Forskningsartikler

Abstract

Late-life depression (LLD) has been linked to increased likelihood of dementia, although mechanisms responsible for this association remain largely unknown. One feature frequently observed in both LLD and dementia is elevated levels of plasma inflammatory markers. The present study aimed to compare the levels of 12 plasma inflammatory markers between older people with LLD and controls, and to explore whether these markers, along with clinical characteristics, can predict dementia in patients with LLD within 3 years of follow-up. Using multiple linear regression with stepwise adjustment, we compared levels of plasma inflammatory markers (IL-1β, IL-1ra, IL-6, IL-10, IL-17a, IL-18, IL-33, TNFα, CD40L, IFN-γ, CCL-2 and CCL-4) between 136 inpatients with LLD (PRODE cohort) and 103 cognitively healthy non-depressed controls (COGNORM cohort). In the PRODE cohort, follow-up data was available for 139 patients (of them 123 had data on baseline plasma inflammatory markers); 36 (25.9%) developed dementia by Year 3 (n = 31 for those with cytokine data). Using Cox proportional hazards regression, we explored whether inflammatory markers and clinical characteristics of LLD (age of onset, treatment response, number of episodes) predicted progression to dementia during follow-up. Levels of IL-1ra, CCL-2, CCL-4, IFN-γ and IL-17a were significantly higher in LLD patients compared to controls in the majority of models. However, none of the inflammatory markers predicted progression from LLD to dementia in the PRODE cohort. Among clinical features, only poor response to treatment significantly predicted higher risk of progression to dementia.

M Bocharova, T Borza, L O Watne, K Engedal, J T O’Brien, G Selbæk, A V Idland, J Hodsoll, A H Young & D Aarsland

Abstract
Background:
There is a growing concern and debate over the inappropriate use of analgesics and psychotropic medications by older adults, especially those with dementia. The long-term effects of the COVID-19 pandemic and lockdown measures on these prescriptions remain uncertain.

Aim:
The primary aim was to examine changes in the prescription of analgesics (opioids and other analgesics) and psychotropics (anxiolytics/sedatives, antidepressants, and antipsychotics) in Norwegian home-dwelling older adults before, during, and up to 2 years after the COVID-19 lockdown, with a particular focus on dementia status. Secondarily, we explored individual characteristics associated with changes in medication prescriptions.

Methods:
A prospective cohort study using baseline data from 10,464 participants (54% females, mean age 76 years [SD 5.8]) from the Norwegian Trøndelag Health Study (HUNT4 70+) linked with the Norwegian Prescription Database. Age- and education-adjusted Poisson regression was applied to examine changes in prescription fills, and multilevel mixed-effects linear regression was used to estimate the mean sum of defined daily dose (DDD) per person per period during the lockdown (March–September 2020) compared to that during the corresponding months (March–September) in 2019, 2021, and 2022.

Results:
Overall, prescriptions of opioids, other analgesics, and anxiolytics/sedatives were higher in 2022 than during the lockdown. People without dementia had increased prescriptions of opioids, other analgesics, and antidepressants after lockdown, whereas no changes were observed among those with dementia. Increases in prescriptions of opioids, other analgesics, anxiolytics/sedatives, and antidepressants between the lockdown and 2022 occurred mainly among those aged < 80 years, without comorbidities or mental distress, with good physical function, low fear of COVID-19, and no social isolation during COVID-19.

Conclusion:
An increase in analgesics and psychotropics after the lockdown was predominantly observed among younger-old and healthier participants. This indicates that in high-income countries, such as Norway, home-dwelling vulnerable individuals seem to have received adequate care. However, the pandemic may have increased the number of vulnerable individuals. These findings should be considered when identifying future nationwide stressors that may impair social interactions and threaten mental health. They also highlight the need to evaluate medication prescriptions for older adults after the pandemic.

Tanja Louise Ibsen, Ekaterina Zotcheva, Sverre Bergh, Debby Gerritsen, Gill Livingston, Hilde Lurås, Svenn-Erik Mamelund, Anne Marie Mork Rokstad, Bjørn Heine Strand, Richard C. Oude Voshaar & Geir Selbæk

Abstract

Background:
Childlessness, as well as having a high number of children, has been reported to be associated with an elevated risk of dementia compared to having 2–3 children. The mechanisms underlying these relationships are not well understood and may be mediated by different midlife risk factors. We examined the mediating role of various factors on the relationship between the number of children and dementia risk. These factors include socioeconomic factors (e.g., occupational complexity), psychosocial (e.g.., social activities, loneliness, life satisfaction), lifestyle (e.g., smoking, physical inactivity, alcohol intake), and chronic diseases (e.g., obesity, diabetes, depression, hearing impairment and hypertension).

Methods:
Using a historic cohort design, we included 9,745 participants born between 1931–48, with a mean age of 78.2 (SD = 6.4) years at the time of cognitive testing in the HUNT4 70 + sub-study (2017–2019). Further measures were obtained through data linkage between information from Statistics Norway and the HUNT1(1984–86), and HUNT2 (1995–97) Surveys. Causal mediation analyses using an inverse odd weighting approach were conducted to decompose the total effect of the number of children (0, 1, or 4 + children vs. 2–3) on the risk of dementia at age 70 + years into direct and indirect effects with mediators assessed at a mean age of 50.7 (SD = 6.4) years. The analyses were adjusted for age, sex, marital status at age 25 years, educational status, and religion assessed during HUNT3 (2006–2008).

Results:
Overall, 15.7% were diagnosed with dementia. The proportions with dementia by the number of children were 22.3% among those with no children, 21.4% for those with one child, 13% for those with 2–3 children (specifically, 12.6% for those with 2 children and 13.4% for those with 3 children), and 19.9% for those with 4 + children. Compared to the reference group of individuals with 2–3 children, the dementia risk was higher among the groups with no children (relative risk (RR): 1.30, 95% confidence interval (CI) (1.12, 1.51)), those with one child (RR: 1.30, 95% CI (1.14, 1.47)) and those with 4 + children (RR: 1.12, 95% CI (1.01, 1.24)). The elevated risks of dementia were not mediated by the socioeconomic, psychosocial, lifestyle, or chronic diseases related factors that we tested. Sex-stratified analysis showed higher dementia risk for men without children and women with one or 4 + children compared to those with 2–3 children, with similar patterns across sexes. None of the mediators contributed to mediation in either group. None of the mediators appeared to contribute through mediation in either group.

Conclusions:
Our findings suggest that the number of children—specifically being childless, having one child, or having four or more children—may influence the risk of dementia. These relationships were not mediated by psychosocial, lifestyle, and socioeconomic factors, or markers of chronic diseases in adulthood considered in this study.

Teferi Mekonnen, Vegard Skirbekk, Ekaterina Zotcheva, Bo Engdahl, Bernt Bratsberg, Astanand Jugessur, Catherine Bowen, Geir Selbæk, Hans-Peter Kohler, Jennifer R. Harris, Sarah E. Tom, Steinar Krokstad, Trine Holt Edwin, Yehani Wedatilake, Katrin Wolfova, Dana Kristjansson, Yaakov Stern, Asta Kristine Håberg & Bjørn Heine Strand

Introduction:
Hearing impairment is associated with dementia. We aimed to clarify the association between hearing impairment and future cognitive test performance measured by the Montreal Cognitive Assessment Scale (MoCA), adjusted for confounders, avoiding reverse causation through long follow-up.

Methods:
We used the Norwegian population-based longitudinal cohort study, The Trøndelag Health Study (HUNT). At baseline, we invited all residents 20+ for an audiometric hearing assessment, and at 20+ years follow-up, we cognitively assessed all persons 70+ including MoCA adjusted for hearing impairment. We analyzed the association using linear regression.
Results:
We included 6879 persons (mean 56.1 years, standard deviation 6.2). At follow-up, the MoCA score was −0.25 (95% confidence interval [CI] −0.35, −0.14), per 10 dB increase in hearing threshold and for persons < 85 years, −0.31 (95% CI −0.42, −0.20).
Discussion:
This study finds a long-term association between hearing impairment and dose related reduced cognitive performance, particularly in those aged < 85.

Christian Myrstad, Bo Lars Engdahl, Sergi Gonzalez Costafreda, Steinar Krokstad, Gill Livingston, Geir Selbæk