Managing depressive symptoms in people with mild cognitive impairment and mild dementia with a multicomponent psychotherapy intervention: a randomized controlled trial.

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.

Behavioural disturbances in patients with frontotemporal lobe degeneration focusing on caregiver burden at home and in nursing homes.

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) http://www.equator-network.org/reporting-guidelines/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.

The effect of psychosocial support on caregivers' perceived criticism and emotional over-involvement of persons with dementia: an assessor-blinded randomized controlled trial.

BACKGROUND: Many relatives of close family members suffering from dementia have taken on the caregiver role. While intervention studies have revealed promising results on caregiver burden, distress, and depression, there is a lack of knowledge about how caregivers' perceived relationship with their ill family member influences the burden of care. This study examined whether a psychosocial intervention influenced this perceived relationship from the caregivers' perspective. We also explored whether the caregivers' perception of the care receiver's attitude and behavior changed over time, and whether caregiver stress and mood differed following the intervention. METHODS: The participating caregivers and care receivers were randomly assigned to a psychosocial intervention comprising education about dementia, counselling and group sessions, or to treatment as usual. The study investigated caregivers' experience of expressed emotion using the Felt Expressed Emotion Rating Scale (FEERS), a self-report questionnaire that captures caregivers' perception of criticism (CC) and emotional over-involvement (EOI) exhibited by the family members with dementia. RESULTS: A total of 208 dyads were enrolled in the study. There were no significant differences between the intervention and control groups in the studied variables. Caregivers' perception of CC and EOI was low but fluctuated somewhat, whereas their mood and stress level were stable during the follow-up period. CONCLUSIONS: According to the FEERS, the intervention did not influence caregivers' perception of CC and EOI, and there was no difference between the intervention and control groups regarding caregivers' perceived relationship. Despite the increased symptoms of dementia, caregivers' level of distress and mood remained stable, and they seemed to maintain a positive perception of the quality of their relationship with the care receiver. TRIAL REGISTRATION: Clinical.Trials.gov Sept. 2009, NCT01287767.

Music Therapy and Physical Activity to Ease Anxiety, Restlessness, Irritability, and Aggression in Individuals With Dementia With Signs of Frontotemporal Lobe Degeneration.

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.].

The coping experiences of spouses of persons with dementia.

AIMS AND OBJECTIVES: To explore how spouses who are caregivers to persons with dementia experience everyday life 6-12 months after participation in the intervention condition in the Norwegian Cognitive Behavioural Therapy for Early Dementia (N-CORDIAL) study. BACKGROUND: There is no current medical curative treatment for cognitive impairment and dementia-associated conditions. These conditions will lead to an increased need for daily assistance and care, as well as greater stress for caregivers. The Norwegian CORDIAL Study is a manual-based randomised controlled trial based on the German CORDIAL study (cognitive rehabilitation and cognitive behavioural treatment for early dementia in Alzheimer's disease), consisting of cognitive rehabilitation, cognitive behavioural therapy and life review methods. DESIGN AND METHODS: A descriptive exploratory study with qualitative semi-structured in-depth interviews with six spouses of persons with dementia who had participated in the Norwegian CORDIAL study. The transcribed text was analysed by systematic text condensation. RESULT: The main theme identified, "An everyday search for meaning," referred to the stress experienced by the caregivers and their coping strategies in everyday life. CONCLUSION: The caregivers had gained increased awareness of coping strategies in everyday life 6-12 months after the intervention. Caregivers who experienced fewer neuropsychiatric symptoms in their spouses with dementia benefitted most from the intervention. RELEVANCE TO CLINICAL PRACTICE: The study is relevant to clinical practice as interventions focusing on how to improve coping strategies may reduce caregiver stress and contribute to postponement of nursing home placement.

Dignity in people with frontotemporal dementia and similar disorders - a qualitative study of the perspective of family caregivers.

BACKGROUND: Frontotemporal dementia (FTD) constitutes on average 10-15% of dementia in younger persons (≤65 years old), but can also affect older people. These patients demonstrate a decline in social conduct, and/or language aphasias, apathy, and loss of insight that is gradual and progressive. Preservation of dignity seems to be highly relevant both before and after admission to different types of institutionalized care, but the research is scant. From the perspective of close relatives, this study aims to develop knowledge related to dignified or undignified care of patients with FTD and similar conditions. METHODS: A qualitative, descriptive, and explorative design were employed to address the aims of this study. We interviewed nine relatives of people with FTD and similar conditions living in nursing homes, and two relatives of people living at home but attending day center 5 days a week. RESULTS: Relatives described the transition from being a close relative to someone who had little influence or knowledge of what constituted the care and the daily life of their loved ones. According to relatives' descriptions, patients are deprived of dignity in various ways: through limited interaction with peers and close relatives, limited confirmation of identity through staff who know them well, lack of possibilities for making autonomous decisions or entertaining meaningful roles or activities. Examples provided from the day care centres show how dignity is maintained through identity-strengthening activities conducted in different places, under various kinds of supervision and care, and together with people representing different roles and functions. CONCLUSIONS: Maintaining a link with the world outside the institution, through closer cooperation between the institution and family members, and/or by the use of day care centres, seems to facilitate prevention of many of the factors that may threaten dignified care.

Polygenic Overlap Between C-Reactive Protein, Plasma Lipids, and Alzheimer Disease.

BACKGROUND: Epidemiological findings suggest a relationship between Alzheimer disease (AD), inflammation, and dyslipidemia, although the nature of this relationship is not well understood. We investigated whether this phenotypic association arises from a shared genetic basis. METHODS AND RESULTS: Using summary statistics (P values and odds ratios) from genome-wide association studies of >200 000 individuals, we investigated overlap in single-nucleotide polymorphisms associated with clinically diagnosed AD and C-reactive protein (CRP), triglycerides, and high- and low-density lipoprotein levels. We found up to 50-fold enrichment of AD single-nucleotide polymorphisms for different levels of association with C-reactive protein, low-density lipoprotein, high-density lipoprotein, and triglyceride single-nucleotide polymorphisms using a false discovery rate threshold <0.05. By conditioning on polymorphisms associated with the 4 phenotypes, we identified 55 loci associated with increased AD risk. We then conducted a meta-analysis of these 55 variants across 4 independent AD cohorts (total: n=29 054 AD cases and 114 824 healthy controls) and discovered 2 genome-wide significant variants on chromosome 4 (rs13113697; closest gene, HS3ST1; odds ratio=1.07; 95% confidence interval=1.05-1.11; P=2.86×10(-8)) and chromosome 10 (rs7920721; closest gene, ECHDC3; odds ratio=1.07; 95% confidence interval=1.04-1.11; P=3.38×10(-8)). We also found that gene expression of HS3ST1 and ECHDC3 was altered in AD brains compared with control brains. CONCLUSIONS: We demonstrate genetic overlap between AD, C-reactive protein, and plasma lipids. By conditioning on the genetic association with the cardiovascular phenotypes, we identify novel AD susceptibility loci, including 2 genome-wide significant variants conferring increased risk for AD.

Variant of TREM2 associated with the risk of Alzheimer's disease.

BACKGROUND: Sequence variants, including the ε4 allele of apolipoprotein E, have been associated with the risk of the common late-onset form of Alzheimer's disease. Few rare variants affecting the risk of late-onset Alzheimer's disease have been found. METHODS: We obtained the genome sequences of 2261 Icelanders and identified sequence variants that were likely to affect protein function. We imputed these variants into the genomes of patients with Alzheimer's disease and control participants and then tested for an association with Alzheimer's disease. We performed replication tests using case-control series from the United States, Norway, The Netherlands, and Germany. We also tested for a genetic association with cognitive function in a population of unaffected elderly persons. RESULTS: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P=3.42×10(-10)). The mutation had a frequency of 0.46% in controls 85 years of age or older. We observed the association in additional sample sets (odds ratio, 2.90; 95% CI, 2.16 to 3.91; P=2.1×10(-12) in combined discovery and replication samples). We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers (P=0.003). CONCLUSIONS: Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes. (Funded by the National Institute on Aging and others.).

Caregiver burden in family carers of people with dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVE: To characterise the differences in caregiver distress between carers of people diagnosed with dementia with Lewy bodies (DLB) and people with Alzheimer's disease (AD), with a view to differentiating and improving support for caregivers. METHODS: This study is a part of two larger Norwegian studies, DemVest (n = 265) and The Norwegian Dementia Register (n = 2220), with data from caregivers and people diagnosed with AD (n = 100) and DLB (n = 86) between 2005 and 2013. The average age was 74.9 years (SD = 7.8). Caregiver distress was rated by the Relative Stress Scale. Diagnosis of the person receiving care was based on a comprehensive standardised assessment program (International Classification of Diseases, Revision 10 or Diagnostic and Statistical Manual for Mental Disorders, fourth edition). Additional data collected from people receiving care were neuropsychiatric symptoms, comorbidity and activities of daily living (ADL) score. Linear regression analyses were applied, first unadjusted and then in stepwise-adjusts in addition to descriptive analyses. RESULTS: Caregivers to people with AD (20.2%) and 40% of caregivers for people with DLB experienced moderate or high caregiver burden with an increased risk of psychiatric disorders in the early stage of dementia. High Relative Stress Scale (RSS) total scores in caregivers was significantly associated with neuropsychiatric symptoms (Neuropsychiatric Inventory, p = 0.004) and also with impaired ADL functioning (Rapid Disability Rating Scale-2, p < 0.0005). CONCLUSION: Caregiver distress differed (RSS total, p = 0.005) between people caring for someone with AD (15.0) and those caring for someone with DLB (19.9). These findings have direct implications for the needs and resources that could be available for these individuals and indicate the need for further research into caregiver burden in carers to people with DLB. Copyright © 2016 John Wiley & Sons, Ltd. ETHICS AND DISSEMINATION: Cohorts were ethically approved by the Regional Ethics Committee for Medical Research Ethics in Eastern and Western Norway.

Manual-based cognitive behavioral and cognitive rehabilitation therapy for young-onset dementia: a case report.

There is a growing attention worldwide to young-onset dementia (YOD) and this group's special challenges and needs. The literature on psychosocial interventions for this population is scarce, and little is known about the specific challenges and benefits of working therapeutically with this group of patients. The aim of this study was to explore if a manual-based structured cognitive behavioral/cognitive rehabilitation program would be beneficial for these patients. One case, a 63-year-old woman with YOD, is presented to illustrate how this intervention can be applied to individual patients to manage depressive symptoms in YOD.

Psychosocial interventions in Alzheimer's disease and amnestic mild cognitive impairment: evidence for gender bias in clinical trials.

BACKGROUND: Alzheimer's disease (AD) affects twice as many women as men. Gender differences in symptom profile, living conditions, coping style and response might affect the outcome of psychosocial interventions (PSIs). OBJECTIVES: Our aim was to review gender differences in the available high-quality phase III trials on PSI in AD and amnestic mild cognitive impairment (aMCI) by considering the gender ratio in the investigated samples. DESIGN: Randomized controlled trials published in 2000-2012 were stepwise analyzed by statistically testing the representativeness of the gender ratio and examining reported gender differences. RESULTS: Forty-five studies (62% of 73 studies) reported gender ratios for each subsample and were included. In these studies, females were underrepresented in the control groups. In the 14 studies (19%) reporting analyses of gender differences, women were underrepresented in both intervention and control groups. However, in the six studies (8%) reporting significant gender differences in outcome, gender distribution was in accordance with prevalence rates. CONCLUSION: Current evidence is insufficient for reliable conclusions on gender differences in PSI outcome in AD and aMCI, as 81% of the available clinical trials either not reported the gender ratio of their samples, or underrepresent females. Further research is needed addressing gender differences, and clinical trials should routinely control for gender bias.

Implementation of a multicomponent psychosocial programme for persons with dementia and their families in Norwegian municipalities: experiences from the perspective of healthcare professionals who performed the intervention.

BACKGROUND: A randomised controlled intervention study was conducted in 17 Norwegian municipalities to provide home-dwelling people with dementia and their families with knowledge and skills to cope with the emerging problems and stresses of everyday life. It included training health professionals to carry out the intervention. Since little is known about possible benefits for health professionals of participating in such a study in terms of knowledge and change of practice as well as their views on whether the intervention is useful, we carried out this study. AIM: To investigate the outcome of the study from the perspective of the healthcare professionals who participated in the intervention. METHOD: Interviews with 19 health professionals were performed during 2012, using three focus groups and six individual interviews. The sample was purposive and included informants aged 34-61 years from 13 municipalities. RESULTS: Three main categories emerged: challenges, new knowledge and service development. The category challenges details the challenges connected with professionals' participation in the intervention and how they dealt with them and is described in three subcategories. The category new knowledge demonstrates the knowledge the professionals achieved while conducting the intervention and is described through three subcategories. Service development presented how the informants' experiences could contribute to improve the provision of care and details in one subcategory. CONCLUSION: The results revealed a need for more knowledge among health professionals about the situation of home-dwelling persons with dementia and their families. The study indicated that health professionals must be more aware of these persons' abilities to find their own solutions to their problems. Structured individual interventions as well as group-based interventions in the early stages of dementia and throughout the course of the disorder seem beneficial. There is a need for better collaboration between the specialist health services, GPs and health workers in the municipalities.

Quality of Life and Relationships in Caregivers of People With Dementia. A Gender Perspective.

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.

Patterns of neuropsychiatric sub-syndromes in Brazilian and Norwegian patients with dementia.

BACKGROUND: Neuropsychiatric symptoms (NPS) affect the majority of patients who have dementia. Neuropsychiatric sub-syndromes with symptoms that occur together and have common neurobiological correlates have been identified. There are scarce data regarding the comparison of the pattern of the neuropsychiatric sub-syndromes in distinct ethnical and cultural populations. We aim at comparing the pattern of the NPS, and the factor analysis of the Neuropsychiatric Inventory (NPI-10) in two samples of outpatients with dementia living in Brazil and Norway. METHODS: This is a cross-sectional study. The sample consists of 168 Brazilian and 155 Norwegian demented patients from psychogeriatric facilities and community-based educational programs. Brazilian patients were diagnosed with Alzheimer's disease (63.7%), vascular dementia (15.5%), or mixed dementia (20.8%), whereas the diagnoses of Norwegian patients were Alzheimer's disease (97.4%) and mixed dementia (2.6%). Principal component analysis with the Varimax rotation was used for factor analysis of the NPI-10. RESULTS: Apathy (80.4 %), agitation/aggression (45.8%), and aberrant motor behavior (45.8%) were the most common symptoms in the Brazilian sample. Apathy (72.3%), dysphoria (61.9%), and anxiety (52.3%) were the most frequent symptoms in the Norwegian sample. Factor analysis of the NPI-10 revealed three syndromes for the Brazilian (Psychosis, Mood, Psychomotor) and Norwegian (Psychosis, Mood, Frontal) groups. CONCLUSIONS: The frequency of individual NPS may differ among distinct populations. However, Psychosis and Depression are common sub-syndromes in diverse ethnical and cultural patients with dementia. Our findings support the syndromic approach for the clinical assessment of the patients with dementia.

The effect of coping on the burden in family carers of persons with dementia.

OBJECTIVES: This study explores the association between coping, measured by the extent of locus of control, and the burden of care on family carers of persons with dementia (PWD). METHOD: Two hundred thirty PWD living at home and their family carers were recruited from 20 Norwegian municipalities. The carers' burden was assessed by the Relatives' Stress Scale (RSS) and coping by the Locus of Control Behaviour Scale. The PWD were assessed by the Neuropsychiatric Inventory (NPI-Q), the Physical Self-Maintenance Scale (PSMS), the Instrumental Activities of Daily Living (IADL) scale, and the Mini Mental Status Examination (MMSE). RESULTS: Locus of control (LoC) was found to be the most important factor associated with the burden on carers of PWD, even when we had controlled for the PWD variables, such as the NPI-Q score. The LoC and the carer's use of hours per day to assist the PWD were the only two variables the carers found that affected the extent of the burden. The NPI-Q was the most important variable in the PWD that affected the burden on the carers. CONCLUSION: Carers who believe that what happens to them is the consequence of their own actions are likely to be less burdened than carers not expecting to have control. This finding gives a possibility to identify carers with a high risk of burden.

The quality of life of people with dementia and their family carers.

BACKGROUND: We aimed to identify factors associated with the quality of life (QoL) of 'persons with dementia' (PWDs) and their family carers. METHOD: Two-hundred and thirty dyads of PWDs and their family carers were included. The PWDs were assessed with the Neuropsychiatric Inventory (NPI-Q), two Activities of Daily Living (ADL) scales, the Cornell Scale and the QoL-Alzheimer's Disease scale (QoL-AD; self- and proxy-reported scores). The carers were assessed with the QoL-AD and the Geriatric Depression Scale. RESULTS: Factors associated with self-reported QoL were depression (ß = -0.26, p < 0.001) and impaired ADL (ß = -0.26, p < 0.001) and with proxy-rated QoL were NPI (ß = -0.18, p = 0.02), depression (ß = -0.32, p < 0.001) and impaired ADL (ß = -0.43, p < 0.001). Factors associated with QoL in carers living together with the PWDs were depression (ß = -0.56, p < 0.001) and having a hobby (ß = 0.19, p = 0.01), whereas depression was associated with QoL in those who lived separately from the PWD (ß = -0.60, p < 0.001). CONCLUSION: Depression and impaired ADL were associated with the self- and proxy-rated QoL of the PWDs, whereas depression in the carers negatively affected their QoL.

Cohort profile: the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) - a national research and quality registry with a biomaterial collection.

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.

Using Polygenic Hazard Scores to Predict Age at Onset of Alzheimer's Disease in Nordic Populations.

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.

The Memory Clinic--outpatient assessment when dementia is suspected.

The patients who are assessed at Oslo University Hospital's Memory Clinic are young--half of them are under 65 years of age. Most are suffering from mild cognitive impairment or dementia at a very early phase while others come to get a second opinion. The assessment takes 2 - 3 hours and is conducted by a doctor and a nurse. It includes a clinical investigation, cognitive testing, an MRI scan with measurement of the medial temporal lobes, a lumbar puncture and single-photon-emission tomography (SPECT of the brain).

Working Memory Training in Amnestic and Non-amnestic Patients With Mild Cognitive Impairment: Preliminary Findings From Genotype Variants on Training Effects.

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.