Forskningsartikler

Abstract

This article synthesizes findings, from the Autism/Dementia Work Group of the 2nd International Summit on Intellectual Disabilities and Dementia, on the nature of autism/autism spectrum disorder and later-age neuropathologies, particularly dementia. The convened group of experts explored genetic, neurobiological, and environmental risk factors that may affect the lifespan and lived experiences of older adults with autism. A review of current literature indicates a lack of comprehensive information on the demographics and factors associated with aging in autistic adults. However, our understanding of autism is evolving, challenging traditional views of it as a static, inherited neurodevelopmental disorder. The relationship between autism and other neurodevelopmental conditions-such as Down syndrome, fragile X syndrome, and tuberous sclerosis complex-reflects the complex genetic landscape of neurodevelopmental disorders. These genetic and familial factors may contribute to progressive health challenges and cognitive decline in later life. Key findings reveal a complex link between autism and dementia, despite limited research on this relationship, particularly among older adults. The overall prevalence of dementia in this population appears to be influenced by co-occurring intellectual disabilities, particularly Down syndrome. While the association between autism and specific types of dementia is still not well understood, the reviewed evidence suggests a notable connection with frontotemporal dementia, although causality has not been established. Exploration of biomarkers may offer further insights. Currently, the relationship between autism, cognitive health, and cognitive decline in older adults remains a complex and underexplored area of research.

M P Janicki, P McCallion, N Jokinen, F K Larsen, D Mughal, V Palanisamy, F Santos, K Service, A Shih, S Shooshtari, A Thakur, G Tiziano & K Watchman

Abstract: 

Background: The COVID-19 pandemic increased social isolation in older adults, promoting mental and cognitive decline. The impact of social media on these effects remains unclear.

Aim: To investigate the long-term association of social isolation with mental and cognitive health in older adults and whether social media use mitigated this association.

Method: Data from the Norwegian Trøndelag Health Study before (2017-2019), during (January 2021), and after the pandemic (2021-2023) were analysed (N = 4844, 53% women, mean age 80 years). Multi-adjusted mixed-effects linear regression estimated differences in changes in mental (CONOR-MHI) and cognitive (MoCA) health related to self-reported social isolation and social media use. Beta (β) represents differences in change in z-score of CONOR-MHI or MoCA.

Results: Social isolation was associated with a steeper decline in mental health than no social isolation (β = 0.07, 95% CI 0.01, 0.13) but was not associated with change in cognitive health. Daily social media use was not related to change in mental health, whereas it was associated with a less steep cognitive decline than no social media use (< 1 h: β = 0.13, 95% CI 0.05, 0.20; ≥ 1 h: β = 0.10, 95% CI 0.01, 0.15). Stratified by social isolation, daily social media use < 1 h was related to a less steep cognitive decline than no social media use in both isolated (β = 0.15, 95% CI 0.02, 0.28) and non-isolated individuals (β = 0.13, 95% CI 0.03, 0.22).

Conclusion: Individuals experiencing social isolation during the pandemic had a steeper decline in mental, but not cognitive health, compared to those not isolated. Social media use did not buffer the decline in mental health but was associated with less steep cognitive decline. The pandemic showed limits of relying solely on digital solutions for social contact.

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

Abstract:

Background: Studies have shown that quantitative EEG is useful in predicting conversion from mild cognitive impairment (MCI) to Alzheimer’s disease dementia (ADD) and dementia with Lewy bodies (DLB). As subcortical pathology is present and executive impairment is common in DLB, we hypothesized that EEG could predict conversion in patients with impaired executive function and any subcortical pathology.
Methods: We included 113 patients with MCI from five Nordic memory clinics, 80 (71%) with amnestic MCI, 17 (15%) with dysexecutive MCI (deMCI), 3 (3%) with aphasic, 2 (2%) with visuospatial and 11 (10%) with unspecific MCI. Patients were examined with EEG in a resting state applying the statistical pattern recognition (SPR) method and followed up for five years. Eleven drop-outs were assessed after baseline. Receiver operating characteristic (ROC) analyses were used to examine the ability of EEG to predict conversion.

Results: Sixty patients converted to dementia, 47 to ADD, eight to vascular dementia, two to DLB, one to frontotemporal dementia and two to unspecific dementia. Eight (11%) recovered and 45 (40%) remained MCI stable. ROC analyses revealed that EEG predicted conversion from dysexecutive MCI to dementia with area under the curve (AUC) of 0.92 (95% CI 0.76-100), sensitivity of 89% and specificity of 100%. Subcortical pathology was present in 89% of the dysexecutive MCI converters. EEG did not predict conversion from amnestic MCI to dementia.
Conclusion: This study demonstrates that quantitative EEG using the SPR method predicts conversion from deMCI to dementia disorders with subcortical pathology with high sensitivity and specificity.

Knut Engedal, Lars-Olof Wahlund, Christian Sandøe Musaeu,  Peter Hoegh, Maria Lage Barca, Thorkell Eli Gudmundsson, Birgitte Bo Andersen, Daniel Ferreira, Mala Naik, Anne Rita Oeksengaard, Jon Snaedal

Abstract:

Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer’s disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments capable. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

Ruixue Ai, Xianglu Xiao, Shenglong Deng, Nan Yang, Xiaodan Xing, Leiv Otto Watne, Geir Selbæk, Yehani Wedatilake, Chenglong Xie, David C. Rubinsztein, Jennifer E. Palmer, Bjørn Erik Neerland, Hongming Chen, Zhangming Niu, Guang Yang, Evandro Fei Fang

Abstarct: 

We examined associations between body mass index (BMI), waist circumference (WC), and dementia risk, and differences in BMI and WC trajectories before dementia diagnosis. We included 9,739 participants (54% women) aged 70+ from the Trøndelag Health Study (HUNT4 70+). BMI was measured four times (1984-2019) and WC three times (1995-2019). Dementia diagnoses were clinically assessed at HUNT4 70+ . Women and men with dementia had higher midlife BMI and WC than those without dementia. These differences diminished closer to diagnosis, especially in women. Midlife obesity in both sexes and midlife overweight, high WC, and overweight/obesity with high WC in men were linked to higher dementia risk. Lower dementia risk was observed with late-life overweight for both sexes, late-life high WC in women, late-life overweight/obesity with normal WC in men or high WC in women. Adiposity measures and their changes influence dementia risk differently in women and men.

Ekaterina Zotcheva, Bjørn Heine Strand, Vegard Skirbekk, Kay Deckers, Steinar Krokstad, Gill Livingston, Archana Singh-Manoux, Geir Selbæk

Abstract

Aims: To describe: (i) Experiences of older patients with cancer after receiving an intervention based on geriatric assessment with management. (ii) Experiences of cancer nurses in municipal health care from implementing an intervention based on geriatric assessment with management and their perspectives on the intervention.

Design: A qualitative, descriptive interview study reported according to COREQ.

Methods: The sample comprises five men and three women with cancer, mean age 75 years, and 11 female cancer nurses. Data collection was performed as individual patient interviews, and individual and small group interviews with cancer nurses. Inductive, thematic analysis was performed.

Results: Three main themes were generated: Systematic approach, Patient-centeredness and Regular and professional contact.

Patient or public contribution: Participants did not review transcripts, participate in analysis, or review results. This was not deemed appropriate, as all interviews were analysed as a whole. User representatives participated in the planning and conducting of the intervention study and implementation procedures.

Trial registration: ClinicalTrials.gov Identifier: NCT03881137.

May Ingvild Volungholen Sollid, Line Melby, Marit Slaaen, Grethe Eilertsen, Inga Marie Røyset, Øyvind Kirkevold

Abstarct:

Despite a well-known inverse association between education and dementia risk, the mediating mechanisms are not well understood. We explored how lifestyle and health risk factors across the life-course mediate the relationship between education and dementia among adults aged 70 + years. We included 7,655 participants with dementia diagnoses and education information, using a historical cohort design linking prospective exposure data across the life course from the HUNT4 70 + Study with registry data from Statistics Norway and earlier HUNT surveys. We conducted causal mediation analysis to assess the mediating roles of occupational characteristics, lifestyle factors (smoking, physical inactivity), and health risk factors (obesity, hypertension, diabetes, hearing impairment, cardiovascular diseases, LDL cholesterol, depression, anxiety) assessed during early, middle, and late adulthood in the relationship between education and dementia in later life. Participants with lower education were more likely to have dementia with odds ratios of 1.99, 1.88, 1.83 for the model’s accounting exposure to mediators during early, middle, and late adulthood, respectively. These associations were partially mediated by the joint effect of health and lifestyle risk factors from early through late adulthood (mediated 11.55-19.50%). Health risk factors from early to late adulthood jointly mediated 6.85-13.06% of the effect of low education on dementia risk later in life. Additionally, lifestyle factors during middle and late adulthood jointly mediated 4.11-4.96% of the total effect of low education on dementia risk later in life. Educational differences in dementia risk can partly mediated by lifestyle and health factors across the life course. These findings suggest potential targets to address varying dementia risks linked to education levels.

Teferi Mekonnen, Vegard Skirbekk, Asta Kristine Håberg, Bo Engdahl, Ekaterina Zotcheva, Astanand Jugessur, Catherine Bowen, Geir Selbaek, Hans-Peter Kohler, Jennifer R Harris, Sarah E Tom, Steinar Krokstad, Trine Holt Edwin, Dana Kristjansson, Merete Ellingjord-Dale, Yaakov Stern, Bernt Bratsberg, Bjørn Heine Strand

Abstract

Background: With the anticipated increase in dementia prevalence over the coming decade, understanding the experience of receiving a dementia diagnosis for people living with cognitive impairment remains limited. This study aims to explore the implications of a family member with cognitive impairment receiving a dementia diagnosis or not from the perspective of their next of kin.

Methods: A qualitative descriptive design was applied using individual interviews for data collection. Participants were recruited based on the cognitive function level of their family members, which was compatible with dementia as assessed with the Montreal Cognitive Assessment Scale (MoCA). The sample consisted of eight participants, comprising family members of five individuals with confirmed dementia diagnoses and three undiagnosed. The analysis was performed using four steps of systematic text condensation to discern codes, categories, and the overarching theme.

Results: Three main categories were created: (1) Impact of observed cognitive decline, (2) Impact of diagnosis on service engagement, and (3) Support and follow-up for family caregivers. The findings show that next of kin who have received a dementia diagnosis for their family members are more proactive in seeking help and services, are better informed about available resources, and are more concerned about future challenges. On the other hand, next of kin to family members without a diagnosis are more inclined to handle the situation on their own, have less access to information and services, and generally express less concern about future problems.

Conclusion: The study reveals the benefits of receiving a timely dementia diagnosis in shaping more effective support systems and policies. This ensures that the next of kin and the person with cognitive impairment can navigate the complexities of dementia with greater confidence and preparedness, thereby enhancing their quality of life.

Inger Molvik, Grete Kjelvik, Geir Selbæk & Anne Marie Mork Rokstad

Abstract:

Werner syndrome (WS), caused by mutations in the RecQ helicase WERNER (WRN) gene, is a classical accelerated aging disease with patients suffering from several metabolic dysfunctions without a cure. While, as we previously reported, depleted NAD+ causes accumulation of damaged mitochondria, leading to compromised metabolism, how mitochondrial NAD+ changes in WS and the impact on WS pathologies were unknown. We show that loss of WRN increases senescence in mesenchymal stem cells (MSCs) likely related to dysregulation of metabolic and aging pathways. In line with this, NAD+ augmentation, via supplementation with nicotinamide riboside, reduces senescence and improves mitochondrial metabolic profiles in MSCs with WRN knockout (WRN-/-) and in primary fibroblasts derived from WS patients compared to controls. Moreover, WRN deficiency results in decreased mitochondrial NAD+ (measured indirectly via mitochondrially-expressed PARP activity), and altered expression of key salvage pathway enzymes, including NMNAT1 and NAMPT; ChIP-seq data analysis unveils a potential co-regulatory axis between WRN and the NMNATs, likely important for chromatin stability and DNA metabolism. However, restoration of mitochondrial or cellular NAD+ is not sufficient to reinstall cellular proliferation in immortalized cells with siRNA-mediated knockdown of WRN, highlighting an indispensable role of WRN in proliferation even in an NAD+ affluent environment. Further cell and animal studies are needed to deepen our understanding of the underlying mechanisms, facilitating related drug development.

Sofie Lautrup, Shi-Qi Zhang, Shinichiro Funayama, Lisa Lirussi, Tina Visnovska, Hoi-Hung Cheung, Marc Niere, Yuyao Tian, Hilde Loge Nilsen, Geir Selbæk, Janna Saarela, Yoshiro Maezawa, Koutaro Yokote, Per Nilsson, Wai-Yee Chan, Hisaya Kato, Mathias Ziegler, Vilhelm A Bohr & Evandro F Fang