Article 8: Sleep and Human Ageing (Mander, Winer, Walker)

Question 1

• less non-REM sleep
• Are old unable to sleep or do they need less sleep?
Sleep Changes with Age
• Macro-level: sleep duration, sleep stages
• Micro-level: quality and quantity of sleep oscilliations
Macro Sleep Changes
• Earlier bedtime/awake
• Longer time to fall asleep
• Shorter overall sleep duration
• More awakenings
• More fragile sleep
• Less SWS sleep
• More time in NREM stages 1 and 2
• Shorter and fewer NREM-REM sleep cycles
• More time spent awake during night
• REM impairment only in 80s
• More naps
• More daytime sleepiness
 Both comorbid with illness
Micro Sleep Architecture Changes with Age
• Large changes in electrical oscillarations
• NONREM sleep and slow waves and spindles
• Maximal decrease in SWS in prefrontal cortex and first NREM cycles
• Shallower SWS less homeostatic discharging
• Increases in SWS after sleep deprivation or suppression of SWS are blunted homeostatic impairment
• Amplitude and density of SWS significantly reducedlarges change in frontal lobe
• Greatest impairment during 1-2 NREM cycles
• Ageing may diminish synchronized neuronal en masse firing sleep oscillarators
• EEG problems
• Slower mean frequency of slow waves whole brain
• Slow wave frequency= biomarker for Alzheimers?
• Frequency range of sleeping spindle is reduced
• Largest impairment in final cycles of night
• Less spindles generated
• Duration and peak and mean amplitude spindle decreases
• In frontal region
• Loss of NREM stages 3,4  SWS, SWS is expressed
Sleep, Ageing and Gender
• Men greater disruption
• Men over 70: 50% reduction of SWS, lighter sleep in NREM stages 1,2
• Reduction in REM sleep in ppl over 70 in both genders
• Homeostatic system
What are the Neurobiological Mechanisms of Age-Related Sleep Impairment?
• Brainstem ascending arousal system, Thalamus, Hypothalamus together with select cortical regions
• Factors like obesity, sleep disorder, harmonal disorder etc
Sleep structure and Stages
• Normal sleep structure: balance between brainstem, midbrain and hypothalamic nuclei
• Area in hypothalamic preoptic area expresses inhibitory neuropeptide galanin (nucleus supraopticus?) cells in area decline with age
• Hypocetin/orexin expression, Lateral hypothalamic area (LHA) awake also decline
• Serotoninraphe nucleus not affected
• Histamintuberomammilary nucleus not affected
• Grey matter
Homeostatic Sleep Drive
• Adenosine slow wave activity (Pressure to sleep)
• Higher in old
• Loss of adenosine A1 receptor
• Not single explanation
• Change in glia
• Less signal from SCN, cells die
• Changed circardian rhythm
Sleep Oscilliations
• Structural brain atrophy impairment in sleep oscilliations
• Grey matter, volume decline
• Regionally specific atrophy in frontal regions, not whole brain
• Reduction of grey matter in hippocampus spindles
• Reduction of white matter spindle expression
Gender Differneces in Sleep
• Young men:
• more galanin expressing but also more rapid decline
• More severe of Hypocetin/orexin expression
• Structural changes within LC
• More grey matter decline
• More metabolic activity reduction
• SWS reduction correlates with less production of growth hormone
• Testosterone decrease correlated with less sleep efficiency and fragmentation
• Testosterone linked to galanin
• Extrinsic influences: alcohol
• NREM important for learning and memory (offline-consolidation of hippocampal-dependent memory processing
Sleep, Ageing and Initial memory Encoding
• Age-related problem: forming new hippocampal-dependent memories, e,g, person-name association
• Sleep deficit impairs memory and cognitive ability
• Chronic sleep restriction: impairment in calcium signaling within hippocampus
• NREM sleep deprivation worse hippocampal encoding ability
Sleeping, Ageing and Memory Consolidation
• Sleep after encodingconsolidation
• Sleep disruption problems with consolidation
• SWS predicts memory accuracy
• Sleep predicts successful retrieval of memory
Sleep Restoration, Ageing and Memory
• Transcranial direct current stimulationenhancement of memory
Do older Adults need less Sleep?
• In Favor:
1. Old sleep less than young when offered extremely long, enforced periods of sleep opportunity
2. Following sleep deprivation, or SWS suppression, old exhibit a smaller rebound in SWS time and SWA compared to younglower homeostatic sleep pressure
3. old suffer less subjective and objective waking sleepiness following selective SWS deprivation than young

• Not in Favor:
1.not lower homeostatic sleep drive but impaired sensitivity to still present homeostatic sleep driveincreasing Adensoine levels, but loss of A1 Adenosine receptors, also neuronal loss in centers that are also involved in sleep homeostatis
2. old report being less sleepy, but rise in subjective sleepiness in first days of chronic sleep restriction in young will often normalize back to lower sleepiness in later deprivation daysold may suffer from same symptoms off chronic sleep restriction
3. Old show smaller relative impairment in performance on vigilance tasks when sleep deprived than young, but old perform worse than young to begin with Baseline
Floor effect: old may have not much further to fall when sleep deprived
4.old show significantly worse performance on other sleep-dependent cognitive functions (learning, long-term memory consolidation)still there when accounted for age, explained by degree of impairment in NREM sleep oscillations

 Sleep need remains, but sleep regulating and/or generating capacities decline!
 Not more sleep time per se but better quality and capacity to express consolidated NREM sleep rich in sleep oscillations
 More likely than decreased need for sleep!

Answer 1

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