent cases, diagnosed in 1995–1999; prediagnostic
cases: diagnosed in 2000 and after. Actual values for odds ratios and 95% confidence intervals are provided in Web Table 3 (which is posted on the
Journal’s Web site (http://aje.oupjournals.org/)). CI, confidence interval; NIH, National Institutes of Health.
Table 2. Daytime Napping in Relation to Parkinson Disease at Different Stages,
a
With Further Adjustment for Nighttime Sleeping or Limited to
Participants Reporting 7–8 Hours of Nighttime Sleeping, NIH-AARP Diet and Health Study
Clinical Stage in Reference to Exposure Assessment in 1996–1997
b
Established Recent Prediagnostic
PD No PD OR
c
95% CI PD No PD OR
c
95% CI PD No PD OR
c
95% CI
Further adjustment for
hours of nighttime
sleeping
None (ref) 77 111,237 1.0 165 111,237 1.0 322 111,237 1.0
<1 hour 135 84,971 1.9 1.4, 2.5 164 84,971 1.1 0.9, 1.4 352 84,971 1.2 1.0, 1.3
1 hours 54 16,997 3.4 2.4, 4.9 65 16,997 2.3 1.7, 3.1 94 16,997 1.5 1.2, 2.0
P for trend <0.0001 <0.0001 0.0004
Limited to participants
reporting 7–8 hours
of nighttime sleeping
None (ref) 39 73,409 1.0 126 73,409 1.0 214 73,409 1.0
<1 hour 72 52,918 2.1 1.4, 3.1 108 52,918 1.0 0.8, 1.3 227 52,918 1.2 1.0, 1.4
1 hour 13 8,485 2.4 1.3, 4.5 40 8,485 2.4 1.7, 3.5 51 8,485 1.6 1.2, 2.2
P for trend 0.0009 <0.0001 0.0019
Abbreviations: CI, confidence interval; NIH, National Institutes of Health; OR, odds ratio; PD, Parkinson disease; ref, reference.
a
Established cases: diagnosed before 1995; recent cases, diagnosed in 1995–1999; prediagnostic cases: diagnosed in 2000 and after.
b
PD: number of Parkinson disease cases; no PD: number of participants without Parkinson disease.
c
Covariates included age, sex, race, smoking status, daily caffeine intake, physical activity, daytime napping, and nighttime sleeping.
Napping, Sleeping, and Parkinson Disease 1037
Am J Epidemiol. 2011;173(9):1032–1038
Page 6
or losses to follow-up had been differentially related to nap-
ping habits by Parkinson disease status. Finally, previous
studies show rapid eye movement sleep behavior disorder
may predate Parkinson disease by a decade (14), whereas
our study did not collect data on this disorder and had a
shorter follow-up interval. Nonetheless, our study suggests
that daytime napping, not atypical nighttime sleep duration,
is associated with a higher future risk of Parkinson disease.
ACKNOWLEDGMENTS
Author affiliations: Epidemiology Branch, National Insti-
tute of Environmental Health Sciences, Research Triangle
Park, North Carolina (Jianjun Gao, Honglei Chen); Depart-
ment of Neurology, Pennsylvania State University-Milton S.
Hershey Medical Center, Hershey, Pennsylvania (Xuemei
Huang); Nutritional Epidemiology Branch, National Cancer
Institute, Rockville, Maryland (Yikyung Park, Arthur
Schatzkin); Occupational and Environmental Epidemiology
Branch, National Cancer Institute, Rockville, Maryland
(Aaron Blair); and AARP, Washington, DC (Albert
Hollenbeck).
Drs. Gao and Huang contributed equally to this manu-
script.
This study was supported by the intramural research pro-
gram of the National Institutes of Health (NIH), the National
Institute of Environmental Health Sciences (Z01-ES-
101986), the National Cancer Institute (Z01 CP010196-
02), and an NIH extramural grant (R01 NS060722) to
Dr. Huang.
Conflict of interest: none declared.
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  • Source
    • "Therefore, knowledge of the role of Ox/Hcrt in EDS suggests a mechanistic basis, at least in part, for the occurrence of EDS seen in PD. Although it is currently not understood at which location within the brain the loss of Ox/Hcrt input could lead to development of EDS, a heavy Ox/Hcrt projection is directed to the pontine tegmentum, and loss of this input demonstrated to be excitatory [57], combined with degeneration of the arousal-related brainstem neurons likely contribute to the EDS symptomology associated with PD [27, 32, 58] [33]. "
    [Show abstract] [Hide abstract] ABSTRACT: Parkinson's disease (PD) is a neurobehavioral disorder characterized by motor symptoms and signs, and non-motor abnormalities such as olfactory dysfunction, pain, sleep disorders and cognitive impairment. Amongst these alterations, sleep disturbances play an important role in the pathology, but presence of disturbed sleep is not currently considered in diagnosis. However, sleeping problems may precede by many years the classic motor abnormalities of PD and should be clinically evaluated as a potential marker before disease onset. The first disturbance reported with this potential was the disorder REM sleep behaviour and currently several other disturbances have gained importance as potential markers, such as excessive daytime sleepiness, restless legs syndrome and new evidence also points to changes in circadian rhythms. Here we present a brief review of the major evidence indicating that sleep disturbances precede the motor symptoms in PD and neurodegeneration occurs in regions that could underlie these phenomena in order to provide support for the conclusion that disturbances of sleep should be considered as valuable preclinical markers for PD.
    Full-text · Article · Nov 2014 · Neurochemical Research
  • Source
    • "A long-established practice in Mediterranean areas, daytime napping, namely siesta, is often linked with good health through a postulated “stress relief” mechanism (6). However, daytime sleepiness, often characterized by daytime napping, has been suggested as an early sign or risk indicator of a range of health problems (7–9). To date, the association between daytime napping and mortality risk is uncertain. "
    [Show abstract] [Hide abstract] ABSTRACT: Epidemiologic studies have reported conflicting results on the relationship between daytime napping and mortality risk, and there are few data on the potential association in the British population. We investigated the associations between daytime napping and all-cause or cause-specific mortality in the European Prospective Investigation Into Cancer-Norfolk study, a British population-based cohort study. Among the 16,374 men and women who answered questions on napping habits between 1998 and 2000, a total of 3,251 died during the 13-year follow-up. Daytime napping was associated with an increased risk of all-cause mortality (for napping less than 1 hour per day on average, hazard ratio = 1.14, 95% confidence interval: 1.02, 1.27; for napping 1 hour or longer per day on average, hazard ratio = 1.32, 95% confidence interval: 1.04, 1.68), independent of age, sex, social class, educational level, marital status, employment status, body mass index, physical activity level, smoking status, alcohol intake, depression, self-reported general health, use of hypnotic drugs or other medications, time spent in bed at night, and presence of preexisting health conditions. This association was more pronounced for death from respiratory diseases (for napping less than 1 hour, hazard ratio = 1.40, 95% confidence interval: 0.95, 2.05; for napping 1 hour or more, hazard ratio = 2.56, 95% confidence interval: 1.34, 4.86) and in individuals 65 years of age or younger. Excessive daytime napping might be a useful marker of underlying health risk, particularly of respiratory problems, especially among those 65 years of age or younger. Further research is required to clarify the nature of the observed association.
    Full-text · Article · Mar 2014 · American journal of epidemiology
  • Source
    • "This result may reflect the fact that EDS and excessive daytime napping are actually separate constructs. However, several earlier studies have suggested an overlap between EDS and excessive daytime napping exists within PD cohorts [3,4,789. Thus the results presented here suggest that the ESS may not be an ideal measure of all elements of daytime sleep disturbance within PD patients. "
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Methods: Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Results: Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. Conclusion: This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms.
    Full-text · Article · Nov 2013 · PLoS ONE
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