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BackgroundDay care services aim to offer meaningful activities and a safe environment for the attendees and a respite for family caregivers while being cost effective. This study compares the use of formal and informal care in users and non-users of day care centres designed for persons with dementia.MethodUsers of day care designed for dementia (DC group) and non-users (NDC group) were followed over a period of 24 months or until nursing home admission (NHA) respectively death. Demographic and clinical characteristics were collected at baseline and after 12 and 24 months. The use of care was recorded by Resource Utilization in Dementia (RUD).ResultsA total of 257 persons with dementia participated in the study, 181 in the DC group and 76 in the NDC group. Users of day care centres cause higher costs due to the expenses for day care, while neither the use of home nursing, secondary care, informal care nor the time until NHA did show any differences between users and non-users. The overall costs were higher in the DC group at baseline and after 12 months, but this difference was no longer present at the end of the two-year study period.ConclusionOur results indicate no potential cost-saving effect of day care designed for people with dementia, as the use of day care did neither result in a reduced use of care nor in a delay of NHA. Future research should balance the non-monetary benefits of day care against its costs for a full cost-effectiveness analysis, most favourable in a RCT-design.

Objectives: To evaluate the relationships of cognitive function and care dependency with oral health in a Norwegian older adult population., Methods: This cross-sectional study included 2623 participants aged 70 and older from the fourth wave of the Trøndelag health study (HUNT4 70+) and the city of Trondheim (Trondheim 70+). Neurocognitive disorders (NCDs) were diagnosed by clinical experts according to the DSM-5 framework. Care dependency referred to nursing home residency. Oral health was assessed by using the Revised Oral Assessment Guide-Jönköping (ROAG-J). Individuals were considered as 'having oral problem' if the score was two or three in at least one of the nine ROAG-J items. Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs)., Results: The prevalence of having oral problems was 19% higher in participants with NCDs than those with normal cognitive function after adjusting for potential confounders (PR 1.19, 95% CI: 1.09-1.29). Further analysis showed a higher prevalence of having oral problems for home dwellers with NCDs (PR 1.23, 95% CI: 1.13-1.33) and nursing home residents (PR 1.32, 95% CI: 1.20-1.45) compared to home dwellers with normal cognitive function., Conclusions: NCDs were associated with an increased prevalence of oral problems in this Norwegian older adult population. The study suggests the need for increasing oral care for home dwellers with NCDs and nursing home residents., (© 2024 The Author(s). Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)

Objective: The quality of the relationship between persons with dementia and family carers influences health and quality-of-life outcomes. Little is known regarding those at higher risk of experiencing a decline in relationship quality, who could potentially benefit the most from interventions. We aimed to identify these risk profiles and explore the underlying factors., Methods: We applied a latent profile analysis to relationship quality data from a 1-year follow-up of 350 dyads of persons with dementia and their informal carers from the Actifcare cohort in eight European countries. Assessments included sociodemographic, clinical, functional, psychosocial and quality-of-life measures. Relationship quality was assessed with the Positive Affect Index. A discriminant analysis explored factors influencing the risk profiles., Results: There were two relationship quality profiles among persons with dementia (gradually decreasing, 74.0%; low but improving, 26%) and two among carers (steadily poor, 57.7%; consistently positive, 42.3%). The 'gradually decreasing' profile (persons with dementia) was related to their levels of dependence and unmet needs, along with carers' social distress and negative feelings, lower baseline RQ and sense of coherence. The 'steadily poor' profile (carers) was influenced by their social distress and negative feelings, lower sense of coherence and perceived social support. These two predominant profiles showed significant decreases in quality-of-life over one year., Conclusions: Specific profiles of persons with dementia and their carers are at risk of worse relationship quality trajectories. By considering modifiable related factors (e.g., carers' stress), our findings can help develop tailored, effective interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Marques, Woods, Jelley, Kerpershoek, Hopper, Irving, Bieber, Stephan, Sköldunger, Sjölund, Selbaek, Røsvik, Zanetti, Portolani, Marôco, Janssen, Tan, de Vugt, Verhey and Gonçalves-Pereira.)

Background: Frailty in older people is a rising global health concern; therefore, monitoring prevalence estimates and presenting projections of future frailty are important for healthcare planning., Aim: To present current prevalence estimates of frailty and pre-frailty and future projections according to both dominant frailty models in a large population-based observational study including adults ≥ 70 years in Norway., Methods: In this population-based observational study, we included 9956 participants from the HUNT4 70 + study, conducting assessments at field stations, homes, and nursing homes. Frailty was assessed using Fried criteria and a 35-item frailty index (HUNT4-FI). Inverse probability weighting and calibration using post-stratification weights and aggregated register data for Norway according to age, sex, and education ensured representativeness, and population projection models were used to estimate future prevalence., Results: According to Fried criteria, the current prevalence rates of frailty and pre-frailty in people ≥ 70 years were 10.6% and 41.9%, respectively, and for HUNT4-FI 35.8% and 33.2%, respectively. Compared to previous European estimates we identified higher overall frailty prevalence, but lower prevalence in younger age groups. Projections suggest the number of Norwegian older adults living with frailty will close to double by 2040., Conclusion: Frailty in older people in Norway is more prevalent than previous European estimates, emphasising the imperative for effective interventions aimed to delay and postpone frailty and ensure healthcare system sustainability in an ageing population. Future planning should consider the great heterogeneity in health and functioning within the 70 + population., (© 2024. The Author(s).)

Competing Interests: Declaration of interests SA declares grants from the Indian Council for Medical Research (2022–25), the Government of Karnataka (2022–23), Rotary Bangalore Midtown (2022–23), Lowes Services India (2022–25), and Wellcome Trust (2023–26); payment for expert testimony received by Indian Council of Medical Research and Ashoka University; and a travel grant paid by University College London for being part of the Lancet Commission. SB declares grants from National Institute for Health and Care Research (NIHR), Economic and Social Research Council, Engineering and Physical Science Research Council, Canadian Institute for Health Research, the Alzheimer's Association, the Alzheimer's Society, Health Education England, Alzheimer's Association, Alzheimer's Society, and Health Education England. He has held the following positions: Non-Executive Director Somerset NHS Foundation Trust, Trustee of the Alzheimer's Society, Executive Dean of the University of Plymouth, and Pro-Vice Chancellor of the University of Nottingham. AB acts as a consultant for Lilly, TauRx Pharmaceuticals, and Eisai and carries out medico–legal work for solicitors. NCF declares consulting fees from F Hoffmann-La Roche, Eli Lilly, Ionis, Biogen, and Siemens; participation in data safety monitoring or advisory board for Biogen; and being a member of the Research Strategy Council for the Alzheimer's Society. LNG declares owning tailored activity programme licences. MK declares grants from Wellcome Trust (221854/Z/20/Z), the Medical Research Council (R024227), the National Institute on Aging (R01AG062553, R01AG056477), and the Academy of Finland (350426). KYL declared fellowship from Medical Research Council. EBL receives grants from the National Institutes of Health (NIH) and royalties from UpToDate. GL declares support for the manuscript from the Alzheimer's Society, the Alzheimer's Society UK, and UK Research and Innovation, who gave grants to pay for travel and accommodation. She is supported by the University College London Hospitals' NIHR Biomedical Research Centre, by North Thames NIHR Applied Research Collaboration, and as an NIHR Senior Investigator and has grants from NIHR Health Technology Assessment, NIHR Programme Grants for Applied Research, the Alzheimer's Association, the Norwegian Research Council, and Wellcome, outside of the submitted work. She works with the Alzheimer's Society as a member of the Research Strategy Council and is a trustee of Nightingale Hammerson care homes. KR declares grants from Canadian Institutes of Health Research, the Canadian Frailty Network, and Research Nova Scotia; royalties from Biotest, Qu Biologics, AstraZeneca UK, BioAge Labs, Congenica, Icosavax, KCR, Faraday Pharmaceuticals, Synairgen Research, Enanta Pharmaceuticals, Pfizer, Boehringer Ingelheim International, Fresenius Kabi Deutschland, Baycrest Geriatric Care, and Shanghai Ark Biopharmaceutical; payment or honoraria from University of British Columbia, Fraser Health Authority, McMaster University, Chinese Medical Association, Wake Forest University Medical School Centre, University of Omaha, and Atria Institute; participation on data safety or advisory board for EpiPharma; and leadership of the Canadian Consortium on Neurodegeneration in Dementia, Cap Breton University, and Nova Scotia Health. KS declares support from the Japan Society for the Promotion of Science fund (22H03352, 21KK0168, 16KK0059). LSS declares support from Della Martin Foundation, the NIH (P30 AG066530, R01 AG051346, R01 AG062687, R01 AG051346, R01 AG055444, P01 AG052350, R01 AG053267, R01 AG074983, R01 AG063826), Abbott, Biohaven, Biogen, Eisai, and Eli Lilly and consulting fees from AC Immune, Cortexyme, Alpha-cognition, BioVie, Athira, Eli Lilly/Avid, Corium, Lundbeck, Merck, Muna Therapeutics, Novo-Nordisk, Neurim, NeuroDiagnostics, Ono, Otsuka, Roche/Genentech, Cognition, Lighthouse, GW Research, ImmunoBrain, and Bristol Myers Squibb. AS declares grants from Wellcome Trust, the Alzheimer's Association, Brain Canada, and the NIHR. YY declares support from the National Natural Science Foundation of China (72374013) and the National Key R&D Program of China (2023YFB4603200, 2023YFC3606400). SW declares an NIHR doctoral training fellowship. GS has participated on advisory boards for the following pharmaceutical companies manufacturing drugs against Alzheimer's disease: Biogen, Roche, and Eisai. LG is an inventor of a training program for health and human service professionals in an evidence-based tailored activity intervention, the Tailored Activity Program; she and her respective universities are entitled to fees. All other authors declare no competing interests.

Background: High blood pressure and poor cardiorespiratory fitness are independent risk factors for dementia. However, few studies have examined if combined longitudinal patterns of these modifiable risk factors are associated with dementia risk., Methods: In this prospective cohort study, we used data from the population-based Trøndelag Health (HUNT) Study, Norway. We applied group-based multidimensional trajectory modeling to identify age-specific multidimensional trajectories of SBP, DBP, and estimated cardiorespiratory fitness across 3 surveys (HUNT1, 1984-1986 to HUNT3, 2006-2008). Dementia was diagnosed in the HUNT4 70+ substudy in 2017-2019. We used multivariate logistic regression to estimate odds ratios (ORs) and risk differences (RDs) of dementia., Results: In total, 7 594 participants (54.9% women) were included, with a mean age of 44.7 (SD 6.3) years at HUNT1. Dementia was diagnosed in 1 062 (14.0%) participants. We identified 2 multidimensional trajectories throughout adulthood within 3 age groups: one with higher systolic blood pressure (SBP) and diastolic blood pressure (DBP), and lower estimated cardiorespiratory fitness (the poorer group), and one with lower SBP and DBP, and higher cardiorespiratory fitness (the better group). After adjustment for sex, apolipoprotein E ε4 status, education, marital status, and diabetes, the better group had consistently lower risk of dementia in all age groups with the lowest OR in the middle-aged group of 0.63 (95% confidence intervals [95% CI]: 0.51, 0.78) with corresponding RD of -0.07 (95% CI: -0.10, -0.04)., Conclusions: Having a beneficial multidimensional trajectory of SBP, DBP, and cardiorespiratory fitness in adulthood was associated with reduced dementia risk. Aiming for optimal SBP, DBP, and estimated cardiorespiratory fitness throughout adulthood may reduce dementia risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Abstract: Treatment of chronic pain in patients with dementia is challenging because they have reduced ability to report pain and are particularly vulnerable to side effects of analgesics. Different types of music-based therapy have been recommended and are used as an alternative to analgesics, but the evidence is lacking. Therefore, we performed a cluster-randomized controlled study (RCT) to reduce pain intensity using music-based caregiving (MBC) over 8 weeks in nursing home patients with dementia and chronic pain. We also investigated if the amount of MBC and different chronic pain syndromes would impact on the effect. Of the 645 patients, 498 patients from 36 wards in 12 nursing homes were screened for dementia and pain. Using the Clinical Dementia Rating Scale and the Mobilization-Observation-Behavior-Intensity-Dementia Pain Scale (range 0-10), 279 (71% females, 42% severe dementia) nursing home patients were randomized to intervention group (n = 134, 18 wards) or control group (n = 145, 18 wards). The main outcome was change in pain intensity before and after the intervention. The study did not reveal any effect of MBC on pain intensity when compared with the control group (B = -0.15, 95% CI [-0.72 to 0.43]). No significant difference was found within the intervention group analyzing the impact of intervention time (B = 0.73, 95% CI [-0.55 to 2.02]) or chronic primary vs secondary pain syndromes (B = 0.45, 95% CI [-0.05 to 0.96]). Our data from this first RCT on music and pain intensity in patients with dementia and chronic pain did not find an effect of MBC on pain., (Copyright © 2024 International Association for the Study of Pain.)

Background/aims: The number of patients suffering from cognitive decline and dementia increases, and new possible treatments are being developed. Thus, the need for time efficient and cost-effective methods to facilitate an early diagnosis and prediction of future cognitive decline in patients with early cognitive symptoms is becoming increasingly important. The aim of this study was to evaluate whether an MRI based software, NeuroQuant® (NQ), producing volumetry of the hippocampus and whole brain volume (WBV) could predict: (1) conversion from subjective cognitive decline (SCD) at baseline to mild cognitive impairment (MCI) or dementia at follow-up, and from MCI at baseline to dementia at follow-up and (2) progression of cognitive and functional decline defined as an annual increase in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score., Methods: MRI was performed in 156 patients with SCD or MCI from the memory clinic at Oslo University Hospital (OUH) that had been assessed with NQ and had a clinical follow-up examination. Logistic and linear regression analyses were performed with hippocampus volume and WBV as independent variables, and conversion or progression as dependent variables, adjusting for demographic and other relevant covariates including Mini-Mental State Examination-Norwegian Revised Version score (MMSE-NR) and Apolipoprotein E ɛ4 ( APOE ɛ4) carrier status., Results: Hippocampus volume, but not WBV, was associated with conversion to MCI or dementia, but neither were associated with conversion when adjusting for MMSE-NR. Both hippocampus volume and WBV were associated with progression as measured by the annual change in CDR-SB score in both unadjusted and adjusted analyses., Conclusion: The results indicate that automated regional MRI volumetry of the hippocampus and WBV can be useful in predicting further cognitive decline in patients with early cognitive symptoms., Competing Interests: KP, TE, and A-BK report work with Roche BN29553 trial; KP and A-BK report work with Novo Nordisk NN6535-4730 trial; TE and A-BK report work with Boehringer-Ingelheim 1346.0023 trial; outside the submitted work. GS reports participation in advisory board meetings for Biogen and Roche regarding new disease-modifying therapies for Alzheimer’s disease. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Amland, Selbæk, Brækhus, Edwin, Engedal, Knapskog, Olsrud and Persson.)

Background: Changes in alcohol consumption may affect older adults' health. We examined prevalence and changes in the alcohol consumption of older women and men (≥65 years) in Norway over a 24-year period., Methods: Data from three population-based health surveys (The Trøndelag Health Study-HUNT2 1995-97, HUNT3 2006-08, HUNT4 2017-19) were used. Alcohol consumption was measured using self-reported measures and an objective measure of alcohol consumption (Phosphatidylethanol 16:0/18:1, PEth). Self-reported lifetime abstinence, former drinking, current drinking, frequent drinking (≥4 times/week), and risk drinking (≥8 units/week) were measured. The PEth concentrations were stratified: <0.03 μmol/l (abstinence/very low level of alcohol consumption); >0.06 μmol/l (indicating >1 unit/day); >0.10 μmol/l (indicating >3 units/day), and >0.30 μmol/l (heavy alcohol consumption)., Results: In HUNT4, the prevalence of self-reported lifetime abstinence, frequent drinking, and risk drinking was 5.2%, 4.4%, and 5.6%, respectively, while prevalence of PEth <0.03 μmol/l was 68.1% and PEth >0.06 μmol/l was 21.2%. Over the course of the three surveys, the prevalence of self-reported lifetime abstinence decreased, while the prevalence of frequent drinking and risk drinking increased. Men were less often abstainers and more often frequent and risky drinkers than women in all three surveys. Gender differences for abstinence and current drinking reduced with time. From HUNT3 to HUNT4, the prevalence of PEth <0.03 μmol/l decreased, while the prevalence of PEth >0.06 μmol/l increased. Men compared to women, had less often PEth <0.03 μmol/l and more often PEth >0.06 and >0.10 μmol/l in HUNT3 and HUNT4. Women and men ≥75 years were just as likely to have PEth >0.30 μmol/l in HUNT4. The gender differences in PEth concentrations were reduced in HUNT4 among those aged 70-74 years or ≥75 years., Conclusion: Alcohol consumption has increased among Norwegian older adults over a 24-year period, but at a slower pace during the last decade., Competing Interests: The authors have declared that no competing interest exist., (Copyright: © 2024 Tevik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes., Methods: Genome-wide association meta-analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P)., Results: AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations., Discussion: AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development., Highlights: It has long been known that psychotic and affective symptoms are often comorbid in individuals diagnosed with Alzheimer's disease. Here we examined for the first time the genetic architecture underlying this clinical observation, determining that psychotic and affective phenotypes in Alzheimer's disease are genetically correlated.Nevertheless, psychotic and affective phenotypes in Alzheimer's disease diverged in their genetic correlations with psychiatric phenotypes assessed in individuals without Alzheimer's disease. Psychosis in Alzheimer's disease was negatively genetically correlated with bipolar disorder and positively with depressive symptoms, whereas the affective phenotypes in Alzheimer's disease were positively correlated with anxiety disorder and more strongly correlated than psychosis with depressive symptoms.Psychosis in Alzheimer's disease, and the joint psychotic and affective phenotype, had significant estimated heritability, whereas the affective in AD did not.Examination of the loci most strongly associated with the psychotic, affective, or joint phenotypes revealed overlapping and unique associations., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information., (© 2024 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background and Objectives: The cognitive reserve hypothesis posits that cognitively stimulating work delays the onset of mild cognitive impairment (MCI) and dementia. However, the effect of occupational cognitive demands across midlife on the risk of these conditions is unclear., Methods: Using a cohort study design, we evaluated the association between registry-based trajectories of occupational cognitive demands from ages 30-65 years and clinically diagnosed MCI and dementia in participants in the HUNT4 70+ Study (2017-19). Group-based trajectory modeling identified trajectories of occupational cognitive demands, measured by the routine task intensity (RTI) index (lower RTI indicates more cognitively demanding occupation) from the Occupational Information Network. Multinomial regression was implemented to estimate the relative risk ratios (RRRs) of MCI and dementia, after adjusting for age, sex, education, income, baseline hypertension, obesity, diabetes, psychiatric impairment, hearing impairment, loneliness, smoking status, and physical inactivity assessed at HUNT1-2 in 1984-1986 and 1995-1997. To handle missing data, we used inverse probability weighting to account for nonparticipation in cognitive testing and multiple imputation., Results: Based on longitudinal RTI scores for 305 unique occupations, 4 RTI trajectory groups were identified (n = 7,003, 49.8% women, age range 69-104 years): low RTI (n = 1,431, 20.4%), intermediate-low RTI (n = 1,578, 22.5%), intermediate-high RTI (n = 2,601, 37.1%), and high RTI (n = 1,393, 19.9%). Participants in the high RTI group had a higher risk of MCI (RRR 1.74, 95% CI 1.41-2.14) and dementia (RRR 1.37, 95% CI 1.01-1.86), after adjusting for age, sex, and education compared with participants in the low RTI group. In a sensitivity analysis, controlling for income and baseline health-related factors, the point estimates were not appreciably changed (RRR 1.66, 95% CI 1.35-2.06 for MCI, and RRR 1.31, 95% CI 0.96-1.78 for dementia)., Discussion: People with a history of cognitively stimulating occupations during their 30s, 40s, 50s, and 60s had a lower risk of MCI and dementia older than 70 years, highlighting the importance of occupational cognitive stimulation during midlife for maintaining cognitive function in old age. Further research is required to pinpoint the specific occupational cognitive demands that are most advantageous for maintaining later-life cognitive function.

Deep learning approaches for clinical predictions based on magnetic resonance imaging data have shown great promise as a translational technology for diagnosis and prognosis in neurological disorders, but its clinical impact has been limited. This is partially attributed to the opaqueness of deep learning models, causing insufficient understanding of what underlies their decisions. To overcome this, we trained convolutional neural networks on structural brain scans to differentiate dementia patients from healthy controls, and applied layerwise relevance propagation to procure individual-level explanations of the model predictions. Through extensive validations we demonstrate that deviations recognized by the model corroborate existing knowledge of structural brain aberrations in dementia. By employing the explainable dementia classifier in a longitudinal dataset of patients with mild cognitive impairment, we show that the spatially rich explanations complement the model prediction when forecasting transition to dementia and help characterize the biological manifestation of disease in the individual brain. Overall, our work exemplifies the clinical potential of explainable artificial intelligence in precision medicine., (© 2024. The Author(s).)

Background: Older adults and people with dementia were anticipated to be particularly unable to use health and care services during the lockdown period following the COVID-19 pandemic. To better prepare for future pandemics, we aimed to investigate whether the use of health and care services changed during the pandemic and whether those at older ages and/or dementia experienced a higher degree of change than that observed by their counterparts., Methods: Data from the Norwegian Trøndelag Health Study (HUNT4 70 + , 2017-2019) were linked to two national health registries that have individual-level data on the use of primary and specialist health and care services. A multilevel mixed-effects linear regression model was used to calculate changes in the use of services from 18 months before the lockdown, (12 March 2020) to 18 months after the lockdown., Results: The study sample included 10,607 participants, 54% were women and 11% had dementia. The mean age was 76 years (SD: 5.7, range: 68-102 years). A decrease in primary health and care service use, except for contact with general practitioners (GPs), was observed during the lockdown period for people with dementia (p < 0.001) and those aged ≥ 80 years without dementia (p = 0.006), compared to the 6-month period before the lockdown. The use of specialist health services decreased during the lockdown period for all groups (p ≤ 0.011), except for those aged < 80 years with dementia. Service use reached levels comparable to pre-pandemic data within one year after the lockdown., Conclusion: Older adults experienced an immediate reduction in the use of health and care services, other than GP contacts, during the first wave of the COVID-19 pandemic. Within primary care services, people with dementia demonstrated a more pronounced reduction than that observed in people without dementia; otherwise, the variations related to age and dementia status were small. Both groups returned to services levels similar to those during the pre-pandemic period within one year after the lockdown. The increase in GP contacts may indicate a need to reallocate resources to primary health services during future pandemics., Trial Registration: The study is registered at ClinicalTrials.gov, with the identification number NCT04792086., (© 2024. The Author(s).)

Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the 2 nations. The inaugural Norway-UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Nursing home (NH) residents are in their last phase of life, and two aims of the NH's medical care in Norway is to prevent unnecessary hospital admissions that would not benefit the resident and to facilitate a peaceful death in familiar surroundings when the time comes. However, little is known about the share of residents dying in NHs and the causes of death. We therefore evaluated the cause and place of death in a cohort of NH residents followed from the time of NH admission until death., Methods: NH residents were followed from admission to the NH and over the entire course of their NH stay. Demographic and clinical data were collected. Cause and place of death were retrieved from the Norwegian Cause of Death Registry., Results: Of 1283 residents, 6.2% died in hospital and 91.2% in a NH. Those who died in hospitals were more often male, died sooner after NH admission, had a less severe degree of dementia and had poorer general health. Dementia was the most common underlying cause of death, followed by cardiovascular disease., Conclusions: Dementia is one of the main causes of death in NH residents. In addition, our findings indicate a low number of inappropriate referrals to hospital during the last stage of life. However, further research should explore whether the terminal phase of NH residents is formed in accordance with their preferences and whether appropriate palliative care is offered., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background and Purpose: The aims were to compare the novel regional brain volumetric measures derived by the automatic software NeuroQuant (NQ) with clinically used visual rating scales of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal (GCA-f), and posterior atrophy (PA) brain regions, assessing their diagnostic validity, and to explore if combining automatic and visual methods would increase diagnostic prediction accuracy., Methods: Brain magnetic resonance imaging (MRI) examinations from 86 patients with subjective and mild cognitive impairment (i.e., non-dementia, n = 41) and dementia (n = 45) from the Memory Clinic at Oslo University Hospital were assessed using NQ volumetry and with visual rating scales. Correlations, receiver operating characteristic analyses calculating area under the curves (AUCs) for diagnostic accuracy, and logistic regression analyses were performed., Results: The correlations between NQ volumetrics and visual ratings of corresponding regions were generally high between NQ hippocampi/temporal volumes and MTA (r = -0.72/-0.65) and between NQ frontal volume and GCA-f (r = -0.62) but lower between NQ parietal/occipital volumes and PA (r = -0.49/-0.37). AUCs of each region, separating non-dementia from dementia, were generally comparable between the two methods, except that NQ hippocampi volume did substantially better than visual MTA (AUC = 0.80 vs. 0.69). Combining both MRI methods increased only the explained variance of the diagnostic prediction substantially regarding the posterior brain region., Conclusions: The findings of this study encourage the use of regional automatic volumetry in locations lacking neuroradiologists with experience in the rating of atrophy typical of neurodegenerative diseases, and in primary care settings., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: Although knowledge about the experience of being diagnosed with dementia is limited, with the expected rise in dementia's prevalence in the coming decades, such knowledge is pivotal for the people diagnosed, their families, and healthcare planners. Thus, the aim of our study was to explore the experience of living with cognitive impairment and dementia and the impact of being diagnosed with dementia., Method: A qualitative design was applied. Participants were recruited based on age-adjusted values below ​​threshold values on the Montreal Cognitive Assessment Scale (i.e. 70-79 years, < 22; 80-89 years, < 21; 90 + years, < 20), and the sample ultimately included 15 participants: six with and nine without a documented dementia diagnosis. Qualitative content analysis was performed on the transcribed interviews in four steps to identify codes, categories, and the overall theme., Results: Three major categories emerged from the interviews: (1) experiences with changes, (2) experiences with being diagnosed with dementia, and (3) existential experience. All participants with and most participants without a dementia diagnosis experienced changes in cognition., Conclusion: Our findings imply that being diagnosed with dementia is a relief because it explains observed cognitive and functional decreases and reduces confusion, shame and stigma. However, it also raises concerns about an unknown future. Most participants not diagnosed with dementia reported having little or no difficulty with everyday living and leading a fulfilling life. Those findings emphasise the significance of timely versus early diagnosis., (© 2024. The Author(s).)

Background: The mouth is a central organ for communication and fluid intake, also for dying nursing home patients. This study describes the prevalence and severity of oral symptoms from nursing home admission until the day of perceived dying and the day of death., Methods: A prospective, longitudinal cohort study including 696 patients who were admitted to 47 Norwegian nursing homes in 35 municipalities. During the first year of their stay, 189 died (27%), of whom 82 participants were assessed on the day they were perceived as dying and 134 on the day of death. Mouth care, nutrition, and bedsores were assessed with the Residents' Assessment Instrument for nursing homes (RAI-NH) and palliative care (RAI-PC). Pain intensity was assessed with the Mobilization-Observation-Behaviour-Intensity-Dementia-2 Pain Scale (MOBID-2)., Results: The proportion of patients with ≥ 6 oral symptoms increased from 16% when perceived as dying to 20% on the day of death (P = 0.001). On the day of death, xerostomia (66%), dysphagia (59%), and mastication problems (50%) were the most frequently observed oral symptoms. Only 16% received mouth care every hour and 12% were in pain during this procedure. Compared to people without dementia, those with a diagnosis of dementia at admission (N = 112, 86%) had xerostomia and mastication problems more frequently (50% vs. 73%; 32% vs. 56% (P = 0.038), respectively) on the day of death., Conclusions: The high extent of oral symptoms such as xerostomia, dysphagia, and mastication problems underline the need for systematic assessment and improved oral palliative care for dying nursing home patients with dementia., Trial Registration: Clinicaltrials.gov NCT01920100 08/08/2013. First submission to BMC oral 15/03/2023., (© 2024. The Author(s).)

Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure., Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference., Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness., Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To evaluate the associations between hearing status and hearing aid use and performance on the Montreal Cognitive Assessment (MoCA) in older adults in a cross-sectional study in Norway., Methods: This study utilized data from the fourth wave of the Trøndelag Health Study (HUNT4, 2017-2019). Hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz (or PTA4) in the better hearing ear were used to determine participants' hearing status [normal hearing (PTA4 hearing threshold, ≤ 15 dB), or slight (PTA4, 16-25 dB), mild (PTA4, 26-40 dB), moderate (PTA4, 41-55 dB), or severe (PTA4, ≥ 56 dB) hearing loss]. Both standard scoring and alternate MoCA scoring for people with hearing loss (deleting MoCA items that rely on auditory function) were used in data analysis. The analysis was adjusted for the confounders age, sex, education, and health covariates., Results: The pattern of results for the alternate scoring was similar to that for standard scoring. Compared with the normal-hearing group, only individuals with moderate or severe hearing loss performed worse in the MoCA. In addition, people with slight hearing loss performed better in the MoCA than those with moderate or severe hearing loss. Within the hearing loss group, hearing aid use was associated with better performance in the MoCA. No interaction was observed between hearing aid use and participants' hearing status with performance on the MoCA test., Conclusion: While hearing loss was associated with poorer performance in the MoCA, hearing aid use was found to be associated with better performance in the MoCA. Future randomized control trials are needed to further examine the efficacy of hearing aid use on the MoCA performance. When compared with standard scoring, the alternate MoCA scoring had no effect on the pattern of results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Moradi, Engdahl, Johannessen, Selbæk, Aarhus and Haanes.)

Background: The Clock Drawing Test (CDT) is used to screen for Alzheimer's disease and other dementia disorders. Normative scores on the version from the Montreal Cognitive Assessment (MoCA) do not exist in the Nordic countries., Objective: To examine the normative scores of the CDT among adults aged 70 years and older., Methods: We included 4,023 cognitively healthy persons aged 70-97 years from a population survey in Norway. They were examined with the CDT, which has a total score between zero and three. A multiple multinominal regression model was applied with a CDT score as the dependent categorical variable and estimated the probabilities of scoring a particular score, stratified by age, sex, and education. These probabilities correspond to an expected proportion of the normative population scoring at, or below a given percentile., Results: None scored zero, 2.1% scored one, 14.9% scored two, and 83% scored three. Higher age, female sex and fewer years of schooling were associated with poorer performance. Scores of zero and one deviated from the normative score regardless of age, sex and education. A score of two was within the norm for a female older than 81 and a male older than 85., Conclusions: The majority (83%) of people 70 years and older had a score of three on the CDT. Lower age, male sex, and higher education were associated with a better performance. Scores of zero and one were below the normative score. Except for the very old, a score of two was also well below the normative score.

Background: More women are living with dementia than men worldwide and there is a need to investigate causes for this female preponderance. While reproductive factors have been investigated as risk factors, the results are conflicting. We aim to clarify this using a large cohort with a long observation time, adjusting for multiple health and lifestyle variables and encompassing a wider range of cognitive impairment., Objective: To study the association between menopause age, menarche age and risk of and risk of mild cognitive impairment (MCI) and dementia., Setting: The Trøndelag Health study (HUNT), a longitudinal population health study in Norway (1984-2019)., Participants: Women who were ≥70 years in 2017-2019 were assessed for cognitive impairment., Measurements: Data on menopause age and menarche age were obtained from questionnaires. Diagnosis of MCI or dementia was set using a standardised procedure by a diagnostic group of nine physicians. Multinomial logistic regression was used to study the association between menopause age, menarche age and risk of MCI and dementia with adjustment for birth year, education, smoking, ApoE4, number of children, diabetes, body mass index, alcohol use and physical inactivity., Results: We evaluated 5314 women where 900 (16.9%) had dementia, and 1747 (32.8%) had MCI. Multiple adjusted relative risk ratio (RRR) and 95% confidence intervals (CI) for dementia were: 0.96(95%CI 0.95-0.98) (p<0.001) for menopause age, 0.97(95%CI 0.94-0.99) (p=0.007) for natural menopause age (excluding hysterectomy and/or oophorectomyp<55 years) and 0.97(95%CI 0.95-0.99) (pp<0.001) for reproductive span (menopause age minus menarche age). Menopause age p<45years was associated with a 56% higher risk compared to mean menopause age 50 years. We found no significant associations between menarche age and dementia and no associations with MCI., Conclusions: Older menopause age and longer reproductive span corresponding to longer oestrogen exposure were associated with a lower dementia risk. Future studies should explore therapeutical options to offset this risk in women., Competing Interests: Geir Selbæk has participated at advisory boards for Biogen and Roche pharmaceutical companies, with disease-modifying therapy in Alzheimer’s disease as subject.

Background: A timely diagnosis of dementia can be beneficial for providing good support, treatment, and care, but the diagnostic rate remains unknown and is probably low., Objective: To determine the dementia diagnostic rate and to describe factors associated with diagnosed dementia., Methods: This registry linkage study linked information on research-based study diagnoses of all-cause dementia and subtypes of dementias, Alzheimer's disease, and related dementias, in 1,525 participants from a cross-sectional population-based study (HUNT4 70+) to dementia registry diagnoses in both primary-care and hospital registries. Factors associated with dementia were analyzed with multiple logistic regression., Results: Among those with research-based dementia study diagnoses in HUNT4 70+, 35.6% had a dementia registry diagnosis in the health registries. The diagnostic rate in registry diagnoses was 19.8% among home-dwellers and 66.0% among nursing home residents. Of those with a study diagnosis of Alzheimer's disease, 35.8% (95% confidence interval (CI) 32.6-39.0) had a registry diagnosis; for those with a study diagnosis of vascular dementia, the rate was 25.8% (95% CI 19.2-33.3) and for Lewy body dementias and frontotemporal dementia, the diagnosis rate was 63.0% (95% CI 48.7-75.7) and 60.0% (95% CI 43.3-75.1), respectively. Factors associated with having a registry diagnosis included dementia in the family, not being in the youngest or oldest age group, higher education, more severe cognitive decline, and greater need for help with activities of daily living., Conclusions: Undiagnosed dementia is common, as only one-third of those with dementia are diagnosed. Diagnoses appear to be made at a late stage of dementia.

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., Funding: The Norwegian National Centre for Ageing and Health with a grant from Health South-East., Competing Interests: SGC has in the last 36 months received grants for research in dementia prevention, including by treating hearing loss, from UK NIHR, grant for dementia risk assessment from Dunhill Medical Trust—UK Charity, and grant for research in dementia prevention, including by treating hearing loss, from Alzheimer’s Research UK—Charity. FL has in the last 36 months received research grants pertaining to hearing loss from National Institutes of Health, research grants pertaining to hearing loss from Eleanor Schwartz Charitable Foundation, consulting fees as consultant on topics related to hearing loss from Frequency Therapeutics and Apple Inc., personal fees as expert witness for the plaintiff in a class action lawsuit against an insurance company in Washington state pertaining to litigation relating to the insurance company’s policy of non-coverage for hearing aids, is a scientific advisory board member for Fondation Pour L’Audition, is a scientific advisory board member (possible stock options pending continued role on the SAB), is a volunteer board of the nonprofit AccessHears, received donation in-kind from Sonova to Johns Hopkins University for hearing technologies used in the NIH-funded ACHIEVE trial, and is director of a public health research center funded in part by a philanthropic donation from Cochlear Ltd., to the Johns Hopkins Bloomberg School of Public Health. GL has since the initial planning of the work received payment made to the institutions University College London Hospitals’ National Institute for Health Research (NIHR), and Biomedical Research Centre, North Thames NIHR Applied Research Collaboration, and as an NIHR Senior Investigator to support academics to work. GS has participated in advisory boards for Biogen, Eisai and Roche concerning antidementia drugs. All other authors declare no competing interests., (© 2023 The Authors.)

Introduction: There is a pressing need for non-invasive, cost-effective tools for early detection of Alzheimer's disease (AD)., Methods: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), Cox proportional models were conducted to develop a multimodal hazard score (MHS) combining age, a polygenic hazard score (PHS), brain atrophy, and memory to predict conversion from mild cognitive impairment (MCI) to dementia. Power calculations estimated required clinical trial sample sizes after hypothetical enrichment using the MHS. Cox regression determined predicted age of onset for AD pathology from the PHS., Results: The MHS predicted conversion from MCI to dementia (hazard ratio for 80th versus 20th percentile: 27.03). Models suggest that application of the MHS could reduce clinical trial sample sizes by 67%. The PHS alone predicted age of onset of amyloid and tau., Discussion: The MHS may improve early detection of AD for use in memory clinics or for clinical trial enrichment., Highlights: A multimodal hazard score (MHS) combined age, genetics, brain atrophy, and memory. The MHS predicted time to conversion from mild cognitive impairment to dementia. MHS reduced hypothetical Alzheimer's disease (AD) clinical trial sample sizes by 67%. A polygenic hazard score predicted age of onset of AD neuropathology., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: There is lack of research on combinations of possible modifiable risk factors for dementia in a life-time perspective. Dementia has currently no cure, and therefore new knowledge of preventive factors is important. The purpose of this study is to investigate if changes in physical activity (PA) in combinations with systolic blood pressure (SBP) trajectories in mid to late life are related to development of dementia in older age., Methods: This prospective cohort study uses data from four consecutive surveys of the HUNT Study, Norway. Dementia was assessed in the HUNT4 70 + sub-study (2017-19). Group-based trajectory modelling identified three SBP trajectories from HUNT1 (1984-86) to HUNT3 (2006-2008): low, middle, and high. Change in PA was categorized into four groups based on high or low PA level at HUNT1 and HUNT3 and were combined with the SBP trajectories resulting in 12 distinct categories. Logistic regression was used to estimate odds ratios (ORs) of dementia., Results: A total of 8487 participants (55% women, mean age (SD) 44.8 (6.5) years at HUNT1) were included. At HUNT4 70 + , 15.2% had dementia. We observed an overall decrease in OR of dementia across the PA/SBP categories when ranked from low to high PA (OR, 0.96; 95% CI, 0.93 to 1.00, P = 0.04). Within PA groups, a low SBP trajectory was associated with lower OR for dementia, apart from those with decreasing PA. The strongest association was observed for people with stable high PA and low SBP trajectory (OR, 0.38; 95% confidence interval (CI), 0.13 to 1.10 and adjusted risk difference, -8.34 percentage points; 95% CI, -15.32 to -1.36)., Conclusion: Our findings illustrate the clinical importance of PA and SBP for dementia prevention and that favorable levels of both are associated with reduced occurrence of dementia., (© 2023. European Group for Research into Elderly and Physical Activity (EGRIPA).)

The aging population and increasing evidence of the detrimental health impacts of loneliness emphasize the importance of studying and predicting changes in loneliness prevalence among older adults. To understand and project changes in loneliness over time, we examined 35-year trends in adults aged 70 and older, considering factors such as sex, age, and living situation. Cross-sectional data from 27,032 home-dwelling adults aged 70 years and older who participated in at least one of the four Norwegian HUNT surveys from 1984 to 2019, and Norwegian population data from Statistics Norway were used for the analyses. Loneliness was self-reported, and the prevalence of loneliness was standardized to the Norwegian population at the survey year by age and sex. The results showed that the prevalence of loneliness significantly decreased between each survey. The higher categories of loneliness (a good amount, very much) decreased, from 11.4% (1995-97), 6.7% (2006-08), and 5.8% (2017-19). Across surveys, loneliness was significantly more common among women, the oldest, and those living alone. The prevalence of loneliness among the oldest adults living alone increased from 2006 to 2019. The gradual decline in loneliness observed from 1995 to 2019 coincided with notable societal changes in Norway. We estimated that the number of older adults experiencing loneliness in Norway could rise from 184,000 in 2020 to 286,000 in 2035, and potentially reach 380,000 in 2050., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Malnutrition is common in older adults and is associated with increased morbidity and mortality rates., Aim: The aim of the study is to describe the prevalence of malnutrition based on low BMI, involuntary weight loss, and reduced food intake, in a Norwegian population of community-dwelling older adults and older adults living in nursing homes., Methods: This population-based study is part of the fourth wave of the Trøndelag Health Study (HUNT4) and includes participants ≥70 years from the HUNT4 70+ cohort. The HUNT4 70+ cohort consist of 9930 (response rate 51.2%) participants. In the current study 8127 older people had complete dataset for inclusion in the analyses. Participants completed a self-report questionnaire and standardised interviews and clinical assessments at field stations, in participants' homes or at nursing homes. Malnutrition was defined using the following criteria: low BMI, involuntary weight loss and severely reduced food intake. The standardised prevalence of malnutrition was estimated using inverse probability weighting (IPW) with weights for sex, age and education of the total population in the catchment area of HUNT., Results: Of the 8127 included participants, 7671 (94.4%) met at field stations, 356 (4.4%) were examined in their home, and 100 (1.2%) in nursing homes. In total, 14.3% of the population were malnourished based on either low BMI, weight loss, or reduced food intake, of which low BMI was the most frequently fulfilled criterion. The prevalence of malnutrition was less common among men than among women (10.1 vs 18.0%, p < 0.001), also after adjustment for age (OR 0.53, 95% confidence interval (CI) 0.46-0.61). The prevalence increased gradually with increasing age and the regression analysis adjusted for sex showed that for each year increase in age the prevalence of malnutrition increased with 4.0% (OR 1.04, 95% CI 1.03-1.05). The prevalence was higher both among older adults examined in their homes (26.4%) and residents in nursing home (23.6%), as compared to community-dwelling older adults who met at field stations (13.5%)., Conclusion: The prevalence of malnutrition is high in the older population. Special attention on prevention and treatment of malnutrition should be given to older women, the oldest age groups, and care-dependent community-dwelling older adults and nursing home residents., Competing Interests: Declaration of competing interest HKS is a board member in NOEN AS. All other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this study was to assess the diagnostic validity of a deep learning-based method estimating brain age based on magnetic resonance imaging (MRI) and to compare it with volumetrics obtained using NeuroQuant (NQ) in a clinical cohort. Brain age prediction was performed on minimally processed MRI data using deep convolutional neural networks and an independent training set. The brain age gap (difference between chronological and biological age) was calculated, and volumetrics were performed in 110 patients with dementia (Alzheimer's disease, frontotemporal dementia (FTD), and dementia with Lewy bodies), and 122 with non-dementia (subjective and mild cognitive impairment). Area-under-the-curve (AUC) based on receiver operating characteristics and logistic regression analyses were performed. The mean age was 67.1 (9.5) years and 48.7% (113) were females. The dementia versus non-dementia sensitivity and specificity of the volumetric measures exceeded 80% and yielded higher AUCs compared to BAG. The explained variance of the prediction of diagnostic stage increased when BAG was added to the volumetrics. Further, BAG separated patients with FTD from other dementia etiologies with > 80% sensitivity and specificity. NQ volumetrics outperformed BAG in terms of diagnostic discriminatory power but the two methods provided complementary information, and BAG discriminated FTD from other dementia etiologies., (© 2023. Springer Nature Limited.)

Background: High levels of occupational physical activity (PA) have been linked to an increased risk of dementia. We assessed the association of trajectories of occupational PA at ages 33-65 with risk of dementia and mild cognitive impairment (MCI) at ages 70+., Methods: We included 7005 participants (49.8% were women, 3488/7005) from the HUNT4 70+ Study. Group-based trajectory modelling was used to identify four trajectories of occupational PA based on national registry data from 1960 to 2014: stable low (30.9%, 2162/7005), increasing then decreasing (8.9%, 625/7005), stable intermediate (25.1%, 1755/7005), and stable high (35.2%, 2463/7005). Dementia and MCI were clinically assessed in 2017-2019. We performed adjusted multinomial regression to estimate relative risk ratios (RRR) with 95% confidence intervals (CI) for dementia and MCI., Findings: 902 participants were diagnosed with dementia and 2407 were diagnosed with MCI. Absolute unadjusted risks for dementia and MCI were 8.8% (95% CI: 7.6-10.0) and 27.4% (25.5-29.3), respectively, for those with a stable low PA trajectory, 8.2% (6.0-10.4) and 33.3% (29.6-37.0) for those with increasing, then decreasing PA; while they were 16.0% (14.3-17.7) and 35% (32.8-37.2) for those with stable intermediate, and 15.4% (14.0-16.8) and 40.2% (38.3-42.1) for those with stable high PA trajectories. In the adjusted model, participants with a stable high trajectory had a higher risk of dementia (RRR 1.34, 1.04-1.73) and MCI (1.80, 1.54-2.11), whereas participants with a stable intermediate trajectory had a higher risk of MCI (1.36, 1.15-1.61) compared to the stable low trajectory. While not statistically significant, participants with increasing then decreasing occupational PA had a 24% lower risk of dementia and 18% higher risk of MCI than the stable low PA group., Interpretation: Consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment, indicating the importance of developing strategies for individuals in physically demanding occupations to prevent cognitive impairment., Funding: This work was supported by the National Institutes of Health (R01AG069109-01) and the Research Council of Norway (296297, 262700, 288083)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 The Author(s).)

Background: Previous population-based, longitudinal studies have shown that delirium is associated with an increased risk of dementia and cognitive decline. However, the underlying biological mechanisms are largely unknown. We aimed to assess the effects of delirium on both cognitive trajectories and any neuronal injury, measured via neurofilament light chain (NfL)., Methods: In this analysis of a prospective, 2-year follow-up, cohort study of participants aged 65 years or older living in Sandefjord municipality, Norway, we included cohort participants who were receiving domiciliary care services at least once per week between May 12, 2015, and July 8, 2016. Individuals with a life expectancy of less than 1 week, with Lewy body dementia, with psychiatric illness (except dementia), or for whom substance misuse was the principal indication for domiciliary services were excluded. Participants had a comprehensive assessment at 6-month intervals for 2 years, which included the Montreal Cognitive Assessment (MoCA) and a blood sample for NfL to measure neuronal injury. All information on clinical diagnoses and medications were cross-referenced with medical records. During any acute change in mental status or hospitalisation (ie, admission to hospital), participants were assessed once per day for delirium with Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria. We also measured NfL from blood samples taken from participants who were acutely hospitalised., Findings: Between May 12, 2015, and July 8, 2016, 210 participants were eligible for inclusion and assessed at baseline (138 [66%] of whom were female and 72 [34%] of whom were male), 203 completed cognitive assessment, and 141 were followed up for 2 years. 160 (76%) of 210 had moderate or severe frailty and 112 (53%) were living with dementia. During the 2-year follow-up, 89 (42%) of 210 participants were diagnosed with one or more episodes of delirium. Incident delirium was independently associated with a decrease in MoCA score at the next 6-month follow-up, even after adjustment for age, sex, education, previous MoCA score, and frailty (adjusted mean difference -1·5, 95% CI -2·9 to -0·1). We found an interaction between previous MoCA score and delirium (β -0·254, 95% CI -0·441 to -0·066, p=0·010), with the largest decline being observed in people with better baseline cognition. Participants with delirium and good previous cognitive function and participants with a high peak concentration of NfL during any hospitalisation had increased NfL at the next 6-month follow-up. Mediation analyses showed independent pathways from previous MoCA score to follow-up MoCA score with contributions from incident delirium (-1·7, 95% CI -2·8 to -0·6) and from previous NfL to follow-up MoCA score with contributions from acute NfL concentrations (-1·8, -2·5 to -1·1). Delirium was directly linked with a predicted value of 1·2 pg/mL (95% CI 1·02 to 1·40, p=0·029) increase in NfL., Interpretation: In people aged 65 years or older, an episode of delirium was associated with a decline in MoCA score. Greater neuronal injury during acute illness and delirium, measured by NfL, was associated with greater cognitive decline. For clinicians, our finding of delirium associated with both signs of acute neuronal injury, measured via NfL, and cognitive decline is important regarding the risk of long-term cognitive deterioration and to acknowledge that delirium is harmful for the brain., Funding: South-Eastern Norway Health Authorities, Old Age Psychiatry Research Network, Telemark Hospital Trust, Vestfold Hospital Trust, and Norwegian National Centre for Ageing and Health., Translation: For the Norwegian translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests HZ has been on scientific advisory boards for AbbVie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; been a consultant for Red Abbey Labs; and has given lectures in symposia sponsored by Fujirebio, Alzecure, Cellectricon, Biogen, and Roche. HZ is a co-founder of Brain Biomarker Solutions in Gothenburg, Sweden, part of the University of Gothenburg Ventures Incubator Program. GS has participated in an advisory board for anti-dementia drugs for Roche and Biogen. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Despite evidence suggesting that insomnia is associated with the risk of dementia and cognitive dysfunction, studies have shown mixed results. Dementia has a long prodromal phase, and studies with long follow-up are required to avoid reverse causality. In our 11-year follow-up study, we assessed whether probable insomnia disorder (PID) based on diagnostic criteria, and insomnia symptoms were associated with risk of all-cause dementia, Alzheimer's disease (AD) and cognition, measured with the Montreal Cognitive Assessment scale. We also examined if Apolipoprotein E genotype modified any associations with dementia through interaction. We analysed data from 7492 participants in the Norwegian Trøndelag Health Study. PID was not associated with all-cause dementia (odds ratio = 1.03, 95% confidence interval = 0.74-1.43), AD (odds ratio = 1.07, 95% confidence interval = 0.71-1.60) or Montreal Cognitive Assessment score (regression coefficient = 0.37, 95% confidence interval = -0.06 to 0.80). The insomnia symptom "difficulties maintaining sleep" was associated with a lower risk of all-cause dementia (odds ratio = 0.81, 95% confidence interval = 0.67-0.98), AD (odds ratio = 0.73, 95% confidence interval = 0.57-0.93), and better Montreal Cognitive Assessment score, mean 0.40 units (95% confidence interval = 0.15-0.64). No interaction with Apolipoprotein E genotype was found. PID and insomnia symptoms did not increase the risk of dementia in our study. More research with longer follow-up is needed, and future studies should explore if the associations to dementia risk vary across insomnia subtypes., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Objectives: Dementia is a major healthcare challenge; however, there is evidence that modifiable risk factors may contribute to reduce dementia risk. The aim of the study was to explore the knowledge and motivation for adopting recommended health behaviours among older adults in Norway., Study Design: The study has a qualitative, descriptive design., Methods: Individual interviews were used for data collection. The study population comprised 15 participants, five men and 10 women, aged ≥73 years, recruited from a region in the centre of Norway. Interviews were analysed according to qualitative content analysis., Results: Three categories were identified and presented as the main findings, as follows: (1) sufficient knowledge about risk reduction for dementia, including the media as the main source of information; (2) current prevention activities and motivation for risk reduction, including physical, social and cognitive activities and a healthy diet; and (3) motivation for prevention of dementia from a life-course perspective, including experience of health problems, desire to live independently and limited awareness of dementia risk factors in midlife., Conclusions: To tailor information about the modifiable risk factors of dementia and develop preventive interventions, knowledge about motivating factors is essential. Promotion of healthy ageing is required in addition to addressing the fear of future illness and dependency., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Earlier studies suggest that being married in later life protects against dementia, and that being single in old age increases the risk of dementia. In this study, we examine midlife marital status trajectories and their association with dementia and mild cognitive impairment (MCI) at ages 70 plus using a large population based sample from Norway. Methods: Based on a general population sample linked to population registries ( N = 8706), we used multinomial logistic regression to examine the associations between six types of marital trajectories (unmarried, continuously divorced, intermittently divorced, widowed, continuously married, intermittently married) between age 44 and 68 years from national registries and a clinical dementia or a MCI diagnosis after age 70. We estimated relative risk ratios (RRR) and used mediation analyses adjusting for education, number of children, smoking, hypertension, obesity, physical inactivity, diabetes, mental distress, and having no close friends in midlife. Inverse probability weighting and multiple imputations were applied. The population attributable fraction was estimated to assess the potential reduction in dementia cases due to marital histories. Results: Overall, 11.6% of the participants were diagnosed with dementia and 35.3% with MCI. Dementia prevalence was lowest among the continuously married (11.2%). Adjusting for confounders, the risk of dementia was higher for the unmarried (RRR = 1.73; 95% CI: 1.24, 2.40), continuously divorced (RRR = 1.66; 95% CI: 1.14, 2.43), and intermittently divorced (RRR = 1.50; 95% CI: 1.09, 2.06) compared to the continuously married. In general, marital trajectory was less associated with MCI than with dementia. In the counterfactual scenario, where all participants had the same risk of receiving a dementia diagnosis as the continuously married group, there would be 6.0% fewer dementia cases. Discussion: Our data confirm that staying married in midlife is associated with a lower risk of dementia and that divorced people account for a substantial share of dementia cases.

Background and Purpose: The declining incidence of stroke, ischaemic heart disease (IHD) and dementia (the 'triple threat') in Norway encourages further investigation. The risks and trends of the three conditions were analysed using data from the Global Burden of Disease study., Methods: Global Burden of Disease 2019 estimations were used for age-, sex- and risk-factor-specific incidence and prevalence of the 'triple threat', their risk-factor-attributed deaths and disability combined, their age-standardized rates per 100,000 population in 2019 and their changes during 1990-2019. Data are presented as means and 95% uncertainty intervals., Results: In 2019, 71.1 thousand Norwegians were living with dementia, 157.2 thousand with IHD and 95.2 thousand with stroke. In 2019, there were 9.9 thousand (8.5 to 11.3) new cases of dementia (35.0% increase since 1990), 17.0 thousand (14.6 to 19.6) with IHD (3.6% decrease) and 8.0 thousand (7.0 to 9.1) with stroke (12.9% decrease) in Norway. During 1990-2019, their age-standardized incidence rates decreased significantly-dementia by -5.4% (-8.4% to -3.2%), IHD by -30.0% (-31.4% to -28.6%) and stroke by -35.3% (-38.3% to -32.2%). There were significant declines in the attributable risks to both environmental and behavioural factors in Norway, but contradictory trends for metabolic risk factors during 1990-2019., Conclusions: The risk of the 'triple threat' conditions is declining in Norway, despite the increased prevalence. This offers the opportunity to find out why and how and to accelerate their joint prevention through new approaches and the promotion of the National Brain Health Strategy., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Research shows that retirement age is associated with later-life cognition but has not sufficiently distinguished between retirement pathways. We examined how retirement age was associated with later-life dementia and mild cognitive impairment (MCI) for people who retired via the disability pathway (received a disability pension prior to old-age pension eligibility) and those who retired via the standard pathway., Methods: The study sample comprised 7210 participants from the Norwegian Trøndelag Health Study (HUNT4 70+, 2017-2019) who had worked for at least one year in 1967-2019, worked until age 55+, and retired before HUNT4. Dementia and MCI were clinically assessed in HUNT4 70+ when participants were aged 69-85 years. Historical data on participants' retirement age and pathway were retrieved from population registers. We used multinomial regression to assess the dementia/MCI risk for women and men retiring via the disability pathway, or early (<67 years), on-time (age 67, old-age pension eligibility) or late (age 68+) via the standard pathway., Results: In our study sample, 9.5% had dementia, 35.3% had MCI, and 28.1% retired via the disability pathway. The disability retirement group had an elevated risk of dementia compared to the on-time standard retirement group (relative risk ratio [RRR]: 1.64, 95% CI 1.14-2.37 for women, 1.70, 95% CI 1.17-2.48 for men). MCI risk was lower among men who retired late versus on-time (RRR, 0.76, 95% CI 0.61-0.95)., Conclusion: Disability retirees should be monitored more closely, and preventive policies should be considered to minimize the dementia risk observed among this group of retirees., (© 2023 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Background: Neuroinflammation is involved in the pathophysiology of Alzheimer's disease (AD), including immune-linked genetic variants and molecular pathways, microglia and astrocytes. Multiple Sclerosis (MS) is a chronic, immune-mediated disease with genetic and environmental risk factors and neuropathological features. There are clinical and pathobiological similarities between AD and MS. Here, we investigated shared genetic susceptibility between AD and MS to identify putative pathological mechanisms shared between neurodegeneration and the immune system., Methods: We analysed GWAS data for late-onset AD (N cases = 64,549, N controls = 634,442) and MS (N cases = 14,802, N controls = 26,703). Gaussian causal mixture modelling (MiXeR) was applied to characterise the genetic architecture and overlap between AD and MS. Local genetic correlation was investigated with Local Analysis of [co]Variant Association (LAVA). The conjunctional false discovery rate (conjFDR) framework was used to identify the specific shared genetic loci, for which functional annotation was conducted with FUMA and Open Targets., Results: MiXeR analysis showed comparable polygenicities for AD and MS (approximately 1800 trait-influencing variants) and genetic overlap with 20% of shared trait-influencing variants despite negligible genetic correlation (rg = 0.03), suggesting mixed directions of genetic effects across shared variants. conjFDR analysis identified 16 shared genetic loci, with 8 having concordant direction of effects in AD and MS. Annotated genes in shared loci were enriched in molecular signalling pathways involved in inflammation and the structural organisation of neurons., Conclusions: Despite low global genetic correlation, the current results provide evidence for polygenic overlap between AD and MS. The shared loci between AD and MS were enriched in pathways involved in inflammation and neurodegeneration, highlighting new opportunities for future investigation., Competing Interests: Declaration of Competing Interest O.A.A. has received speaker's honorarium from Janssen, Sunovion and Lundbeck and is a consultant for cortechs.ai, Milken and Biogen. Dr. Dale is a Founder of and holds equity in CorTechs Labs, Inc., and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc. The terms of these arrangements have been reviewed and approved by UCSD in accordance with its conflict of interest policies. Geir Selbæk has received honoraria as a participant at advisory board meetings for Roche and Biogen. Remaining authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The number of people with dementia is expected to triple by 2050. We present figures showing the prevalence of dementia and mild cognitive impairment in Trondheim, and show how weighting for non-response and nursing home residency affects these figures when comparing Trondheim with Nord-Trøndelag., Material and Method: In the fourth data collection in the Trøndelag Health Study (HUNT4) in the Norwegian county of Trøndelag, people aged 70 and over in Trondheim were invited to participate in HUNT4 Trondheim 70+. The participants were interviewed and underwent cognitive testing. A diagnostic team diagnosed dementia and mild cognitive impairment. Weights adjusting for non-response bias were used in the comparison of Trondheim and Nord-Trøndelag., Results: The prevalence of dementia in Trondheim was estimated at 16.2 % for the age group 70 years and over, after weighting for non-response bias with regard to age, sex, education and proportion of nursing home residents. Unadjusted dementia prevalence was 21.0 % in Trondheim and 15.7 % in Nord-Trøndelag. After weighting, the prevalence was almost identical in the two samples., Interpretation: Weighting for non-response is crucial for obtaining representative figures in prevalence studies of dementia.

Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785., (© 2023. The Author(s).)

Background: Studies exploring the possible protective effect of coffee and tea consumption on dementia have shown inconsistent results so far. We aimed to investigate whether consumption of tea and different types of coffee at midlife are associated with dementia later in life and whether sex or ApoE4 influence such association., Methods: We included 7381 participants from the Norwegian HUNT Study. Self-reported questionnaires assessed daily consumption of coffee and tea at baseline. After 22 years, individuals 70 years or older were screened for cognitive impairment., Results: General coffee consumption and tea consumption was not associated with dementia risk. Compared to daily consumption of 0-1 cups of coffee, daily consumption of ≥8 cups of boiled coffee was associated with increased dementia risk in women (OR: 1.83, 95% CI: 1.10-3.04, p -value for trend = 0.03) and daily consumption of 4-5 cups of other types of coffee was associated with a decrease in dementia risk in men (OR: 0.48, 95% CI: 0.32-0.72, p -value for trend = 0.05). Furthermore, the association between boiled coffee and increased dementia risk was only found in ApoE4 non-carriers. Differences by sex or ApoE4 carrier status were not supported by strong statistical evidence for interaction. Tea consumption was not associated with dementia risk., Conclusion: type of coffee may play a role in the direction of the association between coffee-drinking habits and dementia later in life.