Endogenous melatonin levels and therapeutic use of exogenous melatonin in tension type headache: A systematic review.

BACKGROUND-PURPOSE: A bidirectional relationship appears to connect tension-type headache (TTH) and circadian dysregulation. The present systematic review examined the published evidence for melatonin (MT) supplementation in the prophylaxis of TTH. Initially, we reviewed case-control studies investigating nocturnal MT or 6-sulphatoxymelatonin (aMT6s, a urine-discarded metabolite) in TTH individuals and healthy controls (HC). Secondly, we reviewed studies appraising the use of MT in the prevention of TTH. METHODS: The search strategy involved MEDLINE EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar and OpenGrey. Case-control studies were appraised according to the Newcastle-Ottawa-Scale, whereas randomised controlled trials were assessed based on the risk-of-bias Cochrane tool. Infrequent, as well as frequent, episodic, and chronic TTH patients were evaluated separately in children and adults. RESULTS: Our search strategy yielded two case-control studies. One (high-quality) did not reveal any difference in morning salivary MT concentration between children with frequent episodic TTH and HC. The second (moderate-quality) was indicative of a disturbed nocturnal secretion pattern in adults with chronic TTH. For the second part, five uncontrolled studies were retrieved. In total, 94 adults with chronic TTH were assessed and results were suggestive of a beneficial effect of MT on headache frequency, intensity, induced disability, and induced analgesic consumption. However, the uncontrolled-unblinded designs may have induced an important placebo effect. Non-adult populations and frequent TTH were substantially understudied. CONCLUSIONS: There are not enough studies to designate the role of MT in the prevention of TTH. Given the disease's background, additional relevant research is warranted for chronic TTH.

Nutrient Status in Patients with Frequent Episodic Tension-Type Headache: A Case-Control Study.

OBJECTIVE: To investigate the relationship between frequent episodic tension-type headache (FE-TTH) and 25-hydroxyvitamin-D (25(OH)D), folate, vitamin B12, and magnesium. DESIGN-METHODS: A prospective case-control study involving adults with FETTH and age-sex matched healthy controls (HC) was performed. Individuals under the responsibility of the three provincial Health Centres of the prefecture of Trikala (Central Greece) were recruited during their regular check-up visits. The relationship between FETTH and serum levels of 25(OH)D, vitamin B12, folate, and magnesium was investigated (primary outcomes). Demographics, daily habits, somatometrics, psychometric and sleep quality measurements, laboratory indices, cardiovascular comorbidities and medications taken were also recorded and compared (secondary outcomes). Potential associations of the above-listed parameters with headache parameters (headache frequency, severity and analgesic consumption) were also examined (secondary outcomes). RESULTS: Between September and December 2020, 30 patients with FETTH and 30 HC were successfully recruited. Demographics, comorbidities, regular medications, smoking habits, alcohol and coffee consumption, body mass index measurements, markers of systemic inflammation, folate and vitamin B12 levels were similar between the two groups (P>0.05). Lower serum 25(OH)D was both univariately (P<0.001) and multivariately [OR= 0.72, 95%CI=(0.55, 0.94) per 1ng/ml increase] associated with FETTH, while serum magnesium was found lower in FETTH only according to the univariate approach (P=0.036). Higher levels of depression (P=0.050) and anxiety (P=0.020), as well as poor quality of sleep (P=0.008), were univariately associated with FETTH. Only the effect of anxiety remained significant following the multivariate logistic regression [OR=7.90, 95%CI=(1.00, 62.47)]. Headache parameters were not associated with any one of the assessed variables. DISCUSSION: Lower serum 25(OH)D was related to the presence of FETTH. This finding could imply a potential role for vitamin D in the pathophysiology of TTH.

Vitamin D serum levels in patients with migraine: A meta-analysis.

BACKGROUND/PURPOSE: Dietary habits and nutrients have been associated with migraine. The present study comprises a meta-analysis of observational studies evaluating serum levels of 25-hydroxyvitamin D (25(OH)D) in patients with migraine and healthy controls. METHODS: MEDLINE and Cochrane databases were comprehensively searched. References from retrieved observational studies, reviews and meta-analyses were manually screened. Quality assessment was performed based on the Newcastle-Ottawa Scale. 25(OH)D concentrations were assessed by estimates of mean differences (MD) and their precision [95% confidence intervals (95% CIs)]. Random effects (RE) or fixed effects (FE) model was used based on heterogeneity among trials (homogeneity determined when PQ>0.1 and I2<50%). Publication bias was assessed by funnel plots. RESULTS: Eight studies were included in the primary analysis, while nine studies were involved overall (in primary and secondary analyses). Serum levels of 25(OH)D were determined significantly lower in migraine patients (n=952) in comparison with healthy controls (n=8013) [eight studies, PQ<0.1, I2=94%, RE model MD=-4.11, 95% CI=(-6.48, -1.74)]. Secondary analysis revealed no difference between patients with migraine (n=269) compared to patients with other primary headache disorders (n=223) [three studies, PQ=0.51, I2=0%, FE model MD=-0.15, 95% CI=(-1.57, 1.05)], as well as between patients with tension type headache (n=295) in comparison with healthy controls (n=267) [three studies, PQ<0.1, I2=96%, RE model MD=-7.11, 95% CI=(-15.50, 1.27)]. CONCLUSIONS: 25(OH)D concentration is lower in patients with migraine than healthy individuals. In view of this finding, investigation of the effect of vitamin D supplementation in patients suffering from migraine is warranted.

Cognitive Performance and Incident Alzheimer's Dementia in Men Versus Women.

BACKGROUND: The utility of neuropsychological measurements as forerunners of Alzheimer's Disease Dementia (AD) in individuals with normal cognition or mild cognitive impairment (MCI) is undeniable. OBJECTIVES: To assess the differential prognostic value of cognitive performance in older men versus women. DESIGN: Longitudinal analysis of data acquired from the National Alzheimer's Coordinating Center Uniform Data Set. SETTINGS: Data on older adults (≥60 years) were derived from 43 National Institute on Aging - funded Alzheimer's Disease Research Centers. PARTICIPANTS: 10,073 cognitively unimpaired (CU) older adults followed for 5.5±3.8 years and 3,925 participants with amnestic MCI monitored for 3.5±2.8 years. MEASUREMENTS: The domains of episodic memory, verbal fluency, naming, attention, processing speed and executive function were assessed. Cox proportional hazards models examined associations between individual cognitive domains and AD incidence separately for each participant set. CU and MCI. These predictive models featured individual neuropsychological measures, sex, neuropsychological measure by sex interactions, as well as a number of crucial covariates. RESULTS: Episodic memory and verbal fluency were differentially related to future AD among CU individuals, explaining a larger proportion of risk variance in women compared to men. On the other hand, naming, attention and executive function were differentially related to future AD among participants with MCI, accounting for a greater fraction of risk variance in men than women. CONCLUSION: Cognitive performance is differentially related to risk of progressing to AD in men versus women without dementia.