Pain is common in Alzheimer’s disease and in its preclinical stages including subjective cognitive decline and mild cognitive impairment, but what underlies this association is unclear.
Murdoch University
In a novel study at Murdoch University, supported by the Alzheimer’s Association-USA, a research team is investigating whether degeneration of a small but powerful centre in the brainstem, the locus coeruleus, might explain this connection.
The locus coeruleus is a tiny bilateral cluster of noradrenergic neurons in the upper pons. Among other functions, these neurons regulate attention, arousal and sleep-wake cycles. They also regulate sensory inputs including sight and sound by helping to filter out background activity, thus optimising signal strength.
They use this capacity to control the flow of nociceptive traffic (which signals pain) downstream in the spinal cord and upstream in the thalamus and prefrontal cortex.
Crucially, neurodegeneration in the locus coeruleus starts decades before the onset of memory complaints in people who later develop Alzheimer’s disease. Once it reaches a tipping point, this neurodegeneration disrupts attention and arousal, thereby seriously impacting learning and memory.
Long before this, it could also impact the capacity to control pain. If so, it might be possible to detect early signs of neurodegeneration in the locus coeruleus, a step toward Alzheimer’s disease, by assessing physiological and behavioural responses to pain.
The locus coeruleus provides a bridge between arousal centres in the brain and sympathetic nervous system output which, among other physiological effects, drives pupillary dilatation. This link is so strong that reactivity of the pupils is increasingly being used in physiological studies to track activity in the locus coeruleus.
In the Murdoch University study, pupillary dilatation to a sudden loud noise and to painful stimuli (a weak electric shock and painfully cold water) is being used to assess the functional integrity of the locus coeruleus in people with subtle or more obvious signs of memory impairment.
The hope is that pupillary responses of this nature can be used as a screening tool for early signs of neurodegeneration in the locus coeruleus (a possible precursor of Alzheimer’s disease neuropathology) in the future.
The research team is now seeking volunteers aged between 60 and 85 years with memory difficulties or other signs of mild cognitive impairment to participate in this study which will involve one or two assessment sessions in our lab. If you know of anyone who might be interested in participating, or who would like to know more about the study, please ask them to email p.drummond@murdoch.edu.au or phone 08 9360 2415. The research has been approved by the human research ethics committee at Murdoch University.
Key messages
- Pain is common in dementia
- Reduced ability to control pain could be an early warning sign
- New research is looking at this connection.
Author competing interests – the author is leading the research quoted.