Forskningsartikler

Abstract

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the “LIfestyle for BRAin health” (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta-analyses with a two-round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts.

Colin Rosenau, Sebastian Köhler, Lion M. Soons, Kaarin J. Anstey, Carol Brayne, Henry Brodaty, Knut Engedal, Francesca R. Farina, Mary Ganguli, Gill Livingston, Constantine G. Lyketsos, Francesca Mangialasche, Laura E. Middleton, Marcel G. M. Olde Rikkert, Ruth Peters, Perminder S. Sachdev, Nikolaos Scarmeas, Geir Salbæk, Martin P. J. van Boxtel, Kay Deckers

Abstract

Hand grip strength (HGS) is a key indicator of intrinsic capacity and has shown good predictive ability for morbidity and mortality. Reference values from normative populations are valuable, and such data from the Norwegian population are scarce. Normative values for the digital Jamar+ dynamometer are largely lacking. HGS was assessed in the Norwegian Tromsø study, survey 7 in 2015-2016 for 7824 participants (9324 invited) aged 40+ using a Jamar+ digital dynamometer, and three measurements for each hand were performed following the Southampton protocol. To account for non-response, full Tromsø population data, by age, education and sex, were collected from registry data from microdata.no, a service from Statistics Norway, and were then used as post-stratification weights, to provide standardized HGS values. HGS was higher in men than in women and inversely associated with age. Men and women with a history of non-communicable diseases had lower HGS than those without these conditions, while osteoarthritis was associated with lower HGS only among men. Lower height was associated with lower HGS, especially at younger ages in men. This article provides up-to-date references values for HGS in the community-dwelling population aged 40+ with or without osteoarthritis or non-communicable diseases, in Tromsø, Norway. These reference values will guide clinicians and researchers.

Odd-Einar Svinøy, Gunvor Hilde, Astrid Bergland, Bjørn Heine Strand

Background
Hearing impairment is strongly associated with future dementia. No studies have reported objectively measured hearing impairment in a cohort with a long period of follow-up (>20 years), and few have reported follow-up over 10 years. Hence, there is a need for high quality studies with sufficient follow-up time and data to account for reverse causality and confounding. We aimed to address this knowledge gap.

Methods
This cohort study used individual participant data from The Trøndelag Health Study (HUNT) in Norway. All current residents aged at least 20 years in the former Norwegian Nord-Trøndelag County were invited to participate in four decennial surveys: HUNT1 (1984–1986), HUNT2 (1995–1997), HUNT3 (2006–2008), and HUNT4 (2017–2019) with individuals aged at least 70 years included in a substudy, known as HUNT4 70+. Here, we report the findings of this substudy. HUNT4 70+ comprised 7135 participants who were assessed for dementia using the Diagnostic and Statistical Manual of Mental Disorders 5 criteria and who had audiometry between 1996 and 1998. The primary objective was to investigate, with gold standard audiometric testing and dementia diagnostic assessment, whether hearing impairment was an independent risk factor for all-cause dementia. The secondary objective was to investigate if a risk also applied to Alzheimer dementia and non-Alzheimer dementia. We analysed the association using Poisson regression and adjusted for confounders. This study is registered with ClinicalTrials.gov (NCT04284384).

Findings
At baseline, 1058 (15%) individuals had acquired hearing impairment with a hearing threshold of at least 25 decibel (dB) and, at follow-up, 1089 (15%) had dementia. In the total group, people with hearing impairment had a relative risk (RR) 1.04 (95% confidence interval (CI) 1.00–1.09) per 10 dB increase in hearing thresholds. For individuals younger than 85 years at follow-up the RR was 1.12 (95% CI 1.05–1.21). Associations between hearing impairment and Alzheimer dementia and non-Alzheimer dementia were similar. There was no association for individuals aged at least 85 years.

Interpretation
We found a moderate association between objectively measured hearing impairment and dementia in the younger age group (<85 years). The findings of no association in the older age group (≥85 years) might be due to the competing risk of death. The present study adds to the literature showing that acquired hearing impairment is a risk for dementias over a period which is too long for reverse causation, and with thorough consideration of confounders. Further research is needed to investigate associations between the different aetiologies of hearing loss and dementia subtypes, and risk differences for sexes.

Christian Myrstad, Bo Lars Engdahl, Sergi Gonzales Costafreda, Steinar Krokstad, Frank Lin, Gill Livingston, Bjørn Heine Strand, Beate Øhre, Geir Selbæk

Abstract

Background: Alzheimer’s disease and related dementias (ADRD) involve biological processes that begin years to decades before onset of clinical symptoms. The plasma proteome can offer insight into brain aging and risk of incident dementia among cognitively healthy adults.

Objective: To identify biomarkers and biological pathways associated with neuroimaging measures and incident dementia in two large community-based cohorts by applying a correlation-based network analysis to the plasma proteome.

Methods: Weighted co-expression network analysis of 1,305 plasma proteins identified four modules of co-expressed proteins, which were related to MRI brain volumes and risk of incident dementia over a median 20-year follow-up in Framingham Heart Study (FHS) Offspring cohort participants (n = 1,861). Analyses were replicated in the Cardiovascular Health Study (CHS) (n = 2,117, mean 6-year follow-up).

Results: Two proteomic modules, one related to protein clearance and synaptic maintenance (M2) and a second to inflammation (M4), were associated with total brain volume in FHS (M2: p = 0.014; M4: p = 4.2×10-5). These modules were not significantly associated with hippocampal volume, white matter hyperintensities, or incident all-cause or AD dementia. Associations with TCBV did not replicate in CHS, an older cohort with a greater burden of comorbidities.

Conclusions: Proteome networks implicate an early role for biological pathways involving inflammation and synaptic function in preclinical brain atrophy, with implications for clinical dementia.

Meghan I Short, Alison E Fohner, Håvard K Skjellegrind, Alexa Beiser, Mitzi M Gonzales, Claudia L Satizabal, Thomas R Austin, W T Longstreth, Joshua C Bis, Oscar Lopez, Kristian Hveem, Geir Selbæk, Martin G Larson, Qiong Yang, Hugo J Aparicio, Emer R McGrath, Robert E Gerszten, Charles S DeCarli, Bruce M Psaty, Ramachandran S Vasan, Habil Zare, Sudha Seshadri

Abstract

The study aimed to explore the impact of Alzheimer’s disease (AD) on spouse-carer’s lives and the ways it affects their marital relationship and sexual activity. Data were obtained from qualitative interviews conducted with 11 spouse-carers of people with AD. Using interpretative phenomenological analysis (IPA), three themes emerged: psychological and emotional impact, social impact, and sexual impact. Some spouse-carers reported stress, poor emotional well-being, frustration, doubts about how to deal with the situation, sadness, loneliness, perception of losing connection with the partner, and feelings of companionship disappearing. Meanwhile, other spouse-carers reported closer relations and greater affection for their care-recipients after the diagnosis. Changes in sexual activity were attributed to aging and/or the effects of the illness. Gender influenced the perception of changes in the marital relationship but not in sexual activity. Participants reported conflicting perspectives towards the importance of sexual activity in the marital relationship and the replacement of sexual intercourse with other modes of expressing affection. We believe that understanding the specificities of marital relationships of couples in whom one spouse was diagnosed with AD would be helpful for developing coping strategies for persons living with dementia and their spouses.

Marcela Moreira Lima Nogueira, Jose Pedro Simões Neto, Aud Johannessen, Marcia Cristina Nascimento Dourado