Outcomes relevant to patients and care partners along the trajectory of Alzheimer’s disease

In chapter 2, we identified the most relevant outcomes from the viewpoints of patients and care partners. We used a two-step, mixed methods approach. As a first step we conducted four focus groups in Dutch patients and their care partners to develop a comprehensive list of outcomes considered important by patients and care partners in the prognosis of AD. This resulted in one core outcome list, comprising 13 items. Both patients and care partners selected outcomes from the category “cognition” most often, followed by the categories “functioning and dependency” and “physical health”. The list with outcomes of relevance to patients and care partners was then used to inform subsequent studies on Patient Reported Outcomes (PROs) along the trajectory of AD. In chapter 3, we developed and validated models to predict institutionalization and mortality along the AD continuum of Subjective Cognitive Decline (SCD), Mild Cognitive Impairment (MCI) and AD dementia. In SCD/MCI and dementia stages, the models predicting future institutionalization and mortality included clinical characteristics, imaging and cerebrospinal fluid (CSF) biomarkers after backward selection. Discriminative performance was better in SCD/MCI patients than in patients with AD dementia. Models based on data from amyloid-positive patients, had similar discrimination. The developed prediction models can be used to provide patients and their care partners with prognostic information on time to institutionalization and mortality along the cognitive continuum of AD. In chapter 4, we compared the Quality of Life (QoL) trajectories of amyloid-positive and amyloid-negative SCD and MCI patients and we evaluated QoL trajectories along the AD continuum of SCD, MCI and AD dementia. We showed that QoL decreased at a faster rate over time in amyloid-positive SCD or MCI patients than in amyloid-negative patients. In addition, when we evaluated the full continuum of AD, QoL decreased at a faster rate in patients with amyloid-positive patients with AD dementia compared to amyloid-positive SCD or MCI. Knowledge of QoL trajectories along the full trajectory of AD is essential for the evaluation of the effect of (future) treatments on the QoL of AD patients. In chapter 5, we focused on a positive outcome, as we studied life satisfaction across AD stages, evaluating transportation and meaningful activities as mediators of the associations between these AD stages and life satisfaction in single and multiple mediator models. We found that patients with dementia are less satisfied with life compared to SCD and MCI. These differences in life satisfaction are explained by reduced participation in meaningful activities, which in turn, was largely attributable to decreased use of transportation. Our findings suggest that improving access to transportation. In chapter 7, we studied care partner outcomes and evaluated patient and care partner determinants associated with care partner outcomes in care partners of amyloid-positive patients with SCD, MCI and AD dementia. The outcomes were informal care time, caregiver distress, depression and QoL. We found that both patient and care partner determinants contribute to the care partner outcomes. Care partners spent more time on care when patients had more behavioral symptoms and functional impairment. More behavioral symptoms were related with more caregiver distress. Spouse care partners spent more time on informal care and QoL was lower in female care partners. Behavioral problems and subtle functional impairment of the patient were associated with worse care partner outcomes already in the pre-dementia stages. These results help to identify care partners at risk of high burden. These results demonstrate that it is important that researchers and health care professionals do not only focus on outcomes related to patients, but also on the care partner outcomes, even in the pre-dementia stages

Alzheimers Dement

INTRODUCTION: Inferring the timeline from mild cognitive impairment (MCI) to severe dementia is pivotal for patients, clinicians, and researchers. Literature is sparse and often contains few patients. We aim to determine the time spent in MCI, mild-, moderate-, severe dementia, and institutionalization until death. METHODS: Multistate modeling with Cox regression was used to obtain the sojourn time. Covariates were age at baseline, sex, amyloid status, and Alzheimer's disease (AD) or other dementia diagnosis. The sample included a register (SveDem) and memory clinics (Amsterdam Dementia Cohort and Memento). RESULTS: Using 80,543 patients, the sojourn time from clinically identified MCI to death across all patient groups ranged from 6.20 (95% confidence interval [CI]: 5.57-6.98) to 10.08 (8.94-12.18) years. DISCUSSION: Generally, sojourn time was inversely associated with older age at baseline, males, and AD diagnosis. The results provide key estimates for researchers and clinicians to estimate prognosis

Hypothermia in Preterm Infants in the First Hours after Birth: Occurrence, Course and Risk Factors

BACKGROUND: Hypothermia is associated with increased morbidity and mortality rates. Preterm infants frequently have hypothermia when they are admitted to the NICU, but there is no data on the occurrence of hypothermia during the first hours after admission. OBJECTIVE: To investigate the occurrence of hypothermia in preterm infants in the first three hours of admission and to identify risk factors. METHODS: Infants < 32 weeks of gestation included in a randomized trial with admission temperature as primary outcome were retrospectively analyzed for the occurrence of hypothermia (< 36.5°C) in the first three hours after admission. Risk factors were identified using linear regression analysis and logistic regression. RESULTS: In total 80 infants were included with a median (IQR) gestational age at birth of 29 (27-30) weeks. In 93% of the infants hypothermia occurred in the first three hours after admission. The median (IQR) duration of hypothermia was 101 (34-162) minutes, of which 24 (7-52) minutes the hypothermia was mild, 45 (4-111) minutes moderate, severe hypothermia hardly occurred. Gestational age and the occurrence of hypothermia at birth were independent risk factors for the occurrence of moderate and severe hypothermia and significantly correlated with duration of hypothermia. CONCLUSIONS: Hypothermia occurred often and for a long period in preterm infants in the first three hours of life, low gestational age and admission temperature were independent risk factors

Tidal volumes at birth as predictor for adverse outcome in congenital diaphragmatic hernia

Objective To assess the predictive value of tidal volume (Vt) of spontaneous breaths at birth in infants with congenital diaphragmatic hernia (CDH).Design Prospective study.Setting Tertiary neonatal intensive care unit.Patients Thirty infants with antenatally diagnosed CDH born at Hospital Sant Joan de Deu in Barcelona from September 2013 to September 2015.Interventions Spontaneous breaths and inflations given in the first 10 min after intubation at birth were recorded using respiratory function monitor. Only expired Vt of uninterrupted spontaneous breaths was included for analysis. Receiver operating characteristics (ROC) analysis was performed and the area under the curve (AUC) was estimated to assess the predictive accuracy of Vt.Main outcome measures Mortality before hospital discharge and chronic lung disease (CLD) at day 28 of life.Results There were 1.233 uninterrupted spontaneous breaths measured, and the overall mean Vt was 2.8 +/- 2.1 mL/kg. A lower Vt was found in infants who died (n=14) compared with survivors (n=16) (1.7 +/- 1.6 vs 3.7 +/- 2.1 mL/kg; p=0.008). Vt was lower in infants who died during admission or had CLD (n=20) compared with survivors without CLD (n=10) (2.0 +/- 1.7 vs 4.3 +/- 2.2 mL/kg; p=0.004). ROC analysis showed that Vt <= 2.2 mL/kg predicted mortality with 79% sensitivity and 81% specificity (AUC=0.77, p=0.013). Vt <= 3.4 mL/kg was a good predictor of death or CLD (AUC=0.80, p=0.008) with 85% sensitivity and 70% specificity.Conclusion Vt of spontaneous breaths measured immediately after birth is associated with mortality and CLD. Vt seems to be a reliable predictor but is not an independent predictor after adjustment for observed/expected lung to head ratio and liver position.Developmen

Risk factors for moderate to severe hypothermia > 30 min.

<p>Risk factors for moderate to severe hypothermia > 30 min.</p

Mean temperature every 10^th minute (95% CI) of infants with hypothermia at admission (gray) and infants without hypothermia at admission (black) in the first three hours after admission.

<p>Mean temperature every 10^th minute (95% CI) of infants with hypothermia at admission (gray) and infants without hypothermia at admission (black) in the first three hours after admission.</p

Development of multivariable prediction models for institutionalization and mortality in the full spectrum of Alzheimer's disease

Background: Patients and caregivers express a desire for accurate prognostic information about time to institutionalization and mortality. Previous studies predicting institutionalization and mortality focused on the dementia stage. However, Alzheimer’s disease (AD) is characterized by a long pre-dementia stage. Therefore, we developed prediction models to predict institutionalization and mortality along the AD continuum of cognitively normal to dementia. Methods: This study included SCD/MCI patients (subjective cognitive decline (SCD) or mild cognitive impairment (MCI)) and patients with AD dementia from the Amsterdam Dementia Cohort. We developed internally and externally validated prediction models with biomarkers and without biomarkers, stratified by dementia status. Determinants were selected using backward selection (p<0.10). All models included age and sex. Discriminative performance of the models was assessed with Harrell’s C statistics. Results: We included n=1418 SCD/MCI patients (n=123 died, n=74 were institutionalized) and n=1179 patients with AD dementia (n=413 died, n=453 were institutionalized). For both SCD/MCI and dementia stages, the models for institutionalization and mortality included after backward selection clinical characteristics, imaging, and cerebrospinal fluid (CSF) biomarkers. In SCD/MCI, the Harrell’s C-statistics of the models were 0.81 (model without biomarkers: 0.76) for institutionalization and 0.79 (model without biomarker: 0.76) for mortality. In AD-dementia, the Harrell’s C-statistics of the models were 0.68 (model without biomarkers: 0.67) for institutionalization and 0.65 (model without biomarker: 0.65) for mortality. Models based on data from amyloid-positive patients only had similar discrimination. Conclusions: We constructed prediction models to predict institutionalization and mortality with good accuracy for SCD/MCI patients and moderate accuracy for patients with AD dementia. The developed prediction models can be used to provide patients and their caregivers with prognostic information on time to institutionalization and mortality along the cognitive continuum of AD

A more precise diagnosis by means of amyloid PET contributes to delayed institutionalization, lower mortality, and reduced care costs in a tertiary memory clinic setting

Introduction: We aim to study the effect of a more precise diagnosis, by means of amyloid positron emission tomography (PET), on institutionalization, mortality, and health-care costs. Methods: Between October 27, 2014 and December 31, 2016, we offered amyloid PET to all patients as part of their diagnostic work-up. Patients who accepted to undergo amyloid PET (n = 449) were propensity score matched with patients without amyloid PET (n = 571, i.e., no PET). Matched groups (both n = 444) were compared on rate of institutionalization, mortality, and health-care costs in the years after diagnosis. Results: Amyloid PET patients had a lower risk of institutionalization (10% [n = 45] vs. 21% [n = 92]; hazard ratio [HR] = 0.48 [0.33–0.70]) and mortality rate (11% [n = 49] vs. 18% [n = 81]; HR = 0.51 [0.36–0.73]) and lower health-care costs in the years after diagnosis compared to matched no-PET patients (β = −4573.49 [−6524.76 to −2523.74], P-value < 0.001). Discussion: A more precise diagnosis in tertiary memory clinic patients positively influenced the endpoints of institutionalization, death, and health-care costs

Development of multivariable prediction models for institutionalization and mortality in the full spectrum of Alzheimer's disease

International audienceBACKGROUND: Patients and caregivers express a desire for accurate prognostic information about time to institutionalization and mortality. Previous studies predicting institutionalization and mortality focused on the dementia stage. However, Alzheimer's disease (AD) is characterized by a long pre-dementia stage. Therefore, we developed prediction models to predict institutionalization and mortality along the AD continuum of cognitively normal to dementia.METHODS: This study included SCD/MCI patients (subjective cognitive decline (SCD) or mild cognitive impairment (MCI)) and patients with AD dementia from the Amsterdam Dementia Cohort. We developed internally and externally validated prediction models with biomarkers and without biomarkers, stratified by dementia status. Determinants were selected using backward selection (p<0.10). All models included age and sex. Discriminative performance of the models was assessed with Harrell's C statistics.RESULTS: We included n=1418 SCD/MCI patients (n=123 died, n=74 were institutionalized) and n=1179 patients with AD dementia (n=413 died, n=453 were institutionalized). For both SCD/MCI and dementia stages, the models for institutionalization and mortality included after backward selection clinical characteristics, imaging, and cerebrospinal fluid (CSF) biomarkers. In SCD/MCI, the Harrell's C-statistics of the models were 0.81 (model without biomarkers: 0.76) for institutionalization and 0.79 (model without biomarker: 0.76) for mortality. In AD-dementia, the Harrell's C-statistics of the models were 0.68 (model without biomarkers: 0.67) for institutionalization and 0.65 (model without biomarker: 0.65) for mortality. Models based on data from amyloid-positive patients only had similar discrimination.CONCLUSIONS: We constructed prediction models to predict institutionalization and mortality with good accuracy for SCD/MCI patients and moderate accuracy for patients with AD dementia. The developed prediction models can be used to provide patients and their caregivers with prognostic information on time to institutionalization and mortality along the cognitive continuum of AD

Life satisfaction across the entire trajectory of Alzheimer's disease: A mediation analysis

Introduction: We studied life satisfaction across Alzheimer's disease (AD) stages and studied mobility and meaningful activities as mediators of the associations between these AD stages and life satisfaction. Methods: In this cross-sectional study, we included n = 269 amyloid-positive patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD dementia from the Amsterdam Dementia Cohort. Life satisfaction was measured with the satisfaction with life scale. The mediating role of transportation, work, sports, and hobbies on life satisfaction was examined in single and multiple mediator models. Results: Patients with dementia are less satisfied with life compared to SCD and MCI. These differences in life satisfaction are explained by reduced participation in meaningful activities, which in turn, was largely attributable to decreased transportation use. Discussion: Our findings suggest that improving access to transportation, therewith allowing participation in meaningful activities help to maintain life satisfaction and may be an important target for intervention