Long-term air pollution and traffic noise exposures and cognitive function:A cross-sectional analysis of the Heinz Nixdorf Recall study.

Investigations of adverse effects of air pollution (AP) and ambient noise on cognitive functions are apparently scarce, and findings seem to be inconsistent. The aim of this study was to examine the associations of long-term exposure to AP and traffic noise with cognitive performance. At the second examination of the population-based Heinz Nixdorf Recall study (2006-2008), cognitive performance was evaluated in 4086 participants. Long-term residential exposure to size-specific particulate matter (PM) and nitrogen oxides (NOx) with land use regression, to and traffic noise (weighted 24-h (LDEN) and nighttime (LNIGHT) means), was assessed according to the European Union (EU) Directive 2002/49/EC. Multiple regression models were calculated for the relationship of environmental exposures with a global cognitive score (GCS) and in five cognitive subtests, using single- and two-exposure models. In fully adjusted models, several AP metrics were negatively associated with four of five subtests and with GCS. For example, an interquartile range increase in PM2.5 was correlated with verbal fluency, labyrinth test, and immediate and delayed verbal recall. A 10 dB(A) elevation in LDEN and LNIGHT was associated with GCS. Similar but not significant associations were found for the cognitive subtests. In two-exposure models including noise and air pollution simultaneously, the associations did not change markedly for air pollution, but attenuated numerically for noise. Long-term exposures to AP and traffic noise are negatively correlated with subtests related to memory and executive functions. There appears to be little evidence for mutual confounding.

Long-Term Air Pollution and Traffic Noise Exposures and Mild Cognitive Impairment in Older Adults: A Cross-Sectional Analysis of the Heinz Nixdorf Recall Study.

BACKGROUND: Mild cognitive impairment (MCI) describes the intermediate state between normal cognitive aging and dementia. Adverse effects of air pollution (AP) on cognitive functions have been proposed, but investigations of simultaneous exposure to noise are scarce. OBJECTIVES: We analyzed the cross-sectional associations of long-term exposure to AP and traffic noise with overall MCI and amnestic (aMCI) and nonamnestic (naMCI) MCI. METHODS: At the second examination of the population-based Heinz Nixdorf Recall study, cognitive assessment was completed in 4,086 participants who were 50-80 years old. Of these, 592 participants were diagnosed as having MCI (aMCI, n = 309; naMCI, n = 283) according to previously published criteria using five neuropsychological subtests. We assessed long-term residential concentrations for size-fractioned particulate matter (PM) and nitrogen oxides with land use regression, and for traffic noise [weighted 24-hr (LDEN) and night-time (LNIGHT) means]. Logistic regression models adjusted for individual risk factors were calculated to estimate the association of environmental exposures with MCI in single- and two-exposure models. RESULTS: Most air pollutants and traffic noise were associated with overall MCI and aMCI. For example, an interquartile range increase in PM2.5 and a 10 A-weighted decibel [dB(A)] increase in LDEN were associated with overall MCI as follows [odds ratio (95% confidence interval)]: 1.16 (1.05, 1.27) and 1.40 (1.03, 1.91), respectively, and with aMCI as follows: 1.22 (1.08, 1.38) and 1.53 (1.05, 2.24), respectively. In two-exposure models, AP and noise associations were attenuated [e.g., for aMCI, PM2.5 1.13 (0.98, 1.30) and LDEN 1.46 (1.11, 1.92)]. CONCLUSIONS: Long-term exposures to air pollution and traffic noise were positively associated with MCI, mainly with the amnestic subtype. CITATION: Tzivian L, Dlugaj M, Winkler A, Weinmayr G, Hennig F, Fuks KB, Vossoughi M, Schikowski T, Weimar C, Erbel R, Jöckel KH, Moebus S, Hoffmann B, on behalf of the Heinz Nixdorf Recall study Investigative Group. 2016. Long-term air pollution and traffic noise exposures and mild cognitive impairment in older adults: a cross-sectional analysis of the Heinz Nixdorf Recall Study. Environ Health Perspect 124:1361-1368; http://dx.doi.org/10.1289/ehp.1509824.

Anemia and Mild Cognitive Impairment in the German General Population.

There is increasing evidence that anemia is associated with cognitive impairment. Therefore, the aim of the study was to examine the cross-sectional association of anemia as well as the persistence of anemia over the last five years with mild cognitive impairment (MCI) and MCI subtypes (amnestic/non-amnestic MCI (aMCI/naMCI)). Out of 4,157 participants (50% men, 50-80 years) of the second examination (t1) of a cohort study (baseline (t0) 2000-2003), we included 4,033 participants with available hemoglobin information and complete cognitive assessment. Anemia was defined as hemoglobin <13 g/dl in men (n = 84) and <12 g/dl in women (n = 79). Group comparisons were used to compare the cognitive subtests. To determine the association of MCI with anemia at t1, with anemia five years prior to the cognitive assessment (t0) and anemia at both time points, we used logistic regression models and included 579 participants with MCI and 1,438 cognitively normal participants out of the total cohort. Anemic participants showed lower performances in verbal memory and executive functions. The fully adjusted odds ratios (OR) for MCI, aMCI, and naMCI in anemic versus non-anemic participants were 1.92 (95% -CI, 1.09-3.39), 1.96 (1.00-3.87), and 1.88 (0.91-3.87). Anemia at both times points showed a non-significant association with naMCI (OR 3.74, 0.94-14.81, fully adjusted). Our results suggest that anemia is associated with an increased risk of MCI independent of traditional cardiovascular risk factors. The association of anemia and MCI has important clinical relevance, because many causes of anemia can be treated effectively.

Thyroid-Stimulating Hormone and Mild Cognitive Impairment: Results of the Heinz Nixdorf Recall Study.

BACKGROUND: Although some studies reported on the association of serum thyroid-stimulating hormone (TSH) concentration and cognition, only one population-based study investigated the association of TSH concentration and mild cognitive impairment (MCI). OBJECTIVE: To investigate the gender-specific association of low- and high-normal TSH concentrations with MCI in euthyroid participants. METHODS: Analysis sample 1 included 2,563 euthyroid participants (aged 50-80 years) from the second examination of the population-based Heinz Nixdorf Recall study. Gender-specific TSH quintiles (Q1 low, Q2-Q4 middle, Q5 high TSH concentration) were determined and group comparisons of age- and education-adjusted mean scores were performed for all cognitive subtests. Analysis sample 2 included 378 participants with MCI and 931 cognitively normal participants. MCI was diagnosed according to previously published MCI criteria. Multivariate logistic regression models were performed using TSH quintiles (Q2-Q4 as reference) to assess the association of low- and high-normal TSH concentration with MCI. Models were performed unadjusted and adjusted for sociodemographic and cardiovascular risk factors. RESULTS: Group comparisons showed significant differences only in the immediate recall of the verbal memory task in women. Only women showed a strong association of high-normal TSH concentration with MCI (unadjusted: odds ratio 2.09, 95% confidence interval 1.29-3.37, full adjusted: 1.86, 1.06-3.27). There was no association with low-normal TSH concentration in women and no association of either low- or high-normal TSH concentration with MCI in men. CONCLUSIONS: These results suggest that women with high-normal TSH concentration might be at higher risk of cognitive decline. This needs to be confirmed in the longitudinal analysis.

Ankle-Brachial Index but Neither Intima Media Thickness Nor Coronary Artery Calcification is Associated With Mild Cognitive Impairment.

BACKGROUND: Several studies have reported an association of atherosclerosis with mild cognitive impairment (MCI) and dementia independent of cardiovascular risk factors. OBJECTIVE: To compare the cross-sectional association of the ankle-brachial index (ABI), intima media thickness (IMT), and coronary artery calcification (CAC) with MCI and its subtypes, amnestic MCI (aMCI) and non-amnestic MCI (naMCI) in the population-based Heinz Nixdorf Recall cohort study. METHODS: 4,086 participants performed a validated brief cognitive assessment at the first follow-up examination (2006-2008). MCI was diagnosed according to previously published criteria. Prevalence ratio (PR) regression models adjusted for age, gender, education, cardiovascular risk factors, and APOE genotype were used to compare the association of the ABI, the CAC-Agatston score and the IMT with MCI and its subtypes. RESULTS: We identified 490 participants with MCI (mean age 66.1 ± 7.8, 46.9 % male, aMCI n = 249, naMCI n = 241) and 1,242 cognitively normal participants. A decreasing ABI (per 0.1) was significantly associated with a higher MCI prevalence in fully adjusted models (PR 1.06; 95% confidence interval (CI) 1.01-1.11), whereas an increasing CAC (log(CAC+1)) or IMT (per 0.1 mm) were not associated after adjustment. A decreasing ABI was also significantly associated with naMCI in fully adjusted models (PR 1.12; CI 1.03-1.21) but not with aMCI. CONCLUSIONS: Our data show that the degree of generalized atherosclerosis as measured by the ABI is associated with MCI and with naMCI in a population-based cohort.

Are transversal MR images sufficient to distinguish persons with mild cognitive impairment from healthy controls?

RATIONALE AND OBJECTIVES: Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. This study aims to determine whether current standard magnetic resonance imaging (MRI) is providing markers that can distinguish between subjects with amnestic MCI (aMCI), nonamnestic MCI (naMCI), and healthy controls (HCs). MATERIALS AND METHODS: A subset of 126 MCI subjects and 126 age-, gender-, and education-appropriate HCs (mean age, 70.9 years) were recruited from 4157 participants in the longitudinal community-based Heinz Nixdorf Recall Study. The burden of white matter hyperintensities (WMHs), cerebral microbleeds, and brain atrophy was evaluated on transversal MR images from a single 1.5-T MR scanner by two blinded neuroradiologists. Logistic regression and receiver-operating characteristic analysis were used for statistical analysis. RESULTS: Occipital WMH burden was significantly increased in aMCI, but not in naMCI relative to HCs (P = .01). The combined MCI group showed brain atrophy relative to HCs (P = .01) pronounced at caudate nuclei (P = .01) and temporal horn level (P = .004) of aMCI patients and increased at the frontal and occipital horns of naMCI patients compared to either aMCI or HCs. Microbleeds were equally distributed in the MCI and control group, but more frequent in aMCI (22 of 84) compared to naMCI subjects (3 of 23). CONCLUSIONS: In his cohort, increased occipital WMHs and cortical and subcortical brain atrophies at temporal horn and caudate nuclei level distinguished aMCI from naMCI subjects and controls. Volumetric indices appear of interest and should be assessed under reproducible conditions to gain diagnostic accuracy.

Depression and mild cognitive impairment in the general population: results of the Heinz Nixdorf recall study.

BACKGROUND: The literature suggests an association between depression and mild cognitive impairment (MCI) and dementia, but not all studies have examined this association with regard to MCI subtypes reflecting different dementia etiologies. OBJECTIVE: To examine if there is a cross-sectional relationship of depression and MCI and to examine if the relationship differs depending on the type of depression (currently elevated depressive symptoms or a positive history of lifetime depression or both) and on the MCI subtype (amnestic versus non-amnestic MCI (aMCI/naMCI)). METHODS: From the second examination of the population-based Heinz Nixdorf Recall study (50% men, 50-80 years), 583 participants with MCI (aMCI n = 304; naMCI n = 279) and 1,446 cognitively normal participants were included in the analyses. Currently elevated depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D; score ≥18). Furthermore, participants were asked if they have ever received a previous diagnosis of depression. Log-Poisson regression models (adjusted for sociodemographic/cardiovascular risk factors) were calculated to determine the association of MCI and its subtypes with all depression variables. RESULTS: The fully adjusted prevalence rate ratios for MCI, aMCI, and naMCI in depressed versus non-depressed participants were 2.06 (95% confidence interval, 1.60-2.64), 3.06 (2.21-4.23), and 1.93 (1.46-2.57). A positive history of lifetime depression without current depressive symptoms was solely associated with naMCI (1.31 (0.99-1.73)). CONCLUSION: These results suggest that the relationship of depression/depressive symptoms and MCI might differ depending on the timing of depression and on the MCI subtype. Our longitudinal follow-up will allow us to further elucidate this relationship.

Effect of long-term outdoor air pollution and noise on cognitive and psychological functions in adults.

It has been hypothesized that air pollution and ambient noise might impact neurocognitive function. Early studies mostly investigated the associations of air pollution and ambient noise exposure with cognitive development in children. More recently, several studies investigating associations with neurocognitive function, mood disorders, and neurodegenerative disease in adult populations were published, yielding inconsistent results. The purpose of this review is to summarize the current evidence on air pollution and noise effects on mental health in adults. We included studies in adult populations (≥18 years old) published in English language in peer-reviewed journals. Fifteen articles related to long-term effects of air pollution and eight articles on long-term effects of ambient noise were extracted. Both exposures were separately shown to be associated with one or several measures of global cognitive function, verbal and nonverbal learning and memory, activities of daily living, depressive symptoms, elevated anxiety, and nuisance. No study considered both exposures simultaneously and few studies investigated progression of neurocognitive decline or psychological factors. The existing evidence generally supports associations of environmental factors with mental health, but does not suffice for an overall conclusion about the independent effect of air pollution and noise. There is a need for studies investigating simultaneously air pollution and noise exposures in association mental health, for longitudinal studies to corroborate findings from cross-sectional analyses, and for parallel toxicological and epidemiological studies to elucidate mechanisms and pathways of action.

Association of diabetes mellitus and mild cognitive impairment in middle-aged men and women.

BACKGROUND: Several studies reported on the association of type 2 diabetes (T2DM) with dementia. Studies on the association of T2DM and mild cognitive impairment (MCI) are rare. OBJECTIVE: To evaluate the gender-specific association of T2DM with MCI and MCI subtypes (amnestic MCI (aMCI) and non-amnestic MCI (naMCI)) in a middle-aged (50-65 years) and old-aged (66-80 years) population-based study sample. METHODS: We compared 560 participants with MCI (aMCI n = 289, naMCI n = 271) with 1,376 cognitively normal participants from the Heinz Nixdorf Recall study. Diabetic status was based on self-reported physician's diagnosis or treatment with anti-diabetic medication. We performed group comparisons regarding all cognitive subtests for participants with and without T2DM. Logistic regression models (adjusted for age, education, cardiovascular risk factors, and depression) were used to determine the association of T2DM with MCI and MCI subtypes. RESULTS: In the middle-aged group, fully adjusted models showed an association (odds ratio, 95% CI) of T2DM with MCI that was more pronounced in men (total: 2.03, 1.23-3.36, men: 2.16, 1.12-4.14, women 1.69, 0.73-3.89). T2DM was associated with MCI subtypes (aMCI: 2.01, 1.08-3.73; naMCI: 2.06, 1.06-3.98), whereas, the association was stronger with naMCI in men (2.61, 1.14-5.98) and with aMCI in women (3.02, 1.27-7.17). We found no total or gender-specific association of T2DM with MCI or MCI subtypes in the old-aged group. CONCLUSIONS: Our data show that T2DM is associated with MCI and MCI subtypes in middle-aged, but not in old-aged participants. Furthermore, the results indicate a gender-specific vulnerability of T2DM on cognition, especially in MCI subtypes.

Sleep-disordered breathing, sleep quality, and mild cognitive impairment in the general population.

There is increasing evidence that sleep disorders are associated with cognitive decline. We, therefore, examined the cross-sectional association of sleep-disordered breathing (SDB), sleep quality, and three types of sleep complaints (difficulties initiating sleep, difficulties maintaining sleep, and early morning awakening) with mild cognitive impairment (MCI) and its subtypes. A group of 1,793 participants (51% men; 63.8 ± 7.5 years) of the population-based Heinz Nixdorf Recall study (total sample n = 4,157) received a screening for SDB and self-report measures of sleep complaints. Group comparisons were used to compare performances among five cognitive subtests. Multivariate logistic regression models were calculated to determine the association of MCI (n = 230) and MCI subtypes (amnestic MCI, n = 120; non-amnestic MCI, n = 110) with SDB severity levels, poor sleep quality, and sleep complaints. Severe SDB (apnea-hypopnea index ≥30/h, n = 143) was not associated with MCI, amnestic MCI, or non-amnestic MCI. Poor sleep quality was associated with MCI (Odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.02-2.03; fully adjusted) as well as frequently reported difficulties initiating sleep (OR = 1.94, 1.20-3.14), difficulties maintaining sleep (OR = 2.23, 1.27-4.63), and early morning awakening (OR = 2.30, 1.32-4.00). Severe difficulties initiating sleep (OR = 2.23, 1.21-4.13) and early morning awakening (OR = 2.88, 1.45-5.73) were solely associated with the amnestic MCI subtype, whereas, severe difficulties maintaining sleep (OR = 3.84, 1.13-13.08) were associated with non-amnestic MCI. Our results suggest that poor sleep quality, rather than SDB, is associated with MCI. The selective association of difficulties initiating sleep and early morning awakening with amnestic MCI and of difficulties maintaining sleep with non-amnestic MCI might serve as a marker to improve diagnostic accuracy in the earliest stages of cognitive impairment and will be further investigated in our longitudinal examination.

Automatic segmentation of cerebral white matter hyperintensities using only 3D FLAIR images.

Magnetic Resonance (MR) white matter hyperintensities have been shown to predict an increased risk of developing cognitive decline. However, their actual role in the conversion to dementia is still not fully understood. Automatic segmentation methods can help in the screening and monitoring of Mild Cognitive Impairment patients who take part in large population-based studies. Most existing segmentation approaches use multimodal MR images. However, multiple acquisitions represent a limitation in terms of both patient comfort and computational complexity of the algorithms. In this work, we propose an automatic lesion segmentation method that uses only three-dimensional fluid-attenuation inversion recovery (FLAIR) images. We use a modified context-sensitive Gaussian mixture model to determine voxel class probabilities, followed by correction of FLAIR artifacts. We evaluate the method against the manual segmentation performed by an experienced neuroradiologist and compare the results with other unimodal segmentation approaches. Finally, we apply our method to the segmentation of multiple sclerosis lesions by using a publicly available benchmark dataset. Results show a similar performance to other state-of-the-art multimodal methods, as well as to the human rater.

Elevated levels of high-sensitivity C-reactive protein are associated with mild cognitive impairment and its subtypes: results of a population-based case-control study.

As high-sensitivity C-reactive protein (hsCRP) seems to be associated with an increased risk of cognitive decline, this nested case-control study examined the relation of hsCRP and mild cognitive impairment (MCI) at different time points. 148 MCI cases (106 amnestic, 42 non-amnestic (aMCI/naMCI)) and 148 matched controls were identified from a prospective population based cohort study of 4,359 participants (aged 50-80). HsCRP levels were measured 5 years before (baseline) and at the time of neuropsychological testing (follow-up). Odds ratios (OR) for hsCRP quartiles serum levels were calculated for the two time points using logistic regression analyses and were adjusted for cardiovascular covariates. In the fully adjusted model, baseline hsCRP levels were significantly associated with both MCI and aMCI (OR = 2.29, 95% confidence interval (CI), 1.01-5.15, first versus fourth quartile, respective OR = 2.73, 95% CI, 1.09-6.84). At follow-up, the fourth hsCRP quartile was associated with MCI (OR = 3.60, 95% CI, 1.55-8.33), aMCI (OR = 3.73, 95% CI, 1.52-9.17) and naMCI (OR = 3.66, 95% CI, 1.00-13.77). Elevated hsCRP levels, even detected five years before diagnosis, are associated with an at least twofold increased probability of MCI. These findings suggest that inflammation plays an important role in the development and presence of cognitive impairment.

Population-based distribution and psychometric properties of a short cognitive performance measure in the population-based Heinz Nixdorf Recall Study.

BACKGROUND: Providing a valid and sensitive measure of different domains of cognitive performance in epidemiologic studies of early old-age populations presents a methodological challenge, given the broad range of variability in cognitive functioning in this age group. OBJECTIVES: (1) To provide data on the distribution of cognitive performance scores in a representative sample of an early old-age population, and (2) to assess psychometric properties of a short cognitive performance measure developed within the framework of a cohort study. DESIGN: Population-based cohort study. SETTING AND PARTICIPANTS: As part of the second examination of the Heinz Nixdorf Recall Study, 4,145 participants aged 50-80 years underwent a short cognitive performance assessment composed of 5 subtests with a mean duration of 7.31 min. Additionally, a subsample of 656 participants had a detailed neuropsychological and neurological examination. METHODS: Age- and education-specific cognitive performance scores in the total sample were calculated. Based on data from the subsample, concurrent validity was examined by comparing findings with a clinically validated neuropsychological assessment. RESULTS: In the total sample, younger and more highly educated participants had higher scores of cognitive performance. In the subsample, a good accuracy [area under the curve (AUC) = 0.81 (0.74-0.87)] of the short cognitive performance assessment compared with results from a clinically established Alzheimer disease assessment scale and diagnosis of mild cognitive impairment [AUC = 0.82 (0.78-0.82)] was observed. CONCLUSION: This brief, cognitive performance measure, documenting good psychometric properties, can be useful in future epidemiological investigations exploring different domains and overall cognitive functioning in early old-age populations.

Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study.

This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12-18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of migraine and TTH compared to migraine (OR = 3.136, p = 0.002) or TTH (OR = 1.029, n.s.). Increasing number of headache days per month (OR = 1.092, p ≤ 0.0001) and adherence to lifestyle modifications (OR = 1.269, p = 0.004) predicted primary outcome. 51 of 56 MOH patients were treated successfully. Thirty-five percent of the patients were adherent to pharmacological prophylaxis, 61% to relaxation therapy, and 72% to aerobic endurance sports. MTP is effective in headache treatment. Adherence to therapy was associated with better outcome.

Prevalence of mild cognitive impairment and its subtypes in the Heinz Nixdorf Recall study cohort.

AIMS: We investigated the prevalence of mild cognitive impairment (MCI) and its subtypes according to the original (MCI-original) and modified (MCI-modified; neglecting cognitive complaints) Petersen criteria. METHODS: 4,145 subjects (aged 50-80 years) from a German population-based study completed a cognitive screening test and were poststratified into 2 groups with sample sizes of 1,125 for impaired and 3,020 for age-appropriate performance. Random samples of 445 impaired participants and 211 age-appropriate participants received a detailed neuropsychological evaluation. The prevalence of MCI was estimated by a bias correction estimator based on stratum weights. The association between MCI and age, gender and education was analyzed in a logistic regression model. RESULTS: The estimated MCI prevalence was 7.8% (95% CI: 5.7-9.9%) for the original, and 12.1% (95% CI: 9.8-14.4%) for the modified criteria. In the MCI-original group, amnestic MCI subtypes were slightly less common than non-amnestic MCI subtypes (3.5 vs. 4.3%). MCI-original was associated with lower education and older age. In the MCI-modified group, the amnestic subtypes were more common than the non-amnestic MCI subtypes (7.8 vs. 4.3%), and MCI was associated with age, gender and education. CONCLUSIONS: Prevalence rates of MCI are high in the general population and vary considerably according to the criteria applied.

Prevention of medication overuse in patients with migraine.

This multi-center study compared the therapeutic effect of a cognitive-behavioral minimal contact program (MCT) to the effect of a brochure (bibliotherapy) for the prevention of medication overuse headache (MOH) in migraine patients. Seven German headache centers recruited 182 migraine patients with high triptan or analgesic intake frequency. Patients were randomly allocated to either the MCT-group, receiving both an MCT program and an educational brochure or to the biblio-group receiving only the brochure. All participants continued usual medical treatment. Course of headaches, intake of analgesics or triptans after training, 3 months post-training as well as 1-2 years (mean 15.7 months) later and psychological variables were defined as outcome variables. A significant decline was observed in the number of headache days (11.0-8.8), migraine days (7.3-5.7) and medication intake days (7.4-6.1) from pre to post in the MCT-group (p<0.001 each) and in the biblio-group (p<0.001 each). The pre-to-post-improvements were maintained from pre- to short- and from pre- to long-term follow-up (p<0.001 each) in both groups. Both groups improved significantly from pre to post in psychological variables, e.g. pain acceptance: p<0.001; pain catastrophizing: p<0.001; functional pain coping: p<0.001; and pain related internal control beliefs: p<0.01. Psychological improvements remained stable in both groups at short- and long-term follow-up. During the study, none of the patients developed an MOH. MCT- and bibliotherapy are useful in migraine patients to prevent medication overuse headache or the transition of episodic to chronic headache.