#CamFest Speaker Spotlight

Dr Alpar Lazar is an associate professor and principal investigator in the school of Health Sciences at the University of East Anglia with a strong research interest in the significance of human sleep and circadian rhythmicity in brain health.

He will be speaking on 23rd March 2-4pm at Alzheimer’s Research UK public meeting about how ageing affects sleep and exploring whether age-dependent cognitive and health deterioration could be driven by the gradual sleep disruptions we experience over the years.

Why does your research matter?

We spend on average one third of the day, and ultimately our life, sleeping, which highlights its indispensable contribution to health. And indeed, sleep has been shown to have a major impact on the human brain and the body, ranging from the way our genes work, our growth, immunity and metabolism to complex psychological functions and underlying neural functions.

Sleep drives the recovery process, from the deleterious effects of wakefulness on the brain, including synaptic recalibration, energy replenishment and clearance of toxic waste products that can damage the neurons. Sleep is essential for learning and memory, and lack of sleep exerts a strong negative effect across multiple domains of cognition and emotional control and leads to permanent neural brain damage. Sleep impairment represents a major comorbidity along with most physical and mental health conditions. 

What first got you interested in sleep research?

I was interested to understand the neural underpinning of individual differences in the brain linked to cognitive functions, such as general learning ability, memory and specific cognitive alterations associated with autism spectrum disorders. However, studying the brain and associated cognitive functions during wakefulness is mostly confounded by various factors inherently linked to consciousness, such as attention, motivation and the simultaneous perception of various external stimuli. However, during sleep, the brain returns to a default state where neurons, mostly undisturbed by intrinsic and extrinsic factors, start communicating in their own ‘endogenous’ language as reflected by unique individualised patterns of brain oscillations such as slow waves and sleep spindles. This designates sleep as a unique time window to better understand the brain.

Do we know why sleep deteriorates with age and why some people are affected more than others?

Indeed, sleep complaints are common in older adults with almost every second person aged above 65 experiencing chronic sleep problems, including difficulties falling asleep, maintaining sleep, waking up too early, waking up frequently during the night and generally having a more superficial and less refreshing sleep.  Among the multiple contributions of sleep to life, its role in learning and memory is central.

It is thought that the price we pay for the neural plasticity underlying our learning ability is sleep. Ageing is naturally associated with a decrease in synaptic plasticity and memory. Whether the age-dependent decline in sleep quality and key sleep-dependent oscillatory activity linked to cognitive functions is due to this decrease in our learning ability or whether we learn less as we do not sleep well enough is still not clear.

The relationship is likely bi-directional. Interestingly, the gradual decrease in sleep quality with ageing is not necessarily paralleled by similar changes in sleep duration. While in early adulthood (19-33 years) sleep duration decreases and while there are no changes in mid-adulthood (34-53 years), in late adulthood (54+years) sleep duration increases as people get older. In this third phase, sleep duration shows an inverted u-shape relationship with cognitive performance, with the optimal performance peaking at seven hours of reported sleep.

Importantly, sleep complaints in older adults are not necessarily all due to the physiological ageing process but due to primary sleep disorders such as insomnia, obstructive sleep apnoea and restless leg syndrome to other health conditions ranging from chronic pain disorders to mental health and neurodegeneration. 

What does your research show about the possible links between lack of sleep in older age and conditions such as Alzheimer's?

There is remarkable interest and a vast amount of research output investigating the role of sleep in cognitive decline and dementia worldwide. Sleep deficits have been suggested not only as early biomarkers, but also as mechanistic factors involved in the disease process leading to cognitive decline, neurodegeneration and other co-morbid conditions such as diabetes and depression. Nonetheless, evidence points to a bi-directional relationship, where deteriorating brain health also affects sleep which is dependent on intricate brain networks and other physiological systems (such as the circadian clock). 

My research has been focusing on better understanding the way sleep-wake regulation is altered in people at increased genetic risk of Alzheimer’s Disease (AD). Our preliminary results show that, while there are alterations in the way the body clock works, the response to sleep loss does not appear to be significantly altered in healthy older people with increased genetic risk. This also points to the importance of other risk factors beyond the genetic ones in AD-specific sleep alterations. 

What could understanding that link mean for the treatment of such conditions?

We are convinced that sleep is important for healthy longevity and good sleep could potentially reduce the risk of dementia. However, sleep is an intricate biological phenomenon that relies on multiple physiological systems. Modulating sleep in a way that boosts its positive effects on cognition is not a trivial ambition.

Understanding better the way these physiological systems and their interaction become affected in adults at high genetic risk of dementia could open avenues for more effective interventions at a time when the brain is less affected by the disease. More recently, in collaboration with colleagues working in molecular nutrition, we started to investigate the interaction between gut health and sleep in older people, hoping to find new ways to modulate sleep and brain function.       

Does your research make you more conscious of your own sleep patterns?

Sleep used to have a relatively low priority in my daily life and was superseded by work, sports and socialising. Nonetheless, I had the unfortunate opportunity to closely witness the extent to which the gradual decline in sleep duration and quality insidiously stole the brain and cognitive health of one of my brightest family members. I clearly remember that sleep problems came first many years before any other significant health concerns, and they gradually got worse followed by various brain disorders such as stroke, motor and cognitive impairment.

Although this was just a personal experience with not much scientific value, my years in sleep research convinced me of the huge impact sleep deprivation or mistimed sleep could have on the human brain and body. I cannot change and improve my genetic make-up. However, by working hard to adjust my lifestyle and protect my sleep, I endeavour to increase my daytime performance, quality of life and hopefully my lifespan as well.