Original Article Insomnia disorder increases the risk of subjective memory decline in middle-aged and older adults: a longitudinal analysis of the ...
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SLEEP, 2022, 1–13
https://doi.org/10.1093/sleep/zsac176
Advance Access Publication Date: 25 July 2022
Original Article
Original Article
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Insomnia disorder increases the risk of subjective memory decline
in middle-aged and older adults: a longitudinal analysis of the
Canadian Longitudinal Study on Aging
Jean-Louis Zhao1,2,†, Nathan Cross1,3,4,5,*,†, , Chun W. Yao5,6,7, , Julie Carrier1,5,8,9,
Ronald B. Postuma5,8,10, Nadia Gosselin5,8,9, Lisa Kakinami3,11 and Thien Thanh Dang-Vu1,2,3,4,5,*
1
Institut Universitaire de Gériatrie de Montréal and CRIUGM, CIUSSS du Centre-Sud-de-l’Ile-de-Montréal, Montreal, Canada, 2Department of
Neuroscience, Université de Montreal, Montreal, Canada, 3PERFORM Centre, Concordia University, Montreal, Canada, 4Department of Health,
Kinesiology and Applied Physiology, Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Canada, 5Canadian Sleep
and Circadian Network, Montreal, Canada, 6Integrated Program in Neuroscience, McGill University, Montreal, Canada, 7Research Institute of
McGill University Health Center, Montreal, Canada, 8Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montreal,
CIUSSS du Nord-de-l’Ile-de-Montréal, Montreal, Canada, 9Department of Psychology, Université de Montréal, Montreal, Canada, 10Department
of Neurology and Neurosurgery, McGill University—Montreal General Hospital, Montreal, Canada and 11Department of Mathematics and
Statistics, Concordia University, Montreal, Canada
*Corresponding author. Nathan Cross and Thien Thanh Dang-Vu, Center for Studies in Behavioral Neurobiology and PERFORM Center, Concordia
University, 7141 Sherbrooke St. West, SP 165.30, Montreal, QC, Canada. Email: nathan.cross@concordia.ca; tt.dangvu@concordia.ca.
†
These authors contributed equally.
Abstract
Study Objectives: To examine the longitudinal association between probable insomnia status and both subjective and objective memory decline in middle-aged and
older adults.
Methods: 26 363 participants, ≥45 years, completed baseline and follow-up (3 years after baseline) self-reported evaluations of sleep and memory, and
neuropsychological testing in the following cognitive domains: memory, executive functions, and psychomotor speed. Participants were categorized as having
probable insomnia disorder (PID), insomnia symptoms only (ISO), or no insomnia symptoms (NIS), based on sleep questionnaires. Participants were further grouped
based on their sleep change over time. Prospective odds of self-reported memory worsening were assessed using logistic regression, and associations between
insomnia and cognitive performance were assessed via linear mixed-effects modeling, adjusted for demographic, lifestyle, and medical factors.
Results: An increased odds (OR 1.70; 95% CI 1.29–2.26) of self-reported memory worsening was observed for NIS participants at baseline who developed PID at follow-up
compared to those who developed ISO or remained NIS. Additionally, participants whose sleep worsened from baseline to follow-up (i.e. transitioned from NIS to ISO,
ISO to PID, or NIS to PID) displayed increased odds (OR 1.22; 95% CI 1.10–1.34) of subjective memory worsening at follow-up compared to those who remained insomnia-
free or improved their sleep. There were no significant associations between the development of PID or worsening sleep and performance on neuropsychological tests.
Conclusions: These findings of an increased odds for subjective memory decline in middle-aged and older adults with insomnia disorder suggest insomnia may be
an important target for early interventions addressing age-related cognitive decline.
Statement of Significance
These findings demonstrate an increased odds of experiencing subjective memory decline in middle-aged and older adults who devel-
oped insomnia disorder, compared to adults who developed insomnia symptoms alone or no insomnia symptoms. Subjective memory
complaints often precede the onset of mild cognitive impairment and dementia; therefore, insomnia disorder may contribute to the early
stages of cognitive decline. Clinical management of insomnia in middle-aged and older adults thus may have implications for reducing the
risk of cognitive decline.
Key words: insomnia; cognition; memory; aging; cohort; CLSA
Submitted: 24 March, 2022; Revised: 13 July, 2022
© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights
reserved. For permissions, please e-mail: journals.permissions@oup.com
12 | SLEEP, 2022, Vol. 45, No. 11
Introduction controlling for age-related demographic, lifestyle, and medical
factors. We hypothesized that we would observe higher propor-
Insomnia disorder is characterized by difficulties initiating or
tions of subjective and objective memory decline in adults who
maintaining sleep, or early morning awakenings, accompanied
developed PID at follow-up, compared to those who remained
by daytime impairment and poor self-reported quality of sleep
without insomnia, and that higher proportions of memory
[1]. It is one of the most prevalent sleep disorders, accounting for
decline would also be observed in adults who experienced
about 10% of the adult population [2, 3]. Moreover, nearly one-
worsening of their sleep quality (i.e. developing ISO or PID), com-
third of adults experience insomnia symptoms without impair-
pared to those whose sleep improved over the same interval.
ments of daytime functioning and do not fulfill all criteria for an
insomnia disorder diagnosis [2, 3].
Insomnia has been shown to be associated with cognitive
impairment across multiple domains [4–10]. Concurrently, cog-
Methods
nitive changes occurring with normal aging have also been well Study design and participants
documented [11, 12]. Sleep quality also declines with age, and the
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The sample was derived from the 30 097 participants who com-
link between sleep and age-related cognitive decline has been
pleted the baseline assessments of the comprehensive cohort
previously established [13]. In our previous cross-sectional study,
from the Canadian Longitudinal Study on Aging (CLSA). The
using a large dataset of a comprehensive cohort study [14], we
final sample consisted of 26 363 participants who completed
examined the cognitive performance of middle-aged and older
both the baseline assessments and the first wave follow-up
adults with probable insomnia disorder (PID) based on ques-
assessments (mean duration of 3.0 ± 0.3 years after baseline).
tions aligned with DSM-5 criteria. In that study, we found that
The CLSA is a national, 20-year, prospective cohort study that
PID was associated specifically with poorer memory perform-
started data collection in 2011. The CLSA study design and re-
ance compared to those who experience insomnia symptoms
cruitment process have been comprehensively described and
only (ISO) or no insomnia symptoms (NIS), after controlling for
published elsewhere [14]. This large-scale cohort study collects
age-related demographic, lifestyle, and medical outcomes [15].
information on the biological, medical, cognitive, psychological,
Yet, the predictive role of insomnia disorder in relation to subse-
social, lifestyle, and economic aspects of middle-aged and older
quent memory decline in later life remains unclear. Several lon-
adults. Briefly, individuals were recruited through either health
gitudinal studies have shown links between sleep complaints
registration databases or random digit dialing. Eligible partici-
(e.g. sleep duration, self-reported sleep quality, snoring) and the
pants were aged 45–85 years at the recruitment, lived within 25
increasing risk of cognitive decline or dementia in middle-aged
or 50 km of 1 of 11 data collection sites (depending on the site),
and older adults [16–22]. However, the longitudinal associations
were able to communicate in English or French, and exhibited
between memory and insomnia disorder in older adults remain
an absence of cognitive impairment at baseline. Moreover, per-
to be addressed since earlier studies only evaluated broad sleep
sons living in the three Canadian territories and remote areas,
measures (e.g. sleep duration, overall self-reported sleep quality)
on federal First Nations reserves and other settlements in the
without a probable clinical diagnosis.
provinces, full-time members of the Canadian Armed Forces,
In older individuals, the presence of self-reported “sub-
and institutionalized individuals were excluded from the CLSA.
jective” memory complaints (SMC) (e.g. a complaint of de-
For our study, further exclusion criteria included: any prior diag-
creased memory performance) is associated with an elevated
nosis of dementia, stroke, or major head injury resulting in a
risk of eventual progression to mild cognitive impairment (MCI)
loss of consciousness >20 min. To assess the relationship be-
or dementia (~40.7% over 4-years) [23, 24]. Such conversion to
tween insomnia and self-reported memory decline or objective
MCI and dementia in individuals with SMC may occur pro-
memory performance, medical and sleep comorbidities were
gressively over 10–15 years, depending on factors such as age
not part of the exclusion criteria.
and the presence of other determined dementia risk factors,
Study participants who are part of the CLSA compre-
including sleep quality [25]. Additionally, memory performance
hensive cohort were asked to provide information through
decline assessed through neuropsychological testing, followed
computer-assisted personal interviews, physical examinations,
by a decline in other cognitive domains has been shown to
neuropsychological battery, and biological samples—admin-
often precede the clinical manifestations of dementias such
istered per standardized protocols. Computer-assisted per-
as Alzheimer’s disease [26, 27]. Hence, evaluating the associ-
sonal interviews were administered at home, at baseline, and
ation between insomnia disorder and the presence of SMC or
follow-up. Neuropsychological data were collected during visits
objective memory impairments in older adults is important to
to data collection centers or during in-home interviews (when
capture risk factors that may be involved in the earliest stages
participants were unable to travel to the data collection center),
of cognitive decline.
at baseline and follow-up, for most participants (Supplementary
Therefore, the primary aim of this study was to investigate
Table 1).
the longitudinal relationship between (1) the development of
PID and the emergence of subjective and objective memory de-
cline in middle-aged and older adults, and (2) the trajectory of
Standard protocol approvals, registrations, and patient
insomnia symptoms (i.e. worsening or improving) and the emer-
consents
gence of subjective and objective memory decline. Additionally,
an exploratory aim of this study was to establish whether a The Canadian Longitudinal Study on Aging was approved by 13
longitudinal association exists between the progression of no research ethics boards across Canada, as well as the Canadian
insomnia symptoms to PID and objective deficits across other Institutes of Health Research (CIHR) Advisory Committee on
cognitive domains. We assessed these relationships while Ethical, Legal and Social Issues (ELSI) for the CLSA. WrittenZhao et al. | 3
informed consent was obtained from all individual participants number of words recalled in one immediate recall trial (RAVLT I)
included in the study [14]. and one short delay recall trial (RAVLT II, with a delay of 5 min)
were reported [35]. Furthermore, as part of an exploratory ana-
lysis, participants additionally completed tests that assessed
Sleep and insomnia measures performance across other cognitive domains such as executive
functions and psychomotor speed using well-validated meas-
Measures of sleep habits were collected at baseline and follow-up
ures. Briefly, measures of executive functions were obtained
through structured self-report questions that were designed for
using the Mental Alternation Test (MAT) and the Stroop Test
this study as part of a larger set of measures to assess phys-
(Victoria version), whereas psychomotor speed was assessed
ical functioning. The questions were drawn from validated sleep
via the Choice Reaction Time (CRT) Test. For detailed informa-
questionnaires [28–30] and captured important aspects of sleep
tion, see the Supplementary Data information. All tests were
and their relation to health. The questions covered six domains:
scored in a standardized way in collaboration with a CLSA
(1) participants’ satisfaction with the type of sleep they were
co-investigator who is a clinical neuropsychologist.
getting; (2) hours of nighttime sleep; (3) trouble falling asleep or
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staying asleep; (4) daytime sleepiness; (5) dream enactment be-
havior; (6) if they experienced, recurrent, uncomfortable feelings
or sensations in the legs, or urges to move their legs while sitting
Demographic and lifestyle measures
or lying down (Supplementary Table 2). Sociodemographic measures, including age, sex, language, eth-
Symptoms related to insomnia were drawn from domains 1 nicity, household income, and years of education, were obtained
and 3. These questions were utilized to make a probable diag- through questionnaire-based interviews at baseline and
nosis of insomnia disorder based on standard diagnostic criteria follow-up. In addition, lifestyle variables, including tobacco con-
from the DSM-5 [1]. For detailed information on the questions sumption (current and former smoking habits), weekly alcohol
used, see the Supplementary Data information. Specifically, consumption, and activity level, were also collected at baseline
only participants who experienced difficulties with sleep onset and follow-up. For detailed information on the questions used,
or maintenance three times or more per week, for longer than see the Supplementary Data information.
3 months, and stated that it significantly interfered (≥“Much”)
with their daily functioning, and additionally were dissatisfied
with their sleep pattern (4 | SLEEP, 2022, Vol. 45, No. 11
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Figure 1. (A) Criteria used for categorization into PID and ISO. (B) Study flowchart and group classification for Analysis 1 and Analysis 2. NIS, no insomnia symptoms;
ISO, insomnia symptoms only; PID, probable insomnia disorder.
decline with PID. Secondary outcomes included self-reported progression from no insomnia symptoms (NIS) at baseline to ei-
physician-diagnosed memory problem and the associations ther NIS, insomnia symptoms only (ISO), or probable insomnia
between PID and other cognitive domains (executive functions disorder (PID) at follow-up (NIS to NIS; NIS to ISO; or NIS to PID),
and psychomotor speed) with PID. All analyses were conducted whereas the second analysis (Analysis 2) was based on whether
with R (R version 4.0.0) [36]. Differences in demographic, life- participants had improving (ISO to NIS, PID to ISO, PID to NIS) or
style, and medical characteristics between groups at baseline worsening (NIS to ISO, NIS to PID, ISO to PID) insomnia status.
were assessed using ANOVA with Tukey’s honest significance The association between the different insomnia groups and self-
test, or Pearson’s chi-squared tests. In total, two main analyses reported memory decline or self-reported physician-diagnosed
were performed (Figure 1, B). Briefly, the first analysis (Analysis memory problem at follow-up was analyzed with logistic regres-
1) examined differences between groups based on participants’ sion models (using the default algorithm in R). The associationZhao et al. | 5
between the different insomnia groups and objective measures Participation retention
of cognitive performance over the following domains: memory,
From the individuals who met the criteria for this study at the
executive functions, and psychomotor speed was assessed with
baseline assessment, 2122 (7.5%) withdrew from data collec-
linear mixed-effects models, probing the interaction between
tion at follow-up. Participants who had withdrawn from the
change in cognitive performance and the change in insomnia
study appeared to be older and a higher proportion reported
status, from baseline to follow-up. These analyses were per-
worse insomnia symptoms at baseline (Supplementary Table
formed using the “lmer” function of the “lme4” package in R
3). In total, 12.1% of individuals who were identified as PID at
[36]. All models included participants as a random factor, while
baseline withdrew, compared to 8.1% of participants who were
group, time, as well as their interaction were set as fixed factors.
identified as ISO, and 7.0% of those who were identified as NIS.
Pairwise comparisons with false discovery rate (FDR) correction
Causes for withdrawal included: participants developing health-
method were performed post-hoc, separately for the group-level
related issues; participants changing locations; participants un-
comparison of demographic and clinical characteristics, and for
able to continue due to cognitive decline; participants entering
each linear mixed model for all cognitive tests. While this ap-
long-term care; reasons related to study fatigue; and death [39].
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proach is less conservative than other methods, type II errors
are less likely, and the approach provides better control against
errors originating from multiplicity [37]. Results of the associ-
Insomnia status conversions over time
ations between the insomnia groups and objective measures of
cognitive performance for executive functions and psychomotor Across the entire sample, 12 145 (66.45%) participants who met
speed are shown in the Supplementary Material. the criteria for NIS during baseline remained NIS in the follow-up
For each cognitive outcome, two models were created with assessment, 5652 (30.92%) transitioned to ISO and 481 (2.63%) to
increasing complexity. A minimally adjusted model (model 1) ad- PID. Of the participants who experienced ISO at baseline, 2166
justed for age, sex, a binary variable of total household income (30.31%) remained ISO at follow-up, while 4,804 (67.22%) con-
(>50 000 $ or ≤50 000 $), years of education, ethnicity, language, verted to NIS and 176 (2.46%) to PID. Finally, of the participants
time to follow-up, and percentage loss to follow-up, based on our who experienced PID at baseline, only 27 (2.88%) had persisting
previous findings from the baseline study [14]. Percentage loss PID, while 311 (33.12%) reverted to ISO and 601 (64.00%) to NIS.
to follow-up was included as a covariate in order to reduce any
bias of a difference between groups in this variable. The second
model (model 2) additionally adjusted for a range of a priori fac- Analysis 1—NIS at baseline to NIS, ISO, or PID
at follow-up
tors that were considered relevant in the context of cognitive
aging. These factors included: BMI, alcohol consumption (≥4 Sample characteristics.
times per week), diagnosis of cancer, anxiety disorder, clinical To probe the association between the development of insomnia
depression, or hypertension, current level of smoking, presence disorder in middle and later life with changes in cognition, the
of chronic pain, activity level, a report of daytime sleepiness, a first analysis included 18 278 adults who initially exhibited NIS
witness report of breathing interruption during sleep (i.e. sleep during baseline, disaggregated by insomnia status progression.
apnea), a self-report of RBD (pRBD), a self-report of RLS, a re- In total, 12 145 (66.4%) participants were classified in group 1 (NIS
port of using sleep-related medications including hypnotics, to NIS), 5652 (30.9%) participants in group 2 (NIS to ISO) and 481
antidepressants, antipsychotics, antiepileptics, antihistamines (2.6%) participants in group 3 (NIS to PID). Baseline demographic,
and analgesics, as well as insufficient sleep (6 | SLEEP, 2022, Vol. 45, No. 11
Table 1. Baseline demographic, lifestyle, and medical characteristics of participants in Analysis 1
NIS-NIS NIS-ISO NIS-PID
(Group 1) (Group 2) (Group 3) sig. sig. sig.
n = 12 145 n = 5652 n = 481 2 vs. 1 3 vs. 1 3 vs. 2
Demographics
Age, years ± SD 65.47 (9.99) 65.75 (10.21) 62.24 (8.87) 0.256Zhao et al. | 7
Table 2. Associations between insomnia and subjective memory decline at follow-up—Analysis 1
Subjective memory
Group 2 vs. Group 1† Group 3 vs. Group 1† Group 3 vs. Group 2†
Self-reported memory worsening
Model 1 OR [95% CI] 1.24*** [1.15–1.34] 2.00*** [1.57–2.55] 1.64*** [1.28–2.10]
Model 2 OR [95% CI] 1.19*** [1.10–1.30] 1.70*** [1.29–2.26] 1.45* [1.09–1.94]
Self-reported diagnosed memory problem
Model 1 OR [95% CI] 0.94 [0.60–1.44] 3.92*** [1.86–7.73] 3.75*** [1.79–7.86]
Model 2 OR [95% CI] 0.70 [0.41–1.21] 2.80* [1.16–6.77] 5.55*** [2.02–15.20]
OR, odds ratio; 95% CI, 95% confidence intervals.
Group 1 = NIS to NIS; Group 2 = NIS to ISO; Group 3 = NIS to PID.
Model 1 = adjusted for age, sex, a binary variable of total household income (>50 000 $ or ≤50 000 $), years of education, ethnicity, language, time to follow-up, and
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percentage loss to follow-up; Model 2 = adjusted for age, sex, a binary variable of total household income (>50 000 $ or ≤50 000 $), years of education, ethnicity, lan-
guage, time to follow-up, and percentage loss to follow-up, BMI, alcohol consumption (≥4 times per week), diagnosis of cancer, anxiety disorder, clinical depression,
or hypertension, current level of smoking, presence of chronic pain, activity level, a report of daytime sleepiness, a witness report of breathing interruption during
sleep, a self-report of RBD, a self-report of RLS, a report of using sleep-related medications including hypnotics, antidepressants, antipsychotics, antiepileptics, anti-
histamines, and analgesics, as well as insufficient sleep (8 | SLEEP, 2022, Vol. 45, No. 11
Table 4. Baseline demographic, lifestyle, and medical characteristics of participants in Analysis 2
Improving Worsening
symptoms Symptom- symptoms sig. sig. sig.
group free group group Free vs. Worsening vs. Worsening vs.
n = 5716 n = 12 145 n = 6309 improving improving free
Demographics
Age, years ± SD 65.39 (10.04) 65.47 (9.99) 65.40 (10.15) 0.969 0.998 0.969
Sex, %F 47.81 47.8 59.6 0.975Zhao et al. | 9
such as anxiety and depression compared to participants who Associations between insomnia and objective memory
remained without symptoms or those with improving symp- decline.
toms. Similarly, participants in the “worsening symptoms”
Results of the association between insomnia and declarative
group showed a larger prevalence of sleep-related medication
memory (RAVLT) assessed via linear mixed-effects modeling for
use, specifically for hypnotics and analgesics compared to the
model 2 are reported in Table 6, while results for model 1 are
other groups.
shown in Supplementary Table 10. On the immediate recall trial
(RAVLT I), after adjusting for model 1, there was a significant per-
formance improvement over time (β = 0.70 ± 0.01; 95% CI 0.68–
Associations between insomnia and subjective memory 0.73), as well as a significant group effect (i.e. insomnia groups).
decline.
Participants who had worsening insomnia status (worsening
Results of the logistic regression analysis are shown in symptoms group) performed significantly worse than partici-
Table 5. On the first dichotomous dependent variable—sub- pants who had improving insomnia status (improving symp-
jective memory worsening (Yes/No), 57.2% of participants toms group) across both assessments (β = −0.08 ± 0.03; 95% CI
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across all groups reported experiencing memory worsening −0.14–[−0.01]). However, there were no significant differences
at follow-up. For the minimally adjusted model (model 1), the between all other insomnia groups. There was no significant
odds of having memory worsening at follow-up were 27.3% interaction between time and insomnia groups. After adjusting
greater (OR 1.27; 95% CI 1.17–1.39) for participants who ex- for model 2, the significant positive effect of time remained
hibited deteriorating insomnia status (worsening symptoms (β = 0.72 ± 0.02; 95% CI 0.69–0.75), but the insomnia group effect
group) compared to those who exhibited improving insomnia was no longer significant. Furthermore, there was no significant
status (improving symptoms group) and 28.7% higher (OR 1.29; interaction between time and insomnia groups. On the delayed
95% CI 1.19–1.39) for participants in the “worsening symp- recall trial (RAVLT II), after adjusting for model 1, there was a sig-
toms” group compared to participants who remained without nificant positive effect of time (β = 0.59 ± 0.02; 95% CI 0.56–0.62),
symptoms (symptom-free group). Similarly, after adjusting for as well as a significant insomnia group effect. Similarly, parti-
model 2, the odds of having memory worsening at follow-up cipants in the “worsening symptoms” group performed signifi-
were 21.5% higher (OR 1.22; 95% CI 1.10–1.34) for participants cantly worse than participants in the “improving symptoms”
in the “worsening symptoms” group compared to those in the group across both assessments (β = −0.11 ± 0.04; 95% CI −0.18–
“improving symptoms” group and 21.8% higher (OR 1.22; 95% [−0.04]), however, no significant difference between other in-
CI 1.12–1.33) for the “worsening symptoms” group compared somnia groups was found. There was no significant interaction
to the “symptom-free” group. Furthermore, there were no sig- between time and insomnia groups. After adjusting for model 2,
nificant differences in the odds of having subjective memory the significant positive effect of time (β = 0.59 ± 0.02; 95% CI 0.57–
worsening at follow-up for participants in the “symptom-free” 0.62) remained, but the insomnia group effect was no longer sig-
group compared to the “improving symptoms” group in both nificant. There was no significant interaction between time and
model 1 and model 2. insomnia groups. Results of the associations between insomnia
Lastly, on the second dichotomous dependent variable— and the other cognitive tests are shown in Supplementary Table
self-reported diagnosed memory problem (Yes/No), 0.8% of par- 11. Briefly, there was no significant interaction between time
ticipants across all groups self-reported being diagnosed with and insomnia groups in executive functions in both models.
a memory problem at follow-up. Results were not statistically Moreover, there was no significant interaction between time and
significant after adjusting for model 1 or model 2. insomnia groups in psychomotor speed in all models.
Table 5. Associations between insomnia and subjective memory decline at follow-up—Analysis 2
Subjective memory
Symptom-free vs. improving Worsening symptoms vs. improving Worsening symptoms vs.
symptoms† symptoms† symptom-free†
Self-reported memory worsening
Model 1 OR [95% CI] 0.99 [0.92–1.06] 1.27*** [1.17–1.39] 1.29*** [1.19–1.39]
Model 2 OR [95% CI] 1.00 [0.92–1.08] 1.21*** [1.10–1.34] 1.22*** [1.12–1.33]
Self-reported diagnosed memory problem
Model 1 OR [95% CI] 1.13 [0.74–1.74] 1.35 [0.84–2.17] 1.16 [0.78–1.72]
Model 2 OR [95% CI] 1.09 [0.67–1.78] 0.97 [0.55–1.72] 0.85 [0.52–1.39]
OR, odds ratio; 95% CI, 95% confidence intervals.
Model 1 = adjusted for age, sex, a binary variable of total household income (>50 000 $ or ≤50 000 $), years of education, ethnicity, language, time to follow-up, and
percentage loss to follow-up; Model 2 = adjusted for age, sex, a binary variable of total household income (>50 000 $ or ≤50 000 $), years of education, ethnicity, lan-
guage, time to follow-up, and percentage loss to follow-up, BMI, alcohol consumption (≥4 times per week), diagnosis of cancer, anxiety disorder, clinical depression,
or hypertension, current level of smoking, presence of chronic pain, activity level, a report of daytime sleepiness, a witness report of breathing interruption during
sleep, a self-report of RBD, a self-report of RLS, a report of using sleep-related medications including hypnotics, antidepressants, antipsychotics, antiepileptics, anti-
histamines, and analgesics, as well as insufficient sleep (10 | SLEEP, 2022, Vol. 45, No. 11
Table 6. Estimated fixed effects for declarative memory—Analysis 2
Estimates of fixed effects
Memory Parameter Estimate (SE) df t p 95% CI
RAVLT I
Model 2 Time (baseline vs. follow-up) 0.722 (0.02) 15 250 45.440Zhao et al. | 11
to cognitive decline and dementia [42, 43]. Nevertheless, fol- worsening was only asked during the follow-up assessment and
lowing adjustment of these risk factors, our results demon- was not available at baseline. As such, it is not possible to dis-
strated that symptom-free adults who developed PID remained tinguish whether participants already had subjective memory
at increased odds of subjective memory decline compared with complaints at baseline. However, based on the phrasing of the
adults who converted to ISO or remained NIS. This suggests that question (“Do you feel like your memory is becoming worse?”),
there also still exists an independent association between prob- it is implied that their memory deteriorated since the base-
able insomnia disorder and subjective memory decline. line assessment. Furthermore, the classification of PID was
In contrast, objective neuropsychological testing did not seemingly unstable from baseline to follow-up as only a few
reveal any significant associations between insomnia and participants (2.88%) who had PID at baseline remained PID at
memory performance, or other cognitive domains. Given the follow-up. Therefore, the long-term consequences of persistent
short time interval between both assessments in this study insomnia disorder could not yet be investigated within this co-
(~3 years) and considering the age distribution of the CLSA co- hort. This is surprising as studies have shown that insomnia
hort, it is plausible that the current follow-up period is not a as a disorder is often a persistent condition, with a remission
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long enough duration for the association between insomnia rate of only 14%–41% over 1–5 years [53]. The low rate of per-
and objective cognitive decline to be determined yet within this sistent insomnia disorder within this cohort could partly be due
study cohort. Participants who developed PID and exhibited to the evaluation methods. A classification of PID was meas-
subjective memory decline at this stage could potentially show ured using questions reflecting the DSM-5 criteria, but these
further cognitive decline in the upcoming years. The examin- were not part of a standardized clinical interview conducted by
ation of this cohort in future will be important to understand a qualified clinician. Thus, this cannot be regarded as a definite
if probable insomnia disorder may increase the risk of devel- in-person diagnosis of insomnia disorder, although this would
opment of neurodegenerative diseases and dementia in older be difficult to achieve in such a large sample size. Additionally,
adults over time. despite including percentage lost to follow up as a confound,
However, our results revealed that compared to female par- participants who withdrew from the study before the follow-up
ticipants, male adults with NIS at baseline who developed PID period were likely to be older and a higher proportion reported
exhibited significantly poorer memory performance (RAVLT II) worse insomnia symptoms at baseline, which may have in-
over time compared with those who converted to ISO or re- fluenced these findings. Lastly, another limitation could in-
mained symptom-free, despite females with PID showing a volve the CLSA study design and stringent selection criteria of
greater prevalence of SMC. One possible explanation for this incorporating only cognitively healthy adults with an absence
disparity could be that men are often more reluctant to seek of cognitive impairment, dementia, or history of brain trauma
help and express their symptoms related to health issues [44, at baseline. Participants also seemed to be healthier, more edu-
45], however, the prevalence of SMC among male and female cated, and have higher household income than the general
older adults is mixed in the literature [46–49]. Another explan- Canadian population [39]. Given the profile of the CLSA cohort,
ation could be that women have previously been shown to out- these associations may differ in a sample more representative
perform men on verbal memory tasks, specifically in adults with of the general population. Nonetheless, the fact that significant
SMC [50] which could potentially indicate a sex-specific form of differences in subjective memory performance were still able to
cognitive reserve delaying memory impairment prior to further be detected demonstrates the sensitive relationship between
cognitive decline [51, 52]. However, the interaction between sex insomnia and memory in aging. Stronger associations may be-
and insomnia status on objective memory change in this study come more prevalent as cognitive function declines over time,
was no longer significant after adjusting for age-related demo- and more diagnoses of dementia occur within the cohort.
graphic, lifestyle, and medical factors. Therefore, there appears In conclusion, these findings suggest that insomnia disorder
to be a complex relationship between subjective and objective in middle-aged and older adults is associated with higher pro-
memory impairments in older adults. portions of subjective memory decline, even after controlling for
Taken together, these findings suggest that insomnia as a lifestyle factors and comorbidities. Objective memory deficits
disorder, rather than symptoms of insomnia alone, is important were found only in men who developed probable insomnia dis-
in the context of early changes in cognitive function in later order and could indicate a potential sex effect specific to the
life. Subjective reports of daytime difficulties should be taken onset of insomnia in older adults rather than the worsening of
into consideration when monitoring cognitive decline in older sleep, however this relationship appears complex and any sex
adults with sleep complaints. Insomnia disorder thus may be differences require further targeted investigation. Insomnia dis-
considered part of a combination of adverse factors that occur order may be a predictor of further cognitive decline and early
in middle age and older adults, which are linked to higher risk signs of dementia, however more longitudinal evidence is re-
of cognitive decline and may lead to MCI and dementia in later quired to confirm this.
life. Importantly, adults who had improving sleep symptoms did
not develop subjective memory decline at follow-up, suggesting
that the adverse cognitive effects of insomnia disorder may be Supplementary Material
halted. This highlights the importance of properly diagnosing
Supplementary material is available at SLEEP online.
and managing insomnia as early as possible in older adults.
Adequately treating insomnia disorder might become an im-
portant preventive measure for cognitive decline and mitigate
the incidence of dementias in later life. Acknowledgments
There are some limitations that must be considered in this This research was made possible using the data/biospecimens
study. First, causation cannot be inferred from an observational collected by the Canadian Longitudinal Study on Aging (CLSA).
study. Further, the question surrounding subjective memory Funding for the Canadian Longitudinal Study on Aging (CLSA) is12 | SLEEP, 2022, Vol. 45, No. 11
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