New
research reveals that sleep disorders can signal future risk of
Alzheimer’s, Parkinson’s, and other dementias years before symptoms
appear, offering hope for early intervention and prevention.
Study: Sleep disturbances as risk factors for neurodegeneration later in life. Image Credit: New Africa / Shutterstock
In a recent study published in the journal npj Dementia,
researchers investigated the neurodegenerative impacts of clinically
identified sleep disorders and related disturbances in later life. They
mined biobank data of more than 1 million participants across Finland,
Wales, and the United Kingdom (UK). Study findings revealed a
significant association between these sleep disorders and several
neurodegenerative diseases (NDDs), including dementia, Alzheimer’s
disease (AD), and Parkinson’s disease (PD).
Notably, sleep disruptions were able to predict NDD risk as early as
5-15 years before disease diagnosis. For Alzheimer’s Disease, this risk
appeared largely independent of genetic predisposition, while for
Parkinson’s Disease, an interaction with genetic factors was observed.
These findings highlight the long-term impacts of conditions like sleep
apnea and other formally identified sleep disorders, underscoring the
importance of sleep interventions in preserving late-life neurological
health.
Background
Sleep is a nearly universal, fundamental biological process essential
for optimal cognitive function and overall health. Several studies have
established strong, bi-directional relationships between sleep and
neurodegenerative diseases (NDDs), demonstrating that certain sleep
disorders and significant sleep disturbances can trigger both short-term
cognitive impairment and exacerbate long-term dementia risk.
Consequently, the World Health Organization (WHO) has emphasized the
importance of sleep as a critical health behavior, advocating for
research and interventions to address sleep disorders and enhance sleep
quality across various human populations. Unfortunately, sleep
disturbances are a common and growing global health concern, with
reports estimating that 25% of all Europeans have insomnia.
Furthermore, despite research elucidating several genetic and
environmental contributors to sleep disruptions, the mechanisms
underpinning sleep’s role in NDD etiology remain poorly understood. The
extent to which specific, clinically recognized sleep disorders can
predict NDD risk remains similarly inconclusive. Most studies
investigating sleep-NDD associations have limited sample sizes,
insufficient follow-up durations, and focus on one of a few NDDs,
thereby complicating attempts to establish these outcomes.
About the study
The present study aims to further investigate the associations, and
potential causal links, between sleep and NDDs by leveraging an
extensive medical electronic health records (EHRs) database comprising
more than 1 million individuals across Finland, Wales, and the United
Kingdom (UK), analyzing EHR data from a 20-year period (1999-2018),
drawing from broader records. Study data were obtained from the Secure
Anonymised Information Linkage (SAIL) databank, the FinnGen datasets,
and the UK Biobank (UKB).
Participants’ NDD and sleep disorder diagnoses were classified using
International Classification of Diseases 10th Revision (ICD-10) codes
(e.g., G30 for Alzheimer’s disease and G47.3 for sleep apnea), ensuring
that the study focused on clinically documented conditions rather than
self-reported symptoms. Cohort-specific medical histories were further
used for statistical modeling and meta-analyses, including the
computation of Cox proportional hazard ratios (HRs), polygenic risk
scores (PRSs), and logistic regression models.
To isolate the behavioral impacts of sleep (exposure) on NDD, models
were controlled for participants’ genetic predisposition, age, sex, and
other confounding variables. To facilitate the generalizability of
results and improve the accuracy of outcomes, all analyses were
replicated across multiple populations.
Study findings
Regression and HR analyses revealed strong relationships between
ICD-10 coded sleep disorders and a spectrum of late-life NDDs. Circadian
rhythm-associated sleep disorders (ICD10 code G47, which include
conditions like insomnia, narcolepsy, sleep apnea, and parasomnias,)
were demonstrated as substantial risk factors in the subsequent
development of Alzheimer’s disease (AD; HR = 1.15), Parkinson’s disease
(PD), dementia, and vascular dementia (HR = 1.41).
Non-organic sleep disorders (ICD10 code F51, such as nightmares and
generalized insomnia not due to substances) were similarly associated
with increased dementia (HR = 1.67), PD, and vascular dementia (HR =
2.05) risk. The study also found that the severity of certain sleep
disorders, indicated by recurrent clinical diagnoses, tended to increase
risk for some NDDs. While sleep apnea was demonstrated to be associated
with amyotrophic lateral sclerosis (ALS), a lack of sufficient ALS data
prevented the generalizability of these results.
Notably, many identified associations persisted even after adjusting
for genetic risk factors. Specifically, for Alzheimer’s Disease, the
contributions of diagnosed sleep disorders to neurodegeneration risk
appeared largely independent of genetic factors. However, for
Parkinson’s Disease, the study found evidence of an interaction between
genetic risk and certain sleep disorders.
Individuals with a low genetic predisposition to NDDs still
demonstrated high NDD HRs associated with these sleep conditions,
suggesting that such disorders are significant risk factors,
particularly impactful in those with lower genetic susceptibility.
All identified associations were observed to precede NDD diagnoses by
between 5 and 15 years, suggesting sleep evaluations as an early
indicator of future NDD risk. These findings highlight the potential of
sleep interventions in mitigating late-life neurodegenerative disorders
(NDDs), underscoring the importance of early detection and management of
sleep disorders to enhance overall neurological well-being.
Conclusions
The present study utilizes the largest-scale sleep dataset to date to
elucidate the relationships between clinically documented sleep
disorders and late-life NDD risk. It analyzed EHR data from a 20-year
period, drawing from broader records from more than 1 million
participants, and found clear associations between such sleep disorders
and late-life NDDs. These associations often persisted after adjusting
for participants’ genetic predispositions for conditions like
Alzheimer’s, though interactions with genetic risk were noted for
Parkinson’s Disease.
While utilizing a predominantly European cohort and exclusive EHR (as
opposed to blood assays) data prevents the global generalizability of
these findings, this study presents an ideal first step in
non-invasively combating late-life neurodegeneration.
Notably, formally identified sleep disorders were found to be
accurate and stable predictors of future neurodegeneration risk,
suggesting the assessment of such disorders as both an early indicator
of AD, PD, dementia, and vascular dementia, but also highlighting their
treatment as a modifiable and treatable avenue to healthy neurological
aging.
