Many of us have difficulty getting a good night’s sleep. A bad night’s sleep can affect your whole body. One can have body aches, headaches, blurry vision, and even eye discomfort. This is enough to make one frustrated, irritable, exhausted, and mean.
There are many types of sleep disorders but a common one among my patients is Phase Advancement: the tendency for older adults to go to sleep and wake up earlier than younger adults; the average healthy older adult’s sleep-wake cycle being approximately 60 min earlier than that of healthy younger adults
A. Sleep Drive (aka homeostatic system) and
B. Circadian (aka Alerting Force) systems (Ref 1,2)
They are independent of each other but affect each other.
3. Other key components:
A. Light, blue light exposure
B. Melatonin production and intake
C. Core Body Temperature and Room Temperature of your bedroom.
D. Diet and caffeine intake
E. Exercise: cumulative and timing in relation to bedtime
F. Genetics: can be a big component (see genetic studies below)***
Getting these all to work together can be tough as we get older.
When sleep drive is low, we wake up. But increases steadily throughout the day, and then diminishes rapidly within the first hours of sleep.
The alerting force is regulated by our “biological clock” and follows a daily, circadian rhythm. The biological clock sends the body an alerting signal during the daytime and a sleeping signal at night.
The interaction between the sleep drive and the alerting force determines when we fall asleep and how well we sleep at night.
Misalignment between these two systems will lead to disturbed sleep, early sleep onset, delayed sleep phase disorder, or phase advancement.
1. Avoid electronic screens 2-4hrs before bed time. Avoid screens in bedroom. Get a regular alarm clock.
2. Make the room really dark: invest in black out shades
3. Consider the room temperature: men usually like the bedroom around 55 F; women, warmer: experiment to see if you need the temperature to decrease as you hit midnight.
4. Exercise early morning until 2-4 hrs before bed. Some can exercise and go right to sleep, but most need to get their heart rate and catecholamine level down.
5. Increase serotonin with intimacy or other natural methods: more on this later
6. Consider gluten-free, sugar-free, dairy-free, anti-inflammatory diet: decrease stimulation from certain foods.
7. Caffeine: avoid 4hr before bed is recommended by most experts.
8. Avoid smoking altogether
9. Think about your gut flora: avoid unnecessary anti-biotics; consider taking pro-biotics
10. Melatonin: most often a low dose is enough. Some need to increase to 4mg 2-3hrs before bed. It may not work in some people.
11. Prayer & Meditation: if all else fails, pray and offer up your insomnia for Dr. Cremers.
Advanced Treatment Options:
2. Timed light exposure in the evening:
Laboratory studies have indicated that phase advancement in older adults can be ameliorated by exposure to light levels higher than those experienced at home (Cagnacci, Soldani, Romagnolo, & Yen, 1994; Lack, Wright, Kemp, & Gibbon, 2005).
However, the optimal timing of such light exposure is approximately 4 hr before the time of the core body temperature minimum (CBTmin) (Cagnacci, et al., 1994). The data on using pulsed blue light is controversial and does not seem to help preventing waking up earlier.
The retinal light/dark exposure pattern is the main synchronizer of the circadian system to your position on Earth. (Ref 3)
When this pattern is disrupted or misaligned with social requirements, light intervention can be used to promote sleep consolidation and efficiency by aligning the signals from the biological clock with the sleep drive mechanism, to better control the timing of the sleep/wake cycle (Ref 4).
The relationship between the timing of a light intervention and the changes (magnitude and direction) in circadian time is described by a phase response curve (PRC) (Ref 5). The point on the PRC where the application of a light stimulus changes circadian phase from maximum delay to maximum advance is known as the crossover point.
In humans, this occurs near the time of the core body temperature minimum (CBTmin), which typically occurs during the latter portion of the sleep period and corresponds to when people are most sleepy. In an individual normally entrained to the local 24-hour (h) light/dark cycle, evening light exposure (i.e., prior to CBTmin) delays circadian phase, and morning light exposure (i.e., after CBTmin) advances circadian phase (5).
3. Pharmacotherapy with melatonin or hypnotics for sleep maintenance insomnia: little evidence it helps. The AASM Practice Parameters recommends prescribed sleep scheduling and timed bright light exposure as treatments for ASPD . Bright light therapy in the evening (between 7-9 pm) is typically used and has been shown to delay the timing of circadian rhythms, improve sleep and daytime performance in older individuals with advanced circadian phase and sleep maintenance insomnia symptoms [45,46], although limited compliance may limit its practicality as a long-term treatment.
Based on the phase response curve to melatonin, early morning administration of melatonin (after the nadir of the core body temperature rhythm) would fall in the curve’s advance portion and thus advance the timing of sleep/wake cycle rhythm. However, clinical evidence is lacking regarding its efficacy, and concerns have been raised regarding the safety of taking a potentially sleep promoting agent in the morning [41,42]. Hughes and colleagues  evaluated different delivery strategies of melatonin for ASPD in a controlled study. A 2-week administration of immediate release melatonin 0.5 mg, 4 hours after bedtime or controlled release melatonin 0.5 mg, 30 minutes before bedtime did not improve sleep maintenance, but did result in a non-significant phase delay of approximately 27 minutes . Although hypnotics are used in clinical practice to treat the sleep maintenance symptoms of patients with ASPD, their efficacy and safety in this population has not been specifically studied 
Diagnostic criteria for ASPD includes a stable advance in the timing of the major sleep period relative to the desired sleep time in conjunction with an inability to delay sleep onset and remain asleep until the desired conventional clock time . Given the opportunity to sleep at their preferred sleep schedule, patients also display normal sleep duration and quality. Sleep logs or actigraphy monitoring for at least 7 days are recommended to demonstrate a stable advance in the timing of the sleep period .
ASPD is thought to be less common than DSPD. ASPD is reported more often among older populations . Etiology remains unclear, although patients with ASPD have an earlier timed temperature and melatonin circadian phase, which may be preventing them from sleeping later . Multiple cases of familial advanced sleep phase pattern have been identified in which the ASPD trait segregates with an autosomal dominant mode of inheritance [35,36,39]. Two gene mutations have been identified, the clock gene hPer2 in one family with advanced sleep phase , and the casein kinase 1 delta gene in another family , suggesting that there is heterogeneity of this disorder. Other underlying mechanisms that may be involved include having a short (less than 24 hours) endogenous circadian period  or an attenuated ability to phase delay due to a dominant phase advance region of the PRC to light.
Recap on Definitions for below Key Points:
2. Borbély AA. A two process model of sleep regulation. Hum Neurobiol. 1982;1(3):195–204
3. Wright KP, McHill AW, Birks BR, Griffin BR, Rusterholz T, Chinoy ED. Entrainment of the human circadian clock to the natural light-dark cycle. Curr Biol. 2013;23:1554–8. [PMC free article] [PubMed] [Google Scholar]
Among the many physiological changes in sleep that accompany the aging process is a tendency for older adults to go to sleep and wake up earlier than younger adults. This process, which is termed phase advancement, is responsible for the average healthy older adult’s sleep-wake cycle being approximately 60 min earlier than that of healthy younger adults (Kramer, Kerkhof, & Hofman, 1999; Kripke et al., 2005; Yoon et al., 2003). In some older persons, this physiological shift is especially large, and early evening sleep onset and early morning wakening adversely affect the individual’s quality of life, a condition that is referred to as advanced sleep phase disorder (Palmer et al., 2003).
Laboratory studies have indicated that phase advancement in older adults can be ameliorated by exposure to light levels higher than those experienced at home (Cagnacci, Soldani, Romagnolo, & Yen, 1994; Lack, Wright, Kemp, & Gibbon, 2005). However, the optimal timing of such light exposure is approximately 4 hr before the time of the core body temperature minimum (CBTmin) (Cagnacci, et al., 1994), which in research settings has typically required participants either to be kept awake beyond their typical bedtime or wakened after falling asleep to sit facing a full-spectrum light box for 2 hr or more (Kim et al., 2014; Kolodyazhniy et al., 2011; Lack, et al., 2005). Since such a method would be unacceptable outside the laboratory setting, we hypothesized that light exposure during sleep, if feasible, might be a potent method for creating phase delay in older adults whose lives are adversely affected by advanced sleep phase disorder.
Light delivered through closed eyelids while a person is sleeping, therefore, could potentially result in much greater phase shifts than exposure to light at any other time of the circadian day. Quantifying the stimulus and any resulting phase shift, however, requires measuring the amount of light transmitted through the eyelids. A study by Robinson et al. suggested that the human eyelid functions as a red-pass filter, transmitting 14.5% of 700-nm light but ≤ 3% of light at wavelengths ≤ 580 nm (Robinson, Bayliss, & Fielder, 1991). Similarly, Ando and Kripke showed that eyelid transmittance of red light (615–630 nm) was attenuated to 1/20 (5%), while blue (400–510 nm) and green (540–565 nm) light were attenuated to 1/100 (1%) of the dose on the eyelid surface (Ando and Kripke, 1996). In a more recent study, Bierman et al. showed that mean eyelid transmittance at 490 nm is approximately 0.4% and at 550 nm is approximately 0.5% (Bierman, Figueiro, & Rea, 2011).
In an experiment attempting to phase shift the timing of the circadian clock with light transmitted through closed eyelids, Cole et al. used a light mask that exposed participants to 2700 lux of white light, resulting in an exposure of about 57 lux at the cornea (Cole, Smith, Alcala, Elliott, & Kripke, 2002). In comparison to a placebo stimulus (0.1 lux of red light at the cornea), the white light stimulus produced significant melatonin phase shifts among selected participants with delayed sleep phase disorder. The researchers noted that the light mask was well tolerated by the study’s participants and caused minimal sleep disturbance (Cole, et al., 2002).
Extending this line of research in the first of a series of studies using narrowband spectrum light, Figueiro and Rea demonstrated that green light (wavelength of peak intensity [λmax ] = 527 nm) delivered through the eyelids of sleeping participants using a light-emitting diode (LED) light mask acutely suppressed melatonin and phase shifted dim light melatonin onset (DLMO) when presented prior to the CBTmin (Figueiro and Rea, 2012). The light levels required to affect DLMO when delivered at the eyelids were extremely high, however, ranging from 17,000 to 50,000 lux, and the high heat generated by continuous operation of the LEDs was viewed as a barrier to developing the device for therapeutic use at home.
Employing the Rea et al. model of human circadian phototransduction (Rea, Figueiro, Bierman, & Hamner, 2012; Rea, Figueiro, Bullough, & Bierman, 2005), a subsequent laboratory study by Figueiro et al. demonstrated that flashing (2-s pulses, every 30 s) blue light (λmax = 480 nm) from an LED light mask delayed DLMO if applied before the CBTmin (Figueiro, Plitnick, & Rea, 2014). In a related, placebo-controlled field study of participants reporting a history of early awakening insomnia (compared to an age-matched control group of normal sleepers), Figueiro showed that a 1-week exposure to the same flashing blue light stimulus (experienced for no longer than 3 hr, starting at least 1 hr after bedtime) delayed DLMO by an average of approximately 30 min (Figueiro, 2015). Exposure to a flashing red light (λmax = 640 nm) stimulus of the same timing and duration, however, resulted in only a minimal delay of DLMO. Although this study successfully delayed DLMO among that study’s participants, it remained unknown whether using the light mask for longer durations would delay circadian phase and sleep timing in persons with early sleep onset.
These results are also consistent with those of Sharkey et al., who tested a morning blue light intervention to advance DLMO in college students who exhibited delayed sleep (Sharkey, Carskadon, Figueiro, Zhu, & Rea, 2011). Specifically, they showed that those in the intervention group had the same phase advance as those in the control group. The total light exposures over the course of the day, which were also measured with the Daysimeter, were not significantly different between the two groups. Their conclusion was that both morning and evening light should be monitored in order to obtain the desired phase shift. In the present study, to avoid burden on the participants, there was no control of morning light exposure, which could have counteracted the delaying effect of the light mask intervention. The Daysimeter data also showed no significant differences in hourly CS exposures between the two experimental conditions, with all participants receiving, on average, CS > 0.2 from 9:00 a.m. until 6:00 p.m. For comparison, Figueiro et al. showed that exposure to a CS ≥ 0.3 during the day leads to better sleep, mood, and improved behavior in patients with Alzheimer’s disease and related dementias (Figueiro et al., 2014). Moreover, it is well known that greater amounts of light during the day reduce the impact of evening light on the circadian system (Hébert, Martin, Lee, & Eastman, 2002). Therefore, the impact of the light treatment employed in our study could have been reduced due to participants’ photic history
Genetics and Sleep Issues:
Mechanisms (Per2 and CK1)
Two years after reporting the finding of FASPS, Ptáček’s and Fu’s groups published results of genetic sequencing analysis on a family with FASPS. They genetically mapped the FASPS locus to chromosome 2q where very little human genome sequencing was then available. Thus, they identified and sequenced all the genes in the critical interval. One of these was Period2 (Per2) which is a mammalian gene sufficient for the maintenance of circadian rhythms. Sequencing of the hPer2 gene (‘h’ denoting a human strain, as opposed to Drosophila or mouse strains) revealed a serine-to-glycine point mutation in the Casein Kinase I (CK1) binding domain of the hPER2 protein that resulted in hypophosphorylation of hPER2 in vitro. The hypophosphorylation of hPER2 disrupts the transcription-translation (negative) feedback loop (TTFL) required for regulating the stable production of hPER2 protein. In a wildtype individual, Per2 mRNA is transcribed and translated to form a PER2 protein. Large concentrations of PER2 protein inhibits further transcription of Per2 mRNA. CK1 regulates PER2 levels by binding to a CK1 binding site on the protein, allowing for phosphorylation which marks the protein for degradation, reducing protein levels. Once proteins become phosphorylated, PER2 levels decrease again, and Per2 mRNA transcription can resume. This negative feedback regulates the levels and expression of these circadian clock components.
Without proper phosphorylation of hPER2 in the instance of a mutation in the CK1 binding site, less Per2 mRNA is transcribed and the period is shortened to less than 24 hours. Individuals with a shortened period due to this phosphorylation disruption entrain to a 24h light-dark cycle, which may lead to a phase advance, causing earlier sleep and wake patterns. However, a 22h period does not necessitate a phase shift, but a shift can be predicted depending on the time the subject is exposed to the stimulus, visualized on a Phase Response Curve (PRC). This is consistent with studies of the role of CK1ɛ (a unique member of the CK1 family) in the TTFL in mammals and more studies have been conducted looking at specific regions of the Per2 transcript. In 2005, Fu’s and Ptáček’s labs reported discovery of a mutation in CKIδ (a functionally redundant form of CK1ɛ in the phosphorylation process of PER2) also causing FASPS. An A-to-G missense mutation resulted in a threonine-to-alanine alteration in the protein. This mutation prevented the proper phosphorylation of PER2. The evidence for both a mutation in the binding domain of PER2 and a mutation in CKIδ as causes of FASPS is strengthened by the lack of the FASPS phenotype in wild type individuals and by the observed change in the circadian phenotype of these mutant individuals in vitro and an absence of said mutations in all tested control subjects. Fruit flies and mice engineered to carry the human mutation also demonstrated abnormal circadian phenotypes, although the mutant flies had a long circadian period while the mutant mice had a shorter period. The genetic differences between flies and mammals that account for this difference circadian phenotypes are not known. Most recently, Ptáček and Fu reported additional studies of the human Per2 S662G mutation and generation of mice carrying the human mutation. These mice had a circadian period almost 2 hours shorter than wild-type animals under constant darkness. Genetic dosage studies of CKIδ on the Per2 S662G mutation revealed that depending on the binding site on Per2 that CK1δ interacts with, CK1δ may lead to hypo- or hyperphosphorylation of the Per2 gene.
Melatonin administration in the early morning (after the nadir of the core body temperature rhythm) cause phase delay shifts, whereas when given in the evening, elicit phase advance shifts 
Numerous studies have demonstrated the ability of appropriately timed bright broad-spectrum light, typically between 2500 to 10,000 lux, to induce phase advancement of circadian rhythms [19–21]. For the treatment of DSPD, exposure to bright light shortly after awakening in the morning (close to but after the nadir of the circadian core body temperature rhythm) will advance the timing of circadian rhythms and improve synchronization with the desired sleep and wake times. For example, bright light (2500 lux) for 2 hours in the morning has shown to successfully phase advance the circadian rhythm of core body temperature in DSPD patients .
There is very limited evidence that methylcobalamin (vitamin B12) when combined with bright light in the morning may be effective for the treatment of DSPD[22–25]. Findings that vitamin B12 injected intravenously (0.5 mg/day) at 12:30 pm for 11 days, followed by oral administration (2 mg 3 times per day) for 7 days increased the phase shift induced with a single morning exposure to bright light led to further examination of its effectiveness in treating CRSDs . In an open label study, 28% of patients were effectively treated with either vitamin B12 alone or in combination with bright light . Similar success has been reported in several individual cases . However, administration of 1 mg methylcobalamin 3 times per day after each meal for 4 weeks alone did not show improvements compared to placebo, which suggests that its effects may be dependent on its interaction with light . Therefore, there is insufficient evidence to support vitamin B12 as a treatment for DSPD .
Search for “Blue Light and Eyelid” on Pubmed today 2/5/2021
We report here the development of a brief drug-free rescheduling treatment (“chronotherapy”) for Delayed Sleep Phase (DSP) insomnia, a syndrome characterized by sleep-onset insomnia with difficulty in morning awakening. We postulated that patients with DSP insomnia had an inadequate capacity to achieve phase advance shifts of the circadian pacemaker which times the sleep-wake cycle. Chronotherapy was therefore designed to reset these patients’ biological clocks by the phase delay route. This single 5-6 day treatment was tested in 5 patients with a 4-15 year history of DSP insomnia. All 5 patients reported a lasting resolution of their symptoms substantiated by systematic long-term self-reports and objective polygraphic recording before and after treatment (average follow-up of 260 days; range, 42-910 days). The average sleep onset advanced from 4:50 a.m. before treatment to 12:20 a.m. afterwards, and wake times advanced from 1:00 p.m. to 755 a.m. (for both, p less than 0.001), with no reduction in sleep efficiency. As a result, all 5 patients were able to end their chronic dependence on hypnotic medications.