ObjectivesDelirium is a serious condition, which poses treatment challenges during hospitalisation for COVID-19. Improvements in testing, vaccination and treatment might have changed patient... Show moreObjectivesDelirium is a serious condition, which poses treatment challenges during hospitalisation for COVID-19. Improvements in testing, vaccination and treatment might have changed patient characteristics and outcomes through the pandemic. We evaluated whether the prevalence and risk factors for delirium, and the association of delirium with in-hospital mortality changed through the pandemic.MethodsThis study was part of the COVID-OLD study in 19 Dutch hospitals including patients ≥70 years in the first (spring 2020), second (autumn 2020) and third wave (autumn 2021). Multivariable logistic regression models were used to study risk factors for delirium, and in-hospital mortality. Differences in effect sizes between waves were studied by including interaction terms between wave and risk factor in logistic regression models.Results1540, 884 and 370 patients were included in the first, second and third wave, respectively. Prevalence of delirium in the third wave (12.7%) was significantly lower compared to the first (22.5%) and second wave (23.5%). In multivariable-adjusted analyses, pre-existing memory problems was a consistent risk factor for delirium across waves. Previous delirium was a risk factor for delirium in the first wave (OR 4.02), but not in the second (OR 1.61) and third wave (OR 2.59, p-value interaction-term 0.028). In multivariable-adjusted analyses, delirium was not associated with in-hospital mortality in all waves.ConclusionDelirium prevalence declined in the third wave, which might be the result of vaccination and improved treatment strategies. Risk factors for delirium remained consistent across waves, although some attenuation was seen in the second wave. Show less
Background: The adverse cardiovascular effects of benzodiazepines and Z-drugs (jointly referred as BZDRs) have been of concern. Yet, little is known about the use of BZDRs in relation to mortality... Show moreBackground: The adverse cardiovascular effects of benzodiazepines and Z-drugs (jointly referred as BZDRs) have been of concern. Yet, little is known about the use of BZDRs in relation to mortality risk among older adults with myocardial infarction history (post-MI). Methods: This study is a secondary analysis of the Alpha Omega Cohort study, comprising post-MI patients aged 40-60 years. Self-reported information on the use of BZDRs, including types and dose, was collected at baseline. Four categories of mortality were examined, namely all-cause mortality, cardiovascular (CVD) mortality, cancer mortality, and non-CVD/non-cancer mortality. Associations between BZDRs use, by types and doses, and mortality were estimated with Cox regression models, adjusted for demographic and classic cardiovascular risk factors. Results: A total of 433 (8.9%) out of 4837 (21.8% females) patients reported BZDRs use at baseline. During a median follow-up of 12.4 years, 2287 deaths were documented, of which 825 (36.1%) were due to CVD. BZDRs use was related to a statistically significantly higher risk of all-cause and CVD mortality; adjusted hazard ratios [95% CI] were (1.31 [1.41, 1.52]) and (1.43 [1.14, 1.81]), respectively. These relationships were dose-dependent-patients using BZDRs on an as-needed basis had similar risks compared to the non-uses, whereas patients with a daily use schedule and increasing doses had higher risks (p-value for trend: < 0.001). Conclusion: BZDRs use was independently associated with a higher risk of all-cause and cardiovascular mortality in older post-MI patients, and there was evidence for a dose-dependent relationship. Show less
Klei, V.M.G.T.H. van der; Poortvliet, R.K.E.; Bogaerts, J.M.K.; Blom, J.W.; Mooijaart, S.P.; Teh, R.; ... ; Gussekloo, J. 2022
Objectives: Previous findings suggest a vascular foundation underlying apathy, but transdiagnostic and prospective evidence on vascular apathy is scarce. This study examines the association between... Show moreObjectives: Previous findings suggest a vascular foundation underlying apathy, but transdiagnostic and prospective evidence on vascular apathy is scarce. This study examines the association between vascular disease and the presence and development of apathy symptoms in the very old.Methods: Four cohorts of the Towards Understanding Longitudinal International older People Studies (TULIPS)-consortium were included in a two-staged, individual participant data meta-analysis using generalized linear mixed models, Vascular disease was defined as a history of any clinical atherosclerotic pathology (angina pectoris, myocardial infarction, intermittent claudication, transient ischemic attack, stroke or related surgeries) and was related to apathy symptoms as repeatedly measured by the Geriatric Depression Scale (GDS-3A >= 2) over a maximum of 5 years.Results: Of all 1868 participants (median age 85 years old), 53.9% had vascular disease and 44.3% experienced apathy symptoms. Participants with vascular disease had a 76% higher risk of apathy symptoms at baseline (odds ratio (OR) 1.76, 95% confidence interval (CI) 1.32-2.35), irrespective of depressive symptoms and only partially explained by stroke. Conversely, there was no association of vascular disease with the occurrence of apathy symptoms longitudinally, both in those with apathy at baseline (OR 1.00, 95% CI 0.84-1.20) and without (OR 0.96, 95% CI 0.841.09).Conclusions: Vascular disease in the very old is associated with apathy symptoms cross-sectionally, but not proven longitudinally, independent of depressive symptoms. These findings query a vascular cause underlying apathy symptoms. However, the consistency of our cross-sectional findings in direction and magnitude across the TULIPS-consortium do emphasize international relevance of the interplay of vascular factors and apathy in advanced age, which meaning needs further unravelling. Show less
Objectives: Late-life major depressive disorder (MDD) can be conceptualized as a complex dynamic system. However, it is not straightforward how to analyze the covarying depressive symptoms over... Show moreObjectives: Late-life major depressive disorder (MDD) can be conceptualized as a complex dynamic system. However, it is not straightforward how to analyze the covarying depressive symptoms over time in case of sparse panel data. Dynamic time warping (DTW) analysis may yield symptom networks and dimensions both at the patient and group level. Methods: In the Netherlands Study of Depression in Older People (NESDO) depressive symptoms were assessed every 6 months using the 30-item Inventory of Depressive Symptomatology (IDS) with up to 13 assessments per participant. Our sample consisted of 182 persons, aged >= 60 years, with an IDS total score of 26 or higher at baseline. Symptom networks dimensions, and centrality metrics were analyzed using DTW and Distatis analyses. Results: The mean age was 69.8 years (SD 7.1), with 69.0% females, and a mean IDS score of 38.0 (SD = 8.7). DTW enabled visualization of an idiographic symptom network in a single NESDO participant. In the group-level nomothetic approach, four depressive symptom dimensions were identified: "core symptoms", "lethargy/somatic", "sleep", and "appetite/atypical". Items of the "internalizing symptoms" dimension had the highest centrality, whose symptom changes over time were most similar to those changes of other symptoms. Conclusions: DTW revealed symptom networks and dimensions based on the within-person symptom changes in older MDD patients. Its centrality metrics signal the most influential symptoms, which may aid personalized care. Show less
Wubben, N.; Haaksma, M.; Ramakers, I.H.G.B.; Flier, W.M. van der; Verhey, F.R.J.; Rikkert, M.G.M.O.; Melis, R.J.F. 2022
Objectives: To explain the heterogeneity in dementia disease trajectory, we studied the influence of changing patient characteristics on disease course by comparing the association of dementia... Show moreObjectives: To explain the heterogeneity in dementia disease trajectory, we studied the influence of changing patient characteristics on disease course by comparing the association of dementia progression with baseline comorbidity and frailty, and with time-varying comorbidity and frailty.Methods: We used individual growth models to study baseline and time-varying associations in newly diagnosed dementia patients (n = 331) followed for 3 years. We measured cognition using the Mini-Mental State Examination (MMSE), daily functioning using the Disability Assessment for Dementia (DAD), frailty using the Fried criteria and comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G).Results: Although baseline comorbidity and frailty were associated with decreased daily functioning at diagnosis, their effects clearly diminished over time. In contrast, when incorporating comorbidity and frailty as time-varying covariates, comorbidity was associated with lower daily functioning, and frailty with both lower cognition and daily functioning. Being frail was associated with a 0.9-point lower MMSE score (p = 0.03) and a 14.9-point lower DAD score (p < 0.01). A 1-point increase in CIRS-G score was associated with a 1.1-point lower DAD score (p < 0.01).Conclusions: Time-varying comorbidity and frailty were more consistently associated with dementia disease course than baseline comorbidity and frailty. Therefore, modeling only baseline predictors is insufficient for understanding the course of dementia in a changing patient context. Show less
J. du; Janus, S.; Voorthuis, B.; Manen, J. van; Achterberg, W.; Smalbrugge, M.; ... ; Zuidema, S. 2022
Objective: Several European studies investigated the trends in psychotropic drug prescriptions (PDPs) among nursing home (NH) residents and reported a decline in antipsychotics prescriptions. Since... Show moreObjective: Several European studies investigated the trends in psychotropic drug prescriptions (PDPs) among nursing home (NH) residents and reported a decline in antipsychotics prescriptions. Since the Dutch long-term care system differs from other European systems (e.g. higher threshold for NH admission and trained elderly care physicians), this study explores the trends in PDPs in Dutch NH residents with dementia.Methods: The study used data from nine studies, comprising two cross-sectional studies, one cohort study, and six cluster-randomized controlled trials, collected in Dutch NHs between 2003 and 2018. With multilevel logistic regression analysis, NHs as a random effect, we estimated the trends in PDPs overall and for five specific psychotropic drug groups (antipsychotics, antidepressants, anxiolytics, hypnotics, and anti-dementia drugs), adjusting for confounders: age, gender, severity of dementia, severity of neuropsychiatric symptoms, and length of stay in NHs.Results: The absolute prescription rate of antipsychotics was 37.5% in 2003 and decreased (OR = 0.947, 95% CI [0.926, 0.970]) every year. The absolute prescription rate of anti-dementia drugs was 0.8% in 2003 and increased (OR = 1.162, 95% CI [1.105, 1.223]) per year, The absolute rate of overall PDPs declined from 62.7% in 2003 to 40.4% in 2018.Conclusions: Among Dutch NH residents with dementia, the odds of antipsychotics prescriptions decreased by 5.3% per year while the odds of anti-dementia drug prescriptions increased by 16.2%. There were no distinct trends in antidepressants, anxiolytics, and hypnotics prescriptions. However, overall PDPs were still high. The PDPs in NH residents remain an issue of concern. Show less
Objectives Neuropsychiatric symptoms (NPS) are very common in older patients with dementia. There is increasing evidence that hypoperfusion of the brain plays a role in the development of NPS. The... Show moreObjectives Neuropsychiatric symptoms (NPS) are very common in older patients with dementia. There is increasing evidence that hypoperfusion of the brain plays a role in the development of NPS. The aim of this study is to assess whether there is an association between low systolic blood pressure (SBP) and NPS and if NPS are more prevalent in older people with dementia using antihypertensive medication. Methods We studied the baseline data from participants in theCommunication,Systematic pain treatment,Medication review,Organized activities andSafety study, a multicenter clustered trial with 765 participants from 72 nursing home units from 37 nursing homes in Norway. SBP (lowest quartile vs rest) and use of antihypertensive medication were predictors and Neuropsychiatric Inventory-Nursing Home version (NPI-NH) score (total and clusters) was the outcome. Missing data were imputed, except for missing data in predictors. We used a mixed model analysis adjusted for age, sex and Minimal Mental State Examination (MMSE) score. In a sensitivity analysis, continuous SBP values were used. Results In total, 412 patients were included with a mean age of 86.9 years, 53.9% had a MMSE score of <11. There was no difference in total NPI-NH score between low and high SBP (difference -1.07,P-dj= 0.62). There was no difference between high and low SBP and the NPI clusters. The use of antihypertensive medication was not associated with a different total or cluster NPI-NH score compared to no use (difference -0.99,P-adj= 0.95,P-all= 0.37-0.99, respectively). In the sensitivity analyses with the continuous SBP levels, there was no association between SBP and NPI-NH score (estimate 1.00, 95%CI 0.98-1.01,P= 0.25). Conclusion We found no association between low SBP and NPS, nor between antihypertensive use and NPS. Show less
Objectives We performed a randomized controlled study to evaluate the effects of caregiver training on the well-being of both people with dementia and their caregivers. Before the effect analysis,... Show moreObjectives We performed a randomized controlled study to evaluate the effects of caregiver training on the well-being of both people with dementia and their caregivers. Before the effect analysis, we conducted a process evaluation to estimate internal and external validity. This was anticipated to augment our understanding of the outcomes. Methods We focused on three questions. (a) Was the intervention performed as planned (internal validity)? (b) Can qualitative data be used to inform how the intervention evoked change? (c) Can the study outcomes be extrapolated to all caregivers living with people who have dementia (external validity)? Results Responses from participants assigned to the intervention group suggested that the intervention was feasible, could be performed as planned, and that modelling and discussions between participants were important. However, participant recruitment to the entire study was ultimately laborious because participants had issues with the study design (risk of being assigned to the control group) and referrers lacked familiarity with the training (new type of intervention). Participants were also younger and better educated compared with the general population. Some dropouts in the follow-up period occurred due to the number of questionnaires, and this was more pronounced in the control group. Conclusions Although we achieved high internal validity, we lack certainty about the external validity. We not only experienced general difficulty in recruiting participants but also tended to recruit a biased sample that was relatively young and well educated. These factors combine to limit our ability to extrapolate the results to the general population. Show less
Objectives Caregivers for people with dementia (PWD) have reported needing emotional and social support, improved coping strategies, and better information about the illness and available support... Show moreObjectives Caregivers for people with dementia (PWD) have reported needing emotional and social support, improved coping strategies, and better information about the illness and available support services. In this study, we aimed to determine the effectiveness of an Australian multicomponent community-based training program that we adapted and implemented in a non-medical Dutch health care setting. Methods and design A randomized controlled trial was performed: 142 dyads of cohabiting caregivers and PwD were randomized to control (care as usual) or intervention (training program) groups and outcomes were compared. Programs lasted 1 week, comprised 14 sessions, and were delivered by specialist staff. We included 16 groups of two to six caregivers. The primary outcome was care-related quality of life (CarerQol-7D) at 3 months. The main secondary outcomes for caregivers were self-rated burden, health and mood symptoms, and for PwD were neuropsychiatric symptoms, quality of life, and agitation. Results No significant difference was observed for the primary outcome. However, caregivers experienced fewer role limitations due to physical function (adjusted mean difference, 13.04; 95% confidence interval [95%CI], 3.15-22.93), emotional function (13.52; 95%CI, 3.76-23.28), and pain reduction (9.43; 95%CI, 1.00-17.86). Positive outcomes identified by qualitative analysis included better acceptance and coping and improved knowledge of dementia and available community services and facilities. Conclusion Quantitative analysis showed that the multicomponent course did not affect care-related quality of life but did have a positive effect on experienced role limitations and pain. Qualitative analysis showed that the course met the needs of participating dyads. Show less
Miranda, R.; Steen, J.T. van der; Smets, T.; Noortgate, N. van den; Deliens, L.; Payne, S.; ... ; PACE 2020
Objectives We aimed to investigate the occurrence rates of clinical events and their associations with comfort in dying nursing home residents with and without dementia. Methods Epidemiological... Show moreObjectives We aimed to investigate the occurrence rates of clinical events and their associations with comfort in dying nursing home residents with and without dementia. Methods Epidemiological after-death survey was performed in nationwide representative samples of 322 nursing homes in Belgium, Finland, Italy, the Netherlands, Poland, and England. Nursing staff reported clinical events and assessed comfort. The nursing staff or physician assessed the presence of dementia; severity was determined using two highly discriminatory staff-reported instruments. Results The sample comprised 401 residents with advanced dementia, 377 with other stages of dementia, and 419 without dementia (N = 1197). Across the three groups, pneumonia occurred in 24 to 27% of residents. Febrile episodes (unrelated to pneumonia) occurred in 39% of residents with advanced dementia, 34% in residents with other stages of dementia and 28% in residents without dementia (P= .03). Intake problems occurred in 74% of residents with advanced dementia, 55% in residents with other stages of dementia, and 48% in residents without dementia (P< .001). Overall, these three clinical events were inversely associated with comfort. Less comfort was observed in all resident groups who had pneumonia (advanced dementia,P= .04; other stages of dementia,P= .04; without dementia,P< .001). Among residents with intake problems, less comfort was observed only in those with other stages of dementia (P< .001) and without dementia (P= .003), while the presence and severity of dementia moderated this association (P= .03). Developing "other clinical events" was not associated with comfort. Conclusions Discomfort was observed in dying residents who developed major clinical events, especially pneumonia, which was not specific to advanced dementia. It is crucial to identify and address the clinical events potentially associated with discomfort in dying residents with and without dementia. Show less
Objectives Older adults with psychiatric disorders have a substantially lower life expectancy than age-matched controls. Knowledge of risk factors may lead to targeting treatment and interventions... Show moreObjectives Older adults with psychiatric disorders have a substantially lower life expectancy than age-matched controls. Knowledge of risk factors may lead to targeting treatment and interventions to reduce this gap in life expectancy. In this study, we investigated whether frailty independently predicts mortality in older patients following an acute admission to a geriatric psychiatry hospital.Methods Clinical cohort study with a 5-year follow-up of 120 older patients admitted to a psychiatric hospital between February 2009 and September 2010. On admission, we assessed frailty with a frailty index (FI). We applied Cox regression analyses with time to death as the dependent variable, to examine whether the FI was a predictor for mortality, adjusted for age, sex, level of education, multimorbidity (Cumulative Illness Rating Scale for Geriatrics, CIRS-G scores), functional status (Barthel Index), neuropsychiatric symptoms (NPS), and severity of psychiatric symptoms at admission (Clinical Global Impressions Scale of Severity).Results Of the 120 patients, 63 (53%) patients were frail (FI >= 0.25), and 59 (49%) had died within 5 years. The FI predicted mortality with a hazard ratio (HR) of 1.78 (95% CI, 1.06-2.98) per 0.1 point increase, independent of the covariates. Co-morbidity measured by the CIRS-G and functional status measured by the Barthel Index were not significantly associated.Conclusions Frailty was a strong predictor of mortality, independent of age, gender, multimorbidity, and functional status. This implies that frailty may be helpful in targeting inpatient psychiatric treatment and aftercare according to patients' life expectancy. Show less
Objectives Previous studies have identified several subgroups (ie, latent trajectories) with distinct disease progression among people with dementia. However, the methods and results were not... Show moreObjectives Previous studies have identified several subgroups (ie, latent trajectories) with distinct disease progression among people with dementia. However, the methods and results were not always consistent. This study aims to perform a coordinated analysis of latent trajectories of cognitive and functional progression in dementia across two datasets. Methods Included and analyzed using the same statistical approach were 1628 participants with dementia from the US National Alzheimer's Coordinating Center (NACC) and 331 participants with dementia from the Dutch Clinical Course of Cognition and Comorbidity study (4C-Study). Trajectories of cognition and instrumental activities of daily living (IADL) were modeled jointly in a parallel-process growth mixture model. Results Cognition and IADL tended to decline in unison across the two samples. Slow decline in both domains was observed in 26% of the US sample and 74% of the Dutch sample. Rapid decline in cognition and IADL was observed in 7% of the US sample and 26% of the Dutch sample. The majority (67%) of the US sample showed moderate cognitive decline and rapid IADL decline. Conclusions Trajectories of slow and rapid dementia progression were identified in both samples. Despite using the same statistical methods, the number of latent trajectories was not replicated and the relative class sizes differed considerably across datasets. These results call for careful consideration when comparing progression estimates in the literature. In addition, the observed discrepancy between cognitive and functional decline stresses the need to monitor dementia progression across multiple domains. Show less
Objectives Older age and major depressive disorder (MDD) are both risk factors for the development of cardiovascular diseases. Testosterone has been associated with MDD and metabolic syndrome (MetS... Show moreObjectives Older age and major depressive disorder (MDD) are both risk factors for the development of cardiovascular diseases. Testosterone has been associated with MDD and metabolic syndrome (MetS) in men, although associations in women are less clear. Therefore, we investigated whether testosterone is associated with MetS and whether this association is different for depressed and non-depressed older men and women. Methods In this prospective cohort study, 478 participants (349 patients with MDD and 129 controls) aged between 60 and 93 years from the Netherlands Study of Depression in Older Persons were included. Total testosterone (TT) and sex-hormone binding globulin levels were measured using a second-generation radioimmune assay. Free testosterone (FT) was calculated based on TT. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Results A higher risk for MetS was found in men with low FT and TT (odds ratio [OR]: 0.67, 95% confidence interval [95%CI]: 0.47-0.95 and OR: 0.51, 95%CI: 0.34-0.75), and in women with high FT (OR: 1.41, 95%CI: 1.08-1.82). Strong associations in the same direction were found with adiposity, glucose, and plasma lipid MetS components at baseline, but not with changes in these components at 2-year follow-up. The associations did not significantly differ between MDD patients and controls. Conclusions Independently of having MDD, low testosterone levels in men and, in contrast, high testosterone levels in women were significantly associated with MetS and its components. Show less
