Sleep Disturbances in Alzheimer’s and Parkinson’s Diseases

Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative disorders, and exact a burden on our society greater than cardiovascular disease and cancer combined. While cognitive and motor symptoms are used to define AD and PD, respectively, patients with both disorders exhibit sleep disturbances including insomnia, hypersomnia and excessive daytime napping. The molecular basis of perturbed sleep in AD and PD may involve damage to hypothalamic and brainstem nuclei that control sleep – wake cycles. Perturbations in neurotransmitter and hormone signaling (e.g., serotonin, norepinephrine and melatonin) and the neurotrophic factor BDNF likely contribute to the disease process. Abnormal accumulations of neurotoxic forms of amyloid β-peptide, tau and α-synuclein occur in brain regions involved in the regulation of sleep in AD and PD patients, and are sufficient to cause sleep disturbances in animal models of these neurodegenerative disorders. Disturbed regulation of sleep often occurs early in the course of AD and PD, and may contribute to the cognitive and motor symptoms. Treatments that target signaling pathways that control sleep have been shown to retard the disease process in animal models of AD and PD, suggesting a potential for such interventions in humans at risk for, or in the early stages of these disorders.

Exogenous melatonin for sleep disorders in neurodegenerative diseases: a meta-analysis of randomized clinical trials

“…These findings suggest that melatonin signaling contributes to the pathogenesis of AD in the sleep disturbances [28,29]. However, it is surprising that, in our studies, exogenous melatonin has not produced significant effects on objective sleep outcomes in AD patients.…”

“…Pathological findings of AD include extracellular senile plaques, mainly consisting of b-amyloid (Ab), intracellular neurofibrillary tangles, the loss of neuronal subpopulations, mitochondrial oxidative damage, synaptic loss, proliferation, and activation of astrocytes and microglia [27]. Clinical data reported sleep disturbances such as day-time sleep fragmentation, decreased slow wave sleep (SWS), and frequent day-time napping in at least 25-35 % of AD patients, which lead to significant caregiver distress, healthcare costs, and increased rates of institutionalization [28].…”

Therapeutical Implications of Melatonin in Alzheimer’s and Parkinson’s Diseases

“…PD is a major neurodegenerative disease characterized, in its clinically relevant stages, by the progressive degeneration of dopamine (DA)-containing neurons in the substantia nigra (Rothman and Mattson 2012 ;Seppi et al 2011 ). Typical of PD are cellular inclusions called Lewy bodies.…”

“…They are single or multiple intraneuronal inclusions selectively distributed in the cytoplasm and having various sizes and shapes depending on the brain area that is affected. Lewy bodies have a relatively restricted distribution and are usually associated with DA neurons of the substantia nigra pars compacta (SNpc) and ventral tegmental region, noradrenergic neurons of the locus coeruleus, catecholamine cells of the medulla oblongata, serotoninergic neurons of the raphe nuclei, and specifi c cholinergic neurons (Rothman and Mattson 2012 ;Seppi et al 2011 ). Several studies indicate that accumulation of fi brillar α-synuclein aggregates is associated with PD and other Lewy body diseases (Fornai et al 2005 ).…”

Identifying the causative proteins of similar side effect pairs to explore the common molecular basis of these side effects

“…However, dysfunction in neurotransmitters and hormone signals contribute to this disease process. 35 Adrenergic receptor ADRA2A impacts the neurotransmitter content in the central nervous system. Therefore, drugs targeting this protein will induce various neural symptoms such as somnolence.…”