Pharmacological and Non-Pharmacological Interventions to Enhance Sleep in Mild Cognitive Impairment and Mild Alzheimer’s Disease: A Systematic Review

Abstract

Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer s Disease (AD) progression. Several sleep interventions have been tested in established AD dementia cases. However early intervention is needed in the course of AD at Mild Cognitive Impairment (MCI) or mild dementia stages to help prevent decline and maintain good quality of life. This systematic review aims to summarize evidence on sleep interventions in MCI and mild AD dementia. Seven databases were systematically searched for interventional studies where greater than 75% of participants met diagnostic criteria for MCI/mild AD dementia, with a control group and validated sleep outcome measures. Studies with a majority of participants diagnosed with Moderate to Severe AD were excluded. 20164 references were returned after duplication removal. 284 full papers were reviewed with 12 retained. Included papers reported 11 separate studies, total sample (n=602), mean age 76.3 years. Nine interventions were represented: Cognitive Behavioural Therapy Insomnia (CBT I), A Multi-Component Group Based Therapy, Phase Locked Loop Acoustic Stimulation, Melatonin, Donepezil, Galantamine, Rivastigmine, Tetrahydroaminoacridine and Continuous Positive Airway Pressure (CPAP). Psychotherapeutic approaches utilising adapted CBT-I achieved statistically significant improvements in the Pittsburgh Sleep Quality Index with one study reporting co-existent improved actigraphy variables. Melatonin significantly reduced sleep latency and sleep to wakefulness transitions in a small sample. CPAP demonstrated efficacy in participants with Obstructive Sleep Apnoea. Evidence to support other interventions was limited. There is a paucity of evidence for sleep interventions in MCI and mild AD highlighting a pressing need for high quality experimental studies exploring alternative sleep interventions.

Efficacy of Donepezil Hydrochloride plus Olanzapine for Senile Dementia and Its Effect on the Recovery of Cognitive Function

“…Donepezil hydrochloride plus olanzapine herein significantly improved the cognitive function of patients and considerably relieved the disease condition of patients with Alzheimer's disease [25]. ere was no statistically significant difference in the incidence of adverse reactions between the two groups of patients, which indicated a manageable safety of the combined therapy of donepezil hydrochloride plus olanzapine [26,27].…”

International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders

“…Neurodegeneration is accompanied by sleep difficulties due to reduction of amplitude and phase changes of circadian rhythms such as that of melatonin secretion, as well as the disturbing influences of neurodegenerative processes on sleep. The relation between sleep and neurodegenerative diseases is bidirectional and several studies have shown that sleep disruption is a major contributor to neuropathology (30,(73)(74)(75)(76). Alzheimer disease (AD) patients with disturbed sleep-wake rhythms did not only exhibit reduced amounts of melatonin secretions, but also a higher degree of irregularities in the melatonin pattern, such as variations in phasing of the peak.…”

“…An emerging symptom of this circadian disruption is "sundowning, " a chronobiological phenomenon observed in patients with AD along with sleep and wakefulness disorder. "Sundowning" is characterized by symptoms appearing in the late afternoon or early evening, which include reduced ability to maintain attention to external stimuli, disorganized speech, and thinking, a variety of motor disturbances including agitation, wandering, and repetitious physical behaviors with emotional disturbances (30,(73)(74)(75)(76).…”

The Importance of Diagnosing and the Clinical Potential of Treating Obstructive Sleep Apnea to Delay Mild Cognitive Impairment and Alzheimer’s Disease: A Special Focus on Cognitive Performance

“…The findings of these several studies demonstrated that, despite some statistical limitations, there is sufficient evidence to suggest that CPAP treatment may be effective in improving cognition in OSA patients with MCI and AD. Moreover, treating sleep apnea holds great promise not only to enhance cognition but also to improve quality of life and delay MCI and AD progression [ 73, 74 ]. For instance, several studies demonstrated that OSA increases AD biomarker burden and as such, it is plausible to hypothesize that CPAP treatment would also result in changes of amyloid and tau AD biomarkers.…”