Martha Jokisch

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.

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.

Making Use of Longitudinal Information in Pattern Recognition

Longitudinal designs are widely used in medical studies as a means of observing within‐subject changes over time in groups of subjects, thereby aiming to improve sensitivity for detecting disease effects. Paralleling an increased use of such studies in neuroimaging has been the adoption of pattern recognition algorithms for making individualized predictions of disease. However, at present few pattern recognition methods exist to make full use of neuroimaging data that have been collected longitudinally, with most methods relying instead on cross‐sectional style analysis. This article presents a principal component analysis‐based feature construction method that uses longitudinal high‐dimensional data to improve predictive performance of pattern recognition algorithms. The method can be applied to data from a wide range of longitudinal study designs and permits an arbitrary number of time‐points per subject. We apply the method to two longitudinal datasets, one containing subjects with mild cognitive impairment along with healthy controls, the other with early dementia subjects and healthy controls. Across both datasets, we show improvements in predictive accuracy relative to cross‐sectional classifiers for discriminating disease subjects from healthy controls on the basis of whole‐brain structural magnetic resonance image‐based voxels. In addition, we can transfer longitudinal information from one set of subjects to make disease predictions in another set of subjects. The proposed method is simple and, as a feature construction method, flexible with respect to the choice of classifier and image registration algorithm. Hum Brain Mapp 37:4385–4404, 2016.

OP XI – 2 Associations between outdoor and indoor noise, cognitive performance and depressive symptoms – results from hnr study

Background/aim Long-term exposure to traffic noise has been shown to be associated with cognitive function. Noise is associated with depressive symptoms, which in turn are adversely associated with cognitive performance. We aimed to analyse whether depressive symptoms mediate the association of long-term exposure to traffic noise assessed outdoors and indoors with cognitive performance. Methods In a cross-sectional analysis cognitive function was assessed in 4086 participants at the first follow-up of German Heinz Nixdorf Recall study using five subtests. A global cognitive score (GCS) was calculated as a sum of all subtests. We assessed depressive symptoms using the Centre for Epidemiologic Studies Depression scale 15-item short form (CES-D). Long-term weighted 24 hour exposure to traffic noise was assessed according to the EU directive 2002/49/EC of the baseline residential addresses (LDEN), and corrected for type of window, bedroom orientation and ventilation (LDEN_IN). Multiple linear regression models adjusted for individual risk factors were calculated for the association of noise with cognitive function, with and without adjustment for depressive symptoms. Results In the fully adjusted model, noise was negatively associated with cognitive subtests and with the GCS. For example, a 10 dB(A) increase in LDEN was associated with the GCS (β=-0.34 [95% confidence interval: −0.67; −0.01]). An association of indoor noise with cognitive performance was lower (i.e. for 10 dB(A) increase in LDEN_IN with GCS β=-0.18 [-0.25; −0.10]). Adjustment of noise for CES-D score ≥17 (indicating the presence of depressive symptoms) revealed an Odds Ratios of 1.22 [0.92; 1.62] and 1.04 [0.95; 1.14] for 10 dB(A) LDEN and LDEN_IN, respectively. However, the adjustment for CES-D score did not change the noise-cognitive outcome associations neither for outdoor nor for indoor noise (i.e. for LDEN and GCS β=-0.33 [-0.66; −0.01], and for LDEN_IN and GCS β=-0.18 [-0.25; −0.10]). Conclusion We found associations between traffic noise and cognitive performance, which did not change after adjustment for depressive symptoms. Future longitudinal analyses might shed light on possible mediating pathways between noise, depression and cognition.

COGNITIVE PERFORMANCE OF RETURNERS AND NON-RETURNERS OF A POPULATION-BASED STUDY

to test the null hypothesis of no mean difference between delayed recall memory T-scores and language and executive function, respectively. Results: This pre-dialysis sample included 27 adults with a mean age of 66, a mean education of 13 years, and a mean estimated glomerular filtration rate (eGFR, in ml/min/1.73 m) of 13; the average length of time between the last study visit and participant report of dialysis initiation was 6 months. Delayed recall memory performance was the only measure, on average, which fell in the impaired range (T < 40) and demonstrated the lowest performance (T1⁄4 37.9) compared to both language (T 1⁄4 43.7; p 1⁄4 .03) and executive function (T 1⁄4 43.2; p 1⁄4 .05). Conclusions: Delayed recall memory performance may be preferentially reduced in advanced CKD patients prior to the initiation of HD. Future studies will investigate the pattern of pre-dialysis cognitive performance in a larger sample, further characterize the course of memory changes throughout HD, and determine whether impairment in this domain prior to HD suggests an irreversible neurodegenerative process that may not improve with HD treatment.

10-YEAR STABLE BLOOD PRESSURE AND COGNITIVE FUNCTION

Test re-test reliability was adequate for learning trials, LDFR & d’ (r1⁄4.67 to .73; p<.05). Analysis revealed significant inter-correlations between learning and memory scores (r1⁄4.33 to .93), components of WAOMT and odour identification (r1⁄4.15 to .21), verbal episodic memory (r 1⁄4.17 to .26) and visual episodic memory (r 1⁄4 .16 to .27). Females performed better than males on Trial 3 F(1,113) 1⁄4 4.49, p1⁄4 .4 and recognition hits F(1,113)1⁄4 6.24, p1⁄4 .14, controlling for MoCA scores. Performance decreased with age (r 1⁄4 -.13 to -.20). Conclusions:Relationships were found between conceptually similar constructs of verbal and visual episodic memory and odour identification. Performance was found to decrease with age, and females demonstrated an advantage overall males in learning trial 3 and recognition hits. The WAOMT presents a reliable, valid and simple test of odour episodic memory. Future research implications include examining the longitudinal relationship between OEM and cognitive decline.

COGNITIVE PERFORMANCE AND SUBJECTIVE COGNITIVE DECLINE: DATA FROM THE HEINZ NIXDORF RECALL STUDY

University, Augusta, GA, USA; Northwestern University, Chicago, IL, USA; New York University-Langone Medical Center, New York City, NY, USA; Chiba University, Chiba, Japan; Gladstone Institutes, San Francisco, CA, USA; Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA, USA; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, M€olndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M€olndal, Sweden; University College London, Institute of Neurology, London, United Kingdom. Contact e-mail: D.Bruno@ljmu.ac.uk

ASSOCIATION BETWEEN OLFACTORY FUNCTION AND MILD COGNITIVE IMPAIRMENT: RESULTS OF THE HEINZ NIXDORF RECALL STUDY

*Statistical significance: p value <0.05 THEIR RELATIONSHIP TO DISEASE PROGRESSION Rosa Maria Salinas-Contreras, Gilberto Isaac Acosta-Castillo, Ana Luisa Sosa-Ortiz, National Institute of Neurology and Neurosurgery, Mexico City, Mexico; National Autonomous University of Mexico, Mexico City, Mexico; National Instutute of Neurology and Neurosurgery, Mexico City, Mexico; National Instutute of Neurology and Neurosurgery, Mexico City, Mexico; Dementia Laboratory National Institute of Neurology and Neurosurgery, Mexico City, Mexico; National Institute of Neurology and Neurosurgery, Mexico City, Mexico. Contact e-mail: rox_sali@hotmail.com

Automatic determination of white matter hyperintensity properties in relation to the development of Alzheimer's disease

Alzheimers disease (AD) is the most common form of dementia seen in the elderly. No curing medicine for AD exists at this moment. In the search for an effective medicine, research is directed towards the prediction of conversion of mild cognitive impairment (MCI) to AD. White matter hyperintensities (WMHs) have been shown to contain information regarding the development of AD, although non-conclusive results are found in literature. These studies often use qualitative measures to describe WMHs, which is time consuming and prone to variability. To investigate the relation between WMHs and the development of AD, algorithms to automatically determine quantitative properties in terms of volume and spatial distribution of WMHs are developed and compared between normal controls and MCI subjects. MCI subjects have a significantly higher total volume of WMHs than normal controls. This difference persists when lesions are classified according to their distance to the ventricular wall. Spatial distribution is also described by defining different brain regions based on a common coordinate system. This reveals that MCI subjects have a larger WMH volume in the upper part of the brain compared to normal controls. In four subjects, the change of WMH properties over time is studied in detail. Although such a small dataset cannot be used to give definitive conclusions, the data suggests that progression of WMHs in subjects with a low lesion load is caused by an increase in the number of lesions and by the progression of juxtacortical lesions. In subjects with a larger lesion load, progression is caused by expansion of pre-existing lesions.