Disorders of sleep and autonomic function in Parkinson's disease dementia

Eduardo Tolosa, Judith Navarro-Otano, and Alex Iranzo


Cognitive deterioration is common in Parkinson’s disease (PD) and many patients develop dementia with disease progression. Dementia generally occurs late in PD, as is the case for other symptoms not responsive to levodopa. These symptoms include motor features such as motor blocks (also known as freezing of gait), dysarthria, disequilibrium, and falls as well as non-motor ones such as sleep disturbances and dysautonomia. Some of these symptoms are thought to be disease related, a consequence of the nervous system pathology that occurs in PD. They may also present as adverse effects of antiparkinsonian medication or a manifestation of co-morbidities, frequent in the elderly.

In this chapter we will review sleep disturbances and dysautonomia occurring in PD patients with dementia (PD-D). Although both types of disturbances are known to also occur in early stages of PD, even in the prodromal phases, they can be particularly prominent in advanced PD. Tables 9.1 and 9.2 summarize these disturbances and their management.

Sleep disturbances in PD-D

The main sleep disturbances in PD-D patients include insomnia, rapid eye movement (REM) sleep behaviour disorder (RBD), and excessive daytime sleepiness (EDS).

Insomnia in PD-D

Fragmentation of sleep can have a major impact on quality of life in PD and is a multifactorial problem. Drugs such as selegiline or amantadine can cause insomnia. In advanced disease, ‘off’- state-related parkinsonism during the night can also produce insomnia. Nocturia, common in advanced PD, is also a contributing factor. In PD-D patients, nocturnal hallucinations and RBD might also contribute to sleep disturbances.

REM sleep behaviour disorder

RBD is characterized by dream-enacting behaviours (e.g. kicking, talking, swearing, shouting, jumping out of bed) linked to unpleasant dreams (e.g. being attacked, chased, or robbed) and increased electromyographic activity during REM sleep. Infrequently patients may injure themselves or their bed partner. The pathophysiology of RBD is thought to be related to dysfunction of the brainstem REM sleep centres (the locus subcoeruleus, nucleus gigantocellularis, etc.) and their indirect and

Table 9.1 Treatment of sleep disturbances in Parkinson's disease with dementia

Non-drug strategies

Pharmacological treatment


Sleep hygiene

Quetiapine 25 mg at night

Rapid eye movement sleep behaviour disorder

Clonazepam 0.25-0.5 mg/24 h Melatonin 3-9 mg/24 h

Excessive daytime sleepiness

Sleep hygiene

Methylphenidate, modafinil (could cause nervousness and insomnia)

Table 9.2 Treatment of autonomic dysfunction in Parkinson's disease with dementia

Non-drug strategies

Pharmacological treatment

Orthostatic hypotension

Water intake Salt intake (at least 8 g) Sleeping with elevation of the head end of the bed

Fludrocortisone 0.1-0.2 mg/day Midodrine 5-10 mg three times a day

Constipation Urinary dysfunction

Fluids, high-fibre diet Water restriction at night


Different strategies for overactive bladder, urinary retention, nocturnal polyuria

direct anatomic connections (the amygdala, pallidum, neocortex, etc.) [1]. RBD occurs in about 50% of PD patients. It has been estimated that it can antedate the development of motor symptoms of PD in about 15% of cases [2, 3]. It has not been widely studied whether RBD is more prevalent among PD-D patients than in those without dementia. Marion et al. [4] suggested that RBD worsens with time: a small study in 65 consecutive PD patients showed that the presence of RBD-like symptoms was significantly higher in PD-D (10/13, 77%) than in PD without dementia (14/52, 27%). These studies did not include polysomnographic confirmation of the true presence of unequivocal RBD.

RBD may also predict the development of dementia in PD patients. This is perhaps not surprising considering that idiopathic RBD may also evolve into dementia with Lewy bodies (DLB), a condition pathologically very similar to PD. Some risk factors associated with PD-D such as an akinetic-rigid motor phenotype [5], hallucinations, longer PD duration, male gender, and cholinergic denervation have been also associated with RBD in PD [1, 6-10], whereas other risk factors for PD-D, such as advanced age and depression, have not [7, 8, 11, 12].

In summary, it is not certain from the available data whether RBD is linked to PD-D. Longterm follow-up of PD patients without dementia with and without RBD is necessary to elucidate whether it is associated with a high risk for dementia.

Excessive daytime sleepiness

The causes of EDS in PD are numerous. The most relevant are the effects of dopaminergic medication and the consequences of the disease pathology itself [1]. Other factors that have been found to be associated with excessive sleepiness in PD include dementia, disease severity, disease duration, hallucinations, disruption of the circadian sleep-wake cycle, nocturnal sleep quantity and quality, obstructive sleep apnoea, depression, and genetic susceptibility [1]. The individual contributions of each of these factors, including dementia, have not yet been fully elucidated.

EDS, like RBD, can occur in the early stages of PD, including the pre-motor phase [13]. Studies by Gjerstad et al. [14] and Fabbrini et al. [15] have shown that its prevalence increases with disease duration. However, there are only a few reports that have specifically evaluated the frequency and nature of EDS in PD-D. One such study showed that the frequency of EDS in PD-D (57%) was greater than in PD without dementia (41%) [16]. However, another study showed no differences in scores on the Epworth Sleepiness Scale, as a subjective measure of EDS, between PD and PD-D, although abnormal scale scores were significantly more frequent in PD-D than in PD without dementia [17]. Another study using the Epworth Sleepiness Scale showed that the frequency of PD-D patients reporting EDS increased from 57 to 81% after 2 years of follow-up [16]. In daily clinical practice it is widely recognized that EDS can be a prominent behavioural manifestation occurring in PD-D patients.

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