Effects of Circadian Phase Tailored Light Therapy on Sleep, Mood, and Cognition in Alzheimer's Disease: Preliminary Findings in a Pivotal Study

Abstract

It is shown that the circadian system is affected in patients with Alzheimer's disease (AD) even at an early stage of the disease and that such dysfunction may be detrimental to sleep, mood, and cognitive functioning. Light is a strong central modulator of the circadian rhythms and is potentially beneficial to mood and cognitive functioning via a direct effect or indirectly via its modulating effects on circadian rhythms. This study focuses on tracking the effect of light therapy on sleep quality, mood, and cognition in AD of mild/moderate severity. We performed a single-blind randomized controlled trial to investigate the effects of a light therapy treatment tailored to the individual circadian phase as measured by dim light melatonin onset (DLMO). Such a treatment induced an objective circadian phase shift consistent with the melatonin phase response curve to light exposure, led to a shortening of the phase angle DLMO-falling asleep time, and was associated with an improvement in subjective sleep quality and cognitive performance.

Keywords: Alzheimer’s disease; circadian rhythm; cognition; dim light melatonin onset (DLMO); light therapy; melatonin; sleep quality.

FIGURE 1

Progressive steps of the study protocol. After the recruitment, all the patients once checked for clinical exclusion criteria, performed a full night cardiorespiratory polygraphic recording, and received the first battery of neuropsychological tests [i.e., Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI)] with the addition of Beck’s Depression Inventory. Subsequently, they filled out sleep questionnaires [i.e., Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS)] under medical supervision. The following step consisted of a 7-day/night actigraphic monitoring through a triaxial actigraphic watch (MotionWatch8), assessing the 24-h activity-rest rhythm and objective sleep parameters of subjects. Salivary melatonin collection was then performed to determine the circadian phase of patients by means of dim light melatonin onset (DLMO). These data permitted us to plan a 4-week tailored light (active or sham) exposure by means of Luminette glasses. At the end of the protocol, we reassessed cognitive, sleep, and circadian measures to evaluate a potentially favorable effect of light delivery.

FIGURE 2

Enrollment process flowchart of participants.

FIGURE 3

DLMO shift before (PRE, blue rhombuses) and after (POST, red squares) 4-week Luminette protocol. The x-axis shows any single patient in progressive numbers, and the y-axis shows the hours of the day. DLMO, dim light melatonin onset. After a single-blind 4-week tailored light therapy, patients with AD presented a circadian phase shift toward a later chronotype (mean values). These data are probably the result of a more consistent circadian phase shift in the Early Circadian Phase patients (ECPpts) compared to Late Circadian Phase patients (LCPpts).