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The ageing brain, disrupted circadian cycles and Alzheimer’s

For successful interaction between the human body and environment the brain has a master clock (circadian pacemaker) within the suprachiasmatic nucleus (SCN) of the hypothalamus. In anticipation of variations in the environment, it uses external cues to drive circadian rhythms in activity and rest (sleep), body temperature, feeding behaviour, and hormones, communicating in turn with other brain regions and body tissues.

It is well established that with advancing age the circadian timing system is progressively disturbed, and changes in the SCN have been described for hormonal rhythms, body core temperature, sleep–wakefulness and several other behavioural cycles.

These changes are exacerbated in dementia, particularly Alzheimer’s disease (AD) where the severe circadian dysfunction is one of the most important factors leading to institutionalisation. Some of the strongest evidence to link disruption of the circadian clock and sleep disturbance has come from studies in patients with dementia, and post-mortem brain tissue has revealed degeneration of neuronal populations within the hypothalamus SCN region.

The use of light to affect our health and well-being (e.g., sleep, mood) is an ever- changing field that can be broadly thought of as before and after the discovery of the photopigment melanopsin, which has a peak spectral sensitivity around 480nm. The culmination of this discovery and the technological advancement of LED technology which can fine-tune light spectra has led to some very recent positive clinical trials and studies that indicate how lighting may be used as a positive intervention.

At the Lighting Research Center of the Rensselaer Polytechnic Institute in the US, Marianna Figueiro has conducted two separate studies into tailored lighting interventions with older adults with Alzheimer’s diagnoses. In the earlier one it showed that proving a higher level of circadian stimulus lighting improved night-time sleep and reduced agitation and depression and was well tolerated. In the second trial, which was extended to 24 weeks, the outcomes were repeated and confirmed with evidence of a cumulative effect over time.

Figueiro, Director of the Lighting Research Center, summarised the findings “Our research shows that circadian-effective light, when carefully specified and implemented, can positively impact those living with Alzheimer’s and related dementias in assisted-living and long-term care facilities.”

A more recent study has shown, for the first time, how sleep disturbances giving rise to circadian disruption contribute to development of Alzheimer’s disease.

Dr Jennifer Hurley, who led the research at Rensselaer Polytechnic Institute whose findings show that the human circadian clock controls the brain’s ability to mop up wayward proteins linked to Alzheimer’s disease. This would explain how disruption to circadian rhythms and sleep disturbances might feed into the onset and progression of Alzheimer’s disease, and how preventing such disruption might stave off the condition.

“Circadian disruption is correlated with Alzheimer’s diagnosis and it has been suggested that sleep disruptions could be an early warning sign of Alzheimer’s disease,” said Dr Hurley.

To keep the brain healthy, immune cells called microglia seek out and destroy troublesome proteins that threaten to accumulate in the brain. One type of protein targeted by the cells is called amyloid beta, a hallmark of Alzheimer’s.

Writing in the journal Plos Genetics, Hurley and her team describe how they found a daily rhythm in microglia, which drove regular waves of protein-clearing. When the cells lost their circadian rhythm, the clearing routine faltered.

“The disruption of the proper timing of amyloid beta clearance could be one of the reasons we see an increase in plaques that form in the brain during Alzheimer’s disease,” Hurley said.

While sleep disturbances often arise before Alzheimer’s disease, Hurley and many other scientists suspect there is a complex interplay between the two. Disrupting sleep and circadian rhythms allowed amyloid beta to build up, Hurley said, but this in turn damaged brain cells that ran the circadian clock, causing further accumulation of amyloid beta.

“Taking care of our sleep or circadian rhythms – sometimes called good sleep hygiene – may be able to reduce amyloid beta burden over our lifespan,” she said. “Reducing amyloid burden could mean a reduction in Alzheimer’s symptoms or a delay in the onset or progression of the disease.

The understanding from these studies points to the importance of promoting healthy circadian cycles and, in turn, sleep cycles in older adults and those living with dementia and how circadian lighting interventions can play a critical role for wellbeing.