The Danish Aging and Cognition (DanACo) cohort.

BACKGROUND: With aging populations worldwide, identification of predictors of age-related cognitive decline is becoming increasingly important. The Danish Aging and Cognition Cohort (DanACo) including more than 5000 Danish men was established to investigate predictors of age-related cognitive decline from young adulthood to late mid-life. CONSTRUCTION AND CONTENT: The DanACo cohort was established through two separate data collections with identical designs involving a follow-up examination in late mid-life of men for whom intelligence test scores were available from their mandatory conscription board examination. The cohort consists of 5,183 men born from 1949 through 1961, with a mean age of 20.4 years at baseline and a mean age of 64.4 years at follow-up. The baseline measures consisted of height, weight, intelligence test score and educational level collected at the conscription board examination. The follow-up assessment consisted of a re-administration of the same intelligence test and a comprehensive questionnaire covering socio-demographic factors, lifestyle, and health-related factors. The data were collected in test sessions with up to 24 participants per session. Using the unique personal identification number assigned to all Danes, the cohort has been linked to data from national administrative and health registers for prospectively collected data on socioeconomic and health-related factors. UTILITY AND DISCUSSION: The DanACo cohort has some major strengths compared to existing cognitive aging cohorts such as a large sample size (n = 5,183 men), a validated global measure of cognitive ability, a long retest interval (mean 44.0 years) and the availability of prospectively collected data from registries as well as comprehensive questionnaire data. The main weakness is the low participation rate (14.3%) and that the cohort consists of men only. CONCLUSION: Cognitive decline is a result of a summary of factors across the life-course. The DanACo cohort is characterized by a long retest interval and contains data on a wealth of factors across adult life which is essential to establish evidence on predictors of cognitive decline. Moreover, the size of the cohort ensures sufficient statistical power to identify even relatively weak predictors of cognitive decline.

Preterm birth and subsequent intelligence and academic performance in youth: A cohort study.

INTRODUCTION: Worldwide, more children than before survive preterm birth. Preterm birth can affect long-term cognitive outcomes. The aim of our study was to investigate the association between preterm birth and academic performance and intelligence in youth. MATERIAL AND METHODS: This cohort study included all liveborn children in Denmark from 1978 to 2000. We used uni- and multivariable logistic and linear regressions to analyze associations between gestational age and school graduation, grade point average (GPA), attending conscription, and male intelligence scores at conscription. We adjusted for a priori defined potential confounders. RESULTS: The study included 1 450 681 children and found an association between preterm birth and lower academic performance, with children born extremely preterm having the lowest odds of graduating from lower- and upper secondary education (LSE and USE) and appearing before the conscription board (odds ratios of 0.45 [0.38-0.54], 0.52 [0.46-0.59], and 0.47 [0.39-0.56] for LSE, USE, and conscription, respectively, compared to the term group). Statistically significant differences were observed in LSE for total GPA and core subject GPA with higher GPAs in the term group, which were considered clinically relevant for mathematics with a 0.71 higher grade point for the term compared to the extremely preterm. Conversely, USE differences were less evident, and in linear regression models we found that preterm birth was associated with higher GPAs in the adjusted analyses; however, this was not statistically significant. We demonstrated statistically significant differences in intelligence scores at conscription with lower scores in the three preterm groups (-5.13, -2.73, and - 0.76, respectively) compared to the term group. CONCLUSIONS: Low gestational age at birth was associated with not graduating from LSE and USE, achieving lower GPAs in LSE, not attending conscription, and lower intelligence scores in young adulthood. The findings remained significant after adjusting for potential confounders.

The relationship between self-perceived fatigue, muscle endurance, and circulating markers of inflammation in participants of the Copenhagen aging and Midlife Biobank (CAMB).

BACKGROUND: Fatigue, low muscle endurance, muscle weakness and low-grade inflammation are strongly related to frailty at higher age. When signs of self-perceived fatigue and low muscle endurance are interrelated with low-grade inflammation at midlife, they might be used as early markers for frailty. This study investigated whether the interrelationships among self-perceived fatigue, muscle endurance and inflammation can be observed at midlife. METHODS: A total of 965 participants of the Copenhagen Aging and Midlife Biobank (aged 52 ± 4 years, 536 males, 426 females) were assessed for self-perceived fatigue (20-item multidimensional fatigue inventory), muscle endurance (grip work), circulating markers of inflammation (hsCRP, IL-6, IL-10, TNF-alpha and IFN-γ), daily physical activity (PAS-2), body composition (%body fat assessed by bio-impedance) and self-reported health status. Participants were categorised (correcting for age and gender) according to high fatigue and/or low muscle endurance, differences in inflammatory profile between fatigue categories were assessed by ANCOVA (corrected for PAS-2, %body fat and presence of inflammatory conditions). RESULTS: Overall, muscle endurance, fatigue and inflammatory markers were significantly interrelated. Higher levels of hsCRP (p < 0.001), IL-6 (p < 0.001), IL-10 (p = 0.035) and TNF-alpha (p = 0.028) were observed in participants presenting both low muscle endurance and high fatigue. IFN-γ was highest in those with high fatigue but normal muscle endurance (p = 0.015). CONCLUSIONS: Middle-aged participants with higher fatigue in combination with low muscle endurance show higher levels of inflammation, independently from physical activity, body fat and inflammatory pathology. The underlying mechanisms should be identified and future studies should also investigate whether these individuals show early signs of reduced physiological reserve capacity, which in later life come to full expression by means of frailty.

Real-World Evidence on Clinical Outcomes of Commonly Used Antidepressants in Older Adults Initiating Antidepressants for Depression: A Nationwide Cohort Study in Denmark.

OBJECTIVE: The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes. METHODS: This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders. RESULTS: The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50-1.61; venlafaxine: IRR=1.22, 95% CI=1.12-1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15-1.81; venlafaxine: IRR=1.47, 95% CI=1.20-1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertraline users. These results remained consistent in analyses stratified by sex and age (≤75 years vs. >75 years). CONCLUSIONS: This real-world evidence suggests that clinical outcomes may vary among initiators of commonly used antidepressants in older adults, which may inform benefit-risk evaluation at treatment initiation, and highlights the importance of careful selection of antidepressant treatment.

Early cerebral amyloid-ß accumulation and hypermetabolism are associated with subtle cognitive deficits before accelerated cerebral atrophy.

AIMS: Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aß) in the brain. The deposition of Aß is believed to initiate a detrimental cascade, including cerebral hypometabolism, accelerated brain atrophy, and cognitive problems-ultimately resulting in AD. However, the timing and causality of the cascade resulting in AD are not yet fully established. Therefore, we examined whether early Aß accumulation affects cerebral glucose metabolism, atrophy rate, and age-related cognitive decline before the onset of neurodegenerative disease. METHODS: Participants from the Metropolit 1953 Danish Male Birth Cohort underwent brain positron emission tomography (PET) imaging using the radiotracers [11C]Pittsburgh Compound-B (PiB) (N = 70) and [18F]Fluorodeoxyglucose (FDG) (N = 76) to assess cerebral Aß accumulation and glucose metabolism, respectively. The atrophy rate was calculated from anatomical magnetic resonance imaging (MRI) scans conducted presently and 10 years ago. Cognitive decline was examined from neurophysiological tests conducted presently and ten or 5 years ago. RESULTS: Higher Aß accumulation in AD-critical brain regions correlated with greater visual memory decline (p = 0.023). Aß accumulation did not correlate with brain atrophy rates. Increased cerebral glucose metabolism in AD-susceptible regions correlated with worse verbal memory performance (p = 0.040). CONCLUSIONS: Aß accumulation in known AD-related areas was associated with subtle cognitive deficits. The association was observed before hypometabolism or accelerated brain atrophy, suggesting that Aß accumulation is involved early in age-related cognitive dysfunction. The association between hypermetabolism and worse memory performance may be due to early compensatory mechanisms adapting for malfunctioning neurons by increasing metabolism.

Elevated lipid class concentrations in females with anorexia nervosa before and after intensive weight restoration treatment-A lipidomics study.

OBJECTIVE: To study the plasma lipidome of patients with anorexia nervosa (AN) before and after weight restoration treatment and report associations with AN subtypes and oral contraceptive pill (OCP) usage. METHODS: Quantitative shotgun lipidomics analysis was used to study plasma lipids of 50 female patients with AN before and after weight restoration treatment and 50 healthy female controls (HC). The AN group was assessed with blood samples and questionnaires before and after weight restoration. RESULTS: In total we quantified 260 lipid species representing 26 lipid classes of which 13 lipid class concentrations were elevated in patients with AN at admission compared with HC. Lipid classes remained elevated after weight restoration treatment of 84 days (median; interquartile range 28), and only the concentration of the ceramide lipid class increased between pre- and post-treatment (p = .03), whereas lysophosphatidylcholine (LPC, p = .02), ether-linked Phosphatidylcholine (LPCO, p = .02), and lysophosphatidylethanolamine (LPE, p = .009) decreased. CONCLUSION: In AN, 13 out of 26 lipid class concentrations were elevated at admission and remained elevated post-treatment. Ceramides increased further between pre- and post-weight restoration treatment, which could be related to the rapid weight gain during re-nutrition. Further research is needed to elucidate the effects of weight restoration treatment on short- and long-term lipid profiles in individuals with AN. PUBLIC SIGNIFICANCE STATEMENT: Lipidomics research can increase the understanding of AN, a complex and potentially life-threatening eating disorder. By analyzing lipids, or fats, in the body, we can identify biological markers that may inform diagnosis and develop more effective treatments. This research can also shed light on the underlying mechanisms of the disorder, leading to a better understanding of the processes involved in eating behavior.

Mindfulness in sex therapy and intimate relationships: a feasibility and randomized controlled pilot study in a cross-diagnostic group.

Background: Mindfulness facets can be trained with structured mindfulness interventions, but little is known regarding application on a broader level within sex therapy (e.g. men, partners and different sexual dysfunctions). Aim: To evaluate the feasibility and preliminary efficacy of an 8-week intervention-specifically, mindfulness for sex and intimacy in relationships (MSIR)-as a supplement to treatment as usual (TAU) as compared with only TAU in a clinical sample of men and women referred for sexual difficulties with or without a partner. Methods: In this randomized controlled feasibility pilot study, 34 participants were randomized to MSIR + TAU (n = 15) or TAU (n = 19). Six healthy partners were also included in the study. MSIR was administered as 2 individual evaluations and six 2-hour group sessions of mixed gender and different types of sexual dysfunction. Outcomes: The primary outcome measures were as follows: (1) feasibility, defined as the implementation of recruitment, acceptance, and attendance of intervention in daily clinical practice and the MSIR completion rate; (2) sexual functioning, as measured on a visual analog scale ("bothered by problem") and by validated questionnaires (Changes in Sexual Function Questionnaire for Females and Males, Female Sexual Function Index, Female Sexual Distress Scale, International Index of Erectile Function). Results: MSIR was feasible and well received by patients, with high rates of acceptance and intervention completion. As compared with pretreatment, the MSIR + TAU group and TAU control group were significantly less bothered by their sexual problems at the end of treatment, but the change was significantly larger in the MSIR + TAU group (P = .04). Participants in the MSIR + TAU group did not receive fewer TAU sessions than the TAU group (MSIR + TAU mean, 6 sessions; TAU mean, 8 sessions). Clinical Implications: MSIR could be effectively used in a clinical setting as an add-on to TAU in the treatment of female and male sexual dysfunction and healthy partners. Strengths and Limitations: The major strength of the study is that it is a randomized controlled study. This study is novel in the sense that it included men and women with different types of sexual dysfunction in the same mindfulness group. Limitations include the pilot nature of the study (e.g. a small sample size), and statistical conclusions should be made with caution. More accurate results may be found in a larger sample. Conclusion: Results from this study support already existing evidence that mindfulness-based interventions are feasible and effective for targeting sexual dysfunctions in men and women.

The structure of ICD-11 post traumatic stress disorder in a clinical sample of refugees based on the International Trauma Interview.

BACKGROUND: The ICD-11 proposes fundamental changes to the PTSD diagnostic criteria, prompting thorough validation. While this is ideally carried out based on diagnostic interviews, most-and in the case of transcultural psychiatry all-studies have relied on self-reported measures. In this study, we used the International Trauma Interview (ITI) to assess the factor structure of ICD-11 PTSD symptoms in a sample of trauma-affected refugees. METHOD: The ITI was administered with a sample of refugees (n = 198), originating mainly from the Greater Middle East. The symptom ratings were subjected to a confirmatory factor analysis (CFA), comparing the ICD-11 concordant three-factor model with alternative two- and one-factor models. RESULTS: The overall fit was adequate for both the two- and three-factor models, but favored the two-factor model. Results for both models indicated local misspecifications and that item 5, hypervigilance, displayed a suboptimal loading. CONCLUSION: The results generally support the use of the ITI in a severely trauma-affected refugee population, albeit with particular attention needed in the administration of item 5. The superior fit of a two-factor model warrants further testing across populations.

Early Motor Developmental Milestones and Personality Traits in Midlife: A 50-Year Follow-Up Study.

Background The purpose of this study was to investigate if infants' age at attaining motor developmental milestones is associated with the big five personality traits 50 years later. Methods Mothers of 8395 infants from the Copenhagen Perinatal Cohort recorded a total of 12 motor developmental milestones during the first year of their infant's life. Information on at least one milestone was available for 1307 singletons with adult follow-up scores on the NEO-Five-Factor Inventory. The mean age at personality testing was 50.1 years. Results Slower attainment of motor milestones was associated with increased neuroticism and lower conscientiousness in midlife. All 12 motor developmental milestones explained a total of 2.4% of the variance in neuroticism, while they explained 3.2% of the variance in conscientiousness. These results remained significant after adjustment for the included family and perinatal covariates, as well as adult intelligence. Discussion The personality trait of neuroticism is a general risk factor for psychopathology and has in young adulthood been found to be associated with early motor development. However, evidence on associations of motor developmental milestones with other personality traits has been non-existent. These findings suggest that delays in early motor development may not only characterise individuals with later psychopathology, including schizophrenia, but may also be associated with personality traits such as neuroticism and conscientiousness through the life course.

'Personality and bipolar disorder: personality profiles of patients with remitted bipolar disorder and matched controls in a Danish sample'.

BACKGROUND: The aim of the study was to investigate whether patients with bipolar disorder (BD) in remission differ in personality traits compared with a healthy control group. METHODS: A sample of patients with BD (n = 44) was compared with an individually matched control group (n = 44) using the Danish version of the Revised NEO Personality Inventory (NEO PI-R). Paired t-tests were used to analyze differences between the two groups and multiple regression models to evaluate predictors of NEO scores in the patient group. RESULTS: Patients with BD reported significantly higher scores on both Neuroticism and Openness to Experience and lower scores on Conscientiousness. No differences were found on Extraversion and Agreeableness. The effect size for Neuroticism and its facets had a range from 0.77 to 1.45 SD.Statistically significant group differences were seen on 15 of 30 lower-level traits within all five high-order dimensions. There were large effect sizes for Trust (0.77) and Self-discipline (0.85), while the other statistically significant group differences were smaller with effect sizes in the range from 0.43 to 0.74 SD.However, patients with BD showed a profile with high-order dimensions and lower-level traits within one standard deviation from the mean score except for the lower-level trait Depression. CONCLUSIONS: Our findings suggest that patients with BD differ from healthy control persons with respect to higher levels of Neuroticism, Openness to Experience and lower scores on Agreeableness and on Conscientiousness, but prospective studies are needed to evaluate the implications of this finding.

Association of birth by cesarean section with academic performance and intelligence in youth: A cohort study.

INTRODUCTION: It is suggested that birth by elective cesarean section (CS) reduces the risk of birth-related infant mortality and injury. Other studies suggest an increased risk of somatic immune-related diseases among children born by CS such as asthma, type 1 diabetes, and inflammatory bowel disease. The WHO Statement on Cesarean Section Rates 2015 described an increase in CS globally. The statement concluded that the effects of CS on social and psychological outcomes remain unclear and that more research is needed to fully understand the effects of CS, including effects on cognition and intelligence in the child. Therefore, we aimed to investigate the association between delivery by CS (elective and acute) and school performance and intelligence in youth. MATERIAL AND METHODS: This cohort study included all Danish live-born children in 1978-2000. We retrieved data regarding pregnancies, births, parents, school grades, and intelligence of the children from Danish registers and performed multiple imputations to avoid discarding data. The final cohort after exclusion comprised 1 408 230 children. Associations between CS and school graduation, grades, conscription attendance, and conscription intelligence scores were analyzed using univariate and multivariate logistic and linear regressions. RESULTS: Adjusted odds ratio with 95% CI of graduating from lower (LSE) and upper (USE) secondary education and of attending conscription were significantly lower in the CS group: LSE graduation: 0.87 (0.84-0.89), USE graduation: 0.93 (0.92-0.94), attending conscription: 0.95 (0.93-0.98). The CS group had significantly lower grade point averages (GPA) in LSE with adjusted differences in mean total GPA of -0.090 (-0.10 to -0.007), and mean core subject GPA of -0.098 (-0.11 to -0.08), in USE with total GPA difference of -0.091 (-0.11 to -0.075) and lower mean intelligence scores of -0.36 (-0.46 to -0.27) in adjusted linear models. A sub-analysis revealed lower chances of graduating LSE and USE when born by acute rather than elective CS. CONCLUSIONS: Chances of LSE and USE graduation and of attending conscription were significantly lower for children born by CS. However, even significant differences in mean GPAs and intelligence scores were very small, so performances when graduating school and attending conscription were comparable regardless of delivery mode.

Trends, Patterns and Associated User Characteristics of Antidepressant Prescriptions in Older Adults: A Nationwide Descriptive Cohort Study in Denmark.

BACKGROUND AND OBJECTIVE: Antidepressant use in older adults (≥ 65 years) is understudied in large population-based samples, particularly in recent years and regarding user characteristics. We aimed to describe the trends, patterns, and associated user characteristics of all antidepressant prescriptions redeemed by older adults at community pharmacies in Denmark during 2015-2019. METHODS: This register-based study used a cross-sectional design to characterize antidepressant prescription trends and patterns, and a cohort design to describe user characteristics associated with antidepressant prescription initiation. We used descriptive statistics to characterize trends and patterns, and Poisson regression for analyzing user characteristics. RESULTS: During the years 2015-2019, 17.9% of 1.2 million older adults redeemed 4.84 million antidepressant prescriptions, where 48.5% were selective serotonin reuptake inhibitors, followed by noradrenergic and specific serotonergic antidepressants (26.2%), serotonin-norepinephrine reuptake inhibitors (12.7%), tricyclic antidepressants (11.2%), and others (1.4%). Amitriptyline and nortriptyline, considered potentially inappropriate medications, were among the 10 most frequently redeemed antidepressants. Only 60.5% of prescriptions had a treatment indication of depression. Prescription-proportion trends by drug classes and individual antidepressants remained consistent. A higher incidence rate ratio (IRR) and 95% confidence interval (CI) of initiating antidepressants was associated with female sex (IRR 1.20, 95% CI 1.07-1.34), older age (e.g., 81-85 years vs. 65-70 years: IRR 1.74, 95% CI 1.44-2.11), living in rural areas (North Denmark vs. Capital Region: IRR 1.31, 95% CI 1.09-1.58), and having somatic and psychiatric diagnoses (e.g., per one psychiatric diagnosis: IRR 1.10, 95% CI 1.05-1.15), while a lower ratio was associated with being non-Western (vs. Danish: IRR 0.50, 95% CI 0.28-0.89) and having hospital contacts for psychiatric treatment (per each contact: IRR 0.96, 95% CI 0.93-1.00). CONCLUSION: SSRIs were the most commonly redeemed antidepressants, with consistent trends in Danish older adults. Besides clinical conditions, sociodemographics, e.g., sex, age, ethnicity, and place of residence, may influence antidepressant use.

Concurrent use of polypharmacy and potentially inappropriate medications with antidepressants in older adults: A nationwide descriptive study in Denmark during 2015-2019.

OBJECTIVE: Concurrent polypharmacy and potentially-inappropriate-medication (PIMs) use with antidepressants in older adults is understudied. We investigated the prevalence and associated user characteristics of concurrent polypharmacy (≥5 drugs) and PIMs with antidepressants in all older adults (≥65 years) in Denmark based on prescriptions filled at community pharmacies during 2015-2019. METHOD: We applied a cross-sectional and cohort study design using socio-demographic and clinical data from Danish registers. RESULTS: A total of 261,479 older adults (mean age 76 years, females 63%) redeemed at least one prescription of antidepressants during 2015-2019. The prevalence of polypharmacy was 73%, and PIMs was 56%, with over 80% using at least one other nervous system drug or cardiovascular system drug concomitantly with antidepressants. Characteristics associated with higher concurrent use of polypharmacy and PIM with antidepressants were older age, marital status as widow/widower/separated/single, place of residence predominantly in the rural regions, non-western origin, and having somatic diagnoses. Some characteristics showed opposite directions of the associations with the two outcomes, including previous antidepressant use and psychiatric diagnoses being associated with higher use of polypharmacy but lower use of PIM. CONCLUSION: High polypharmacy and PIM use with antidepressants underline the importance of regularly reviewing pharmacological treatments in older adults with depression.

Midlife perceived stress is associated with cognitive decline across three decades.

BACKGROUND: Research indicates detrimental effects of stress on brain health and cognitive functioning, but population-based studies using comprehensive measures of cognitive decline is lacking. The present study examined the association of midlife perceived stress with cognitive decline from young adulthood to late midlife, controlling for early life circumstances, education and trait stress (neuroticism). METHODS: The sample consisted of 292 members of the Copenhagen Perinatal Cohort (1959-1961) with continued participation in two subsequent follow-up studies. Cognitive ability was assessed in young adulthood (mean age 27 years) and midlife (mean age 56 years) using the full Wechsler Adult Intelligence Scale (WAIS), and perceived stress was measured at midlife using the Perceived Stress Scale. The association of midlife perceived stress with decline in Verbal, Performance and Full-Scale IQ was assessed in multiple regression models based on Full Information Maximum Likelihood estimation. RESULTS: Over a mean retest interval of 29 years, average decline in IQ score was 2.42 (SD 7.98) in Verbal IQ and 8.87 (SD 9.37) in Performance IQ. Mean decline in Full-scale IQ was 5.63 (SD 7.48), with a retest correlation of 0.83. Controlling for parental socio-economic position, education and young adult IQ, higher perceived stress at midlife was significantly associated with greater decline in Verbal (ß = - 0.012), Performance (ß = - 0.025), and Full-scale IQ (ß = - 0.021), all p < .05. Across IQ scales, additionally controlling for neuroticism in young adulthood and change in neuroticism had only minor effects on the association of midlife perceived stress with decline. CONCLUSIONS: Despite very high retest correlations, decline was observed on all WAIS IQ scales. In fully adjusted models, higher midlife perceived stress was associated with greater decline on all scales, indicating a negative association of stress with cognitive ability. The association was strongest for Performance and Full-scale IQ, perhaps reflecting the greater decline on these IQ scales compared to Verbal IQ.

Power and distribution of evoked gamma oscillations in brain aging and cognitive performance.

AIMS: Gamma oscillations (≈25-100 Hz) are believed to play an essential role in cognition, and aberrant gamma oscillations occur in brain aging and neurodegeneration. This study examined age-related changes in visually evoked gamma oscillations at two different time points 5 years apart and tested the hypothesis that the power of gamma oscillations correlated to cognitive skills. METHODS: The cohort consists of elderly males belonging to the Metropolit 1953 Danish Male Birth Cohort (first visit, N=124; second visit, N=88) over a 5-year period from 63 to 68 years of age. Cognitive functions were assessed using a neuropsychological test battery measuring global cognition, intelligence, memory, and processing speed. The power of steady-state visual evoked potentials (SSVEP) was measured at 8 Hz (alpha) and 36 Hz (gamma) frequencies using EEG scalp electrodes. RESULTS: Over the 5-year period cognitive performance remained relatively stable while the power of visually evoked gamma oscillations shifted from posterior to anterior brain regions with increasing age. A higher-than-average cognitive score was correlated with higher gamma power in parieto-occipital areas and lower in frontocentral areas, i.e., preserved distribution of the evoked activity. CONCLUSIONS: Our data reveal that the distribution of visually evoked gamma activity becomes distributed with age. Preserved posterior-occipital gamma power in participants with a high level of cognitive performance is consistent with a close association between the ability to produce gamma oscillations and cognition. The data may contribute to our understanding of the mechanisms that link evoked gamma activity and cognition in the aging brain.

Changes in hippocampal volume during a preceding 10-year period do not correlate with cognitive performance and hippocampal blood‒brain barrier permeability in cognitively normal late-middle-aged men.

Hippocampal blood-brain barrier (BBB) permeability may increase in normal healthy ageing and contribute to neurodegenerative disease. To examine this hypothesis, we investigated the correlation between blood-brain barrier (BBB) permeability, regional brain volume, memory functions and health and lifestyle factors in The Metropolit 1953 Danish Male Birth Cohort. We used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a gadolinium-based contrast agent to assess BBB permeability in 77 participants in the cohort. BBB permeability was measured as Ki values in the hippocampus, thalamus and white matter. Over a 10-year period, we observed progressive atrophy of both the left and right hippocampus (p = 0.001). There was no significant correlation between current BBB permeability and hippocampal volume, prior atrophy or cognition. The hippocampus volume ratio was associated with better visual and verbal memory scores (p < 0.01). Regional BBB differences revealed higher Ki values in the hippocampus and white matter than in the thalamus (p < 0.001). Participants diagnosed with type II diabetes had significantly higher BBB permeability in the white matter (p = 0.015) and thalamus (p = 0.016), which was associated with a higher Fazekas score (p = 0.024). We do not find evidence that BBB integrity is correlated with age-related hippocampal atrophy or cognitive functions. The association between diabetes, white matter hyperintensities and increased BBB permeability is consistent with the idea that cerebrovascular disease compromises BBB integrity. Our findings suggest that the hippocampus is particularly prone to age-related atrophy, which may explain some of the cognitive changes that accompany older age, but this prior atrophy is not correlated with current BBB permeability.

Psychotherapy readiness domains as predictors of psychotherapy outcome in trauma-affected refugees.

INTRODUCTION: Little is known about predictors of psychotherapy outcome in trauma-affected refugees. Knowledge on outcome predictors can help clinicians identify patients prior to treatment who are not likely to benefit from standardized psychotherapy and take additional measures to adjust treatment to the individual patient. Given the dynamic nature of psychotherapy readiness domains, they represent potential targets to be worked with in therapy in order to improve outcomes. METHODS: Psychotherapy readiness domains (locus of control, cognitive functioning, motivation for therapy, and personality functioning) were examined as potential predictors of psychotherapy outcome in trauma-affected refugees. Secondary analyses were conducted on data from a pragmatic randomized controlled trial. Study participants (N = 190) were refugees with PTSD who received flexible manual-based Cognitive Behavioral Therapy (CBT) at a psychiatric outpatient clinic in Denmark. Psychotherapy readiness domains were assessed via semi-structured interviews at the beginning of psychotherapy. Outcome variables were pre-post change in PTSD symptomology and global level of functioning. RESULTS: Multiple regression analyses revealed that higher motivation for psychotherapy predicted improvement in PTSD symptomology and global level of functioning. Moreover, higher cognitive functioning predicted improvement in global level of functioning. LIMITATIONS: The predictor rating scales need further psychometric evaluations in cross-cultural contexts. CONCLUSIONS: These findings highlight the importance of considering motivation in psychotherapy offered to trauma-affected refugees. Further research is needed to identify potential barriers to motivation in this diverse patient population and to determine whether motivational interventions can lead to improved treatment outcomes.

Social, psychological and health characteristics associated with stability and change in adult alcohol consumption.

BACKGROUND: Many studies analyzing health effects of alcohol consumption have operationalized alcohol intake from a single baseline measure without further follow-up. Consequently, there is a lack of knowledge about stability and change in alcohol consumption over the life course and the social, psychological, lifestyle, and health characteristics associated with different alcohol consumption trajectories. OBJECTIVES: The aims of the study were to describe the prevalence of different adult-life alcohol consumption trajectories among Danish men and to analyze social, psychological, lifestyle and health characteristics associated with these trajectories. METHODS: For 2510 Danish men, retrospective decade-based information on alcohol consumption during life period 26-60 years was obtained in late midlife and information on individual characteristics was obtained in young adulthood, late midlife and from national hospital registries. The men were allocated to one of six a priori defined alcohol consumption trajectories. RESULTS: About 65% of Danish men had a stable moderate consumption, drinking 1-21 units weekly while the five other consumption trajectories were comparatively rare: 3% stable abstainers, 4.7% stable high-risk drinkers, 10.9% with increasing and 12.7% with decreasing consumption. Moderate consumption over the adult life-course was associated with the most favorable social, psychological, lifestyle and health characteristics while the other trajectories were generally associated with less favorable characteristics to varying degrees-e. g. this was the case for the stable abstaining trajectory and in particular the trajectory with decreasing consumption. CONCLUSION: The findings suggest that the majority of Danish men drink moderately in the life period from young adulthood to late midlife, and deviance from this 'normal' moderate consumption trajectory is associated with less favorable social, psychological, lifestyle and health characteristics. Some of these characteristics may influence alcohol consumption patterns, but for some of the trajectories, alcohol consumption may influence health as well as social and psychological functioning.

Antidepressant effects of a psychedelic experience in a large prospective naturalistic sample.

BACKGROUND: Over the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap. AIM: Here, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes. METHOD: Individuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were N = 302, N = 182, N = 155 and N = 109, respectively. RESULTS: Relative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16. CONCLUSION: These results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.