In the Literature - November 2016

VBCN - November 2016 Volume 3, No 3

In This Article

Sleep Disturbances Lead to Cognitive Decline

The Northern Manhattan Study (NOMAS) showed that individuals with sleep disturbances have worse cognitive performance and subclinical markers of vascular disease, which are contributors to cognitive decline and dementia, compared with individuals without sleep symptoms.

However, it is unclear whether specific cognitive domains are affected by these sleep disturbances. A new cross-sectional analysis examined the effect of sleep disturbances on cognitive processes and their change over time in NOMAS (Ramos AR, et al. Neurology. 2016;87:1511-1516).

The researchers hypothesized that frequent snoring, daytime sleepiness, and short or long sleep duration would lead to worse cognitive performance and decline in 4 domains, including language, episodic memory, cognitive function, and processing speed.

The study included 711 participants from NOMAS with sleep data and neuropsychologic assessment, 687 of whom had repeat neuropsychological testing performed 5 years later. The mean age at baseline was 63 years, with 62% women and 67% of Hispanic/Latino origin.

In the cross-sectional analysis, 711 participants with frequent snoring had worse executive function (β = –12; P = .04) and processing speed (β = –13; P = .02) compared with individuals without frequent snoring, but the researchers observed no differences in episodic memory and language. In addition, the participants with severe daytime sleepiness (β = –26; P = .009) had worse executive function compared with participants with no sleepiness, but there were no changes in the other 3 neuropsychologic domains between the 2 groups.

In the adjusted longitudinal analysis, frequent snoring (β = –29; P = .0007), severe daytime sleepiness (β = –29; P = .05), and long sleep duration (β = –29; P = .04) were associated with a decline in executive function. There was no decline in episodic memory, processing speed, or language in patients with these sleep symptoms. The researchers also found that further adjustments for depression did not significantly change the association between frequent snoring (β = –13; P = .044) and severe daytime sleepiness (β = –27; P = .0089) with executive function. After adjusting for depression, the participants with frequent snoring (β = –29; P = .0010), severe daytime sleepiness (β = –29; P = .05), and long sleep duration (β = –29; P = .04) had worse executive function compared with participants without these sleep disturbances.

In this diverse urban cohort of older adults, sleep disturbances represent a modifiable factor for cognitive function. The researchers suggest evaluating cognitive function in treatment studies for the prevention of neurocognitive disorders.

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Alemtuzumab Demonstrates Superior Outcomes versus Interferon-ß-1a in Relapsing-Remitting Multiple Sclerosis

The CARE-MS I and CARE-MS II clinical trials in patients with relapsing-remitting multiple sclerosis demonstrated that alemtuzumab (Lemtrada) provided greater benefit on magnetic resonance imaging (MRI) disease activity and reduction in brain volume loss compared with subcutaneous interferon (IFN)-β-1a. A new study evaluated additional MRI outcomes for these 2 head-to-head clinical trials, including analyses of lesion numbers, risk for new lesions, and brain atrophy by year (Arnold DL, et al. Neurology. 2016;87:1464-1472).

The phase 3, randomized, 2-year, rater-blinded, active-controlled, head-to-head clinical trials compared alemtuzumab with IFN-β-1a in patients with relapsing-remitting multiple sclerosis who had active disease and were treatment-naive (CARE-MS I) or who had an inadequate response to another therapy (CARE-MS II). Patients were randomized in a 2:1 ratio to receive alemtuzumab 12 mg daily via intravenous infusion on 5 consecutive days and a second course was administered on 3 consecutive days 12 months later, or 44-µg subcutaneous IFN-β-1a 3 times weekly.

Both treatments prevented increases in T2-hyperintensive lesion volume from baseline. Alemtuzumab was more effective than IFN-β-1a on the majority of lesion-based end points in both studies (P <.05). The risk for new or enlarging T2 lesions was significantly lower with alemtuzumab than with IFN-β-1a during the 2-year study period, and in year 2 for patients in the CARE-MS I study (risk reduction [RR], 34%; odds ratio [OR], 0.66 vs RR, 57%; OR, 0.43, respectively) and for patients in the CARE-MS II study (RR, 62%; OR, 0.38 vs RR, 73%; OR, 0.27, respectively). At year 2, the risk for gadolinium-enhancing lesions was significantly reduced with alemtuzu­mab versus IFN-β-1a in both studies (RR, 70%; OR, 0.30 vs RR, 69%; OR, 0.31, respectively).

Reduced risk for new T1-hypointense lesions and for gadolinium-enhancing lesion conversion to T1-hypointense black holes was observed with alemtuzumab versus IFN-β-1a in the CARE-MS II study. The patients in the CARE-MS II study had a significantly lower risk for new T1 lesions compared with IFN-β-1a in year 1 (51% reduction; OR, 0.49), in year 2 (79% reduction; OR, 0.21), and over the 2-year study period (63% reduction; OR, 0.37). Gadolinium-enhancing lesions that formed in year 1 were significantly less likely to evolve into chronic black holes by year 2 in patients who received alemtuzumab compared with those who received IFN-β-1a in the CARE-MS II study (RR, 67%; P = .0078).

In both studies, alemtuzumab slowed brain volume loss over 2 years compared with IFN-β-1a (CARE-MS I, 0.87% vs 1.49%, respectively; CARE-MS II, 0.62% vs 0.81%, respectively).

For patients with active relapsing-remitting multiple sclerosis, these findings provide Class I evidence that alemtuzumab is superior to IFN-β-1a on multiple MRI end points.

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Aprepitant Relieves Nausea Associated with Dihydroergotamine Use for Migraine

Nausea is a common side effect of the intravenous migraine drug dihydroergotamine, which is an effective treatment option for patients with refractory migraine. In a new study, researchers described the use of oral aprepitant (Emend), a substance P/neurokinin-1 receptor antagonist, for the treatment of hospitalized patients with dihydroergotamine-induced nausea between 2011 and 2015 (Chou DE, et al. Neurology. 2016;87:1613-1616).

The researchers performed a retrospective chart review of patients with refractory migraine headache who were admitted to the hospital for a 5-day course of intravenous dihydroergot­amine (cumulative dose of 11.25 mg) and who received aprepitant as an antiemetic therapy for refractory nausea, either at the onset of dihydroergot­amine administration or during the treatment course.

Aprepitant was administered as a loading dose of 125 mg on day 1 and as 80 mg daily 30 minutes before the first dose of dihydroergotamine thereafter. The patients were classified using the beta version of the International Classification of Headache Disorders, Third Edition. The efficacy of aprepitant was assessed by determining a 50% reduction in the average or peak daily nausea score, cessation of emesis after the administration of aprepitant, and a ≥50% reduction in the average daily as-needed antinausea medications.

The investigators reviewed hourly diary data and clinical notes, and identified 74 patients, of whom 24 had daily dairies, with chronic migraine with or without aura, with or without medication overuse, or new daily persistent headache of a migrainous type. Of the 57 patients who received aprepitant during hospitalization, 36 had a ≥50% reduction in the average daily number of as-needed antinausea medications, and 52 patients reported that the addition of aprepitant improved their nausea. The mean or peak daily nausea scores, or both, were reduced in 21 of 24 patients with hourly diary data. Overall, 12 patients who had vomiting had a cessation of emesis after aprepitant was added. In addition, aprepitant was well-tolerated, with no reports of adverse effects attributed to the medication.

This study provides Class IV evidence that aprepitant can relieve di­hydroergotamine-induced nausea and vomiting in patients with medically refractory migraine. Given its tolerability profile, the researchers recommend that clinicians consider aprepitant in refractory dihydroergotamine-induced nausea and emesis, and more broadly in migraine-associated nausea and vomiting.

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Positive Effect of Hormone Therapy on Physical Function in Postmenopausal Women with Multiple Sclerosis

Data are limited regarding the effect of hormonal changes in menopause on women with multiple sclerosis, and whether hormone therapy modulates these changes. A new observational study assessed whether hormone therapy is associated with improved physical quality of life in postmenopausal women with multiple sclerosis (Bove R, et al. Neurology. 2016;87:1457-1463).

The study included 95 women from the prospective Nurses’ Health Study with definite or probable multiple sclerosis who had completed a physical functioning assessment (PF10; subscale of the 36-item Short-Form Health Survey [SF-36] quality-of-life survey) between 3 and 10 years after their final menstrual period.

The participants were grouped according to hormone therapy exposure. The researchers defined women who received hormone therapy as women who, at the time of their first postmenopausal SF-36/PF10 assessment, had used estrogen with or without progesterone for at least 12 months. The researchers used a linear regression model, adjusting for age, multiple sclerosis duration, menopause type, and menopause duration.

Overall, 61 (64%) patients received hormone therapy, and 34 (36%) patients were not exposed to hormone therapy. Women who received hormone therapy differed from those who did not in multiple sclerosis duration (P = .02) and menopause type (P = .01).

Hormone therapy use was associated with significantly better patient-reported physical functioning scores compared with not receiving hormone therapy. The average PF10 scores were 23 points higher in women who received hormone therapy than in women who did not receive hormone therapy (56.5 vs 33.4, respectively; P = .004), and the average Physical Component Scales scores were 9.1 points higher in women who received hormones versus those who did not in the 59 women with these available scores (adjusted P = .02). In addition, a longer duration of hormone therapy was associated with higher PF10 scores (P = .02 in the age-adjusted analysis and P = .06 in the analysis adjusted for age, multiple sclerosis duration, and menopause type and duration).

“Given variable effects of exogenous hormones noted on MS [multiple sclerosis] course, the current study showing no apparent negative effects of HT [hormone therapy] is reassuring,” stated the researchers.

Although the current study does not permit a thorough assessment of causality, the findings suggest that systemic hormone therapy poses no harm to women with multiple sclerosis. Further studies may be warranted to assess the protective effect of hormone therapy on neurodegeneration in multiple sclerosis.

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