Blood pressure and cognitive decline - the impact of hypertension over one decade.

BACKGROUND: Midlife hypertension is a risk factor for cognitive decline in late-life but little is known about the impact of long-term hypertension on cognitive change over time. METHODS: We examined blood pressure and cognitive function in 2777 participants (baseline: 2000-2003, 45-75 years, 48.4% men) from the Heinz Nixdorf Recall study. Blood pressure was assessed at three study visits and cognitive function was assessed at both follow-ups (mean follow-up: 5.1 years). Z-score differences in five neuropsychological tests, defining cognitive decline, were derived from linear regression models including age and education. The association of cognitive decline over 5 years and blood pressure over 10 years (classified as: normal blood pressure (>10 years, reference), prevalent hypertension (>10 years), incident hypertension t1 (>5 years), incident hypertension t2 (<5 years), temporary hypertension (at least one hypertensive reading)) was calculated using linear regression models resulting in coefficient b and 95% confidence interval. We calculated interactions with age (linear and with a cutoff at 65 years). RESULTS: Participants with prevalent hypertension showed a greater cognitive decline in both verbal memory tests. Incident hypertension t1 was associated with a greater decline in the visuospatial organization test. There was no interaction with age. CONCLUSION: This study showed that prevalent high blood pressure over 10 years is related to cognitive decline. Prevalent hypertension with longer exposure time may be more detrimental than temporary hypertension for cognitive function.

Sociodemographic data and APOE-ε4 augmentation for MRI-based detection of amnestic mild cognitive impairment using deep learning systems.

Detection and diagnosis of early and subclinical stages of Alzheimer's Disease (AD) play an essential role in the implementation of intervention and prevention strategies. Neuroimaging techniques predominantly provide insight into anatomic structure changes associated with AD. Deep learning methods have been extensively applied towards creating and evaluating models capable of differentiating between cognitively unimpaired, patients with Mild Cognitive Impairment (MCI) and AD dementia. Several published approaches apply information fusion techniques, providing ways of combining several input sources in the medical domain, which contributes to knowledge of broader and enriched quality. The aim of this paper is to fuse sociodemographic data such as age, marital status, education and gender, and genetic data (presence of an apolipoprotein E (APOE)-ε4 allele) with Magnetic Resonance Imaging (MRI) scans. This enables enriched multi-modal features, that adequately represent the MRI scan visually and is adopted for creating and modeling classification systems capable of detecting amnestic MCI (aMCI). To fully utilize the potential of deep convolutional neural networks, two extra color layers denoting contrast intensified and blurred image adaptations are virtually augmented to each MRI scan, completing the Red-Green-Blue (RGB) color channels. Deep convolutional activation features (DeCAF) are extracted from the average pooling layer of the deep learning system Inception_v3. These features from the fused MRI scans are used as visual representation for the Long Short-Term Memory (LSTM) based Recurrent Neural Network (RNN) classification model. The proposed approach is evaluated on a sub-study containing 120 participants (aMCI = 61 and cognitively unimpaired = 59) of the Heinz Nixdorf Recall (HNR) Study with a baseline model accuracy of 76%. Further evaluation was conducted on the ADNI Phase 1 dataset with 624 participants (aMCI = 397 and cognitively unimpaired = 227) with a baseline model accuracy of 66.27%. Experimental results show that the proposed approach achieves 90% accuracy and 0.90 F1-Score at classification of aMCI vs. cognitively unimpaired participants on the HNR Study dataset, and 77% accuracy and 0.83 F1-Score on the ADNI dataset.

The role of depressive symptoms within the association of long-term exposure to indoor and outdoor traffic noise and cognitive function - Results from the Heinz Nixdorf Recall study.

OBJECTIVES: Traffic noise is negatively associated with cognitive function, and its perception can differ between depressed and non-depressed people. We studied the role of depressive symptoms in the association between traffic noise and cognitive function. We studied the role of depressive symptoms in the association between traffic noise and cognitive function. METHODS: During the first follow-up examination (2006-2008) of the German Heinz Nixdorf Recall study, cognitive function (five subtests and an additive global summary score, GCS) and depressive symptoms (CES-D score) were assessed in 2745 participants (aged 50-80, 49.8% women). Mild cognitive impairment (MCI) was diagnosed according to the Petersen criteria in 380 participants. Long-term exposure to traffic noise was modeled as weighted 24-h mean (LDEN) and night-time mean (LNIGHT) at the façade of the baseline addresses, and was corrected for indoors (LDEN_IN and LNIGHT_IN). We developed multiple linear and logistic regression models adjusted for individual-level characteristics to investigate cross-sectionally the role of depressive symptoms in the association of traffic noise with cognitive function. RESULTS: Overall, 8.6% participants had depressive symptoms. The median noise values were LDEN 52.1 dB(A) and LDEN_IN 34.7 dB(A). Associations were slightly stronger for cognitive subtests in those with severe depression (CES-D>21), i.e., per 10 dB(A) LDEN and verbal fluency: ß = -0.04 [-0.11; 0.03] for CES-D≤21 and ß = -0.09 [-0.24; -0.06] for CES-D>21. Additional adjustment of the main model for CES-D did not change the association between noise and cognitive outcomes. Estimates using indoor noise exposure were generally stronger and more precise. CONCLUSIONS: Depressed people may be more susceptible to adverse effects of noise than non-depressed. Modeled estimates of indoor noise exposure is possibly a more appropriate measure of exposure.

Associations between self-reported sleep characteristics and incident mild cognitive impairment: The Heinz Nixdorf Recall Cohort Study.

Associations of sleep characteristics with mild cognitive impairment (MCI) have been examined in cross-sectional, but rarely in longitudinal studies. Incident MCI and sleep characteristics were assessed in 1,890 participants of the first and second follow-up of the Heinz Nixdorf Recall study, a population-based cohort study in Germany (age at first follow-up 50-80 years, mean follow-up 5.2 years). MCI was assessed with extensive cognitive tests. Sleep questionnaires including PSQI (Pittsburgh Sleep Quality Index) were used to assess sleep quality, sleep disturbances, time asleep, and time in bed. Relative risks (RR) of developing MCI when exposed to sleep characteristics were assessed in regression models adjusted for sociodemographic and cardiovascular risk factors. Poor sleep quality (PSQI > 5) (RR = 1.43, 95% CI: 1.12-1.82, fully adjusted, reference: PSQI ≤ 5) and difficulties initiating sleep (almost nightly versus never) (RR = 1.40, 0.94-2.08) were associated with incident MCI. For time in bed, the risk of MCI was increased for ≤ 5 hours (RR = 2.86, 1.24─6.60, reference:7 to <8 hours). In this longitudinal study with older participants, MCI risk was increased in persons with poor sleep quality, difficulties initiating sleep, and short time in bed.

Subjective cognitive decline, APOE ε4, and incident mild cognitive impairment in men and women.

INTRODUCTION: Possible joint effects of subjective cognitive decline (SCD) and apolipoprotein E (APOE) ε4 genotype on incident mild cognitive impairment (MCI) were examined for men and women separately. METHODS: Cognitively normal participants with and without SCD were included from the first follow-up examination of the population-based Heinz Nixdorf Recall study. Sex-stratified logistic regression models estimated main effects and interactions (additive, multiplicative) of SCD at the first follow-up (yes+/no-) and APOE ε4 (positive+/negative-) groups for MCI 5 years later. RESULTS: Odds for MCI 5 years later were higher in SCD/APOE ε4 group +/+ than the sum of groups +/- and -/+ in women, with a trend for positive interaction. Odds for incident MCI in men was highest in group +/-, with no interaction effect. DISCUSSION: Our findings indicate that APOE ε4 may play an important role in the association of SCD and incident MCI, especially considering sex. Further studies need to examine these associations with larger sample sizes.

Normative data from linear and nonlinear quantile regression in CANTAB: Cognition in mid-to-late life in an epidemiological sample.

INTRODUCTION: Normative cognitive data can help to distinguish pathological decline from normal aging. This study presents normative data from the Cambridge Neuropsychological Test Automated Battery, using linear regression and nonlinear quantile regression approaches. METHODS: Heinz Nixdorf Recall study participants completed Cambridge Neuropsychological Test Automated Battery tests: paired-associate learning, spatial working memory, and reaction time. Data were available for 1349-1529 healthy adults aged 57-84 years. Linear and nonlinear quantile regression analyses examined age-related changes, adjusting for sex and education. Quantile regression differentiated seven performance bands (percentiles: 97.7, 93.3, 84.1, 50, 15.9, 6.7, and 2.3). RESULTS: Normative data show age-related cognitive decline across all tests, but with quantile regression revealing heterogeneous trajectories of cognitive aging, particularly for the test of episodic memory function (paired-associate learning). DISCUSSION: This study presents normative data from Cambridge Neuropsychological Test Automated Battery in mid-to-late life. Quantile regression can model heterogeneity in age-related cognitive trajectories as seen in the paired-associate learning episodic memory measure.

Olfactory Function is Associated with Cognitive Performance: Results of the Heinz Nixdorf Recall Study.

BACKGROUND: There is strong evidence for an association of olfactory dysfunction and neurodegenerative diseases. Studies on the association of olfaction and cognition in the general population are rare. OBJECTIVE: To evaluate gender- and age-specific associations of olfactory function and cognitive performance in a well characterized population-based study sample. METHODS: At the third examination of the Heinz Nixdorf Recall study (n = 3,087), 2,640 participants (48% men; 68.2±7.2 years) underwent Sniffin' Sticks Screening Test measuring olfactory function on a scale of 0-12 points. Olfactory function was rated as anosmic, hyposmic, or normosmic (≤6, 7-10 or ≥11 points, respectively). All participants performed eight validated cognitive subtests. Age- (55-64 years, 65-74 years, 75-86 years) and gender-stratified multivariate analysis of covariance was used to evaluate group differences in cognitive performance. RESULTS: Women showed better olfactory function than men (p < 0.001). For middle-aged participants, olfactory groups differed in almost all cognitive subtests. The analyses revealed no gender effects, although associations were slightly greater for women than for men. Anosmics showed the worst cognitive performance and normosmics showed the best cognitive performance. In the young- and old-aged groups, a quantitative association was found for anosmics in all subtests and for normosmics and hyposmics in almost all subtests. CONCLUSION: This is the first study reporting on age-specific associations of olfactory function and cognitive performance in the general population. The association found in middle-aged participants (65-74 years) may serve as a marker to improve identification of persons at high risk for cognitive decline and dementia.

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 (ß)=-0.16 [95% confidence interval: -0.33; 0.01] and ß=-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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Higher glucose levels associated with lower memory and reduced hippocampal microstructure.

OBJECTIVES: For this cross-sectional study, we aimed to elucidate whether higher glycosylated hemoglobin (HbA1c) and glucose levels exert a negative impact on memory performance and hippocampal volume and microstructure in a cohort of healthy, older, nondiabetic individuals without dementia. METHODS: In 141 individuals (72 women, mean age 63.1 years ± 6.9 SD), memory was tested using the Rey Auditory Verbal Learning Test. Peripheral levels of fasting HbA1c, glucose, and insulin and 3-tesla MRI scans were acquired to assess hippocampal volume and microstructure, as indicated by gray matter barrier density. Linear regression and simple mediation models were calculated to examine associations among memory, glucose metabolism, and hippocampal parameters. RESULTS: Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Moreover, mediation analyses indicated that beneficial effects of lower HbA1c on memory are in part mediated by hippocampal volume and microstructure. CONCLUSIONS: Our results indicate that even in the absence of manifest type 2 diabetes mellitus or impaired glucose tolerance, chronically higher blood glucose levels exert a negative influence on cognition, possibly mediated by structural changes in learning-relevant brain areas. Therefore, strategies aimed at lowering glucose levels even in the normal range may beneficially influence cognition in the older population, a hypothesis to be examined in future interventional trials.