Abstract
Objectives: Young onset dementia (YOD) often comes with neuropsychiatric symptoms (NPS) that are burdening for patients and caregivers and are predictors for institutionalization. The course of NPS in institutionalized patients with YOD is unknown. This study aims to fill this gap.
Method: This study is part of the BEYOND-study, a descriptive longitudinal cohort study of institutionalized YOD patients. Eighty-nine patients were included in this two-year follow-up study, of which 50 completed the whole follow-up. Clinically relevant NPS were assessed using the Neuropsychiatric Inventory-Nursing Home version with a threshold of FxS ≥4. Mean scores and prevalence were calculated of all patients alive at the moment of a given assessment. Cumulative percentages were calculated in patients with complete follow-up.
Results: 82–94% of the residents had at least one NPS at any of the five assessments. Over the two year course, 94% of the patients developed at least one new symptom of which 58% developed irritability, 52% agitation, 44% disinhibition and 44% eating change. All patients had any NPS during follow-up. Apathy had the highest overall prevalence rate and was the most persistent symptom over the two-year course, followed by eating changes, aberrant motor behaviour and irritability. The course during follow-up was variable for all NPS with no clear increase or decrease.
Conclusion: The severity and prevalence of NPS in institutionalized YOD patients fluctuated during follow-up. Apathy and hyperactive symptoms were most severe and persistent. Future research should focus on the influence of psychotropic drug use and dementia subtype on the course of NPS.
Introduction
Young onset dementia (YOD) is defined as dementia with first symptom onset before the age of 65. Multiple studies estimated prevalence- rates of 50–100 cases per 100.000 persons (Harvey, Skelton-Robinson, & Rossor, 2003; Withall, Draper, Seeher, & Brodaty, Citation2014). These studies also suggest wider range and different spread of etiologies in community dwelling patients when compared to community dwelling patients with Late Onset Dementia (LOD). This wider range was also found in institutionalized patients with YOD where a wide variety of underlying diagnoses were found and high prevalence rates of alcohol-related and Frontotemporal Dementia (Mulders, Zuidema, Verhey, & Koopmans, Citation2014).
In patients with YOD in nursing homes the gap between needs and surroundings might be bigger than in institutionalized patients with LOD due to more men, more vitality, wider spread of dementia subtype and more advanced dementia (Bakker et al., Citation2013; Mulders et al., Citation2014). All these characteristics combined could lead to different and more neuropsychiatric symptoms (NPS) or a different course of NPS over time than the research which has been done on institutionalized patients with LOD suggests. Knowledge about this course is necessary to psycho-educate patients with YOD and their caregivers, to educate staff and deliver more adequate care concerning NPS.
We found three studies that compared NPS in community dwelling patients with YOD with patients with LOD, but these studies only included patients with Alzheimer’s disease (Mushtaq et al., Citation2016; Toyota et al., Citation2007; van Vliet et al., Citation2012). In these studies, more NPS was detected in LOD patients than in YOD patients. In one study YOD patients showed more eating changes and irritability and less depression and delusions than patients with LOD (van Vliet et al., Citation2012), whereas the other two studies found lower rates of delusions, agitation, disinhibition, aberrant motor behaviour and a lower total NPI score in YOD compared to LOD (Mushtaq et al., Citation2016; Toyota et al., Citation2007).
Longitudinal research in community dwelling patients with YOD showed that 54.4–79.7% of the patients had any NPS, which is a lower rate than the 90% described in the institutionalized population (Mulders et al., Citation2016; van Vliet et al., Citation2012). This could be expected because of disease progression and NPS as a risk factor for institutionalisation (Bakker et al., Citation2013). Mulders et al demonstrated a higher prevalence of agitation, disinhibition, irritability and aberrant motor behaviour and apathy and less prevalent psychotic symptoms correlated with dementia severity in institutionalized YOD patients (Mulders et al., Citation2016). The progression and course of these NPS in institutionalized YOD patients is yet unknown.
Therefore aim of this work is to provide insight in the progression and course of NPS over time using a longitudinal explorative study to describe the course of neuropsychiatric symptoms over a two-year period in patients with young onset dementia residing in Dutch nursing homes.
Method
Study design
This study is part of the Behaviour and Evolution Of Young Onset Dementia (BEYOND) study (Mulders et al., Citation2014, Citation2016), which is a cohort study with a cross-sectional part and a longitudinal part. All the nursing homes included in the cross-sectional part, that deliver specialized care for YOD patients, were asked to participate in this longitudinal part of the BEYOND study. Two nursing homes agreed to participate and were included in a two year follow-up with six monthly assessments. Patients were included provided: (1) they had a diagnosis of dementia according to DSM-IV-TR (American Psychiatric Association, Citation2000), (2) that first symptoms were before the age of 65, (3) that patients resided in the special care unit for at least four weeks before inclusion.
Baseline characteristics were retrieved from the medical record. These included age, gender, age at onset, date of admission to the nursing home, marital status and education. Most patients had an adequate examination and diagnostic workup which established the diagnosis and dementia subtype. The remaining five were recorded as not otherwise specified. The types of dementia were categorized into Alzheimer dementia (AD), Vascular dementia (VaD), Frontotemporal dementia (FTD), alcohol-related dementia (AlcD) and other including not otherwise specified.
The severity of dementia was assessed with the global deterioration scale (GDS). The GDS is a seven-point scale (1–7) ranging from ‘no global impairment’ (1) to ‘very severe global impairment’ (7). The scale is widely used for the assessment of dementia severity and correlates well with behavioural, and neuropsychological measures (Reisberg, Ferris, de Leon, & Crook, Citation1982). Cognitive functioning was assessed at baseline with the Severe impairment Battery-short version (SIB-s) and Mini mental state (MMSE). The SIB-s is a cognitive assessment instrument able to test cognition into the later stages of dementia (Folstein, Folstein, & McHugh, Citation1975; Saxton et al., Citation2005). SIB-s has been translated into Dutch and has been validated in Dutch nursing homes with dementia patients (de Jonghe, Wetzels, Mulders, Zuidema, & Koopmans, Citation2009).
Ethical considerations
The BEYOND study has been carried out in accordance with the applicable rules concerning the review of research ethics committees and informed consent. The study was reviewed and approved by the Regional Medical Ethics Committee Arnhem-Nijmegen.
Assessment of neuropsychiatric symptoms
NPS were assessed using the Dutch version of the Neuropsychiatric inventory- Nursing Home (NPI-NH), which includes 12 NPS (Cummings et al., Citation1994; Kat et al., Citation2002). The frequency (F) and severity (S) were rated on a four (1–4) and three (1–3) point Likert scale respectively. A symptom-score was calculated for each symptom by multiplying frequency and severity (FxS- score; range 0–12). NPSs with an FxS score ≥4 were considered clinically relevant. Based on previous research, we clustered NPI-NH items in three subsyndromes: hyperactivity (agitation, disinhibition, irritability and/or aberrant motor behaviour), psychosis (delusions and/or hallucinations) and mood (depression and/or anxiety) (Aalten et al., Citation2008; Mulders et al., Citation2016).
Statistical analysis
Statistical analysis was carried out using SPSS version 22. To asses any possible bias the baseline characteristics of the cross-sectional and this longitudinal part of the BEYOND study were compared. The baseline characteristics of the patients who completed the follow up were compared to those who did not, using T-tests and χ2-tests. In the first three assessments there was one NPI -assessment missing in different patients, these data were excluded from that assessment.
The outcomes of the statistical analysis were severity scores and frequency parameters. The mean severity score was calculated without a threshold (NPI ≥0) of all patients alive at the given assessment. These outcomes were analysed using the Friedman test. The following frequency parameters were calculated: point prevalence, resolution, persistence, incidence, and cumulative percentages. The point prevalence was defined as the proportion of residents with a specific symptom at each assessment. The cumulative two-year prevalence was defined as the percentage of residents with the symptom during at least one of the four intervals. Cumulative incidence was defined as the proportion of residents that did not show the specific symptom at baseline but developed the symptom at any of the following assessments. Cumulative resolution was defined as the proportion of residents who showed resolution of a symptom at any of the four intervals. Cumulative persistence was defined as the proportion of residents that had a symptom for at least two subsequent assessments, indicating a duration of symptoms of at least 6 months. Prevalence-rates were calculated from all patients alive at the moment of a given assessment. All cumulative percentages were calculated only in patients with complete follow-up.
Results
Residents
Eighty-nine residents were included in this study. Compared to the total group of 230 residents of the cross-sectional part of the BEYOND study (Mulders et al., Citation2014). Our study subgroup differed in dementia severity with more residents in GDS stage 2–4 and 5 and less residents in GDS stage 7. Fifty residents (56%) completed the whole two-year follow-up. The number of residents decreased at every assessment to N = 77, N = 67, N = 56, N = 50. Thirty residents died during follow-up, nine residents moved to another nursing home. These patients had a higher age and a higher stage of dementia and lower SIB-s and MMSE scores ().
Table 1. Participants characteristics
Neuropsychiatric symptoms
Delusions, agitation, aberrant motor behaviour, nighttime behaviour and the total score of the NPI changed statistically significant over the two-year follow-up with a variable course. Nighttime behaviour and total NPI increased in the first year and decreased in the second year. The other symptoms increased and decreased alternately over the complete course.
At any of the five assessments 82–96% of the residents had one or more clinically relevant symptoms and 52–73% showed two or more. The prevalence showed a variable course during the follow-up. Ninety-four percent developed a new symptom during the follow-up, of which irritability, agitation, disinhibition and eating change developed most often. All residents that had no clinically relevant symptoms at baseline developed symptoms during the follow-up. Twenty-two percent of the residents became completely symptom free during any of the four intervals, with irritability, eating change, disinhibition and depression showing the highest resolution over the intervals.
Overall Apathy was most prevalent and persistent of all NPS. Other persistent symptoms were eating change, irritability and aberrant motor behaviour ().
Table 2. Mean severity scores NPI (FxE ≥0 at baseline) at successive assessments.
Table 3. Point prevalence (%) at each assessment and cumulative prevalence (%) of NPI symptoms (FxE ≥4).
Table 4. Frequency parameters (%) of NPI symptoms (FxS >4) in residents with complete follow-up (N = 50).
Subsyndromes
Hyperactivity and mood subsyndromes changed significantly over time. During the follow-up, the course showed to be variable with no clear increase or decrease. Hyperactivity was the most prevalent subsyndrome. Sixty percent developed hyperactive behaviour with 64% persisting for at least two successive assessments. Cumulative incidence and cumulative resolution were high which indicates the variable course of hyperactivity.
Half of the residents developed mood symptoms during any of the intervals and half of the residents became symptom free during any of the intervals. For 16% of the residents mood symptoms were present in two consecutive assessments. The psychosis subsyndrome was the least prevalent and persistent. Sixteen percent of all residents developed psychosis over the two-year follow-up, of which 4% was present in at least two assessments ().
Discussion
This study is the first longitudinal study investigating the course of neuropsychiatric symptoms with a two-year follow-up in YOD residents of nursing homes. Eighty percent of the residents had at least one clinically relevant neuropsychiatric symptom at the moment of the assessments. Apathy was most prevalent and persistent of all symptoms. Clustered hyperactive and mood symptoms showed a variable course because of high resolution and high incidence which is also shown in significant change in the severity of these NPI clusters over time with no clear increase or decrease.
When comparing our data with those of van Vliet et al. that included community-dwelling YO-AD patients, the prevalence and cumulative incidence of any NPS were higher in our sample. Apathy, agitation, disinhibition, irritability and eating change had higher prevalence and incidence rates in our population compared to theirs. However, we found lower rates of depression and anxiety. Overall persistence was comparable, although apathy, disinhibition and irritability were more persistent in this study (van Vliet et al., Citation2012). These differences may be explained by more advanced dementia, other subtypes than Alzheimer’s disease and NPS as a risk factor for institutionalisation (Bakker et al., Citation2013).
Compared to a review on the prevalence and course of NPS in institutionalised LOD residents, we found higher prevalence rates of disinhibition, apathy and any NPS and lower prevalence rates of delusions (Selbaek, Engedal, & Bergh, Citation2013). Other NPS covered the prevalence ranges of this review when compared to our data. Overall it showed a different NPS pattern, in which hyperactivity cluster was more and psychosis and mood cluster were less prevalent in institutionalised YOD patients compared to institutionalised LOD patients. Two studies in this review showed a decline in severity and prevalence of depression. The change in severity of depression was not significant in our study. It showed an increase of depression in the first year and a decrease in the second year, however the numbers were to small to conclude differences in the course of depression between LOD and YOD patients. (Payne et al., Citation2002; Wetzels, Zuidema, de Jonghe, Verhey, & Koopmans, Citation2010).
Wetzels et al. and our study had a similar study design, which makes a comparison between institutionalized patients with YOD and LODpossible. The severity of agitation, elevation, apathy, nighttime behaviour, eating change and total scores exceeds in patients with YOD. Delusions, agitation, aberrant motor behaviour and nighttime behaviour fluctuate significantly over time, which is not shown in LOD patients in nursing homes (Wetzels et al., Citation2010). The course and pattern of NPS in patients with YOD in nursing homes differs from patients with LOD in nursing homes which is in accordance with the cross sectional part of the BEYOND study (Mulders et al., Citation2016).
Persistence of apathy and all NPS exceeded the range presented in the review of Selbaek et al about institutionalized LOD patients (Selbaek et al., Citation2013). Earlier research showed that apathy might be less recognized and it might be seen as a symptom of dementia rather than apathy as a treatable NPS. (Clarke et al., Citation2011; Smith & Buckwalter, Citation2005) The high persistence supports the poor response to treatment that was found in research regarding treatment of apathy (Harrison, Aerts, & Brodaty, Citation2016). Nevertheless apathy is associated with caregiver distress, cognitive decline, neuro-anatomical changes and poor illness outcomes (Clarke et al., Citation2011; Harrison et al., Citation2016; Lavretsky, Ballmaier, Pham, Toga, & Kumar, Citation2007). More attention and knowledge on apathy in this specific group of institutionalized patients is necessary to screen and treat apathy more effectively and to educate caregivers and staff.
Strengths and limitations
Our study is a sample of the BEYOND- study. Only 2 nursing homes and 89 participants were included, which results in limited power to detect significant results and may result in selection bias and a possible influence of the specific nursing homes. Therefore, the results may not be entirely generalizable.
Part of our sample was lost to follow-up. This group had a higher age and a higher GDS, which might result in selective loss of patients in the later stages of dementia. Therefore, this could result in bias. The loss during follow up and the sample size limited the possibility to compare different subtypes of dementia and determine influence on the course.
We used a threshold to calculate frequency parameters of clinically relevant NPS. It is possible that resolution in some instances is not complete resolution but just a score under the threshold, resulting in an overestimation of resolution, suggesting a more variable course, while in reality there may only be fluctuation in severity.
Conclusion and implications
This study showed a variable course of NPS in institutionalized patients with YOD with high overall prevalence, persistence and severity showing in apathy and hyperactive symptoms.
The amount of NPS and the higher persistence indicates the necessity of specialised care units with a focus on detection and treatment of NPS. These should focus on apathy and hyperactive symptoms as they are most prevalent.
This is the first study describing the course of NPS in patients with YOD in nursing homes. Future research should be done to analyse the course of NPS in different etiologies of dementia. Also psychotropic drug-use and their influence on the course of NPS in patients with YOD needs further attention to specify if the variable course might be influenced by starting or discontinuation of psychotropic drugs. This could benefit psycho-education and more fitting interventions for caregivers and patients.
Acknowledgements
We are grateful for the cooperation of the residents and staff of the participating nursing homes and H. Bor for his contributions to the statistical analysis.
Disclosure statement
No potential conflict of interest was reported by the authors.
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Appendix
Frequency parameters (%) of NPI symptoms (FxS >4) of the intervals between each assessment, calculated with residents alive at the next assessment.