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Papers by Bo Engdahl

Research paper thumbnail of Increased mortality risk for adults aged 25–44 years with long-term disability: A prospective cohort study with a 35-year follow-up of 30,080 individuals from 1984–2019 in the population-based HUNT study

The Lancet Regional Health - Europe

Research paper thumbnail of Genome-Wide Association Identifies the First Risk Loci for Psychosis in Alzheimer Disease

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alz... more Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD+P). AD+P affects ∼50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD-P). Although the estimated heritability of AD+P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5,445 AD+P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p=1.26×10−8) and one spanning the 3’-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56-0.76), p=3.24×10−8), had genome-wide significant associations with AD+P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD+P demonstrated neg...

Research paper thumbnail of Childhood Sensorineural Hearing Loss and Educational Attainment in Adulthood: Results From the HUNT Study

Ear & Hearing, 2019

Although the educational achievement gap between people without hearing loss and people with hear... more Although the educational achievement gap between people without hearing loss and people with hearing loss is well-documented, few studies are based on large, nonclinical samples. The present study aims to investigate the educational attainment among Norwegian adults diagnosed with sensorineural hearing loss as children, compared with a matched control group of people without hearing loss. Design: A prospective cohort design was applied. Between 1954 and 1986, the children in the first, fourth, and/or seventh grade in all primary schools in Nord-Trøndelag County participated in the School Hearing Investigation in Nord-Trøndelag, in which they underwent audiometric screening. Those with positive results had their hearing further tested by means of pure tone audiometry at 0.25, 0.5, 1, 2, 4, and 8 kHz with airand bone-conduction thresholds, as well as a full examination by an ear, nose, and throat (ENT) specialist. In the present study, 216 persons were classified with moderate-severe hearing loss (41 to 100 dB HL), 293 with mild hearing loss (26 to 40 dB HL), and 240 with slight hearing loss (16 to 25 dB HL). Age-matched controls were recruited from the Norwegian Health Study, which was conducted in the same county. A total of 48,606 people participated in the present study. Data on educational attainment up to 2014 was provided by Statistics Norway. Control variables comprised sex, age, mothers', and fathers' education. The relation between childhood sensorineural hearing loss and educational attainment was tested by means of multinomial logistic regression models; first for the total sample (born between 1941 and 1979), and then for two different birth cohorts born between 1941 and 1959 and between 1960 and 1979. Results: Percentwise, the educational attainment level in general has increased, both among people without hearing loss and people with hearing loss, and especially for women. However, 27.5% of people without hearing loss obtained higher education, whereas the corresponding numbers for those with mild or moderate-severe hearing loss were 18.8%, and 21.3%, respectively. The results from the regression analyses showed that in the total sample, compared with having primary education, people with moderate-severe or mild hearing loss were about half as likely to achieve higher education as people without hearing loss (odds ratio (OR) = 0.63 and 0.49, respectively). An interaction term between sensorineural hearing loss and sex was specified but it was not significant. In the older cohort, we found a significant association between mild hearing loss and higher education (OR = 0.40), and between moderate-severe hearing loss and secondary education (OR = 0.65). In the younger cohort, there was a significant association between mild hearing loss and higher education (OR = 0.56) and between slight hearing loss and secondary education (OR = 0.61). Conclusions: The results from this study indicate that the achievement gap between people without hearing loss and those with hearing loss remains. Future studies should try to pinpoint what might be hindering people with slight, mild, moderate, or severe hearing loss in pursuing higher education. Parents, health personnel, institutions for higher education, and policy makers alike should take this into consideration when making plans and policies.

Research paper thumbnail of Otitis Media in Childhood and Disease in Adulthood: A 40-Year Follow-Up Study

Ear & Hearing, 2019

The pathogenesis of chronic suppurative otitis media (CSOM) includes complex interactions between... more The pathogenesis of chronic suppurative otitis media (CSOM) includes complex interactions between microbial, immunologic, and genetic factors. To our knowledge, no study has focused on the association between childhood otitis media, immune regulation, inflammatory conditions, and chronic disease in adulthood. The present study aims to assess whether CSOM in childhood predicts immunerelated inflammatory disorders or cardiovascular disease in adulthood. Another aim is to assess the association with oto-vestibular diseases in adulthood. Design: Population cohort study in Norway comprised 51,626 participants (mean age 52 years) who underwent a hearing investigation at 7 to 13 years of age where 189 were diagnosed with CSOM (otorhinolaryngologist diagnose) and 51,437 had normal hearing thresholds (controls). Data on adult disease were obtained from the Norwegian Patient Registry (ICD-10 codes from the specialist health services). We estimated associations with logistic regression analyses. Results: The associations between CSOM in childhood and disease in adulthood were as follows: chronic sinusitis (odds ratio 3.13, 95% confidence interval 1.15 to 8.52); cardiovascular disease (1.38, 1.01 to 1.88); hearing loss (5.58, 3.78 to 8.22); tinnitus (2.62, 1.07 to 6.41). The adult hearing loss among cases with childhood CSOM was most frequently registered as sensorineural. There was no statistically significant increased risk of later asthma (1.84 [0.98 to 3.48]), inflammatory bowel disease, inflammatory joint disease, systemic tissue disease, or vestibulopathy. The estimates were adjusted for age, sex, socioeconomic status, and smoking. Conclusion: Our large cohort study, which is the first to focus on the link between otitis media in childhood and immune-related inflammatory disorders later in life, does not confer a clear association. CSOM in childhood was strongly related to adult tinnitus and hearing loss, which was most frequently registered as sensorineural.

Research paper thumbnail of Childhood sensorineural hearing loss and adult mental health up to 43 years later: results from the HUNT study

BMC Public Health, 2019

Background: Hearing loss is a global public health problem putting millions of people at risk of ... more Background: Hearing loss is a global public health problem putting millions of people at risk of experiencing impediments in communication and potentially impaired mental health. Many studies in this field are based on small, cross sectional samples using self-report measures. The present study aims to investigate the association between childhood sensorineural hearing loss and mental health in adult men and women longitudinally in a large cohort with a matched control group, and hearing is measured by pure-tone audiometry. Studies of this kind are virtually non-existing. Methods: The present study combines data from two large studies; the School Hearing Investigation in Nord-Trøndelag (SHINT) carried out yearly from 1954 to 1986, and the second wave of the Nord-Trøndelag Health Study (HUNT 2) conducted from 1995 to 1997. The participants were 7, 10 or 13 years during the SHINT, and between 20 and 56 years old during HUNT 2. The total sample consisted of 32,456 participants (of which 32,104 in the reference group). Participants with a sensorineural hearing loss in SHINT of 41 dB or more were classified with moderatesevere hearing loss (N = 66), 26-40 dB as mild (N = 66) and 16-25 dB as slight (N = 220). Mental health in adulthood was measured in HUNT 2 by symptoms of anxiety and depression, subjective well-being, and self-esteem. The association between childhood sensorineural hearing loss and adult mental health was tested by means of ANOVA. Results: There was a significant relation between slight childhood sensorineural hearing loss and lowered subjective well-being in women (B = −.25, p = 0.038). Further investigation of the results revealed a significant association between slight hearing loss and symptoms of anxiety and depression (B = .30, p = 0.054) and between mild hearing loss and lowered self-esteem (B = .63, p = 0.024) among women aged 20-39 years. There were no significant relations between childhood sensorineural hearing loss and any of the three mental health outcomes among men. Conclusions: This study suggests that women with slight or mild sensorineural hearing loss from childhood experience elevated levels of symptoms of anxiety and depression, lowered subjective well-being and lowered selfesteem. However, the results should be interpreted with caution due to a lack of power in some analyses.

Research paper thumbnail of Long-term ototoxicity in testicular cancer survivors (TCSs) after cisplatin-based chemotherapy: associations with Gluthatione-S-Transferase (GST)-T1, -P1, and -M1 genotypes

Journal of Clinical Oncology, 2005

Research paper thumbnail of Otoacoustic Emissions in the General Adult Population of Nord-Trondelag, Norway: I. Distributions by Age, Gender, and Ear Side: Emisiones Otoacústicas En La Poblacioan Adulta General De Nord-Trøndelag, Noruega: I. Distribuciones Por Edad, Género Y Oído Estudiado

Research paper thumbnail of No association between time of onset of hearing loss (childhood versus adulthood) and self-reported hearing handicap in adults

American journal of audiology, Jan 23, 2015

To examine the association between time of onset of hearing loss (childhood versus adulthood) and... more To examine the association between time of onset of hearing loss (childhood versus adulthood) and self-reported hearing handicap in adults. Population-based cohort study of 2,024 adults (mean 48 years) with hearing loss (binaural PTA 0.5-4 kHz ≥ 20 dB HL) who completed a hearing handicap questionnaire. In childhood, the same persons (n = 2,024) underwent audiometry in a school investigation (at ages 7, 10 and 13 years), in which 129 were diagnosed with sensorineural hearing loss (binaural PTA 0.5-4 kHz ≥ 20 dB HL) while 1,895 had normal hearing thresholds. Hearing handicap was measured in adulthood as the sum-score of various speech perception and social impairment items (altogether 15 items). The sum-score increased with adult hearing threshold level (p <.001). After adjustment for adult hearing threshold level, hearing aid use, adult age, sex and socioeconomic status, there was no significant difference in hearing handicap sum-score between the group with childhood-onset hearin...

Research paper thumbnail of Associations between parental hearing impairment and children's mental health: Results from the Nord-Trøndelag Health Study

Social science & medicine (1982), 2015

Some previous studies indicate that parental hearing loss may have negative consequences in the p... more Some previous studies indicate that parental hearing loss may have negative consequences in the parent-child relationship. However, most of these studies are qualitative or have apparent methodological shortcomings. This study is the first of its kind conducted in a large population-based sample with audiometrically measured hearing loss aimed at investigating the extent to which parental hearing loss affects adolescents' mental health. Questionnaires were administered to the adult (>19 years) and adolescent (age 13-19 years) population of Nord-Trøndelag county, Norway (1995-97), which collected information on mental and somatic health, including hearing loss. For adults participating in the study, pure tone audiometry tests were also administered. In total, 4047 fathers and 4785 mothers with self-reported hearing loss data were identified. The corresponding numbers with measured hearing loss data included 4079 fathers and 4861 mothers. The associations between the degrees of...

Research paper thumbnail of Temporary Threshold Shift and Otoacoustic Emissions after Industrial Noise Exposure

Scandinavian Audiology, 1995

The objective of the present study was to investigate whether employees in a noise-exposed enviro... more The objective of the present study was to investigate whether employees in a noise-exposed environment developed changes in cochlear function as manifested by elevation of pure-tone threshold and/or reduction in transient evoked otoacoustic emission (TEOAE) amplitude. Pure-tone air-conduction audiometry, otoacoustic emissions (OAEs) and tympanometry were recorded in 13 healthy employees on three consecutive days both before and after 7 h of noise exposure. Employees exposed to an industrial noise level of 85-90 dBA developed significant pure-tone air-conduction threshold elevation at 4 and 6 kHz. A significant reduction of the TEOAE amplitude was found. There was no correlation between temporary threshold shift (TTS) and TEOAE reduction.

Research paper thumbnail of Effekt av Forsvarets lavflygingsaktivitet på friluftsopplevelser i fjellet -en studie fra Aurlandsdalen

Research paper thumbnail of The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry (Impact Factor: 3.35). 09/2013; DOI:10.1016/j.jagp.2013.06.007 Source: PubMed

Research paper thumbnail of Childhood sensorineural hearing loss: effects of combined exposure with aging or noise exposure later in life

European Archives of Oto-Rhino-Laryngology, 2015

The aim of the study was to examine childhood high-frequency sensorineural hearing loss (HF-SNHL)... more The aim of the study was to examine childhood high-frequency sensorineural hearing loss (HF-SNHL) and the effects of combined exposure with aging or noise exposure on HF hearing thresholds in adulthood. Population-based cohort study of 30,003 adults (mean age 40 years) underwent an audiometry and completed a hearing questionnaire. At age 7-13 years, the same people had participated in a longitudinal school hearing investigation, in which 283 participants were diagnosed with HF-SNHL [PTA 3-8 kHz C 25 dB HL (mean 45 dB HL), worse hearing ear], and 29,720 participants had normal hearing thresholds. The effect of childhood HF-SNHL on adult hearing threshold was significantly moderated by age. Age stratified analyses showed that the difference in HF hearing thresholds between adults with and without childhood HF-SNHL was 33 dB (95 % CI 31-34) in young adults (n = 173, aged 20-39 years) and 37 dB (95 % CI 34-39) in middle-aged adults (n = 110, aged 40-56 years). The combined exposure of childhood HF-SNHL and noise exposure showed a simple additive effect. It appears to be a super-additive effect of childhood-onset HF-SNHL and aging on adult hearing thresholds. An explanation might be that already damaged hair cells are more susceptible to age-related degeneration. To exclude possible birth cohort effects, the finding should be confirmed by a study with several audiometries in adulthood.

Research paper thumbnail of Reproducibility and Short-term Variability of Transient Evoked Otoacoustic Emissions

Scandinavian Audiology, 1994

The reproducibility and short-term, less than 3 days, variability of transient evoked otoacoustic... more The reproducibility and short-term, less than 3 days, variability of transient evoked otoacoustic emissions (TEOAEs) were studied in 23 young, otologically healthy subjects engaged either in strenuous physical exercise or relatively sedentary occupations. Tympanometry was also performed. TEOAEs were highly reproducible. No differences were found between the two subject groups, nor any significant diurnal variations in TEOAE amplitudes. The latter were, however, significantly (p = 0.005) correlated to middle ear pressures. Tympanometry should therefore be performed in studies of possible intrinsic or extrinsic influences on TEOAE amplitudes.

Research paper thumbnail of Noise-induced hearing loss: the diagnosis depends on the doctor's belief

Occupational and environmental medicine, 2015

Schink et al 1 state that musicians more often than others are diagnosed with noise-induced heari... more Schink et al 1 state that musicians more often than others are diagnosed with noise-induced hearing loss (NIHL), reporting a HR of 3.6. In addition to reporting a slightly increased risk of being diagnosed with tinnitus, the authors conclude that “Professional musicians have a high risk of contracting hearing disorders”. Although the findings appear convincing, I think the results should be interpreted otherwise. The high risk of differential misclassification in the outcome seems overlooked. As NIHL …

Research paper thumbnail of Sensorineural hearing loss in children: The association with Apgar score. A registry-based study of 392371 children in Norway

International Journal of Pediatric Otorhinolaryngology, 2014

Research paper thumbnail of Otoacoustic emissions and pass/fail separation using artificial neural network

Transient evoked otoacoustic emissions (TEOAE) are low-level sounds produced by the healthy inner... more Transient evoked otoacoustic emissions (TEOAE) are low-level sounds produced by the healthy inner ear in response to a transient stimulus such as a short acoustic click 1. It is believed that outer hair cells within the cochlea are involved in complex active amplification mechanisms of weak incoming sound vibrations. The TEOAE generation is assumed to be a partial product of this amplification [1]. Several studies have evidenced that the presence of TEOAE correlates with the hearing level [1,2,3,4,5]. While this relationship is reported to be frequency specific, the relationship is too weak to predict the pure tone hearing levels. Nevertheless, TEOAE appeared to be useful in screening tests in neonates [7], in population exposed by noise [8] and to monitor the influence of drugs [9]. The detection of TEOAE is difficult because of noise in the recorded signal. The performance can, however, be improved by looking into separate frequency bands and time intervals and combining extracted parameters [10,11,12,13]. An average of cross correlation coefficients, as calculated between components of successive subaverages after splitting them into three frequency bands and windowing in time has been used as a criterion for TEOAE detection [12,13]. The TEOAE generation is well known to be closely related with nonlinearities which are present in the cochlea and which are responsible for the high dynamic range of the hearing system. Thus, it would be natural to think about more complex relationship than linear in associating hearing level and time-frequency features extracted from TEOAE. So far, the most published attempts to model the mentioned association have relied on linear relationship and they have used linear multivariate models [4,6] or simple averaging of features [12,13]. In one study by Buller and Lutman [15] an artificial neural network (ANN) was used in TEOAE classification. The task for the neural network was in this case to mimic a human expert in classifying the shapes of TEAOE waveforms into four beforehand-described classes. In our study we have used a neural network, which used a set of TEOAE features as inputs and audiometric data as the targets in the training procedure. The purpose of this study is to compare two approaches in separation of normal and hearing impaired subjects: a linear and a more complex, which could account not only for linear, but also for possible nonlinear association of features extracted from TEOAE to hearing level as obtained from pure tone audiometry. Artificial neural networks are known to be capable to realize any complex relationship, when sufficient amount of training data is available [14]. Thus a nonlinear classifier was established by training of an ANN and for comparison a linear classifier implemented as a simple average of the features.

Research paper thumbnail of Use of psychotropic drugs and analgesics among users of antiobesity drugs-a population based study

Pharmacoepidemiology and Drug Safety, 2009

The aim of the present study was to investigate to what extent patients using prescription antiob... more The aim of the present study was to investigate to what extent patients using prescription antiobesity drugs (orlistat, sibutramine and rimonabant) concomitantly or concurrently used psychotropic drugs and analgesics and the association between this drug use and the patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gender and age. An additional aim was to investigate the sequence of drug therapy among users of both antiobesity drugs and antidepressants or antipsychotics, respectively. Data were retrieved from the Norwegian Prescription Database (NorPD). All patients who had an antiobesity drug (ATC code A08A) dispensed from a Norwegian pharmacy between January 2004 and December 2007 were included in the study. One in four patients using antiobesity drugs had at least on one occasion used a psychotropic drug concomitantly. The most commonly used psychotropic drugs were anxiolytics/hypnotics/sedatives (17.7%) and antidepressants (14.7%). Analgesics were used by 36.2%. A significantly higher percentage of women used anxiolytics/hypnotics/sedatives (18.8% vs. 14.0%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0005), antidepressants (16.1% vs. 9.5%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0005), antipsychotics (4.0% vs. 2.9%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0005) and analgesics (37.8% vs. 30.5%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0005) concomitantly with antiobesity drugs when compared to men. One out of ten patients using sibutramine had at least on one occasion used an interacting drug concomitantly. Use of psychotropic drugs and analgesics among patients using antiobesity drugs is extensive, especially among women. Clinicians prescribing sibutramine should be more aware of drug interactions with other prescribed drugs. There is still insufficient information on psychiatric disorders among these patients.

Research paper thumbnail of Concomitant use of anti-dementia drugs with psychotropic drugs in Norway-a population-based study

Pharmacoepidemiology and Drug Safety, 2011

Concomitant use of anti-dementia drugs with psychotropic drugs is potentially problematic in pati... more Concomitant use of anti-dementia drugs with psychotropic drugs is potentially problematic in patients with dementia. The aim of this study was to investigate how frequently patients in Norway use anti-dementia drugs concomitantly with psychotropic drugs. Analyses are based on data from the Norwegian Prescription Database. All patients who had an anti-dementia drug (ATC-code N06D) dispensed from a Norwegian pharmacy between January 2004 and July 2009 were included. A total of 33,816 individuals received anti-dementia drugs at some time during this period. The total concomitant use of anti-dementia drugs with psychotropic drugs was 57.4% in men and 65.8% in women. Compared with men, a significantly higher percentage of women used antidepressants (35.8% versus 27.2%), mild hypnotics (28.8% versus 23.6%), benzodiazepines (25.4% versus 20.8%) and opioids (22.8% versus 17.4%) concomitantly with anti-dementia drugs. Concomitant use of antipsychotics with anti-dementia drugs was about 16% for both male and female patients. Of the total sample, 11.9% of the women and 11.7% of the men used acetylcholinesterase inhibitor (AChEI) anti-dementia drugs concomitantly with an interacting psychotropic drug. The concomitant use of psychotropic drugs with anti-dementia drugs was extensive, especially among women. Co-medication with potentially interacting drugs occurred at a rate of one in 10. The concomitant use of anti-dementia drugs with psychotropic drugs identified in this study may inform the ongoing clinical debate about drug use in this patient group.

Research paper thumbnail of Birthweight and the risk of childhood sensorineural hearing loss

Paediatric and Perinatal Epidemiology, 2007

The aim of this study was to estimate the impact of birthweight on the risk of sensorineural hear... more The aim of this study was to estimate the impact of birthweight on the risk of sensorineural hearing loss in children. The study was a nested case-control study. Cases (n = 327) were identified through the Norwegian county registers of children with hearing loss, and controls (n = 391 992) were all children without hearing loss born in the same counties, identified through the Norwegian Medical Birth Registry of Norway. Case definition was mean sensorineural hearing loss (MHL) Ն35 decibel (dB) hearing level (HL) in the better-hearing ear averaged over the pure-tone hearing thresholds at 500, 1000 and 2000 Hz, diagnosed before the age of 5 years. Birthweight <1500 g, as compared with 3500-3999 g, gave an adjusted odds ratio for sensorineural hearing loss of 6.3 [95% CI 2.4, 16.4], controlled for gestational age, gender, parity, maternal age and concurrent birth defects. The risk of hearing loss decreased with increasing birthweights, with adjusted odds ratios of 4.4, 3.8, 1.7 and 1.4 for the birthweights 1500-1999, 2000-2499, 2500-2999 and 3000-3499 g respectively. The risk of both mild to moderate (MHL 35-70 dBHL) and severe/profound hearing losses (MHL >70 dBHL) were influenced by birthweight.

Research paper thumbnail of Increased mortality risk for adults aged 25–44 years with long-term disability: A prospective cohort study with a 35-year follow-up of 30,080 individuals from 1984–2019 in the population-based HUNT study

The Lancet Regional Health - Europe

Research paper thumbnail of Genome-Wide Association Identifies the First Risk Loci for Psychosis in Alzheimer Disease

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alz... more Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD+P). AD+P affects ∼50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD-P). Although the estimated heritability of AD+P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5,445 AD+P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p=1.26×10−8) and one spanning the 3’-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56-0.76), p=3.24×10−8), had genome-wide significant associations with AD+P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD+P demonstrated neg...

Research paper thumbnail of Childhood Sensorineural Hearing Loss and Educational Attainment in Adulthood: Results From the HUNT Study

Ear & Hearing, 2019

Although the educational achievement gap between people without hearing loss and people with hear... more Although the educational achievement gap between people without hearing loss and people with hearing loss is well-documented, few studies are based on large, nonclinical samples. The present study aims to investigate the educational attainment among Norwegian adults diagnosed with sensorineural hearing loss as children, compared with a matched control group of people without hearing loss. Design: A prospective cohort design was applied. Between 1954 and 1986, the children in the first, fourth, and/or seventh grade in all primary schools in Nord-Trøndelag County participated in the School Hearing Investigation in Nord-Trøndelag, in which they underwent audiometric screening. Those with positive results had their hearing further tested by means of pure tone audiometry at 0.25, 0.5, 1, 2, 4, and 8 kHz with airand bone-conduction thresholds, as well as a full examination by an ear, nose, and throat (ENT) specialist. In the present study, 216 persons were classified with moderate-severe hearing loss (41 to 100 dB HL), 293 with mild hearing loss (26 to 40 dB HL), and 240 with slight hearing loss (16 to 25 dB HL). Age-matched controls were recruited from the Norwegian Health Study, which was conducted in the same county. A total of 48,606 people participated in the present study. Data on educational attainment up to 2014 was provided by Statistics Norway. Control variables comprised sex, age, mothers', and fathers' education. The relation between childhood sensorineural hearing loss and educational attainment was tested by means of multinomial logistic regression models; first for the total sample (born between 1941 and 1979), and then for two different birth cohorts born between 1941 and 1959 and between 1960 and 1979. Results: Percentwise, the educational attainment level in general has increased, both among people without hearing loss and people with hearing loss, and especially for women. However, 27.5% of people without hearing loss obtained higher education, whereas the corresponding numbers for those with mild or moderate-severe hearing loss were 18.8%, and 21.3%, respectively. The results from the regression analyses showed that in the total sample, compared with having primary education, people with moderate-severe or mild hearing loss were about half as likely to achieve higher education as people without hearing loss (odds ratio (OR) = 0.63 and 0.49, respectively). An interaction term between sensorineural hearing loss and sex was specified but it was not significant. In the older cohort, we found a significant association between mild hearing loss and higher education (OR = 0.40), and between moderate-severe hearing loss and secondary education (OR = 0.65). In the younger cohort, there was a significant association between mild hearing loss and higher education (OR = 0.56) and between slight hearing loss and secondary education (OR = 0.61). Conclusions: The results from this study indicate that the achievement gap between people without hearing loss and those with hearing loss remains. Future studies should try to pinpoint what might be hindering people with slight, mild, moderate, or severe hearing loss in pursuing higher education. Parents, health personnel, institutions for higher education, and policy makers alike should take this into consideration when making plans and policies.

Research paper thumbnail of Otitis Media in Childhood and Disease in Adulthood: A 40-Year Follow-Up Study

Ear & Hearing, 2019

The pathogenesis of chronic suppurative otitis media (CSOM) includes complex interactions between... more The pathogenesis of chronic suppurative otitis media (CSOM) includes complex interactions between microbial, immunologic, and genetic factors. To our knowledge, no study has focused on the association between childhood otitis media, immune regulation, inflammatory conditions, and chronic disease in adulthood. The present study aims to assess whether CSOM in childhood predicts immunerelated inflammatory disorders or cardiovascular disease in adulthood. Another aim is to assess the association with oto-vestibular diseases in adulthood. Design: Population cohort study in Norway comprised 51,626 participants (mean age 52 years) who underwent a hearing investigation at 7 to 13 years of age where 189 were diagnosed with CSOM (otorhinolaryngologist diagnose) and 51,437 had normal hearing thresholds (controls). Data on adult disease were obtained from the Norwegian Patient Registry (ICD-10 codes from the specialist health services). We estimated associations with logistic regression analyses. Results: The associations between CSOM in childhood and disease in adulthood were as follows: chronic sinusitis (odds ratio 3.13, 95% confidence interval 1.15 to 8.52); cardiovascular disease (1.38, 1.01 to 1.88); hearing loss (5.58, 3.78 to 8.22); tinnitus (2.62, 1.07 to 6.41). The adult hearing loss among cases with childhood CSOM was most frequently registered as sensorineural. There was no statistically significant increased risk of later asthma (1.84 [0.98 to 3.48]), inflammatory bowel disease, inflammatory joint disease, systemic tissue disease, or vestibulopathy. The estimates were adjusted for age, sex, socioeconomic status, and smoking. Conclusion: Our large cohort study, which is the first to focus on the link between otitis media in childhood and immune-related inflammatory disorders later in life, does not confer a clear association. CSOM in childhood was strongly related to adult tinnitus and hearing loss, which was most frequently registered as sensorineural.

Research paper thumbnail of Childhood sensorineural hearing loss and adult mental health up to 43 years later: results from the HUNT study

BMC Public Health, 2019

Background: Hearing loss is a global public health problem putting millions of people at risk of ... more Background: Hearing loss is a global public health problem putting millions of people at risk of experiencing impediments in communication and potentially impaired mental health. Many studies in this field are based on small, cross sectional samples using self-report measures. The present study aims to investigate the association between childhood sensorineural hearing loss and mental health in adult men and women longitudinally in a large cohort with a matched control group, and hearing is measured by pure-tone audiometry. Studies of this kind are virtually non-existing. Methods: The present study combines data from two large studies; the School Hearing Investigation in Nord-Trøndelag (SHINT) carried out yearly from 1954 to 1986, and the second wave of the Nord-Trøndelag Health Study (HUNT 2) conducted from 1995 to 1997. The participants were 7, 10 or 13 years during the SHINT, and between 20 and 56 years old during HUNT 2. The total sample consisted of 32,456 participants (of which 32,104 in the reference group). Participants with a sensorineural hearing loss in SHINT of 41 dB or more were classified with moderatesevere hearing loss (N = 66), 26-40 dB as mild (N = 66) and 16-25 dB as slight (N = 220). Mental health in adulthood was measured in HUNT 2 by symptoms of anxiety and depression, subjective well-being, and self-esteem. The association between childhood sensorineural hearing loss and adult mental health was tested by means of ANOVA. Results: There was a significant relation between slight childhood sensorineural hearing loss and lowered subjective well-being in women (B = −.25, p = 0.038). Further investigation of the results revealed a significant association between slight hearing loss and symptoms of anxiety and depression (B = .30, p = 0.054) and between mild hearing loss and lowered self-esteem (B = .63, p = 0.024) among women aged 20-39 years. There were no significant relations between childhood sensorineural hearing loss and any of the three mental health outcomes among men. Conclusions: This study suggests that women with slight or mild sensorineural hearing loss from childhood experience elevated levels of symptoms of anxiety and depression, lowered subjective well-being and lowered selfesteem. However, the results should be interpreted with caution due to a lack of power in some analyses.

Research paper thumbnail of Long-term ototoxicity in testicular cancer survivors (TCSs) after cisplatin-based chemotherapy: associations with Gluthatione-S-Transferase (GST)-T1, -P1, and -M1 genotypes

Journal of Clinical Oncology, 2005

Research paper thumbnail of Otoacoustic Emissions in the General Adult Population of Nord-Trondelag, Norway: I. Distributions by Age, Gender, and Ear Side: Emisiones Otoacústicas En La Poblacioan Adulta General De Nord-Trøndelag, Noruega: I. Distribuciones Por Edad, Género Y Oído Estudiado

Research paper thumbnail of No association between time of onset of hearing loss (childhood versus adulthood) and self-reported hearing handicap in adults

American journal of audiology, Jan 23, 2015

To examine the association between time of onset of hearing loss (childhood versus adulthood) and... more To examine the association between time of onset of hearing loss (childhood versus adulthood) and self-reported hearing handicap in adults. Population-based cohort study of 2,024 adults (mean 48 years) with hearing loss (binaural PTA 0.5-4 kHz ≥ 20 dB HL) who completed a hearing handicap questionnaire. In childhood, the same persons (n = 2,024) underwent audiometry in a school investigation (at ages 7, 10 and 13 years), in which 129 were diagnosed with sensorineural hearing loss (binaural PTA 0.5-4 kHz ≥ 20 dB HL) while 1,895 had normal hearing thresholds. Hearing handicap was measured in adulthood as the sum-score of various speech perception and social impairment items (altogether 15 items). The sum-score increased with adult hearing threshold level (p <.001). After adjustment for adult hearing threshold level, hearing aid use, adult age, sex and socioeconomic status, there was no significant difference in hearing handicap sum-score between the group with childhood-onset hearin...

Research paper thumbnail of Associations between parental hearing impairment and children's mental health: Results from the Nord-Trøndelag Health Study

Social science & medicine (1982), 2015

Some previous studies indicate that parental hearing loss may have negative consequences in the p... more Some previous studies indicate that parental hearing loss may have negative consequences in the parent-child relationship. However, most of these studies are qualitative or have apparent methodological shortcomings. This study is the first of its kind conducted in a large population-based sample with audiometrically measured hearing loss aimed at investigating the extent to which parental hearing loss affects adolescents' mental health. Questionnaires were administered to the adult (>19 years) and adolescent (age 13-19 years) population of Nord-Trøndelag county, Norway (1995-97), which collected information on mental and somatic health, including hearing loss. For adults participating in the study, pure tone audiometry tests were also administered. In total, 4047 fathers and 4785 mothers with self-reported hearing loss data were identified. The corresponding numbers with measured hearing loss data included 4079 fathers and 4861 mothers. The associations between the degrees of...

Research paper thumbnail of Temporary Threshold Shift and Otoacoustic Emissions after Industrial Noise Exposure

Scandinavian Audiology, 1995

The objective of the present study was to investigate whether employees in a noise-exposed enviro... more The objective of the present study was to investigate whether employees in a noise-exposed environment developed changes in cochlear function as manifested by elevation of pure-tone threshold and/or reduction in transient evoked otoacoustic emission (TEOAE) amplitude. Pure-tone air-conduction audiometry, otoacoustic emissions (OAEs) and tympanometry were recorded in 13 healthy employees on three consecutive days both before and after 7 h of noise exposure. Employees exposed to an industrial noise level of 85-90 dBA developed significant pure-tone air-conduction threshold elevation at 4 and 6 kHz. A significant reduction of the TEOAE amplitude was found. There was no correlation between temporary threshold shift (TTS) and TEOAE reduction.

Research paper thumbnail of Effekt av Forsvarets lavflygingsaktivitet på friluftsopplevelser i fjellet -en studie fra Aurlandsdalen

Research paper thumbnail of The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry (Impact Factor: 3.35). 09/2013; DOI:10.1016/j.jagp.2013.06.007 Source: PubMed

Research paper thumbnail of Childhood sensorineural hearing loss: effects of combined exposure with aging or noise exposure later in life

European Archives of Oto-Rhino-Laryngology, 2015

The aim of the study was to examine childhood high-frequency sensorineural hearing loss (HF-SNHL)... more The aim of the study was to examine childhood high-frequency sensorineural hearing loss (HF-SNHL) and the effects of combined exposure with aging or noise exposure on HF hearing thresholds in adulthood. Population-based cohort study of 30,003 adults (mean age 40 years) underwent an audiometry and completed a hearing questionnaire. At age 7-13 years, the same people had participated in a longitudinal school hearing investigation, in which 283 participants were diagnosed with HF-SNHL [PTA 3-8 kHz C 25 dB HL (mean 45 dB HL), worse hearing ear], and 29,720 participants had normal hearing thresholds. The effect of childhood HF-SNHL on adult hearing threshold was significantly moderated by age. Age stratified analyses showed that the difference in HF hearing thresholds between adults with and without childhood HF-SNHL was 33 dB (95 % CI 31-34) in young adults (n = 173, aged 20-39 years) and 37 dB (95 % CI 34-39) in middle-aged adults (n = 110, aged 40-56 years). The combined exposure of childhood HF-SNHL and noise exposure showed a simple additive effect. It appears to be a super-additive effect of childhood-onset HF-SNHL and aging on adult hearing thresholds. An explanation might be that already damaged hair cells are more susceptible to age-related degeneration. To exclude possible birth cohort effects, the finding should be confirmed by a study with several audiometries in adulthood.

Research paper thumbnail of Reproducibility and Short-term Variability of Transient Evoked Otoacoustic Emissions

Scandinavian Audiology, 1994

The reproducibility and short-term, less than 3 days, variability of transient evoked otoacoustic... more The reproducibility and short-term, less than 3 days, variability of transient evoked otoacoustic emissions (TEOAEs) were studied in 23 young, otologically healthy subjects engaged either in strenuous physical exercise or relatively sedentary occupations. Tympanometry was also performed. TEOAEs were highly reproducible. No differences were found between the two subject groups, nor any significant diurnal variations in TEOAE amplitudes. The latter were, however, significantly (p = 0.005) correlated to middle ear pressures. Tympanometry should therefore be performed in studies of possible intrinsic or extrinsic influences on TEOAE amplitudes.

Research paper thumbnail of Noise-induced hearing loss: the diagnosis depends on the doctor's belief

Occupational and environmental medicine, 2015

Schink et al 1 state that musicians more often than others are diagnosed with noise-induced heari... more Schink et al 1 state that musicians more often than others are diagnosed with noise-induced hearing loss (NIHL), reporting a HR of 3.6. In addition to reporting a slightly increased risk of being diagnosed with tinnitus, the authors conclude that “Professional musicians have a high risk of contracting hearing disorders”. Although the findings appear convincing, I think the results should be interpreted otherwise. The high risk of differential misclassification in the outcome seems overlooked. As NIHL …

Research paper thumbnail of Sensorineural hearing loss in children: The association with Apgar score. A registry-based study of 392371 children in Norway

International Journal of Pediatric Otorhinolaryngology, 2014

Research paper thumbnail of Otoacoustic emissions and pass/fail separation using artificial neural network

Transient evoked otoacoustic emissions (TEOAE) are low-level sounds produced by the healthy inner... more Transient evoked otoacoustic emissions (TEOAE) are low-level sounds produced by the healthy inner ear in response to a transient stimulus such as a short acoustic click 1. It is believed that outer hair cells within the cochlea are involved in complex active amplification mechanisms of weak incoming sound vibrations. The TEOAE generation is assumed to be a partial product of this amplification [1]. Several studies have evidenced that the presence of TEOAE correlates with the hearing level [1,2,3,4,5]. While this relationship is reported to be frequency specific, the relationship is too weak to predict the pure tone hearing levels. Nevertheless, TEOAE appeared to be useful in screening tests in neonates [7], in population exposed by noise [8] and to monitor the influence of drugs [9]. The detection of TEOAE is difficult because of noise in the recorded signal. The performance can, however, be improved by looking into separate frequency bands and time intervals and combining extracted parameters [10,11,12,13]. An average of cross correlation coefficients, as calculated between components of successive subaverages after splitting them into three frequency bands and windowing in time has been used as a criterion for TEOAE detection [12,13]. The TEOAE generation is well known to be closely related with nonlinearities which are present in the cochlea and which are responsible for the high dynamic range of the hearing system. Thus, it would be natural to think about more complex relationship than linear in associating hearing level and time-frequency features extracted from TEOAE. So far, the most published attempts to model the mentioned association have relied on linear relationship and they have used linear multivariate models [4,6] or simple averaging of features [12,13]. In one study by Buller and Lutman [15] an artificial neural network (ANN) was used in TEOAE classification. The task for the neural network was in this case to mimic a human expert in classifying the shapes of TEAOE waveforms into four beforehand-described classes. In our study we have used a neural network, which used a set of TEOAE features as inputs and audiometric data as the targets in the training procedure. The purpose of this study is to compare two approaches in separation of normal and hearing impaired subjects: a linear and a more complex, which could account not only for linear, but also for possible nonlinear association of features extracted from TEOAE to hearing level as obtained from pure tone audiometry. Artificial neural networks are known to be capable to realize any complex relationship, when sufficient amount of training data is available [14]. Thus a nonlinear classifier was established by training of an ANN and for comparison a linear classifier implemented as a simple average of the features.

Research paper thumbnail of Use of psychotropic drugs and analgesics among users of antiobesity drugs-a population based study

Pharmacoepidemiology and Drug Safety, 2009

The aim of the present study was to investigate to what extent patients using prescription antiob... more The aim of the present study was to investigate to what extent patients using prescription antiobesity drugs (orlistat, sibutramine and rimonabant) concomitantly or concurrently used psychotropic drugs and analgesics and the association between this drug use and the patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gender and age. An additional aim was to investigate the sequence of drug therapy among users of both antiobesity drugs and antidepressants or antipsychotics, respectively. Data were retrieved from the Norwegian Prescription Database (NorPD). All patients who had an antiobesity drug (ATC code A08A) dispensed from a Norwegian pharmacy between January 2004 and December 2007 were included in the study. One in four patients using antiobesity drugs had at least on one occasion used a psychotropic drug concomitantly. The most commonly used psychotropic drugs were anxiolytics/hypnotics/sedatives (17.7%) and antidepressants (14.7%). Analgesics were used by 36.2%. A significantly higher percentage of women used anxiolytics/hypnotics/sedatives (18.8% vs. 14.0%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0005), antidepressants (16.1% vs. 9.5%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0005), antipsychotics (4.0% vs. 2.9%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0005) and analgesics (37.8% vs. 30.5%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0005) concomitantly with antiobesity drugs when compared to men. One out of ten patients using sibutramine had at least on one occasion used an interacting drug concomitantly. Use of psychotropic drugs and analgesics among patients using antiobesity drugs is extensive, especially among women. Clinicians prescribing sibutramine should be more aware of drug interactions with other prescribed drugs. There is still insufficient information on psychiatric disorders among these patients.

Research paper thumbnail of Concomitant use of anti-dementia drugs with psychotropic drugs in Norway-a population-based study

Pharmacoepidemiology and Drug Safety, 2011

Concomitant use of anti-dementia drugs with psychotropic drugs is potentially problematic in pati... more Concomitant use of anti-dementia drugs with psychotropic drugs is potentially problematic in patients with dementia. The aim of this study was to investigate how frequently patients in Norway use anti-dementia drugs concomitantly with psychotropic drugs. Analyses are based on data from the Norwegian Prescription Database. All patients who had an anti-dementia drug (ATC-code N06D) dispensed from a Norwegian pharmacy between January 2004 and July 2009 were included. A total of 33,816 individuals received anti-dementia drugs at some time during this period. The total concomitant use of anti-dementia drugs with psychotropic drugs was 57.4% in men and 65.8% in women. Compared with men, a significantly higher percentage of women used antidepressants (35.8% versus 27.2%), mild hypnotics (28.8% versus 23.6%), benzodiazepines (25.4% versus 20.8%) and opioids (22.8% versus 17.4%) concomitantly with anti-dementia drugs. Concomitant use of antipsychotics with anti-dementia drugs was about 16% for both male and female patients. Of the total sample, 11.9% of the women and 11.7% of the men used acetylcholinesterase inhibitor (AChEI) anti-dementia drugs concomitantly with an interacting psychotropic drug. The concomitant use of psychotropic drugs with anti-dementia drugs was extensive, especially among women. Co-medication with potentially interacting drugs occurred at a rate of one in 10. The concomitant use of anti-dementia drugs with psychotropic drugs identified in this study may inform the ongoing clinical debate about drug use in this patient group.

Research paper thumbnail of Birthweight and the risk of childhood sensorineural hearing loss

Paediatric and Perinatal Epidemiology, 2007

The aim of this study was to estimate the impact of birthweight on the risk of sensorineural hear... more The aim of this study was to estimate the impact of birthweight on the risk of sensorineural hearing loss in children. The study was a nested case-control study. Cases (n = 327) were identified through the Norwegian county registers of children with hearing loss, and controls (n = 391 992) were all children without hearing loss born in the same counties, identified through the Norwegian Medical Birth Registry of Norway. Case definition was mean sensorineural hearing loss (MHL) Ն35 decibel (dB) hearing level (HL) in the better-hearing ear averaged over the pure-tone hearing thresholds at 500, 1000 and 2000 Hz, diagnosed before the age of 5 years. Birthweight <1500 g, as compared with 3500-3999 g, gave an adjusted odds ratio for sensorineural hearing loss of 6.3 [95% CI 2.4, 16.4], controlled for gestational age, gender, parity, maternal age and concurrent birth defects. The risk of hearing loss decreased with increasing birthweights, with adjusted odds ratios of 4.4, 3.8, 1.7 and 1.4 for the birthweights 1500-1999, 2000-2499, 2500-2999 and 3000-3499 g respectively. The risk of both mild to moderate (MHL 35-70 dBHL) and severe/profound hearing losses (MHL >70 dBHL) were influenced by birthweight.