#13
Anders Fjell

Relation of sleep patterns to brain and cognitive health

Public health recommendations and clinical paradigms often treat sleep need as a rigid, universally applicable constant affecting brain health and cognitive function. However, this “one-size-fits-all” approach struggles to reconcile the acute neurocognitive deficits seen in laboratory sleep deprivation with observational data.

In this presentation, I will argue that individual sleep need is a dynamic, negotiable quantity regulated by ecological niches, motivational states, and adaptive plasticity rather than a hard-coded biological requirement. We integrate cross-disciplinary evidence, including behavioral ecology, evolutionary modeling, and large-scale neuroimaging. Our empirical framework utilizes the Lifebrain consortium database, analyzing over 51,000 cross-sectional and 8,000 longitudinal MRIs to examine the purported causal link between sleep duration and brain atrophy. We find no phenotypic or genotypic evidence that short sleep causes accelerated brain atrophy or structural decline in healthy adults. Cross-sectional “sweet spots” for maximal cortical thickness and cognitive performance converge around 6.5–7 hours, below many current recommendations. Furthermore, we demonstrate that humans and other species exhibit remarkable sleep flexibility; when sleep is reduced gradually in motivated, naturalistic settings, typical vigilance deficits are often mitigated or absent.

In conclusion, these findings challenge “sleep essentialism” and the notion of a sleeplessness epidemic. We conclude that the brain’s sleep-wake balance is highly conserved and adaptive, and that the evidence linking natural variation in sleep patterns to brain health is surprisingly weak. Future research and clinical guidelines should shift focus from rigid duration targets toward understanding individual variance in sleep need and the psychological and environmental factors that facilitate successful adaptation to sleep loss.

#14
Géraldine Rauchs 

Sleep apnea and Alzheimer’s disease neuroimaging biomarkers

Background: Obstructive sleep apnea (OSA) is highly prevalent among older populations, affecting up to 50% of this population. Moreover, approximately 75% of patients attending memory clinics suffer from OSA, with varying levels of severity. OSA is characterized by recurrent episodes of upper airway obstruction during sleep resulting in intermittent hypoxia and sleep fragmentation. These disturbances promote oxidative stress, inflammation, and vascular dysfunction, which may contribute to an increased risk of Alzheimer’s disease (AD). We investigated the impact of OSA on brain integrity using multimodal neuroimaging.

Methods: We conducted three studies in participants from the Age-Well randomized controlled trial. Participants were cognitively unimpaired, aged over 65y, and retired for at least one year. They underwent in-home polysomnography, from which the Apnea-Hypopnea Index (AHI, number of respiratory events per hour of sleep) was derived as a measure of OSA severity. Participants also underwent multimodal neuroimaging, including structural MRI, FDG-PET, amyloid-PET (with early and late acquisitions reflecting perfusion and amyloid burden respectively). In addition, high-resolution hippocampal MRI and FLAIR sequences were acquired to quantify medial temporal lobe subregion volumes and white matter hyperintensities.

Results: Moderate to severe OSA (AHI ≥15 events/hour) was associated with greater amyloid burden, gray matter volume, perfusion and glucose metabolism in the posterior cingulate cortex and the precuneus. Interestingly, these brain changes occur in the absence of objective cognitive impairment, cognitive and sleep complaints, or excessive daytime sleepiness. We further found that higher OSA severity was associated with lower medial temporal lobe subregion volumes in amyloid-positive individuals,

whereas no such association was observed in amyloid-negative participants. Finally, OSA severity was associated with greater volumes of white matter hyperintensities, mainly in frontal and temporal areas, as well as in the corpus callosum.

Conclusion: Taken together, these findings demonstrate that untreated sleep apnea is associated with structural, functional, vascular and molecular alterations in regions vulnerable to Alzheimer’s disease, in older adults who are cognitively unimpaired. These results support the need to screen and treat for OSA to reduce Alzheimer’s disease risk. We also obtained promising evidence showing that some lifestyle factors may mitigate the detrimental effects of OSA on brain health.

#15
Angeliki Tsapanou

Links between objective sleep measures and hippocampal subfield volumes 

Sleep patterns often shift as people age, a phenomenon frequently associated with the onset of neurodegenerative conditions. Additionally, distinct alterations occur in brain structure as individuals grow older, particularly within the hippocampus, a region known for its role in cognition and sleep regulation. Yet, how exactly changes in sleep relate to specific subfields within the hippocampus is still unclear.

We conducted a study involving non-demented healthy adults from the ALBION cohort. Participants underwent objective sleep measurements using wrist Actiwatch and WatchPAT devices, along with structural MRI scans to assess hippocampal volume. The study aimed to examine the relationship between objectively measured sleep metrics and the morphology of twenty-two distinct hippocampal subregions.

In total, 75 non-demented participants with 63 mean years of age were included in the study. Results indicated that a higher frequency of awakenings during sleep was associated with increased volume in the right presubiculum body (beta=0.630, pFDR < 0.036), suggesting a potential compensatory mechanism in response to disrupted sleep patterns. Longer sleep duration showed a tendency to be associated with smaller volumes of the right presubiculum body, hinting at a possible negative impact of prolonged sleep on this brain region. Similar trends were observed regarding sleep apnea and the presubiculum body volume.

Further analysis based on age stratification revealed that in younger participants, longer sleep duration was linked to decreased volume of the presubiculum body, while a greater number of awakenings was correlated with increased volume of the same region. Among older participants, higher frequencies of awakenings were associated with larger volumes in various hippocampal subfields.

These findings shed light on the complex relationship between sleep characteristics and brain structure, highlighting potential age-related differences. The study provides valuable insights into how sleep disruptions may impact hippocampal morphology and cognitive function of cognitively healthy adults. Further research is warranted to elucidate the underlying mechanisms and implications for neurodegenerative diseases.

#16
Grégory Hammad

Sex-dependent loss of lateral hypothalamic integrity due to habitual napping

Background: Studies about napping in the ageing population suggest a complex association with cognitive functions and neurodegenerative diseases. Recently, it has been shown in rodents and post-mortem human tissues that orexinergic neurons (OrxN), located in the hypothalamus and crucial to stabilize wakefulness, are the earliest neuronal population to be affected by phosphorylated tau deposition in Alzheimer’s disease and that OrxN loss might precede neuronal loss in the locus coeruleus. Here, we hypothesise that napping in humans, as a marker of destabilized wakefulness, is associated with loss of in-vivo hypothalamic integrity in cognitively unimpaired older participants.

Methods: 30 healthy older nappers and 30 age- and gender matched no-nappers (mean age (±SD): 69.0±5.3 years, 37% female) were included. Locomotor activity was recorded using actimetry during (13±2) days in order to assess napping habits. Microstructural integrity of grey matter tissue in different hypothalamic regions were quantified through 3T quantitative MRI-derived iron contents (R2* maps).

Results: Our Bayesian mixed-effects models indicate that napping habits are linked to hypothalamic integrity, with female nappers showing increased R2* values within the posterior hypothalamic region (Nap: beta=0.48, 95% C.I.=[0.06, 0.92], Posterior*Sex: beta=0.30, 95% C.I.=[0.01, 0.61], Nap*Posterior*Sex: beta=-0.57, 95% C.I.=[-1.04, -0.11]).

Conclusions: Our results show for the first time that, in women, habitual napping is associated with in-vivo elevated iron levels, a marker of neuronal cell death, in the posterior hypothalamic region, where the lateral hypothalamic area, containing orexinergic neurons, is located. While longitudinal data from our cohort of habitual nappers are being analyzed to determine if napping suppression can help to mitigate loss of lateral hypothalamic integrity, we anticipate that these new findings will enhance our understanding of the origins and consequences of habitual napping in both normal ageing and neuropathological conditions, and pave the way to potential preventive interventions.