Jonna Lorenz

 was similar among patients with Parkinson’s disease, dementia with Lewy bodies and isolated rapid eye movement sleep behavior disorder after adjusting for medication differences, but medication may worsen symptoms in patients with Parkinson’s disease, a recent study concluded.

The study included 54 patients with Parkinson disease, 24 with dementia with Lewy bodies (DLB) and 21 with isolated rapid eye movement sleep behavior disorder (iRBD). A second set of study groups compared those with and without RBD.

Investigators aimed to compare sleep stability, transitions, arousals and cycle structure among patients with the three disorders, hypothesizing that sleep instability, arousals and cycle structure changes would increase based on the disorder.

The patients underwent video-polysomnography between January 2015 and June 2021. 

The study found that sleep instability was similar among patients with different alpha-synucleinopathies.

“Our study did not find significant differences in sleep stability/transition variables between iRBD, Parkinson disease (PD), and DLB, which could signify that these disorders have the same degree of sleep stability dysfunction, possibly concerning an early derangement of mesopontine structures responsible for both NREM and REM regulation—a preliminary finding that would benefit from confirmation by studies powered by larger samples, in which subtler differences could become significant,” the study authors, led by Paulo Bugalho, MD, MSci, PhD, of the department of neurology at Hospital de Egas Moniz and Centro Hospitalar de Lisboa Ocidental in Lisbon, Portugal, wrote.

Impairment of sleep cycling was more pronounced among patients with Parkinson’s disease.

“These differences could be due to the specificities of the neuropathological progression in PD, but the fact that they did not persist after adjusting for differences in medication suggests that other factors, particularly dopaminergic medication, should be contributing specifically to sleep fragmentation in PD patients,” the authors wrote.

There were no significant differences among those with RDB and those without.

The study authors noted that Parkinson disease, DLB and iRBD all are connected to alpha-synuclein accumulation in the brain stem and could be considered different stages of the same neuropathological process. Rapid eye movement sleep behavior disorder is common in both PD and DLB and often comes before diagnosis, at which point it is considered isolated RBD.

Other sleep problems include sleep fragmentation, reduction or abolition of REM sleep, changes in NREM sleep spindles, K complexes and slow-wave activity.

An 8-hour night of sleep typically includes four to six sleep cycles. The number of sleep cycles was low among all three groups in the study, with 24% of participants not having any sleep cycle and 54.24 having only one or two sleep cycles.

The mean number of sleep cycles was 2.9 in the iRBD group, 1.39 in the Parkinson disease group and 2.25 in the DLB group. Those differences diminished after the investigators repeated the analysis with medication as a co-variate.

“This could mean that dopaminergics, more frequently used in PD, could promote arousals in this disorder, while acetylcholinesterase inhibitors, more frequently used in DLB, could have a protective effect on arousal in this population,” the study authors wrote.

Sleep stability in isolated rapid eye movement sleep behavior disorder, Parkinson's disease, and dementia with Lewy bodies

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Patients with Parkinson disease had more pronounced sleep instability than those with other disorders marked by alpha-synuclein buildup, but those differences diminished after adjusting for medication differences, a new study found.

Medication May Worsen Sleep Instability in Patients with Parkinson Disease

A recent study in Singapore shed light on associations between 

The study reviewed 6 studies including 2 case-control studies, 3 longitudinal cohort studies and 1 cross-sectional study published before May 2022.

“In this systematic review, we found that AMD patients had significantly poorer sleep quality and a greater incidence of sleep apnea compared to controls,” corresponding author Raymond P. Najjar, PhD, assistant professor in the Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, told 

. “The converse was also true, with evidence suggesting an association between sleep disturbances (e.g., sleep apnea and insomnia), with a 1.5-3 times increased likelihood of AMD, particularly late-stage AMD. That said, only a limited number of studies investigated these associations between AMD and sleep. More research needs to be done on this topic.”

Only 6 studies met criteria for inclusion in the review. Studies that were not published in English language, qualitative studies, grey literature and papers without full access were excluded.

The review included studies that involved participants with any subtype of clinically diagnosed AMD and those involving participants with any type of sleep dysfunction that evaluated AMD. Sleep dysfunction was explored as an exposure in two studies, AMD was explored as an exposure in one study, and three studies explored either as an exposure.

“We were surprised by the limited number of studies focusing on the associations between AMD and sleep,” Najjar said.

The review found that people with AMD had greater rates of sleep apnea and poor sleep quality and those with sleep apnea and insomnia were at greater risk of developing AMD. Studies evaluataing the relationship between self-reported sleep quality and the likelihood of AMD were conflicting.

Findings of evaluations of AMD as an exposure and sleep quality and/or quantity as an outcome included higher Pittsburgh Sleep Quality Index (PSQI) global scores among participants with AMD compared with controls (6.5 vs 4.5, p=0.013). Another study found that participants with neovascular AMD were 2.84 times more likely to have very bad sleep quality and 3.19 times more likely to use sleep medication than controls.

AMD patients also were more likely to develop sleep apnea, with a large British study showing a rate ratio relative to healthy controls of 1.24.

When AMD was evaluated as an outcome, one study found that clinical diagnosis of insomnia was an independent risk factor for AMD, with an adjusted hazard ratio (HR) of 1.33 (95% CI, 1.18 – 1.48; 

<.001). Two other studies showed contradictory findings of the effect of sleep quality on AMD, with one showing that sleeping less than 6 hours was associated with a greater likelihood of neovascular AMD and another finding that sleeping more than eight hours was associated with a greater risk of geographic atropy.

The review also included a finding that participants with sleep apnea were more likely to develop AMD within 10 years than those with sleep apnea (rate ratio [RR], 1.44, 95% CI, 1.32 – 1.57). Another longitudinal study showed that participants with sleep apnea were 1.39 times more likely to develop AMD than controls.

Based on our findings, clinicians are encouraged to investigate the presence of sleep disorders when treating patients with AMD as part of holistic clinical care,” Najjar said. “Similarly, ocular health should be monitored regularly in patients with clinically diagnosed insomnia, sleep apnea or other sleep disorders for potential early detection and management of AMD or even other ocular diseases like glaucoma.”

More research with better measures of sleep is needed to confirm the relationships between AMD and sleep dysfunction and determine the underlying cause.

“Our investigation highlighted a gap in the objective investigation of sleep quality and quantity in patient with AMD,” Najjar said. “Additional studies, using objective characterization of sleep (i.e., wrist actigraphy, polysomnography) in patients with AMD are required. We are working on that.”

Associations between age-related macular degeneration and sleep dysfunction: A systematic review

Research on the links between AMD and sleep dysfunction is limited but suggests a bidirectional relationship, a systematic review found.

Age-Related Macular Degeneration Associated with Sleep Dysfunction

 is associated with a higher risk of ocular changes.

The case-control study included 40 nonsegmental vitiligo patients recruited from outpatient clinics of Al-Azhar University hospitals in Egypt and 40 healthy controls.

“Our research highlights the important fact that vitiligo is a systemic condition that is not only limited to the skin but can also affect ocular melanocytes within the retinal pigment epithelium and the uveal tract,” corresponding author Mahmoud Rageh, MD, of Al-Azhar University in Cairo, Egypt, told 

The study was consistent with prior research showing a greater risk of ocular abnormalities, uveitis and subclinical inflammatory fundus dipigmentation among patients with vitiligo.

Study participants were aged 18-40 years old, with men representing 52.5% of the patient group and 40% of the control group. Among those in the patient group, 55% had acrofacial lesions and 45% had generalized lesions. Duration of the idiopathic systemic autoimmune disorder among study participants ranged from 1-13 years with a mean of 3.71.

“We found that duration of vitiligo did not show any significant impact on the ocular abnormalities encountered in our study,” Rageh said.

The study included dermatological and ocular examinations. Slit lamp fundus examinations revealed significant abnormalities in 57.5% of vitiligo patients compared with 6.3% of the controls. Abnormalities included retinal hypopigmentation, retinal hyperpigmentation, iris nevus, iris depigmentation, elevated disc, tigroid fundus and conjunctival nevus.

Differences also were noted in central macular thickness measured by optical coherence tomography, with the highest value among those in the control group. The highest error of refraction value was in the control group.

Melanocytes in the retinal pigment epithelium and uveal tract share common developmental origins, physiology and morphology with those in the skin and protect against ultraviolet light.

“Ocular problems may be closely connected to vitiligo as the depigmentation process in vitiligo patients can influence ocular melanocytes resulting in alterations in macular thickness, iris and retinal pigmentation,” Rageh said. “However, no impairment of vision was detected since ocular melanocytes aren't involved in the detection or transmission of visual pathway.”

The study called for routine ocular examination in vitiligo patients.

“We need to continue our research for defining the possible risks and optimal management plans for vitiligo and other dermatological diseases,” Rageh said.

Vitiligo, characterized by white lesions on the skin, affects about 1% of people worldwide, including 1 million to 2 million people in the United States. Nonsegmental vitiligo usually develops gradually in adulthood and makes up about 90% of vitiligo cases.

 includes phototherapy with topical corticosteroids, calcineurin inhibitors or vitamin-D analogue. The 

 the topical JAK inhibitor ruxolitinib in July as the first indicated treatment for the condition. Tofacitinib also has shown promise in clinical trials.

Ocular changes of non-segmental vitiligo: A case-control study

Nonsegmental vitiligo not only affects the skin but can destroy melanocytes in other areas of the body including the eye, new research shows.

Study Analyzes Ocular Abnormalities Among Patients with Nonsegmental Vitiligo

Patients with psoriasis who were younger, less obese and had less severe psoriasis were more likely to achieve complete skin clearance from treatment with guselkumab, a monoclonal antibody targeting interleukin 23, a recent study found.

The study was a post-hoc analysis of pooled data from VOYAGE-1 and VOYAGE-2 studies. Out of 664 participants included in the analysis, 271 achieved super-response, which is defined by a Psoriasis Area and Severity Index (PASI) 100 response at weeks 20 and 28.

“Although most patients with moderate-to-severe psoriasis receiving biologics will require continuous long-term treatment due to the chronic nature of their disease, data from this post hoc analysis suggest that guselkumab-treated patients with super-response have distinguishable baseline demographic and disease characteristics,” the authors, led by Kristian Reich, MD, PhD (equivalent), of University Medical Center Hamburg-Eppendorf in Germany, wrote.

“These results may allow clinicians to predict which patients at their baseline might achieve super-response, which may be beneficial in drug selection, managing patient expectations of treatment response, and improving patient-physician communication; however, the clinical relevance of these findings requires further study.”

The study used a stepwise logistic regression analysis to evaluate which factors were potentially predictive of super-response. Patients who achieved super-response compared with those with non-super-response were:

Lighter, with a median body weight of 187 pounds vs 198 pounds

Less obese, with a BMI of 30 or above among 35.4% vs 45.3%

Had lower baseline IGA scores of 4 among 16.2% vs. 26.5%

Less likely to have nail psoriasis, 49.1% vs 64.9%

Less previous use of systemic non-biologic treatments, 60.9% vs 69%

Less likely to have metabolic syndrome at baseline, 19.9% vs 25.4%

Factors that were similar between the two groups included diabetes mellitus and hypertension, cigarette use, and baseline blood pressure, fasting glucose, and lipid levels.

“Based on the stepwise logistic regression model, only patient age at study entry, baseline body weight (≤90 kg vs >90 kg), baseline PASI, and baseline IGA score were significant predictors of super-response status,” the authors wrote.

Patients who achieved super-response were more likely to demonstrate early clinical responses, with 5.5% demonstrating a PASI 75 response as early as Week 2 compared with 1.8% of those with non-super-response. PASI 90 was achieved as early as Week 4 among 10% of those who achieved super-response versus 3.6% of those who didn’t, and PASI 100 was achieved as early as Week 8 among 22.5% versus 3.3%.

Limitations of the study include that it is a post hoc analysis with a relative small number of patients, super-response was only evaluated through Week 28 and super-response status was not analyzed for the adalimumab comparator group.

Guselkumab is the first IL-23 inhibitor approved for adults with psoriasis.

 found that guselkumab was associated with longer adherence and greater proxy remission rates than other biologic therapies, including adalimumab, secukinumab and ixekizumab.

Another recent study found that guselkumab was 

 and efficacious in patients with moderate to severe psoriasis regardless of previous biologic therapies, comorbidities or psoriasis manifestation in difficult-to-treat areas. The interleukin 23 biologic also was associated with sustained tolerability and consistent psoriasis clearance 

“The availability of new biologics approved for psoriasis now makes achievement of clear skin a pragmatic treatment goal,” the study authors wrote. “Guselkumab, a first-in-class novel IL-23 p19 inhibitor, is effective and safe in the treatment of patients with moderate-to-severe plaque psoriasis, and complete clearance can be obtained in a significant proportion of patients.”

Super-Response to Guselkumab Treatment in Patients With Moderate-to-Severe Psoriasis: Age, Body Weight, Baseline Psoriasis Area and Severity Index, and Baseline Investigator’s Global Assessment Scores Predict Complete Skin Clearance

Journal of the European Academy of Dermatology and Venerology

A post-hoc analysis of clinical trial data found that psoriasis patients who were younger, less obese and had less severe psoriasis were more likely to achieve super-response to biologic treatment with guselkumab.