Sleep–wake changes and cognition in neurodegenerative disease

Abstract

With the increasing aging population, neurodegenerative disorders will become more common in clinical practice. These disorders involve multiple pathophysiological mechanisms that differentially affect cognition, mood, and physical functions. Possibly due to the involvement of common underlying neurobiological circuits, sleep and/or circadian (sleep–wake) changes are also common in this disease group. Of significance, sleep–wake changes are often a prodromal feature and are predictive of cognitive decline, psychiatric symptoms, quality of life, need for institutional care, and caregiver burden. Unfortunately, in neurodegenerative disease, few studies have included detailed polysomnography or neuropsychological assessments although some data indicate that sleep and neurocognitive features are related. Further studies are also required to address the effects of pharmacological and nonpharmacological treatments on cognitive functioning. Such research will hopefully lead to targeted early intervention approaches for cognitive decline in older people.

Introduction

With global increases in life expectancy and population size, neurodegenerative disorders affecting older adults will soon become a global health problem and will be more prominent in clinical practice. Depending on the nature and distribution of pathology, these disorders present with a variety of distinct features including cognitive impairment (e.g., memory loss), psychiatric features (e.g., depression, psychosis), and physical signs (e.g., tremor). Patients with neurodegenerative conditions are also commonly affected by sleep–wake (i.e., sleep and/or circadian) disturbances, with estimates being as high as 70% for early stage dementia (Rongve et al., 2010). Of significance, they are recognized to be an indicator of poor prognosis and are associated with a higher incidence of cognitive and neuropsychiatric problems (Gagnon et al., 2008, Marion et al., 2008, Naismith, Norrie, et al., 2009b, Naismith et al., 2010a, Rongve et al., 2010, Vendette et al., 2007). Sleep–wake disturbances are also linked to poor quality of life (Naismith et al., 2010c) as well as caregiver burden, health, and well-being (Gallagher-Thompson et al., 1992, Happe and Berger, 2002, Mills et al., 2009).

Although sleep–wake disturbances in neurodegenerative disorders can relate to a range of pathophysiological mechanisms, dysfunction of neural circuitry is likely to play a key role (Gagnon et al., 2008). This is not surprising, as the principal regulators of arousal, circadian rhythms, and sleep reside within the central nervous system. While the hypothalamus and brainstem are critical regions, the sleep–wake system has numerous cortical projections and utilizes many neurotransmitters and modulatory hormones that overlap with those affected by neurodegenerative and neuropsychiatric diseases (Fuller et al., 2006, Saper et al., 2005, Wulff et al., 2010). Therefore, it is likely that specific sleep–wake, cognitive, and behavioral features of these diseases have shared neurobiological underpinnings. It is worth noting that holistic consideration of sleep perturbations in neurodegenerative diseases must also incorporate the various external influences on sleep, which contribute to large inter- and intraindividual variability. Thus, they may reflect not only changes to the neural circuitry but also other confounds such as pain, anxiety, medications, sedentary lifestyle, medical comorbidities, and changes to mental state. Conversely, disruptions to the sleep–wake system have widespread effects on cognition, mood, metabolism, immune functioning, and medical morbidities. Thus, there are likely complex multifactorial relationships influencing the clinical manifestation of sleep–wake and cognitive disturbance (Gagnon et al., 2008, Wulff et al., 2010).

In this chapter, we will firstly overview the sleep–wake and circadian changes that occur with normal aging, followed by an overview of sleep–wake changes in Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), and frontotemporal dementia (FTD). We will then address both mild cognitive impairment (MCI) and late-life depression; clinical syndromes that are considered to be “at-risk” states for dementia. While the focus in this chapter will be on cognition, there is a general dearth of detailed studies linking sleep–wake disturbances with detailed neuropsychological measures. We will then highlight some of the pertinent literature linking sleep–wake and cognition, particularly memory, as these data provide important insights into neural mechanisms of memory consolidation during sleep as well as insights into potential intervention targets. Finally, we will provide a summary of some of the treatments for sleep–wake disorders in older people, with an emphasis on those that may have relevance for neuropsychiatric and neurodegenerative diseases affecting older adults.