Light and the Effect on Metabolic Syndrome and Alzheimer's Disease

Alzheimer's disease (AD) and type 2 diabetes (T2DM) pose linked, major threats to aging
societies worldwide, but the relationship between these two diseases remains poorly
understood. Hence, insulin resistance may account for the close epidemiological association
between AD and T2DM. A major gap in the understanding of this association, however, is how
brain insulin resistance develops in the context of AD. Studies show that circadian
disruption impairs metabolic control and increases the risk for diabetes and obesity. Vice
versa, disrupted sleep and depression are closely linked to impaired metabolic control and
increased diabetes risk in the general population. Notably, AD is associated with circadian
disruption, which may be amplified by exposure to irregular light-dark patterns or constant
dim light. To what extent circadian disruption contributes to increased diabetes risk in AD
remains unclear. Here, the investigator aims to test whether a novel tailored lighting
intervention (TLI) designed to promote circadian entrainment in AD patients can improve
metabolic control. Preliminary data from ongoing studies demonstrates a beneficial effect of
light treatment on sleep and depression. Given the close association of sleep on metabolic
control, these data support the hypothesis that light therapy that promotes entrainment can
restore metabolic control in AD patients. Specifically, the investigator will test the
efficacy of a practical, scientifically sophisticated 24-hour lighting system for increasing
circadian entrainment in older adults with AD and related dementias (ADRD). The major goal is
to demonstrate that a practical, effective, tailored, nonpharmacological intervention that
promotes circadian entrainment can be used to improve sleep, reduce inflammation, and
ameliorate glucose intolerance and insulin resistance in AD/ADRD patients.

Aim 1: Test if a TLI that promotes entrainment can improve sleep, depression, inflammation,
and glucose tolerance in patients with moderate to late stages ADRD. In a randomized,
placebo-controlled, crossover study involving 60 ADRD patients who live in controlled
environments, the investigators will investigate whether an 8-week exposure to a TLI designed
to increase circadian entrainment (urinary melatonin and activity-rest patterns) will improve
inflammation and glucose tolerance (oral glucose tolerance test), and reduce sleep
disturbances (actigraphy, Pittsburgh Sleep Quality Index, PSQI) and depressive symptoms
(Cornell Scale for Depression in Dementia, CSDD) compared to a control, circadian-inactive
light.

Aim 2: Test if a TLI that promotes entrainment can improve sleep disturbances, inflammation,
insulin sensitivity (Si) and glucose disposal (Sg) and cognition in patients with MCI and
mild ADRD and sleep disturbances. Using a single-arm, between-subjects, placebo-controlled
study the investigators will investigate if long-term (6-month) exposure to TLI improves
glucose homeostasis and insulin sensitivity in patients with MCI and mild AD who suffer from
sleep disturbance and are living at home. Participants will be recruited from the Mount Sinai
AD research center (ADRC) and randomized to receive the TLI (or comparison control treatment)
at home. The investigators hypothesize that, compared to the comparison light, a TLI will
increase entrainment, improve sleep, reduce depression, reduce inflammation, improve
metabolic control, increase insulin sensitivity, and reduce susceptibility to T2DM and
metabolic disease during and after the completion of the 6-month intervention.

Inclusion Criteria:

- Diagnosis of mild to moderate Alzheimer's disease or related dementia,

- type 2 diabetes

- sleep disturbance as determined by a score ≥ 5 on the PSQI

Exclusion Criteria:

- insulin-dependent diabetes,

- urinary incontinence

- obstructing cataracts

- macular degeneration

- blindness

- severe sleep apnea or

- restless leg syndrome (RLS)