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INTRODUCTION: Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes. METHODS: Genome‐wide association meta‐analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P). RESULTS: AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations. DISCUSSION: AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development. Highlights: It has long been known that psychotic and affective symptoms are often comorbid in individuals diagnosed with Alzheimer's disease. Here we examined for the first time the genetic architecture underlying this clinical observation, determining that psychotic and affective phenotypes in Alzheimer's disease are genetically correlated.Nevertheless, psychotic and affective phenotypes in Alzheimer's disease diverged in their genetic correlations with psychiatric phenotypes assessed in individuals without Alzheimer's disease. Psychosis in Alzheimer's disease was negatively genetically correlated with bipolar disorder and positively with depressive symptoms, whereas the affective phenotypes in Alzheimer's disease were positively correlated with anxiety disorder and more strongly correlated than psychosis with depressive symptoms.Psychosis in Alzheimer's disease, and the joint psychotic and affective phenotype, had significant estimated heritability, whereas the affective in AD did not.Examination of the loci most strongly associated with the psychotic, affective, or joint phenotypes revealed overlapping and unique associations. [ABSTRACT FROM AUTHOR]

We aimed to assess the association between occupational noise exposure and long-term hearing decline. This prospective cohort study used linear regression to investigate the association between occupational noise exposure and 20-year hearing decline, adjusted for important confounders. The Norwegian cohort (N = 4,448) participated in two population-based health studies with pure-tone audiometry; HUNT2 1996–1998 and HUNT4 2017–2019. Exposure assessments included a quantitative job exposure matrix (JEM) and questionnaires. The participants (40.2% men, 20–39 years at baseline) had a mean 20-year decline (3–6 kHz) of 11.3 ± 9.8 decibels (dB). There was a positive association between 20-year logarithmic average noise level (JEM-based, LEX,20y) and 20-year hearing decline among men. Compared with no exposure ≥80 dB during follow-up, minimum 5 years of exposure ≥85 dB (JEM-based) predicted 2.6 dB (95% CI: 0.2–5.0) larger 20-year decline for workers aged 30–39 years at baseline, and −0.2 dB (95% CI: −2.2 to 1.7) for workers aged 20–29 years. Combining JEM information with self-reported noise exposure data resulted in stronger associations. This large longitudinal study shows an association between JEM-based noise exposure level and increased 20-year hearing decline among men. Contrary to expectations, the associations were weaker among younger workers, which might reflect a latency period. [ABSTRACT FROM AUTHOR]

Objectives: It has been suggested that noise exposure can accelerate hearing decline after the noise exposure has ceased. We aimed to assess long‐term hearing decline in persons with and without prior occupational noise exposure. Methods: We conducted a population‐based longitudinal study in Norway using the Trøndelag Health Study (HUNT) from 1996 to 1998 (baseline) and from 2017 to 2019 (follow‐up). The sample included 1648 participants with baseline age ≥55 years (42% men, mean age 60 years) and <5 years occupational noise exposure after baseline. We analyzed the association between occupational noise exposure before baseline and mean hearing decline between 1998 and 2018 (20‐year decline) at each frequency, adjusted for age, sex, education, and impulse noise exposure before baseline. Results: Occupational noise exposure before baseline (N = 603) was associated with baseline hearing loss, but not with later accelerated 20‐year decline, at any frequency. Noise‐exposed persons had less subsequent 20‐year decline at 3 kHz than did nonexposed. Restricting the noise‐exposed group to persons who also had a baseline Coles notch (hearing thresholds at 3, 4, or 6 kHz of 10 dB or more compared with thresholds at 1 or 2 kHz and 6 or 8 kHz; N = 211), the exposed group showed less 20‐year decline at both 3 and 4 kHz, as well as less accelerated 20‐year decline at 8 kHz, compared with the nonexposed. Conclusion: Our large long‐term longitudinal study shows no increased risk of continuing hearing decline after occupational noise exposure has ceased. The finding supports a conclusion that ear damage stops when the noise exposure is ended. [ABSTRACT FROM AUTHOR]

Objectives: Earlier studies suggest that being married in later life protects against dementia, and that being single in old age increases the risk of dementia. In this study, we examine midlife marital status trajectories and their association with dementia and mild cognitive impairment (MCI) at ages 70 plus using a large population based sample from Norway. Methods: Based on a general population sample linked to population registries (N = 8706), we used multinomial logistic regression to examine the associations between six types of marital trajectories (unmarried, continuously divorced, intermittently divorced, widowed, continuously married, intermittently married) between age 44 and 68 years from national registries and a clinical dementia or a MCI diagnosis after age 70. We estimated relative risk ratios (RRR) and used mediation analyses adjusting for education, number of children, smoking, hypertension, obesity, physical inactivity, diabetes, mental distress, and having no close friends in midlife. Inverse probability weighting and multiple imputations were applied. The population attributable fraction was estimated to assess the potential reduction in dementia cases due to marital histories. Results: Overall, 11.6% of the participants were diagnosed with dementia and 35.3% with MCI. Dementia prevalence was lowest among the continuously married (11.2%). Adjusting for confounders, the risk of dementia was higher for the unmarried (RRR = 1.73; 95% CI: 1.24, 2.40), continuously divorced (RRR = 1.66; 95% CI: 1.14, 2.43), and intermittently divorced (RRR = 1.50; 95% CI: 1.09, 2.06) compared to the continuously married. In general, marital trajectory was less associated with MCI than with dementia. In the counterfactual scenario, where all participants had the same risk of receiving a dementia diagnosis as the continuously married group, there would be 6.0% fewer dementia cases. Discussion: Our data confirm that staying married in midlife is associated with a lower risk of dementia and that divorced people account for a substantial share of dementia cases. [ABSTRACT FROM AUTHOR]

The risk of noise injury from recreational firearm use is well known. Despite preventive measures it is uncertain whether it has become less harmful. We assessed whether the association between recreational firearm use and hearing has changed during the last two decades. We used a repeated cross-sectional design and determined hearing thresholds by pure-tone audiometry. Frequency-specific associations between recreational firearm use and hearing thresholds were assessed by multivariate linear regression stratified by sex and adjusted for age and other covariates. Two cross-sectional population-based cohorts 20 years apart (1998 and 2018) comprised 27,580 (53% women, mean age 53 years) and 26,606 individuals (56% women, mean age 54 years), respectively. Recreational firearm use was reported by 28% in 1998 and 30% in 2018. The proportion that reported wearing hearing protection increased. Exposure to recreational firearms was associated with elevated thresholds at 3-6 kHz in both cohorts. The association increased with the number of lifetime shots. The associations increased by age and were substantially smaller in the most recent cohort. Analyses of two cohorts revealed a reduction in the association between recreational firearm use and hearing over 20 years, coinciding with the introduction of hearing preservation measures. [ABSTRACT FROM AUTHOR]