Project PhD

The effect of APOE genotype on sleep, activity-rest patterns and their interaction with cognitive performance

The PhD project focused on cognition, sleep, rest-activity patterns and APOE-ε4 genotype in the context of early markers of Alzheimer's Disease

Background

Alzheimer's disease (AD) is the most common type of dementia manifesting mainly over the age of 65 with no curative treatment available. The risk of AD is increased in APOE-ɛ4 allele carriers and those with sleep and circadian disturbances. APOE-ε4 polymorphism was also shown to be associated with spatial navigation impairment, which has been proposed to serve as a potential early marker of AD. Yet, the interrelationships between APOE-ɛ4 carriership, sleep, rest-activity patterns and spatial navigation in healthy older adults are still unclear. The presented PhD project addresses this research gap.

Project Aim

Research Questions

  1. Does APOE-ε4 allele carriership affect self-reported sleep, chronotype, and cognition independently of potential confounding factors such as age, and biological sex in healthy elderly adults?
  2. What is the association between spatial navigation, self-reported sleep, chronotype and cognition in healthy elderly adults?
  3. Does the APOE-ε4 allele carriership modulate associations between self-reported sleep, chronotype and spatial navigation in healthy elderly adults?
  4. Does the APOE-ε4 allele affect actigraphy-assessed circadian rest-activity patterns in the habitual environment regardless of possible confounding factors such as age and biological sex?
  5. What are the relationship between the actigraphy-assessed circadian rest-activity rhythmicity in the habitual environment and spatial navigation and how is the association modulated by the APOE-ε4 allele carriership?
  6. Does the APOE-ε4 allele affect self-reported sleep quality and sleep efficiency as measured by sleep diary in the habitual environment regardless of possible confounding factors such as age and biological sex?
  7. What is the association of subjective sleep quality as measured by sleep diary in the habitual environment with spatial navigation and how is the association modulated by the APOE-ε4 allele carriership?
  8. To what extent are objectively and subjectively measured vigilance, working memory, episodic memory performance and subjective mental effort affected by low and high sleep pressure conditions and time of day (i.e. circadian phase) in healthy elderly men and women?
  9. What is the effect of sleep pressure and time of the day on allocentric and egocentric navigation?
  10. Does the genetic risk of AD (APOE-ε4 allele carriership) modulate the effect of sleep loss and time of the day on objectively and subjectively measured vigilance, working memory, episodic memory and subjective mental effort?
  11. Does the genetic risk of AD (APOE-ε4 allele carriership) modulate the effect of sleep loss and time of the day on spatial navigation?
  12. Does objectively measured baseline sleep architecture differ between the low (APOE ε4 allele non-carriers) and high (ε4 allele carriers) genetic risk of AD in healthy elderly?
  13. Does the genetic risk of AD (APOE-ε4 allele carriership) affect sleep propensity and sleep architecture across consecutive naps?
  14. Does the APOE-ε4 allele modulate the homeostatic response of sleep duration and architecture to sleep loss (comparison of sleep architecture parameters between Baseline and Recovery Nights)?

Project Aims

  • Objective 1: to investigate the impact of the APOE-ε4 allele on sleep, circadian rest-activity patterns and cognition
  • Objective 2: to study the impact of APOE-ε4 allele carriership on the relationship between sleep, circadian rest-activity patterns and spatial navigation
  • Objective 3: to examine the effects of homeostatic sleep pressure and time of the day (i.e., circadian phase) on allocentric and egocentric spatial navigation and their modulation by APOE-ε4 allele carriership

Project Activity

  • helping set up the sleep lab and start the project (e.g., creating the computerized cognitive tasks)
  • data collection including running cognitive assessments, DNA extraction, APOE genotyping, running circadian protocol
  • preparation of databases and data analyses including sleep staging of all the sleep episodes
  • presenting during conferences on the university, European and International level

Anticipated Impact

Our results suggest that APOE-ɛ4 carriership in healthy elderly adults has a limited impact on subjective and objective sleep quality, daytime sleepiness and circadian rhythmicity measures besides evidence for a decrease in circadian rest-activity amplitude and a marginal decrease in the percentage of total sleep time in N2 at baseline night. Yet, recovery sleep revealed an altered physiological recovery process in APOE-ɛ4 allele carriers that was reflected as a low percentage of deep sleep following total sleep deprivation protocol. Further, the outcomes suggest that spatial navigation performance is modulated neither by time-of-a-day nor is affected by increasing sleep pressure or by their associations with APOE-ɛ4 carriership.

Who is involved?

Papers/resources

Contact

Dr Adriana Michalak, University of East Anglia

PhD