Forskningsartikler

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

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