Angela Winkler

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.

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

Outcome and periprocedural time management in referred versus directly admitted stroke patients treated with thrombectomy

Background: After thrombectomy has shown to be effective in acute stroke patients with large vessel occlusion, the potential benefit of secondary referral for such an intervention needs to be validated. Aims: We aimed to compare consecutive stoke patients directly admitted and treated with thrombectomy at a neurointerventional centre with patients secondarily referred for such a procedure from hospitals with a stroke unit. Methods: Periprocedure times and mortality in 300 patients primarily treated in eight neurointerventional centres were compared with 343 patients referred from nine other hospitals in a prospective multicentre study of a German neurovascular network. Data on functional outcome at 3 months was available in 430 (76.4%) patients. Results: In-hospital mortality (14.8% versus 11.7%, p = 0.26) and 3 months mortality (21.9% versus 24.1%, p = 0.53) were not statistically different in both patient groups despite a significant shorter symptom to groin puncture time in directly admitted patients, which was mainly caused by a longer interfacility transfer time. We found a nonsignificant trend for better functional outcome at 3 months in directly admitted patients (modified Rankin Scale 0–2, 44.0% versus 35.7%, p = 0.08). Conclusions: Our results show that a drip-and-ship thrombectomy concept can be effectively organized in a metropolitan stroke network. Every effort should be made to speed up the emergency interfacility transfer to a neurointerventional centre in stroke patients eligible for thrombectomy after initial brain imaging.

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 physicians 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.

Associations of long-term exposure to air pollution and road traffic noise with cognitive function—An analysis of effect measure modification

BACKGROUND Adverse effects of traffic-related air pollution (AP) and noise on cognitive functions have been proposed, but little is known about their interactions and the combined effect of co-exposure. METHODS Cognitive assessment was completed by 4086 participants of the population-based Heinz Nixdorf Recall cohort study using five neuropsychological subtests and an additively calculated global cognitive score (GCS). We assessed long-term residential concentrations for size-fractioned particulate matter (PM) and nitrogen oxides with land use regression. Road traffic noise (weighted 24-h (LDEN) and night-time (LNIGHT) means) was assessed according to the EU directive 2002/49/EC. Linear regression models adjusted for individual-level characteristics were calculated to estimate effect modification of associations between AP and noise with cognitive function. We used multiplicative interaction terms and categories of single or double high exposure, dichotomizing the potential effect modifier at the median (AP) or at an a priori defined threshold (road traffic noise). RESULTS In fully adjusted models, high noise exposure increased the association of AP with cognitive function. For example, for an interquartile range increase of PM2.5 (IQR 1.43), association s with GCS were: estimate (β)=-0.16 [95% confidence interval: -0.33; 0.01] and β=-0.48 [-0.72; -0.23] for low and high LDEN, respectively. The association of noise with GCS was restricted to highly AP-exposed participants. We observed stronger negative associations in those participants with double exposure compared to the addition of effect estimates of each single exposure. CONCLUSIONS Our study suggests that AP and road traffic noise might act synergistically on cognitive function in adults.

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

ABSTRACT 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.

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.

N-Terminal Pro-B Type Natriuretic Peptide is Associated with Mild Cognitive Impairment in the General Population

BACKGROUND N-terminal pro-B type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and is linked with silent cardiac diseases. While associations of cognitive impairment with manifest cardiovascular diseases are established, data on whether subclinical elevation of NT-proBNP levels below clinically established threshold of heart failure is related with cognitive functioning, especially mild cognitive impairment (MCI), is rare. OBJECTIVE Aim of the present study was to investigate the cross-sectional association of NT-proBNP levels and MCI in a population-based study sample without heart failure. METHODS We used data from the second examination of the population based Heinz-Nixdorf-Recall-Study. Subjects with overt coronary heart disease and subjects with NT-proBNP levels indicating potential heart failure (NT-proBNP≥300 pg/ml) were excluded from this analysis. Participants performed a validated brief cognitive assessment and were classified either as MCI [subtypes: amnestic-MCI (aMCI), non-amnestic-MCI (naMCI)], or cognitively-normal. RESULTS We included 419 participants with MCI (63.1±7.4 y; 47% men; aMCI n = 209; naMCI n = 210) and 1,206 cognitively normal participants (62.42±7.1 y; 48% men). NT-proBNP-levels≥125 pg/ml compared to <125 pg/ml were associated with MCI in fully adjusted models (OR 1.65 (1.23;2.23) in the total sample, 1.73 (1.09;2.74) in men and 1.63(1.10;2.41) in women). For aMCI, the fully adjusted OR was 1.53 (1.04;2.25) and for naMCI, the fully adjusted OR was 1.34 (1.09; 166) in the total sample. CONCLUSION Within normal ranges and without manifest heart failure, higher NT-proBNPlevels are associated with MCI and both MCI subtypes independent of traditional cardiovascular risk factors and sociodemographic parameters.

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.