Post-COVID-19 patients in geriatric rehabilitation substantially recover in daily functioning and quality of life.

BACKGROUND: After an acute infection, older persons may benefit from geriatric rehabilitation (GR). OBJECTIVES: This study describes the recovery trajectories of post-COVID-19 patients undergoing GR and explores whether frailty is associated with recovery. DESIGN: Multicentre prospective cohort study. SETTING: 59 GR facilities in 10 European countries. PARTICIPANTS: Post-COVID-19 patients admitted to GR between October 2020 and October 2021. METHODS: Patients' characteristics, daily functioning (Barthel index; BI), quality of life (QoL; EQ-5D-5L) and frailty (Clinical Frailty Scale; CFS) were collected at admission, discharge, 6 weeks and 6 months after discharge. We used linear mixed models to examine the trajectories of daily functioning and QoL. RESULTS: 723 participants were included with a mean age of 75 (SD: 9.91) years. Most participants were pre-frail to frail (median [interquartile range] CFS 6.0 [5.0-7.0]) at admission. After admission, the BI first steeply increased from 11.31 with 2.51 (SE 0.15, P < 0.001) points per month and stabilised around 17.0 (quadratic slope: -0.26, SE 0.02, P < 0.001). Similarly, EQ-5D-5L first steeply increased from 0.569 with 0.126 points per month (SE 0.008, P < 0.001) and stabilised around 0.8 (quadratic slope: -0.014, SE 0.001, P < 0.001). Functional recovery rates were independent of frailty level at admission. QoL was lower at admission for frailer participants, but increased faster, stabilising at almost equal QoL values for frail, pre-frail and fit patients. CONCLUSIONS: Post-COVID-19 patients admitted to GR showed substantial recovery in daily functioning and QoL. Frailty at GR admission was not associated with recovery and should not be a reason to exclude patients from GR.

Course of fear of falling after hip fracture: findings from a 12-month inception cohort.

OBJECTIVES: To examine the course of fear of falling (FoF) up to 1 year after hip fracture, including the effect of prefracture FoF on the course. DESIGN: Observational cohort study with assessment of FoF at 6, 12 and 52 weeks after hip fracture. SETTING: Haaglanden Medical Centre, the Netherlands. PARTICIPANTS: 444 community-dwelling adults aged 70 years and older, admitted to hospital with a hip fracture. MAIN OUTCOME MEASURE: Short Falls Efficacy Scale International (FES-I), with a cut-off score ≥11 to define elevated FoF levels. RESULTS: Six weeks after hip fracture the study population-based mean FES-I was located around the cut-off value of 11, and levels decreased only marginally over time. One year after fracture almost one-third of the population had FoF (FES-I ≥11). Although the group with prefracture FoF (42.6%) had slightly elevated FES-I levels during the entire follow-up, the effect was not statistically significant. Patients with persistent FoF at 6 and 12 weeks after fracture (26.8%) had the highest FES-I levels, with a mean well above the cut-off value during the entire follow-up. For the majority of patients in this group, FoF is still present 1 year after fracture (84.9%). CONCLUSIONS: In this study population, representing patients in relative good health condition that are able to attend the outpatient follow-up at 6 and 12 weeks, FoF as defined by an FES-I score ≥11 was common within the first year after hip fracture. Patients with persistent FoF at 12 weeks have the highest FES-I levels in the first year after fracture, and for most of these patients the FoF remains. For timely identification of patients who may benefit from intervention, we recommend structural assessment of FoF in the first 12 weeks after fracture.

How to Conduct International Geriatric Rehabilitation Research?

With an ageing global population and an increasing focus on aging in place, the number of people in need of geriatric rehabilitation (GR) is rapidly increasing. As current GR practice is very heterogenous, cross-country comparisons could allow us to learn from each other and optimise the effectiveness of GR. However, international GR research comes with many challenges. This article summarises the facilitators and barriers relating to the recruitment of rehabilitation centres, the inclusion of patients, and data collection, as experienced by experts in the field of international GR research. The three most important methodological recommendations for conducting cross-national collaborative research in the field of GR are (1) make use of existing (inter)national networks and social media to aid recruitment of GR centres; (2) clearly define the GR treatment, setting, and patient characteristics in the inclusion criteria; and (3) use a hierarchical study structure to communicate transparently and regularly with both national and local coordinators. International GR research would greatly benefit from the implementation of a core dataset in regular GR care. Therefore, future studies should focus on developing an international consensus regarding the outcomes and corresponding cross-culturally validated measurement instruments to be used during GR.

Development and Validation of Risk Prediction Models for Coronary Heart Disease and Heart Failure After Treatment for Hodgkin Lymphoma.

PURPOSE: Previous efforts to predict absolute risk of treatment-related cardiovascular diseases (CVDs) have mostly focused on childhood cancer survivors. We aimed to develop prediction models for risk of coronary heart disease (CHD) and heart failure (HF) for survivors of adolescent/adult Hodgkin lymphoma (HL). METHODS: For model development, we used a multicenter cohort including 1,433 5-year HL survivors treated between 1965 and 2000 and age 18-50 years at HL diagnosis, with complete data on administered chemotherapy regimens, radiotherapy volumes and doses, and cardiovascular follow-up. Using cause-specific hazard models, covariate-adjusted cumulative incidences for CHD and HF were estimated in the presence of competing risks of death because of other causes than CHD and HF. Age at HL diagnosis, sex, smoking status, radiotherapy, and anthracycline treatment were included as predictors. External validation for the CHD model was performed using a Canadian cohort of 708 HL survivors treated between 1988 and 2004 and age 18-50 years at HL diagnosis. RESULTS: After a median follow-up of 24 years, 341 survivors had developed CHD and 102 had HF. We were able to predict CHD and HF risk at 20 and 30 years after treatment with moderate to good overall calibration and moderate discrimination (areas under the curve: 0.68-0.74), which was confirmed by external validation for the CHD model (areas under the curve: 0.73-0.74). On the basis of our model including prescribed mediastinal radiation dose, 30-year risks ranged from 4% to 78% for CHD and 3% to 46% for HF, depending on risk factors. CONCLUSION: We developed and validated prediction models for CHD and HF with good overall calibration and moderate discrimination. These models can be used to identify HL survivors who might benefit from targeted screening for CVD and early treatment for CVD risk factors.

Evaluating the feasibility, experiences, facilitators of and barriers to carers and volunteers delivering Namaste Care to people with dementia in their own home: a qualitative interview study in the UK and the Netherlands.

OBJECTIVES: To evaluate the feasibility, facilitators of and barriers to delivering Namaste Care by volunteers and family carers to community-dwelling people with dementia, and to map family carers and volunteers' experiences with the programme. DESIGN: Qualitative interview study with two phases: (1) preparation phase; (2) pilot phase. SETTING: Private residences of community-dwelling people with dementia in the UK and the Netherlands. PARTICIPANTS: Family carers and volunteers of community-dwelling people with dementia (phase 1: 36 Dutch interviews, phase 2: 9 Dutch and 16 UK interviews). INTERVENTION: Namaste Care is a multicomponent psychosocial programme, originally developed for people with dementia residing in long-term care facilities. Meaningful activities were offered by carers and volunteers. Each person with dementia was offered 10 one-hour sessions. RESULTS: Phase 1: Namaste Care was deemed feasible for community-dwelling people with dementia and no major adaptations to the programme were considered necessary. Phase 2: perceived effects of Namaste Care on people with dementia included improved mood and increased interaction. The programme appeared enriching for both family carers and volunteers, providing joy, respite from care and new insights for coping with challenging behaviour. A flexible attitude of the Namaste provider facilitated its delivery. High caregiver burden and a strained relationship between the family carer and person with dementia were considered barriers. Experiences of family carers and volunteers with Namaste Care were very positive (mean satisfaction rating: 8.7 out of 10, SD=0.9, range 7-10). CONCLUSION: We recommend offering Namaste Care delivered by volunteers, preferably multiple sessions per week of 1.5-2 hours to optimise quality of life of community-dwelling people with dementia. Working with well-matched, flexible Namaste providers is pivotal. Family involvement should be encouraged, although the extent should be adapted depending on preference, caregiver burden and the relationship between the family carer and the person with dementia. TRIAL REGISTRATION NUMBER: NL5570.

Systematic review of measurement properties of the Canadian Occupational Performance Measure in geriatric rehabilitation.

PURPOSE: The Canadian Occupational Performance Measure (COPM) is used to inventory problems experienced by the patient to set goals and evaluate treatment. We aimed to make a systematic overview of measurement properties for people in geriatric rehabilitation. METHODS: Seven electronic databases were searched for psychometric studies investigating content validity, construct validity, responsiveness, or reliability of the COPM in geriatric rehabilitation populations aged ≥ 60 years. Two reviewers independently abstracted data and assessed methodological quality from included studies. RESULTS: Of 292 identified articles, 13 studies were included. The COPM showed good test-retest reliability (two studies), moderate inter-rater reliability (one study), and good content validity (one study with some risk of bias). Four studies with minimal risk of bias showed good construct validity as their hypotheses were confirmed. Responsiveness was moderate in three studies with adequate methodological quality. CONCLUSION: All measurement properties have been studied in geriatric rehabilitation populations, and indicate that the COPM gives relevant information for geriatric rehabilitation, and scores can be assessed reliably and are responsive to change. Although there were many studies on construct validity, authors had different opinions on what exactly COPM-scores tell us, as they used a variety of comparator instruments and different hypotheses. Consensus on exact interpretation of the scores is needed.

Activities for Residents of Dutch Nursing Homes during the COVID-19 Pandemic: A Qualitative Study.

To protect nursing home residents from getting infected with COVID-19, several measures have been imposed. The aim of this study was to describe the impact of these measures on activities for Dutch nursing home residents, the conditions under which the activities could take place, and the considerations when making decisions about the (dis)continuation of activities. The study consisted of the data of the qualitative MINUTES-study. Textual units derived from documentation of an outbreak team (OT) meetings on activities, well-being, informal caregivers, and volunteers from 39 long-term care organizations were re-analyzed using a content analysis. The results shows that OTs more often discussed restarting and continuing activities than stopping activities during the COVID-19 pandemic. There were differences between time periods, but activities never completely stopped according to the minutes. Activities were offered in an adapted way, often under certain conditions, such as organizing activities at other locations (e.g., outside), with limited group size, and following specific guidelines. The main focus of the considerations made were the ability to adhere to the guidelines, the well-being of residents, ensuring safety, and balancing benefits versus risks given vaccination availability and coverage. Overall, the study showed that organizing activities for nursing home residents despite COVID-19 measures is possible.

Polypharmacy and trajectories of health-related quality of life in older adults: an Australian cohort study.

BACKGROUND: Health-related quality of life (HRQoL) is an important outcome measure when considering medical treatment; however, the impact of polypharmacy on trajectories of HRQoL over time is unknown. This study aimed to investigate the association between polypharmacy status and trajectories of HRQoL in older adults. METHODS: A longitudinal cohort study of 2181 community-dwelling adults, 65 years and older, who participated in the 2013 to 2017 waves of the Household Income and Labour Dynamics in Australia (HILDA) Survey. Polypharmacy was defined as the regular use of ≥ 5 prescription medications. Polypharmacy status was categorised into no polypharmacy, in 2013 only (baseline only polypharmacy), in 2017 only (incident polypharmacy) or at both time points (persistent polypharmacy). HRQoL was assessed through the SF-36 questionnaire generating two summary scores: physical component summary (PCS) and mental component summary (MCS). Linear mixed-effects models stratified according to polypharmacy status and change in comorbidities were used to assess trajectories of HRQoL. RESULTS: Older adults with persistent polypharmacy had lowest scores for HRQoL measures from 2013 to 2017. After adjusting for all covariates, those with incident polypharmacy had the steepest annual decline in both the PCS and MCS: - 0.86 in PCS and - 0.76 in MCS for those with decreasing or stable comorbidities, and - 1.20 in PCS and - 0.75 in MCS for those with increasing comorbidities. CONCLUSIONS: Polypharmacy was associated with poorer HRQoL, even after adjusting for confounders. Incident polypharmacy was found to be associated with a clinically important decline in HRQoL and this should be considered when prescribing additional medication to older adults.

Joint trajectories of episodic memory and odor identification in older adults: patterns and predictors.

Emerging evidence suggests that olfactory function is closely linked to memory function. The aims of this study were to assess whether olfactory and episodic memory functions follow similar age-related decline trajectories, to identify different patterns of decline, as well as predictors of the patterns. 1023 participants from the Memory and Aging Project were followed for up to 8 years with annual episodic memory and odor identification assessments. Trajectories were modelled using growth mixture models. Multivariate logistic regression was used to identify pattern predictors. Three patterns of joint trajectories were identified; Class 1- stable average performance in both functions (n=690, 67.4%); Class 2- stable average episodic memory and declining odor identification (n=231, 22.6%); and Class 3- decline in both functions (n= 102, 10.0%). Class predictors included age, sex, APOE ε4 status, cognitive activity level and BMI. Participants in Class 3 were most likely to develop dementia. Episodic memory and olfactory function show similar trajectories in aging. Such classification can contribute to a better understanding of the factors related to cognitive decline and dementia.

Frailty as a predictor of mortality in older adults within 5 years of psychiatric admission.

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 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.

Survival time tool to guide care planning in people with dementia.

OBJECTIVE: To develop survival prediction tables to inform physicians and patients about survival probabilities after the diagnosis of dementia and to determine whether survival after dementia diagnosis can be predicted with good accuracy. METHODS: We conducted a nationwide registry-linkage study including 829 health centers, i.e., all memory clinics and ≈75% of primary care facilities, across Sweden. Data including cognitive function from 50,076 people with incident dementia diagnoses ≥65 years of age and registered with the Swedish Dementia Register in 2007 to 2015 were used, with a maximum follow-up of 9.7 years for survival until 2016. Sociodemographic factors, comorbidity burden, medication use, and dates of death were obtained from nationwide registries. Cox proportional hazards regression models were used to create tables depicting 3-year survival probabilities for different risk factor profiles. RESULTS: By August 2016, 20,828 (41.6%) patients in our cohort had died. Median survival time from diagnosis of dementia was 5.1 (interquartile range 2.9-8.0) years for women and 4.3 (interquartile range 2.3-7.0) years for men. Predictors of mortality were higher age, male sex, increased comorbidity burden and lower cognitive function at diagnosis, a diagnosis of non-Alzheimer dementia, living alone, and using more medications. The developed prediction tables yielded c indexes of 0.70 (95% confidence interval [CI] 0.69-0.71) to 0.72 (95% CI 0.71-0.73) and showed good calibration. CONCLUSIONS: Three-year survival after dementia diagnosis can be predicted with good accuracy. The survival prediction tables developed in this study may aid clinicians and patients in shared decision-making and advance care planning.

Co-occurrence of cognitive impairment and physical frailty, and incidence of dementia: Systematic review and meta-analysis.

INTRODUCTION: Cognitive impairment and frailty are important health determinants, independently associated with increased dementia risk. In this meta-analysis we aimed to quantify the association of the co-occurrence of cognitive impairment no dementia (CIND) and physical frailty with incident dementia. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used when reporting this review. We performed a systematic search on PubMed, Web of Science, and Embase databases for relevant articles. Longitudinal studies enrolling individuals with both CIND and physical frailty and reporting dementia incidence were eligible. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. RESULTS: Out of 3684 articles, five (14302 participants) were included in the meta-analysis. In comparison to participants free from frailty and CIND, the pooled hazard ratio for dementia was 3.83 (95% confidence interval [CI]: 2.64-5.56) for isolated CIND, 1.47 (95%CI: 0.89-2.40) for isolated physical frailty, and 5.36 (95%CI: 3.26-8.81) for their co-occurrence. DISCUSSION: The co-occurrence of cognitive impairment and physical frailty is a clinical marker of incident dementia.

Cognitive and functional progression of dementia in two longitudinal studies.

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 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.

Predicting Cognitive and Functional Trajectories in People With Late-Onset Dementia: 2 Population-Based Studies.

OBJECTIVES: Previous studies have shown large heterogeneity in the progression of dementia, both within and between patients. This heterogeneity offers an opportunity to limit the global and individual burden of dementia through the identification of factors associated with slow disease progression in dementia. We explored the heterogeneity in dementia progression to detect disease, patient, and social context factors related to slow progression. DESIGN: Two longitudinal population-based cohort studies with follow-up across 12 years. SETTING AND PARTICIPANTS: 512 people with incident dementia from Stockholm (Sweden) contributed to the Kungsholmen Project and the Swedish National Study of Aging and Care in Kungsholmen. METHODS: We measured cognition using the Mini-Mental State Examination and daily functioning using the Katz Activities of Daily Living Scale. Latent classes of trajectories were identified using a bivariate growth mixture model. We then used bias-corrected logistic regression to identify predictors of slower progression. RESULTS: Two distinct groups of progression were identified; 76% (n = 394) of the people with dementia exhibited relatively slow progression on both cognition and daily functioning, whereas 24% (n = 118) demonstrated more rapid worsening on both outcomes. Predictors of slower disease progression were Alzheimer's disease (AD) dementia type [odds ratio (OR) 2.07, 95% confidence interval (CI) 1.15-3.71], lower age (OR 0.88, 95% CI 0.83-0.94), fewer comorbidities (OR 0.77, 95% CI 0.66-0.90), and a stronger social network (OR 1.72, 95% CI 1.01-2.93). CONCLUSIONS/IMPLICATIONS: Lower age, AD dementia type, fewer comorbidities, and a good social network appear to be associated with slow cognitive and functional decline. These factors may help to improve the counseling of patients and caregivers and to optimize the planning of care in dementia.

The Impact of Frailty and Comorbidity on Institutionalization and Mortality in Persons With Dementia: A Prospective Cohort Study.

OBJECTIVES: The predictive value of frailty and comorbidity, in addition to more readily available information, is not widely studied. We determined the incremental predictive value of frailty and comorbidity for mortality and institutionalization across both short and long prediction periods in persons with dementia. DESIGN: Longitudinal clinical cohort study with a follow-up of institutionalization and mortality occurrence across 7 years after baseline. SETTING AND PARTICIPANTS: 331 newly diagnosed dementia patients, originating from 3 Alzheimer centers (Amsterdam, Maastricht, and Nijmegen) in the Netherlands, contributed to the Clinical Course of Cognition and Comorbidity (4C) Study. MEASURES: We measured comorbidity burden using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and constructed a Frailty Index (FI) based on 35 items. Time-to-death and time-to-institutionalization from dementia diagnosis onward were verified through linkage to the Dutch population registry. RESULTS: After 7 years, 131 patients were institutionalized and 160 patients had died. Compared with a previously developed prediction model for survival in dementia, our Cox regression model showed a significant improvement in model concordance (U) after the addition of baseline CIRS-G or FI when examining mortality across 3 years (FI: U = 0.178, P = .005, CIRS-G: U = 0.180, P = .012), but not for mortality across 6 years (FI: U = 0.068, P = .176, CIRS-G: U = 0.084, P = .119). In a competing risk regression model for time-to-institutionalization, baseline CIRS-G and FI did not improve the prediction across any of the periods. CONCLUSIONS: Characteristics such as frailty and comorbidity change over time and therefore their predictive value is likely maximized in the short term. These results call for a shift in our approach to prognostic modeling for chronic diseases, focusing on yearly predictions rather than a single prediction across multiple years. Our findings underline the importance of considering possible fluctuations in predictors over time by performing regular longitudinal assessments in future studies as well as in clinical practice.

Understanding and predicting the longitudinal course of dementia.

PURPOSE OF REVIEW: To date, most research in dementia has focused either on the identification of dementia risk prediction or on understanding changes and predictors experienced by individuals before diagnosis. Despite little is known about how individuals change after dementia diagnosis, there is agreement that changes occur over different time scales and are multidomain. In this study, we present an overview of the literature regarding the longitudinal course of dementia. RECENT FINDINGS: Our review suggests the evidence is scarce and findings reported are often inconsistent. We identified large heterogeneity in dementia trajectories, risk factors considered and modelling approaches employed. The heterogeneity of dementia trajectories also varies across outcomes and domains investigated. SUMMARY: It became clear that dementia progresses very differently, both between and within individuals. This implies an average trajectory is not informative to individual persons and this needs to be taken into account when communicating prognosis in clinical care. As persons with dementia change in many more ways during their patient journey, heterogeneous disease progressions are the result of disease and patient characteristics. Prognostic models would benefit from including variables across a number of domains. International coordination of replication and standardization of the research approach is recommended.

Acetylcholinesterase inhibitors and risk of stroke and death in people with dementia.

INTRODUCTION: The aim of this study was to investigate the association between acetylcholinesterase inhibitor (AChEI) use and risk of ischemic stroke and death in people with dementia. METHODS: A cohort study of 44,288 people with dementia registered in the Swedish Dementia Registry from 2007 to 2014. Propensity score-matched competing risk regression models were used to compute hazard ratios and 95% confidence intervals for the association between time-dependent AChEI use and risk of stroke and death. RESULTS: Compared with matched controls, AChEI users had a lower risk of stroke (hazard ratio: 0.85, 95% confidence interval: 0.75-0.95) and all-cause death (hazard ratio: 0.76, 95% confidence interval: 0.72-0.80). After considering competing risk of death, high doses (≥1.33 defined daily doses) of AChEI remained significantly associated with reduced stroke risk. DISCUSSION: The use of AChEIs in people with dementia may be associated with reduced risk of ischemic stroke and death. These results call for a closer examination of the cardiovascular effects of AChEIs.

Cognitive and functional progression in Alzheimer disease: A prediction model of latent classes.

OBJECTIVE: We sought to replicate a previously published prediction model for progression, developed in the Cache County Dementia Progression Study, using a clinical cohort from the National Alzheimer's Coordinating Center. METHODS: We included 1120 incident Alzheimer disease (AD) cases with at least one assessment after diagnosis, originating from 31 AD centres from the United States. Trajectories of the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating sum of boxes (CDR-sb) were modelled jointly over time using parallel-process growth mixture models in order to identify latent classes of trajectories. Bias-corrected multinomial logistic regression was used to identify baseline predictors of class membership and compare these with the predictors found in the Cache County Dementia Progression Study. RESULTS: The best-fitting model contained 3 classes: Class 1 was the largest (63%) and showed the slowest progression on both MMSE and CDR-sb; classes 2 (22%) and 3 (15%) showed moderate and rapid worsening, respectively. Significant predictors of membership in classes 2 and 3, relative to class 1, were worse baseline MMSE and CDR-sb, higher education, and lack of hypertension. Combining all previously mentioned predictors yielded areas under the receiver operating characteristic curve of 0.70 and 0.75 for classes 2 and 3, respectively, relative to class 1. CONCLUSIONS: Our replication study confirmed that it is possible to predict trajectories of progression in AD with relatively good accuracy. The class distribution was comparable with that of the original study, with most individuals being members of a class with stable or slow progression. This is important for informing newly diagnosed AD patients and their caregivers.

The clinical course and interrelations of dementia related symptoms.

ABSTRACTBackground:Dementia is a neurodegenerative syndrome that interferes with multiple aspects of life, including cognition, daily functioning, and behavior. Despite the large heterogeneity in symptom development, these three domains are seldom studied simultaneously. This study investigates how trajectories of these domains are interrelated within individuals over time, and how they in turn are related to dementia severity and quality of life (QoL). METHODS: We used data from a longitudinal clinical cohort study, including 331 dementia patients. Cognitive status was measured using the Mini-Mental State Examination, daily functioning was measured with the disability assessment for dementia and neuropsychiatric symptoms (NPS) were scored using the neuropsychiatric inventory. We investigated the relationships in the time course of the various dementia domains using random effects multilevel models and parallel-process growth models. RESULTS: Changes in cognition and daily functioning were highly correlated over time (r = 0.85, p < 0.01), as were changes in NPS and functioning (r = -0.60, p < 0.01), while changes in cognition and NPS were not (r = -0.20, p = 0.06). All three domains were strongly associated with dementia severity over time (p < 0.01). Decreased functioning and increased NPS were both associated with decreased QoL (ß = 2.97, p < 0.01 and ß = -2.41, p < 0.01, respectively), while cognition was not (ß = 0.01, p = 0.93). CONCLUSION: This study demonstrates the heterogeneity of dementia progression between individuals and between different dementia domains within individuals. To improve our understanding of dementia progression, future research should embrace a broader perspective encompassing multiple outcome measures along with the patient's profile, including neurological factors as well as physical, social, and psychiatric health.