Sleep problems remain a significant hallmark of Alzheimer’s disease and related dementias. And growing evidence hints that disrupted sleep patterns could play a role in the progression of the disease – long before symptoms emerge.
As a result, scientists have increasingly turned to sleep research as it relates to Alzheimer’s biomarkers.
One such study – published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association – covered 128 middle-aged (and older) adults from across the AD spectrum and uncovered fresh insight into the link between REM sleep latency (REML) and AD biomarkers. Researchers found that REML, the lag time between dozing off and the first phase of REM sleep, correlates with markers of Alzheimer’s pathology.
Specifically, the team found a connection between prolonged REML and higher amyloid beta (Aβ) deposition, elevated plasma levels of phosphorylated tau at threonine 181 (p-tau181), and lower levels of brain-derived neurotrophic factor (BDNF).
Alzheimer’s and Sleep
Two major pathological hallmarks characterize Alzheimer’s: Aβ plaques and tau neurofibrillary tangles. And multiple animal and human studies have shown that sleep deprivation can exacerbate these pathologies:
- In rodent models, experimental sleep deprivation revealed increased tau accumulation and its spread.
- And human studies have confirmed that poor sleep quality (including disrupted sleep stages) can lead to heightened Aβ and tau levels.
Among the stages of sleep, slow-wave sleep (SWS) — the deepest phase of sleep outside of REM — has received most of the attention from researchers because of its role in memory consolidation and the brain’s glymphatic clearance system.
However, evidence from the Framingham Heart Study suggests that age-related reductions in SWS can accelerate dementia risk, highlighting its role in Alzheimer’s.
On the other hand, researchers have overlooked REM sleep – long recognized for its role in learning and memory – and its potential role in dementia pathophysiology. Now, data has emerged that shows how REM sleep disruptions, particularly in APOE ε4 carriers, could be an early warning sign of future dementia.
This paper builds on the established research with its fresh analysis of REML and how it ties back to Alzheimer’s.
Key Findings on REML and Alzheimer’s Pathology
Working with positron emission tomography (PET) imaging, the researchers found that individuals with prolonged REML had greater Aβ plaque deposits and higher plasma p-tau181 levels – even after adjusting for demographic and genetic factors.
The team also identified lower BDNF levels, a protein critical for neuronal health and cognitive function, in participants with extended REML.
Notably, the paper’s authors noted that prolonged REML could reflect either a prolonged first sleep stage or wakefulness during the earlier cycles. This reinforces the complexity of Alzheimer’s sleep disturbances and the need for further research.
The findings also revealed a connection between less REM sleep percentage and elevated p-tau181 levels. Even so, this relationship faded after the researchers corrected for multiple comparisons. These results echo earlier research that suggests that REM sleep disturbances could act as an early indicator of neurodegeneration.
Clinical Implications
The authors posit that the link between prolonged REML and AD biomarkers might stem from neurodegeneration in cholinergic networks and the dysregulation of neurotransmitters that regulate REM sleep. Tau pathology in the basal forebrain and alterations in the orexinergic system — known to promote arousal — could add to these disturbances.
The study’s findings have practical clinical implications. Since REML could be a barometer of early Alzheimer’s detection, which could help identify someone at risk before clinical symptoms ever appear. This is critical since pathological changes like Aβ and tau accumulation typically precede cognitive decline by a decade – or longer.
And the research highlights the potential of therapeutic interventions targeting sleep architecture. Drugs such as orexin receptor antagonists, already approved for insomnia treatment, have shown promising results in reducing tau phosphorylation and Aβ concentrations. At the same time, melatonin also appears to demonstrate neuroprotective effects in some preclinical models.
By addressing sleep disturbances early, clinicians might have an opportunity to mitigate the neurodegenerative processes underlying Alzheimer’s and offer some much-needed hope for at-risk populations.
Further Reading
Researchers Uncover Five Different Types of Alzheimer’s
Your Chances of a Dementia Diagnosis Depend on Where You Live
Lancet Commission Identifies 2 New Modifiable Dementia Risk Factors
