OVERVIEW

Sleep–wake disturbance is seen as a major component of virtually every neurodegenerative disease
Symptoms arising from poor quality sleep and impaired daytime wakefulness may mimic those arising from the underlying neurodegenerative process
Patients with Parkinson’s disease (PD) can develop virtually any type of sleep-related symptom, often in advance of physical or motor signs of the illness
Fragmented overnight sleep and narcoleptic levels of daytime sleepiness are relatively common in PD and increase with age
Motor symptoms responsive to dopaminergic therapy may account for many overnight symptoms in PD
Advanced PD with cognitive impairment is associated with very severe sleep disturbance, often with hallucinations and nocturnal confusion
Alzheimer’s disease (AD) commonly leads to disturbed circadian rhythms and sleep–wake disturbance, often with minimal insight from the patient
Promoting daytime alertness by non-pharmacological means may improve quality of life in AD sufferers
In motor neuron disease (MND), an early sign of diaphragmatic weakness is poor quality overnight sleep with daytime lethargy secondary to nocturnal hypoventilation
Non-invasive ventilation is now an established and proven treatment for many MND patients with hypoventilation

Significant disturbance of the sleep–wake cycle is increasingly recognised as an integral, important and sometimes treatable element of all the common neurodegenerative disorders. The ability of carers to cope with poor or disturbed sleep in the home is often a major cause of concern, potentially leading to early institutionalised care. Many have also highlighted the inevitable rising prevalence of age-related sleep disorders as a consequence of ageing populations in developed countries.

The vast majority of neurodegenerative conditions reflect abnormal accumulation of mis-folded proteins within nerve cells, either as a pathological marker or a likely direct cause of eventual neuronal death. Preventing or slowing down this neurodegenerative process represents a future therapeutic ‘holy grail’. Results from basic science at the cellular level suggest that significant sleep deprivation or chronic poor quality sleep may actually accelerate abnormal protein accumulation within cells, potentially fuelling any neurodegenerative process. As a corollary, whether improving sleep quality could be ‘neuroprotective’ in those with underlying neurodegeneration remains a tantalising but entirely credible speculation.

At a practical level, optimising a subject’s daytime alertness in the context of a neurodegenerative illness will, at the very least, have a positive influence on attention, cognition and possibly mood. Unfortunately, many drugs used in dementia and related disorders may have the opposite effects.

Parkinson’s disease

Idiopathic Parkinson’s disease (PD) is characterised primarily by rest tremor, rigidity and slowed movements with impaired gait and abnormal postural reflexes. These recognisable motor symptoms are variably responsive to dopaminergic medication, at least initially.

Numerous other non-motor symptoms affecting cognitive, neuropsychiatric and autonomic domains are now recognised in PD. These are often as debilitating as the motor aspects and frequently more difficult to manage. Their presence usually reflects more widespread neuronal death within the brain and undermines the simple notion that PD is merely due to a cerebral deficiency of dopamine.

Although initial clinical descriptions of the disease by James Parkinson himself described subjects as having ‘constant sleepiness’ and ‘extreme exhaustion’ (Box 9.1), the extensive and complex sleep-related problems in PD have only recently been characterised.

Box 9.1

Sleep becomes much disturbed; the tremulous motions of the limbs occur during sleep and augment until they awaken the patient. [in the final stages there is]…constant sleepiness with slight delirium and other marks of extreme exhaustion.

A quote from James Parkinson’s original essay on the ‘Shaking Palsy’ written in 1817.

Indeed, the complete range of sleep-related symptoms may sometimes be seen in the same patient. It is difficult to define a typical patient profile, however, and any treatments should always be individualised.

Insomnia

Even allowing for age-related deterioration in sleep quality, an inability to stay asleep effectively is extremely common in PD. The potential causes are varied and multifactorial (Table 9.1). Nocturnal motor symptoms may predominate, especially if the subject is under-treated with dopaminergic drugs. Reported difficulties with turning in bed or limb tremor interfering with sleep continuity are particularly common complaints. Another indicator that dopaminergic medication effects are wearing off is severe pain in the latter part of the night, typically in the feet, reflecting dystonia. These various nocturnal motor and painful symptoms may respond to longer-acting drugs, particularly the dopamine agonists, taken before bed.

Table 9.1 Potential causes of impaired sleep maintenance in Parkinson’s disease (PD).

Mechanisms of insomnia in PD	Comments
Nocturnal motor symptoms	Bradykinesia, tremor, dystonia (usually early morning)
Primary sleep disorders	Due to PD pathology in brainstem ‘sleep centres’, restless legs syndrome, sleep apnoea
Effects of medication	All PD treatments may disturb overnight sleep
Depression	Often not recognised in PD, partly due to lack of facial expression
Abnormal circadian timing	A theoretical but credible cause of poor sleep in PD
Nocturia	Often reflects bladder instability and can be a major cause of concern

Fragmentation of sleep is almost certainly also secondary to the underlying disease process in PD. This is not surprising given that many areas of the brainstem, including key nuclei involved in sleep control, carry the characteristic pathological hallmark of PD, the Lewy body. Long-term hypnotic medication to improve sleep continuity may, therefore, often be justified if significant sleep maintenance insomnia is seen in PD.

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