Self-reported outcome measures are rarely described in individuals with mild cognitive impairment (MCI). In this study, we investigated the effect of computerized working memory training on self- and relatives reported executive function measures. A total of 50 individuals with MCI were recruited from five memory clinics in Southern Norway and underwent a 5-week/20–25 sessions computerized working memory training program. Both individuals and relatives scored the “Behavior Rating Inventory of Executive Function for Adults” (BRIEF-A) before, and at least four months after finalizing training. Statistical analyses included paired t-tests and mixed ANOVA with rater type (participant/informant) and time (baseline/4-months). Mixed ANOVA revealed significant (adjusted p ≤ 0.025) participant-informant x time interactions for Working Memory, Metacognition Index and Global Executive Composite, suggesting that the changes in ratings over time differed between participants and informants. Post hoc tests revealed that at baseline participants rated themselves as significantly more impaired (adjusted p ≤ 0.036) than informants on the Working Memory scale, the Metacognitive Index and the Global Executive Composite. After training, no significant differences were found between participant and informant reports. After training participants reported significant improvements on Working Memory (adjusted p = 0.038), Metacognition Index (adjusted p = 0.038), with working memory improving from above the established clinically significant impairment threshold to the normal range. The change in Global Executive Composite was not significant after correction for multiple comparisons (adjusted p = 0.057). No significant changes were found for relatives’ reported scores between the two time points. Excluding participants developing dementia during the study enhanced the difference in mean values before and after the intervention for these outcomes. Computerized working memory training significantly improved self-reported executive function in individuals with MCI. While informant reports remained stable, the prior significant discrepancy between self- and informant ratings converged after training due to this improvement. These findings suggest that training can enhance subjective cognitive experience and awareness, offering potential clinical benefits for individuals with MCI. Our study highlights self-report measures as valuable and sensitive outcomes in MCI interventions, capturing the personal experiences of cognitive change. ClinicalTrials.gov, NCT01991405. Registered on 18.11.2013.

Home-dwelling people with dementia rely on their family members to be able to stay at home. This affects the family caregivers’ quality of life (QoL). However, less is known about how male and female caregivers differ in their QoL. Our study aimed to investigate gender differences in caregivers’ quality of life (QoL), whether emotional relationships influence QoL, and how their QoL changes over time. The study applied a cross-sectional and a longitudinal design to examine a total of 208 caregivers, 158 female and 50 male caregivers, and their family member with dementia. Regression analysis and t-tests were performed to identify what characteristics about caregivers and care receivers influence male and female QoL, and whether caregivers’ QoL developed after one year. Both male and female caregivers’ depression influenced their QoL. For females, their own social distress influenced their QoL, and for males, their experience of their care receivers’ overemotional attitude influenced their QoL. From baseline to one-year follow-up their QoL decreased while their distress and experience of care receivers’ emotional attitudes was stable. Significant gender-specific differences were found, indicating that gender must be considered when approving caregivers’ needs and planning interventions for caregivers.

Background: Polygenic hazard scores (PHS) estimate age-dependent genetic risk of late-onset Alzheimer’s disease (AD), but there is limited information about the performance of PHS on real-world data where the population of interest differs from the model development population and part of the model genotypes are missing or need to be imputed. Objective: The aim of this study was to estimate age-dependent risk of late-onset AD using polygenic predictors in Nordic populations. Methods: We used Desikan PHS model, based on Cox proportional hazards assumption, to obtain age-dependent hazard scores for AD from individual genotypes in the Norwegian DemGene cohort ( n = 2,772). We assessed the risk discrimination and calibration of Desikan model and extended it by adding new genotype markers (the Desikan Nordic model). Finally, we evaluated both Desikan and Desikan Nordic models in two independent Danish cohorts: The Copenhagen City Heart Study (CCHS) cohort ( n = 7,643) and The Copenhagen General Population Study (CGPS) cohort ( n = 10,886). Results: We showed a robust prediction efficiency of Desikan model in stratifying AD risk groups in Nordic populations, even when some of the model SNPs were missing or imputed. We attempted to improve Desikan PHS model by adding new SNPs to it, but we still achieved similar risk discrimination and calibration with the extended model. Conclusion: PHS modeling has the potential to guide the timing of treatment initiation based on individual risk profiles and can help enrich clinical trials with people at high risk to AD in Nordic populations.

Purpose The Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) was established to harmonise and improve the quality of diagnostic practice across clinics assessing persons with cognitive symptoms in Norwegian specialist healthcare units and to establish a large research cohort with extensive clinical data.Participants The registry recruits patients who are referred for assessment of cognitive symptoms and suspected dementia at outpatient clinics in Norwegian specialist healthcare units. In total, 18 120 patients have been included in NorCog during the period of 2009–2021. The average age at inclusion was 73.7 years. About half of the patients (46%) were diagnosed with dementia at the baseline assessment, 35% with mild cognitive impairment and 13% with no or subjective cognitive impairment; 7% received other specified diagnoses such as mood disorders.Findings to date All patients have a detailed baseline characterisation involving lifestyle and demographic variables; activities of daily living; caregiver situation; medical history; medication; psychiatric, physical and neurological examinations; neurocognitive testing; blood laboratory work-up; and structural or functional brain imaging. Diagnoses are set according to standardised diagnostic criteria. The research biobank stores DNA and blood samples from 4000 patients as well as cerebrospinal fluid from 800 patients. Data from NorCog have been used in a wide range of research projects evaluating and validating dementia-related assessment tools, and identifying patient characteristics, symptoms, functioning and needs, as well as caregiver burden and requirement of available resources.Future plans The finish date of NorCog was originally in 2029. In 2021, the registry’s legal basis was reformalised and NorCog got approval to collect and keep data for as long as is necessary to achieve the purpose of the registry. In 2022, the registry underwent major changes. Paper-based data collection was replaced with digital registration, and the number of variables collected was reduced. Future plans involve expanding the registry to include patients from primary care centres.

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology. A genome-wide association study performed in 1,126,563 individuals identifies seven new loci associated with Alzheimer’s disease and implicates microglia and immune cells in late-onset disease.

Working memory training (WMT) effects may be modulated by mild cognitive impairment (MCI) subtypes, and variations in APOE -epsilon ( APOE -ε) and LMX1A genotypes. Sixty-one individuals (41 men/20 women, mean age 66 years) diagnosed with MCI (31 amnestic/30 non-amnestic) and genotyped for APOE -ε and LMX1A completed 4 weeks/20–25 sessions of WMT. Cognitive functions were assessed before, 4 weeks and 16 weeks after WMT. Except for Processing Speed, the non-amnestic MCI group (naMCI) outperformed the amnestic MCI (aMCI) group in all cognitive domains across all time-points. At 4 weeks, working memory function improved in both groups ( p < 0.0001), but at 16 weeks the effects only remained in the naMCI group. Better performance was found after training for the naMCI patients with LMX1A -AA genotype and for the APOE -ε4 carriers. Only the naMCI- APOE -ε4 group showed improved Executive Function at 16 weeks. WMT improved working memory and some non-trained cognitive functions in individuals with MCI. The naMCI group had greater training gain than aMCI group, especially in those with LMX1A -AA genotype and among APOE- ε4-carriers. Further research with larger sample sizes for the subgroups and longer follow-up evaluations is warranted.

Aim and objective To explore the challenges faced by family caregivers of people with frontotemporal dementia and other forms of dementia affecting the frontal and temporal lobes causing behavioural disturbances through a qualitative approach with in-depth interviews. Background Studies of different forms of dementia involving degeneration of the frontal and temporal lobes have mainly focused on the neurophysiology and physiology of the disease and on caregivers' health. Few studies have described the challenges and burdens connected with everyday life and in relation to suitable nursing home placement that are faced by family caregivers. Method and design This study used a descriptive and explorative design. Eleven semi-structured interviews with family caregivers of patients from special units in four nursing homes were conducted in 2014. Data were analysed based on Kvale and Brinkmann's three contexts of interpretation: self-understanding, common sense and theoretical understanding. Checklist for qualitative studies: Standards for Reporting Qualitative Research (SRQR) Results Two central themes were derived from the data: changes in behaviour and personality were perceived as incomprehensible, frightening and increasingly difficult to manage. Family caregivers experienced challenges in finding suitable care facilities when they were not able to continue providing home care. Due to behavioural disturbances and lack of relevant competencies among health personnel, family members were often moved between nursing homes. Conclusion Pronounced personality and behavioural disturbances such as tactlessness and aggression in a family member with dementia are experienced by caregivers as stressful and burdensome and may lead to feelings of shame and guilt. A lack of suitable care facilities adds to the stress and difficulties of the families and entails an additional and unresolved burden. Relevance to Clinical Practice The study reveals a need for more knowledge among those organising health services as well as healthcare professional dealing with this patient category to ease the burden on next of kin.

Abstract Objective: To evaluate the feasibility and effectiveness of the CORDIAL program, a psychosocial intervention consisting of cognitive behavioral therapy (CBT), cognitive rehabilitation, and reminiscence to manage depressive symptoms for people with mild cognitive impairment (MCI) or dementia. Design: We conducted a randomized controlled trial, based on a two-group (intervention and control), pre-/post-intervention design. Setting: Participants were recruited from five different old age psychiatry and memory clinics at outpatients’ hospitals. Participants: Hundred and ninety-eight people with MCI or early-stage dementia were included. Intervention: The intervention group (n = 100) received 11 individual weekly sessions of the CORDIAL program. This intervention includes elements from CBT, cognitive rehabilitation, and reminiscence therapy. The control group (n = 98) received treatment-as-usual. Measurements: We assessed Montgomery–Åsberg Depression Rating Scale (MADRS) (main outcome), Neuropsychiatric Inventory Questionnaire, and Quality of Life in Alzheimer’s disease (secondary outcomes) over the course of 4 months and at a 10-month follow-up visit. Results: A linear mixed model demonstrated that the depressive symptoms assessed by MADRS were significantly more reduced in the intervention groups as compared to the control group (p < 0.001). The effect persisted for 6 months after the intervention. No significant differences between groups were found in neuropsychiatric symptoms or quality of life. Conclusion: Our multicomponent intervention, which comprised 11 individual sessions of CBT, cognitive rehabilitation, and reminiscence therapy, reduced depressive symptoms in people with MCI and dementia.

SummaryLate-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases1. Late-onset Alzheimer’s disease is caused by a combination of many genetic variants with small effect sizes and environmental influences. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified2,3. Here we show that increased sample sizes allowed for identification of seven novel genetic loci contributing to Alzheimer’s disease. We highlighted eight potentially causal genes where gene expression changes are likely to explain the association. Human microglia were found as the only cell type where the gene expression pattern was significantly associated with the Alzheimer’s disease association signal. Gene set analysis identified four independent pathways for associated variants to influence disease pathology. Our results support the importance of microglia, amyloid and tau aggregation, and immune response in Alzheimer’s disease. We anticipate that through collaboration the results from this study can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants which contribute to Alzheimer’s pathology. Furthermore, the increased understanding of the mechanisms that mediate the effect of genetic variants on disease progression will help identify potential pathways and gene-sets as targets for drug development.

OBJECTIVES:To examine the mediating effects of depression and anxiety in the relationship between self-efficacy and quality of life among people with mild cognitive impairment (MCI) or mild dementia. METHOD:A total of 196 patients diagnosed with MCI or dementia due to Alzheimer disease completed structured measures of self-efficacy, quality of life, and depressive and anxiety symptoms. We examined direct and mediated effects by fitting structural equation models to data. RESULTS:Our analyses supported that the effects of self-efficacy on quality of life may be partially mediated by depression and anxiety. Both anxiety and depression had significant mediating effects, with depression showing a stronger effect. CONCLUSION:These results suggest that increased self-efficacy may have a positive effect on quality of life in people with MCI or dementia-partly by reducing depression and anxiety. These findings may have important practical implications for tailoring therapeutic interventions.

Background and aim People with dementia depend on a relative to be able to stay at home longer However, being a caregiver has shown to influence on their quality of life (QoL). Depression is the most common factor associated with low caregiver QoL, while relational factors have shown to be a protective factor. Less is known about how female and male caregivers approve to the caregiving demands, and thus how these demands influence their QoL. In this study, we aimed at investigating what factors influenced on QoL related to gender and how these fluctuated with time. Method In this longitudinal design, a total of 208 caregivers, 158 female mean age 62.5 and 50 male caregivers, mean age 67.9 were assessed for Quality of Life-Alzheimer Disease (QoL). In addition, depression, family relationship and caregivers’ burden of care were assessed. Linear regression analyses were applied to explore the bivariate and multivariate associations between the dependent variable QoL and potential explanatory variables. The same questionnaires were completed at one-year follow-up, and the results from the remaining 176 caregivers were compared with their baseline scorings. Results Caregivers’ depressive feelings were the strongest predictors of caregivers’ QoL. What differed in the explained perceived QoL was feeling of social isolation in female caregivers, and male caregivers’ perception of their care receivers’ emotionally overinvolved attitude towards them. Additionally, female caregivers expressed a higher burden and cared for a relative more affected by their dementia. After one year, their QoL declined, more for male than female, while their level of depressive feelings, distress and level of EOI remained unchanged. Conclusion The study revealed that except for depressive feelings, female and male caregivers faced their caring experience, differently. The implication of these findings is that gender must be considered when planning for interventions. While female caregivers might need more time for leisure activities, male caregivers need ways to deal with their emotional relationship with their care receivers. Treatment of their depressive feelings seems to be crucial. They would also need approaches specifically targeting the different stages as dementia develop.

The purpose of the current study was to evaluate whether a combined intervention of physical activity and music therapy could reduce anxiety, restlessness, irritability, and aggression among individuals with severe dementia. An exploratory design was used to evaluate a combined intervention of physical activity, music therapy, and daily walking. Interventions were systematically implemented for 8 weeks. Target groups were individuals with dementia with frontal lobe symptoms in institutional care. Primary outcome measure was the Brøset Violence Checklist (BVC). Four men and two women (mean age = 84.3 years) and their primary caretakers ( n = 6) participated. The most prominent symptoms among participants at baseline were confusion, irritability, and verbal threats. The individual BVC total scores indicated significant improvements ( p = 0.03). Implementation of individualized music therapy combined with increased physical activity for 8 weeks was a feasible intervention that reduced anxiety, restlessness, irritability, and aggression in the current study. [ Journal of Psychosocial Nursing and Mental Health Services, 57 (5), 29–37.]

Objective We investigated if a 5-week computerized adaptive working memory training program (Cogmed®) of 20 to 25 sessions would be effective in improving the working memory capacity and other neuropsychological functions compared to a non-adaptive working memory training program (active-controlled) in adult patients with mild cognitive impairment (MCI). Methods This randomized double-blinded active control trial included 68 individuals aged 43 to 88 years, 45 men and 23 women, who were diagnosed with MCI at four Memory clinics. The study sample was randomized by block randomization to either adaptive or non-adaptive computerized working memory training. All participants completed the training, and were assessed with a comprehensive neuropsychological test battery before the intervention, and at 1 and 4 months after training. Results Compared to the non-adaptive training group, the adaptive training group did not show significantly greater improvement on the main outcome of working memory performance at 1 and 4 months after training. Conclusion No difference were found between the two types of training on the primary outcome of working memory, or on secondary outcomes of cognitive function domains, in this sample of MCI patients. Hence, the hypothesis that the adaptive training program would lead to greater improvements compared to the non-adaptive training program was not supported. Within group analyses was not performed due to the stringent RCT design.

Late onset Alzheimer’s disease (AD) is the most common form of dementia with more than 35 million people affected worldwide, and no curative treatment available. AD is highly heritable and recent genome-wide meta-analyses have identified over 20 genomic loci associated with AD. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci exist. Here, we performed the largest genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 AD cases, 383,378 controls). AD-by-proxy status is based on parental AD diagnosis and showed strong genetic correlation with AD (rg=0.81). Genetic meta-analysis identified 29 risk loci, of which 9 are novel, and implicating 215 potential causative genes. Independent replication further supports these novel loci in AD. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver and microglia). Furthermore, gene-set analyses indicate the genetic contribution of biological mechanisms involved in lipidrelated processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomisation results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying more of the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD to guide new drug development. Main text Alzheimer’s disease (AD) is the most frequent neurodegenerative disease with roughly 35 million people affected.1 Results from twin studies indicate that AD is highly heritable, with estimates ranging between 60 and 80%.2 Genetically, AD can be roughly divided into 2 subgroups: 1) familial

We examined how caregivers experienced the influence of dementia on their relationships with afflicted family members. Family caregivers (n = 15; 11 women and four men; age 39–92 years) of people with dementia participated in semi-structured interviews. The data were analyzed according to Kvale and Brinkman. The analysis identified one overarching theme, experiences of companionship, and four subthemes, namely experiences of loss and loneliness; role change; communication alteration; and caring considerations and coping resources. The caregivers described their companionship with the family member, including warm feelings of reciprocity, as well as contradictory feelings, such as feelings of being burdened. They expressed a desire to continue caring for their relative and emphasized the positive aspects of their relationship. Knowledge about dementia, together with a good relationship with their ill family member, facilitated the caring role. These results highlight the importance of receiving information about dementia-related challenges and the implications of being a caregiver.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.