Trajectories of Occupational Cognitive Demands and Risk of Mild Cognitive Impairment and Dementia in Later Life: The HUNT4 70+ Study.

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.

Marital Histories and Associations With Later-Life Dementia and Mild Cognitive Impairment Risk in the HUNT4 70+ Study in Norway.

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.

Associations Between Intrathecal Levels of Vitamin D, Cytokines, and Core Biomarkers of Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: Several studies have examined association between vitamin D levels in serum and cognition, but little is known of vitamin D levels in cerebrospinal fluid (CSF) and association with Alzheimer's disease (AD). OBJECTIVE: In this cross-sectional, explorative study we investigated possible associations of vitamin D in CSF with biomarkers for AD, amyloid-ß, tau protein/phosphorylated tau protein in CSF, and with the cytokines IL-6, IL-8, and TNF-α in CSF in patients with cognitive impairment and cognitively healthy controls. METHODS: We included 100 outpatients ≥65 years referred for assessment of cognitive impairment and 76 age- and sex-matched cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D), amyloid-ß, tau protein and phosphorylated tau protein, as well as IL-6, IL-8, and TNF-α, were analyzed in CSF in both groups. RESULTS: Higher levels of 25(OH)D in CSF in all groups together were associated with lower levels of tau protein (p = 0.01) and phosphorylated tau protein (p = 0.005). We found no association between 25(OH)D levels in CSF and pathological levels of amyloid-ß in CSF nor levels of IL-6 or TNF-α in CSF. Higher levels of 25(OH)D in CSF were associated with higher levels of IL-8 in CSF (p = 0.002). However, vitamin D explained only 6% of variance in IL-8. There was no significant difference between the patient groups and the control group regarding the association between 25(OH)D in CSF and any of the three cytokines in CSF. CONCLUSION: Participants with higher CSF levels of 25(OH)D exhibited reduced CSF levels of tau protein and phosphorylated tau protein.

Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Postoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status. METHODS AND ANALYSIS: This five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 µg/kg/hour. The infusion rate will be decreased to 0.2 µg/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first.Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery. ETHICS AND DISSEMINATION: This trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05029050.

Deep neural networks learn general and clinically relevant representations of the ageing brain.

The discrepancy between chronological age and the apparent age of the brain based on neuroimaging data - the brain age delta - has emerged as a reliable marker of brain health. With an increasing wealth of data, approaches to tackle heterogeneity in data acquisition are vital. To this end, we compiled raw structural magnetic resonance images into one of the largest and most diverse datasets assembled (n=53542), and trained convolutional neural networks (CNNs) to predict age. We achieved state-of-the-art performance on unseen data from unknown scanners (n=2553), and showed that higher brain age delta is associated with diabetes, alcohol intake and smoking. Using transfer learning, the intermediate representations learned by our model complemented and partly outperformed brain age delta in predicting common brain disorders. Our work shows we can achieve generalizable and biologically plausible brain age predictions using CNNs trained on heterogeneous datasets, and transfer them to clinical use cases.

The Effect of the NorGeP-NH on Quality of Life and Drug Prescriptions in Norwegian Nursing Homes: A Randomized Controlled Trial.

BACKGROUND: The effect of the Norwegian General Practice-Nursing Home (NorGeP-NH) criteria has never been tested on clinical outcomes in nursing home (NH) residents. We performed a cluster-randomized trial in Norwegian NHs and tested the effect of NorGeP-NH on QoL (primary outcome), medication prescriptions, and physical and mental health (secondary outcomes) for the enrolled residents; Methods: Fourteen NHs were randomized into intervention NHs (iNHs) and control NHs (cNHs). After baseline data collection, physicians performed NorGeP-NH on the enrolled residents. We assessed the difference between cNHs and iNHs in the change in primary outcome from baseline to 12 weeks and secondary outcomes from baseline to eight and 12 weeks by linear mixed models; Results: One hundred and eight residents (13 lost to follow-up) and 109 residents (nine lost to follow-up) were randomized to iNHs and cNHs, respectively. Difference in change in QoL at 12 weeks between cNHs and iNHs was not statistically significant (mean (95% CI)): -1.51 (-3.30; 0.28), p = 0.101). We found no significant change in drug prescriptions over time. Difference in depression scores between cNHs and iNHs was statistically significant after 12 weeks. CONCLUSIONS: Our intervention did not affect QoL or drug prescriptions, but reduced depression scores in the iNHs. NorGeP-NH may be a useful tool, but its effect on clinical outcomes may be scarce in NH residents. Further studies about the effectiveness of NorGeP-NH in other healthcare contexts and settings are recommended.

The course of depressive symptoms and mortality in older patients with cancer.

OBJECTIVE: The Geriatric Depression Scale (GDS-15), a self-report questionnaire, emphasizes the psychological dimension of depression. We aimed to investigate whether GDS-15 scores were associated with mortality in older patients with cancer and describe the course of individual symptoms on the GDS-15. METHODS: An observational, multicenter, prospective study of 288 patients 70 years or older with cancer followed over 24 months. The patients were assessed with the GDS-15 at inclusion, and after four and 12 months. An extended Cox regression model assessed the association between time-dependent GDS-15 scores and mortality. RESULTS: After adjusting for cancer-related prognostic factors, a one-point increase in GDS-15 sum score increased risk of death by 12%. GDS-15 mean score increased during the first four months of the study, as did odds for the presence of the GDS-15 symptoms 'feel you have more problems with memory than most', 'not feel full of energy', and 'think that most people are better off than you'. The most prevalent and persistent GDS-15 symptom was 'prefer to stay at home, rather than going out and doing new things', and 'not to be in good spirits most of the time' was the least prevalent. CONCLUSIONS: More severe depressive symptoms, as measured by the GDS-15, were associated with higher mortality in older patients with cancer. The importance of emotional distress and how to alleviate it should be investigated further in these patients.

Physical performance across the cognitive spectrum and between dementia subtypes in a population-based sample of older adults: The HUNT study.

BACKGROUND: Literature on physical performance in older adults across the cognitive spectrum remains inconclusive, and knowledge on differences between dementia subtypes is lacking. We aim to identify distinct physical-performance deficits across the cognitive spectrum and between dementia subtypes. METHODS: 11,466 persons were included from the 70-year-and-older cohort in the fourth wave of the Trøndelag Health Study (HUNT4 70+). Physical performance was assessed with the Short Physical Performance Battery (SPPB), 4-meter gait speed, five-times-sit-to-stand (FTSS), grip strength and one-leg-standing (OLS). Clinical experts diagnosed dementia per DSM-5 criteria. Multiple linear and logistic regression were performed to analyze differences between groups. Age, sex, education, somatic comorbidity, physical activity and smoking status were used as covariates. RESULTS: Gait speed declined across the cognitive spectrum, beginning in people with subjective cognitive decline (SCD). Participants with mild cognitive impairment (MCI) additionally showed reduced lower-limb muscle strength, balance and grip strength. Those with dementia scored lowest on all physical-performance measures. Participants with Alzheimer's disease (AD) had a higher SPPB sum score and faster gait speed than participants with vascular dementia (VaD) and Lewy body dementia (LBD); participants with VaD and LBD had lower odds of being able to perform FTSS and OLS than participants with AD. CONCLUSIONS: Physical performance declined across the spectrum from cognitively healthy to SCD to MCI and to dementia. Participants with AD performed better on all assessments except grip strength than participants with VaD and LBD. Stage of cognitive impairment and dementia subtype should guide exercise interventions to prevent mobility decline and dependency.

Characteristics of patients assessed for cognitive decline in primary healthcare, compared to patients assessed in specialist healthcare.

Objective: The aim of this study was to describe patients assessed for cognitive decline in primary healthcare, compared to patients assessed in specialist healthcare and to examine factors associated with depression.Design: This was an observational study.Setting: Fourteen outpatient clinics and 33 general practitioners and municipality memory teams across Norway.Subjects: A total of 226 patients assessed in primary healthcare and 1595 patients assessed in specialist healthcare outpatient clinics.Main outcome measures: Cornell scale for depression in dementia (CSDD), Mini-Mental Status Examination (MMSE), Clock drawing test, Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Instrumental Activities of Daily Living, Personal Self-Maintenance Scale, Relatives' stress scale (RSS), and Neuropsychiatric Inventory Questionnaire (NPI-Q)Results: Patients assessed in primary healthcare were older (mean age 81.3 vs 73.0 years), less educated, had poorer cognition (MMSE median 22 vs 25), more limitations in activities of daily living (ADL), more behavioural and psychological symptoms of dementia (BPSD), more depressive symptoms (CSDD median 7 vs 5), more often lived alone (60% vs 41%) and were more often diagnosed with dementia (86% vs 47%) compared to patients diagnosed in specialist healthcare. Depression was associated with female gender, older age, more severe decline in cognitive functioning (IQCODE, OR 1.65), higher caregiver burden (RSS, OR 1.10) and with being assessed in primary healthcare (OR 1.53).Conclusion: Post-diagnostic support tailored to patients diagnosed with dementia in primary healthcare should consider their poor cognitive function and limitations in ADL and that these people often live alone, have BPSD and depression.Key pointsPeople diagnosed in Norwegian primary healthcare had more needs than people diagnosed in specialist healthcare. • They were older, less educated, had poorer cognitive functioning and activity limitations, more often lived alone, and had more BPSD and depression. • Depression was associated with being female, older, having cognitive decline, being assessed in primary care and the caregiver experiencing burden • Post diagnostic support for people with dementia should be tailored to the individual's symptoms and needs.

Palliative treatment and care for dying nursing home patients with COVID-19. / Behandling, omsorg og pleie for døende sykehjemspasienter med covid-19.

Frail elderly patients with multimorbidity are at high risk of serious illness and death in cases of corona virus infection. Unlike 'normal deaths' in nursing homes with time to prepare, the condition can change rapidly and cause organ failure. In this article we describe palliative non-invasive and invasive interventions for frail elderly patients in nursing homes who are dying due to COVID-19.

The Association Between Circulating Inflammatory Markers and the Progression of Alzheimer Disease in Norwegian Memory Clinic Patients With Mild Cognitive Impairment or Dementia.

OBJECTIVE: Neuroinflammation may play an important role in the pathogenesis and progression of Alzheimer disease (AD). The aim of the present study was to detect whether increased inflammatory activity at baseline could predict cognitive and functional decline in patients with amnestic mild cognitive impairment (aMCI) or AD dementia after 2 years. METHODS: Serum samples from 242 memory clinic patients with an aMCI (n=88) or AD dementia (n=154) were analyzed for C-reactive protein and for 14 other inflammatory markers [interleukin (IL)-1ß, interleukin-1 receptor antagonist, IL-6, IL-10, IL-12p40, IL-17a, IL-18, IL-22, IL-33, tumor necrosis factor, cluster of differentiation 40 ligand, interferon-γ, chemokine ligand (CCL) 2, and CCL4] by bead-based multiplex immunoassay. Disease progression was measured by the annual increase in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) and annual decrease in the score on the Mini-Mental State Examination (MMSE). RESULTS: No association between increased levels of the inflammatory markers and change on the CDR-SB or MMSE score was found, but there was a significant difference in baseline IL-6 and interleukin-1 receptor antagonist levels between aMCI and AD dementia groups. CONCLUSION: Increased levels of inflammatory markers were not associated with faster progression as measured by the annual change on the CDR-SB or MMSE score.

Modifiable factors affecting older patients' quality of life and physical function during cancer treatment.

BACKGROUND: Maintaining physical function and quality of life (QoL) are prioritized outcomes among older adults. We aimed to identify potentially modifiable factors affecting older patients' physical function and QoL during cancer treatment. METHODS: Prospective, multicenter study of 307 patients with cancer ≥70 years, referred for systemic treatment. Pre-treatment, a modified geriatric assessment (mGA) was performed, including registration of comorbidities, medications, nutritional status, cognitive function, depressive symptoms (Geriatric Depression Scale-15 [GDS]), and mobility (Timed Up and Go [TUG]). Patient-reported physical function (PF)-, global QoL-, and symptom scores were assessed at baseline, two, four, and six months by the EORTC Quality of Life Core Questionnaire-C30. The impact of mGA components and symptoms on patients' PF and global QoL scores during six months was investigated by linear mixed models. To identify groups following distinct PF trajectories, a growth mixture model was estimated. RESULTS: 288 patients were eligible, mean age was 76.9 years, 68% received palliative treatment. Higher GDS-scores and poorer TUG were independently associated with an overall level of poorer PF and global QoL throughout follow-up, as were more pain, dyspnea, and appetite loss, and sleep disturbance. Three groups with distinct PF trajectories were identified: a poor group exhibiting a non-linear statistically (p < .001) and clinically significant decline (≥10 points), an intermediate group with a statistically (p = .003), but not clinically significant linear decline, and a good group with a stable trajectory. Higher GDS-scores and poorer TUG, more pre-treatment pain and dyspnea were associated with higher odds of belonging to the poor compared to the good PF group. CONCLUSION: Depressive symptoms, reduced mobility, and more physical symptoms increased the risk of decrements in older patients' PF and global QoL scores during cancer treatment, and represent potential targets for interventions aiming at improving these outcomes.

Factors associated with alcohol consumption and prescribed drugs with addiction potential among older women and men - the Nord-Trøndelag health study (HUNT2 and HUNT3), Norway, a population-based longitudinal study.

BACKGROUND: Little is known about factors associated with alcohol consumption and use of drugs with addiction potential in older adults. The aim of this study was to explore the association between socio-demographic variables, physical and mental health and the later (11 years) use of frequent drinking, prescribed drugs with addiction potential and the possible combination of frequent drinking and being prescribed drugs with addiction potential in older adults (≥ 65 years). METHODS: In this longitudinal study, we used data from two surveys of the Nord-Trøndelag Health Study (HUNT2 1995-1997 and HUNT3 2006-2008), a population based study in Norway. We totally included 10,656 individuals (5683 women) aged 54 years and older when they participated in HUNT2. Frequent drinking was defined as drinking alcohol 4 days or more per week. Data on prescribed drugs with addiction potential were drawn from the Norwegian Prescription Database. Drugs with addiction potential were defined as at least one prescription of benzodiazepines, z-hypnotics or opioids during one year for a minimum of two consecutive years between 2005 and 2009. RESULTS: The typical frequent drinker in HUNT3 was younger, more educated, lived in urban areas, and reported smoking and drinking frequently in HUNT2 compared to the non-frequent drinker in HUNT3. The typical user of prescribed drugs with addiction potential in HUNT3 was an older woman who smoked and was in poor health, suffered from anxiety, had been hospitalized in the last 5 years and used anxiety or sleep medication every week or more often in HUNT2. The typical individual in HUNT3 with the possible combination of frequent drinking and being prescribed drugs with addiction potential had more education, smoked, drank frequently and used anxiety or sleep medication in HUNT2. CONCLUSION: Individuals who were identified as frequent drinkers in HUNT2 were more likely to be frequent drinkers in HUNT3, and to have the possible combination of frequent drinking and being prescribed drugs with addiction potential in HUNT3. Health care professionals need to be aware of use of alcohol among older adults using drugs with addiction potential.

Comorbid Dementia and Cancer in Residents of Nursing Homes: Secondary Analyses of a Cross-Sectional Study.

BACKGROUND: Life expectancy is increasing continuously, which increases the likelihood of developing dementia or cancer. Both dementia and cancer are serious conditions that give manifold symptoms. The interaction of these conditions is however complex and less explored. OBJECTIVES: The aim of this study was to identify the prevalence of cancer and differences regarding neuropsychiatric symptoms (NPS) and medication among nursing home (NH) patients with and without dementia and cancer. METHODS: This is a cross-sectional study of Norwegian NH patients (N = 1825). Participants were categorized according to degree of dementia (Clinical Dementia Rating > 1) and cancer diagnoses. Differences in NPS and other symptoms, as well as the use of medication, were explored. RESULTS: Eighty-four percent of NH patients had dementia, and 5.5% had comorbid dementia and cancer. Patients with comorbid dementia and cancer received significantly more analgesics compared with patients without cancer but with dementia (P < .05). Compared with patients without dementia but with cancer, patients with comorbid dementia and cancer had significantly more NPS, including sleep disturbances and agitation. CONCLUSIONS: Patients with comorbid dementia and cancer receive more analgesics than patients with dementia but still display more agitation and sleep disturbances than patients with cancer and patients with neither dementia nor cancer, suggesting that symptoms may not be treated adequately. IMPLICATIONS FOR PRACTICE: The results indicate a considerable strain for patients with comorbid dementia and cancer and highlight essential challenges for the clinician who is responsible for treatment and care. Nurses should pay attention to agitation and sleep disturbances among patients with comorbid dementia and cancer.

Geriatric assessment is superior to oncologists' clinical judgement in identifying frailty.

BACKGROUND: Frailty is a syndrome associated with increased vulnerability and an important predictor of outcomes in older cancer patients. Systematic assessments to identify frailty are seldom applied, and oncologists' ability to identify frailty is scarcely investigated. METHODS: We compared oncologists' classification of frailty (onc-frail) based on clinical judgement with a modified geriatric assessment (mGA), and investigated associations between frailty and overall survival. Patients ⩾70 years referred for medical cancer treatment were eligible. mGA-frailty was defined as impairment in at least one of the following: daily activities, comorbidity, polypharmacy, physical function or at least one geriatric syndrome (cognitive impairment, depression, malnutrition, falls). RESULTS: Three hundred and seven patients were enroled, 288 (94%) completed the mGA, 286 (93%) were rated by oncologists. Median age was 77 years, 56% had metastases, 85% performance status (PS) 0-1. Overall, 104/286 (36%) were onc-frail and 140/288 (49%) mGA-frail, the agreement was fair (kappa value 0.30 (95% CI 0.19; 0.41)), and 67 mGA-frail patients who frequently had localised disease, good PS and received curative treatment, were missed by the oncologists. Only mGA-frailty was independently prognostic for survival (HR 1.61, 95% CI 1.14; 2.27; P=0.007). CONCLUSIONS: Systematic assessment of geriatric domains is needed to aid oncologists in identifying frail patients with poor survival.

Potentially inappropriate medications and drug-drug interactions in home-dwelling people with mild dementia.

OBJECTIVES: The objectives of this study were to describe the use of psychotropic drugs among home-dwelling people with mild dementia, to identify potentially inappropriate medications (PIM) and drug-drug interactions (DDI), and to analyze potential variables associated with having PIM and DDI. METHODS: Patients (n = 251) with a first-time diagnosis of mild dementia (defined as a mini-mental state examination score >20) were included from outpatient clinics. Prevalence of psychotropic drug use, polypharmacy, and psychotropic polypharmacy were investigated. The prevalence of PIM and DDI were defined using the Norwegian general practice criteria and an interactions database, respectively. Variables associated with having PIM and DDI were assessed using a multivariable logistic regression analysis adjusting for relevant demographic and clinical variables. RESULTS: Almost 96% of the patients used one or more medications. Polypharmacy was found in 45% of the patients, and nearly 70% of the patients were using one or more psychotropic drugs. Psychotropic polypharmacy was found in seven patients. PIM were identified in 35 patients (14%), while only four severe DDI were found. Female sex and number of medications were significantly associated with having PIM, whereas only number of medications was significantly associated with having DDI. CONCLUSION: Few patients had PIM or severe DDI, indicating that the quality of prescribing was acceptable. However, psychotropic drug use was common in home-dwelling people with mild dementia despite limited evidence of benefit in dementia. More knowledge is needed about the potential risks associated with psychotropic drug use and having PIM and DDI in people with mild dementia. Copyright © 2016 John Wiley & Sons, Ltd.

Signs of Imminent Dying and Change in Symptom Intensity During Pharmacological Treatment in Dying Nursing Home Patients: A Prospective Trajectory Study.

OBJECTIVES: To investigate whether it is possible to determine signs of imminent dying and change in pain and symptom intensity during pharmacological treatment in nursing home patients, from day perceived as dying and to day of death. DESIGN: Prospective, longitudinal trajectory trial. SETTING: Forty-seven nursing homes within 35 municipalities of Norway. PARTICIPANTS: A total of 691 nursing home patients were followed during the first year after admission and 152 were assessed carefully in their last days of life. MEASUREMENTS: Time between admission and day of death, and symptom severity by Edmonton symptom assessment system (ESAS), pain (mobilization-observation-behavior-intensity-dementia-2), level of dementia (clinical dementia rating scale), physical function (Karnofsky performance scale), and activities of daily living (physical self-maintenance scale). RESULTS: Twenty-five percent died during the first year after admission. Increased fatigue (logistic regression, odds ratio [OR] 1.8, P = .009) and poor appetite (OR 1.2, P = .005) were significantly associated with being able to identify the day a person was imminently dying, which was possible in 61% of the dying (n = 82). On that day, the administration of opioids, midazolam, and anticholinergics increased significantly (P < .001), and was associated with amelioration of symptoms, such as pain (mixed-models linear regression, 60% vs 46%, P < .001), anxiety (44% vs 31%, P < .001), and depression (33% vs 15%, P < .001). However, most symptoms were still prevalent at day of death, and moderate to severe dyspnea and death rattle increased from 44% to 53% (P = .040) and 8% to 19% (P < .001), respectively. Respiratory symptoms were not associated with opioids or anticholinergics. CONCLUSION: Pharmacological treatment ameliorated distressing symptoms in dying nursing home patients; however, most symptoms, including pain and dyspnea, were still common at day of death. Results emphasize critical needs for better implementation of guidelines and staff education. TRIAL REGISTRATION: ClinicalTrials.govNCT01920100.

Comparing comorbidity scales: Attending physician score versus the Cumulative Illness Rating Scale for Geriatrics.

OBJECTIVES: Assessing comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and its comprehensive manual is time consuming. We investigated if similar information could be obtained by a simpler assessment based on the original CIRS. MATERIALS AND METHODS: Data from a randomized chemotherapy trial (RCT) on advanced NSCLC (non-small cell lung cancer) were analyzed. Baseline comorbidity was assessed by 1) trained oncologists using hospital records and the CIRS-G manual (CIRS-G), 2) by patients' oncologists/pulmonologists (local investigators=LI-score) using a brief set of instructions. By both methods, the severity of comorbidity in 14 organ systems was graded 0 (no problem) to 4 (extremely severe). The agreement between methods was assessed using Bland-Altman analysis and weighted kappa statistics. The impact of comorbidity on survival was analyzed by Cox regression. RESULTS: Complete data were available for 375/446 (84%) patients enrolled in the RCT. Median age was 65years (25-85). Overall, more comorbidities and higher severity were registered by the CIRS-G compared to the LI-score. Severe comorbidity was registered for 184 (49%) and 94 (25%) patients according to the CIRS-G and LI-scores, respectively. Mean total score was 7.0 (0-17) (CIRS-G) versus 4.2 (0-16) (LI-score), and mean severity index (total score/number of categories with score >0) was 1.73 (SD 0.46) versus 1.43 (SD 0.78). Neither the CIRS-G scores nor the LI-scores were prognostic for survival. CONCLUSION: The CIRS-G scores and LI-scores had poor agreement, indicating that assessment method affects the registration of comorbidity. Thorough descriptions of comorbidity registrations in trials are paramount due to lack of a standardized assessment.