key: cord-0935222-thyuh49h authors: Sizoo, Eefje M.; Thunnissen, Josi A.; van Loon, Anouk M.; Brederveld, Claire L.; Timmer, Helma; Hendriks, Simone; Smalbrugge, Martin title: The course of neuropsychiatric symptoms and psychotropic drug use in Dutch nursing home patients with dementia during the first wave of COVID‐19: A longitudinal cohort study date: 2022-02-21 journal: Int J Geriatr Psychiatry DOI: 10.1002/gps.5693 sha: f5e073007c4f8629cdbda9d03f8da4012c8db0bf doc_id: 935222 cord_uid: thyuh49h OBJECTIVE: To describe the course of neuropsychiatric symptoms in nursing home residents with dementia during the step‐by‐step lifting of restrictions after the first wave of the COVID‐19 pandemic in the Netherlands, and to describe psychotropic drug use (PDU) throughout the whole first wave. METHODS: Longitudinal cohort study of nursing home residents with dementia. We measured neuropsychiatric symptoms using the Neuropsychiatric Inventory‐Questionnaire (NPI‐Q). From May to August 2020, the NPI‐Q was filled in monthly. Psychotropic drug use was retrieved from the electronic prescription system, retrospectively for the months February to April and prospectively for the months May to August. RESULTS: We followed 252 residents with dementia in 19 Dutch nursing homes. Agitation was the most prevalent type of neuropsychiatric symptom at each assessment. Overall, the prevalence and severity of agitation and depression significantly decreased over time. When considering more in detail, we observed that in some residents specific neuropsychiatric symptoms resolved (resolution) while in others specific neuropsychiatric symptoms developed (incidence) during the study period. For the majority of the residents, neuropsychiatric symptoms persisted over time. Psychotropic drug use remained stable over time throughout the whole first wave of the pandemic. CONCLUSIONS: At group level, lifting the measures appeared to have beneficial effects on the prevalence and severity of agitation and depression in residents with dementia. Nevertheless, on an individual level we observed high heterogeneity in the course of neuropsychiatric symptoms over time. Despite the pressure of the pandemic and the restrictions in social contact imposed, PDU remained stable. People with dementia living in NH frequently display neuropsychiatric symptoms neuropsychiatric symptoms (NPS), with a 2-year cumulative prevalence of up to 96%. 1 NPS are defined as behavioral and psychological problems -including agitation, aggression, depression, psychosis and apathy -and can be elicited by a multitude of causes, both related to disease or extrinsic factors. 2, 3 Importantly, these symptoms can pose a heavy burden on the resident and his or her surroundings and decrease the quality of life. 4 In more than half of the NH residents with dementia, psychotropic drugs are prescribed, in particular antidepressants, benzodiazepines and antipsychotics. 5 When the COVID-19 pandemic reached the Netherlands, NH residents were strongly affected. 6 The mortality risk in NH residents living in The Netherlands with a proven COVID-19 infection was high in the first wave of the pandemic, 7 in particular in residents with dementia. 8 As many of their European counterparts, the Dutch government decided that from March 19 th 2020 all NHs had to take restrictive measures. 9 These measures included a national NH visiting ban in order to minimize the interaction between residents and others. The visitor ban proved to be a double-edged sword: crucial to curb the rising infection rate and mortality, but at the cost of social contact. Previous studies in this area have underscored the vital importance of social interaction for the quality of life of the NH residents. [10] [11] [12] The behavior of residents with dementia is strongly influenced by contact with others, social activities, and the general surroundings. 4, 13, 14 Therefore, it is probable that the COVID-19 induced restrictions in social contact affect the prevalence and expression of neuropsychiatric symptoms of residents with dementia. A limited number of largely retrospective studies have been conducted to examine to what extent the restrictions in social contact imposed by the measures influenced NPS and PDU in people with dementia. It was found that, except for psychotic behavior, all NPS increased. [15] [16] [17] [18] [19] [20] Two studies reporting on PDU found an increase in the proportion of dementia patients using psychotropic drugs, in particular antipsychotic drugs. 21, 22 Notably, these studies only included dementia patients living at home [17] [18] [19] 22 or in a retirement home. 20 It is challenging to extrapolate these results to the NH population, as the severity of dementia and behavioral problems in NH residents is likely to be much higher. 23 NH professionals participating in a survey during the first COVID-19 wave reported that the effect of lockdown differed per individual: they noted an increase in some residents and a decrease in others. 24 However, none of these studies investigated NPS and PDU over time on individual resident level. Therefore, the aim of this study was to describe the course of NPS in a cohort of NH residents with dementia from May 2020 until August 2020 during and after the first wave of COVID-19. In this period the COVID-19 restrictions were lifted step-by-step in the Netherlands. We describe both changes in the overall prevalence of NPS in general and the course of NPS within the study population in more detail, defining the incidence, persistence, and resolution of separate NPS over time. Secondly, we describe PDU over time between February 2020 and August 2020, throughout the whole first wave of COVID-19. We performed a longitudinal cohort study, comprised of both prospective and retrospective data. Data collection started in May 2020, in a period with severe restrictions in social contact. Retrospective data was collected from February 2020 -before the lockdown -and onwards, and prospective data collection continued during the decrease of the restrictions until August 2020. Data was collected at psychogeriatric units of 19 NHs, a convenience sample of units in NHs associated with the vocational training for elderly care physician (ECP) in Amsterdam. Residents lived in the north or central part of the Netherlands, comprising both rural and urban areas. Inclusion criteria were: a reported diagnosis of dementia in the medical chart and admittance to the psychogeriatric unit before January 1 st 2020. Residents were excluded if they were expected to die within a month after the start of the study in May 2020. Data was collected and pseudonymized by elderly care physicians (ECPs) in training, further referred to as 'ECPs'. 25 In May 2020, ECPs obtained patient characteristics, gender, age, and type of dementia from the medical chart. Severity of dementia was estimated by the ECP using the Global Deterioration Score (GDS). 26 A GDS score of 1-3 was classified as 'mild', GDS 4-5 was classified as 'moderate' and GDS 6-7 'severe'. Once a month in May, June, July, and August, the ECPs filled in a case report form on the pandemic-related restrictions on social contact in NHs, NPS and PDU for every resident. Furthermore, PDU data was collected retrospectively for the months February, March and April 2020. We used the Neuropsychiatric Inventory-Questionnaire Neuropsychiatric Inventory-Questionnaire (NPI-Q), a validated questionnaire, to measure the occurrence (present or absent) and severity (mild, moderate, or severe) of NPS in residents with dementia. 27 The NPI-Q includes 12 scales of behavior: delusions, hallucinations, agitation/ aggression, depression, anxiety, euphoria, apathy, disinhibition, irritability, repetitive motor behavior, nighttime disturbances, and appetite/changes in eating habits. We categorized NPS into five types of challenging behavior as defined by the Dutch Multidisciplinary guideline problem behavior in dementia 2 namely: depression, anxiety, apathy, psychotic behavior, and agitation. For depression, anxiety, and apathy, the corresponding single NPI-Q items were used. Following previous studies, the symptoms delusions and hallucinations were combined in a new scale for psychotic behavior and agitation was defined as a combination of the symptoms agitation/aggression, disinhibition, and irritability. 28 For the combined scales psychotic behavior and agitation 'present' was defined if at least one of the individual NPI-Q symptoms was present at that assessment. To determine the severity of these combined scales, the mean of the respectively two or three subscales was calculated at each assessment. Euphoria, repetitive motor behavior, nighttime disturbances, and appetite/changes in eating habits were not analyzed over time. However, to get an overview of the complete NPI-Q over time, the proportion of the residents who showed any of the 12 symptoms was calculated for each assessment and referred to as 'NPI-Q Total'. PDU was retrieved from the electronic prescription system. For prospectively collected PDU, the reference date was set on the day of the NPI-Q assessments and the reference date for retrospective PDU was respectively in week eight (February), 12 (March), 17 (April) 2020. PDU was grouped into antipsychotics, antidepressants, benzodiazepines and anti-dementia drugs, and dichotomized to either present or absent. Among as needed prescriptions, only as needed benzodiazepine use was included in the analysis. We used IBM SPSS Statistics 26 th Edition for statistical analysis. Baseline characteristics and measurements were analyzed by means of descriptive statistics. We reported percentages per group for dichotomous or ordinal data, and mean and standard deviation for continuous variables. We used logistic generalized estimating equation (GEE) with an exchangeable correlation structure to assess longitudinal changes in point prevalence for each NPS and PDU. The Friedman test was used to analyze the severity of the NPS over time. Since the Friedman test cannot be conducted on participants with missing data, these analyses were done in the population with complete data at each assessment. Results are presented with 95% confidence intervals (CI) and all reported p values are two-sided. We applied Bonferroni correction because of multiple comparisons within each NPS. To gain more insight into the course of NPS within the population, we calculated resolution, persistence, and incidence for every interval between two successive assessments. 1,29 Resolution described the proportion of residents showing an NPS at one assessment, but absence of the NPS in the next. Persistence was defined as the proportion of residents showing a specific NPS at two succeeding assessments. Resolution and persistence together make 100%. Incidence describes the population that developed an NPS between two assessments and was calculated over residents not showing the specific symptom at the previous assessment. The cumulative prevalence is the proportion of participants who showed an NPS atleast one assessment during the study period (4 months). The cumulative incidence is defined as the ratio of participants without a specific NPS at the start of the study, who developed this in a succeeding assessment. To calculate the percentages of the parameters for each interval, complete data at every assessment is needed. Therefore, these analyses were performed on participants with complete data at each assessment. The Dutch Medical Ethics Review Committee (METC) of the Amsterdam University Medical Center (UMC), location VUmc approved the study protocol. Residents were followed by their own ECP. A legal representative received a letter with information and the purpose of the study and could object against use of data for this study. SIZOO ET AL. At baseline, 265 residents met the inclusion criteria of whom 252 were included in this study ( Figure 1 ). During the study, the number of residents decreased to 240, 234 and 221 in respectively June, July, and August due to death, relocation, or unknown reasons ( Figure 1 ). In June, there was missing data for 17 residents. Among these 17 residents, one had died after the third assessment, but before the end of the study. Thus, 221 residents survived the study, and a total of 205 (92.8%) had complete data for each assessment. The mean age of residents was 84 years (SD 9) and 71.4% were female. Alzheimer's disease was the most prevalent type of dementia (41.3%) and the majority of the residents were suffering from severe dementia (69.8%). All resident characteristics are presented in Table 1 . The prevalence of all NPS from May until August is shown in Figure 2 and Table S1. In May, agitation was the most prevalent type of challenging behavior (75%), followed by apathy (38%), anxiety (36%) and depression (34%). Psychotic behavior was the least prevalent (28%). Longitudinal change in the prevalence of NPS are summarized in Table S3 ). For apathy, anxiety, and psychotic behavior, no significant changes over time were found in prevalence and severity (Tables S2 and S3 ). In Table 3 , we present resolution, persistence, and incidence of specific NPS at each successive interval. Although agitation and depression decreased over time, the incidence rate fluctuated (16.1%-21.1% for agitation and 6.6%-13.2% for depression). For apathy, anxiety, and psychotic behavior, the overall prevalence averaged. Still, the NPS resolved in some residents (resolution) and developed in others (incidence). At each interval, persistence was higher than resolution for all types of NPS. Examples of restrictions in freedom of movement were: except from the unit, the NH was closed for the resident, specific public areas in the NH were closed for the resident, the courtyard was closed for the resident. Proportion of residents with a present NPS at the first assessment to residents with a present NPS at the next assessment. c Proportion of residents without a present NPS at the first assessment to residents with a present NPS at the next assessment. d Proportion of the resident that had a present NPS at least at one assessment. e Proportion of resident without a present NPS in May to residents that developed a NPS at least one successive assessment. benzodiazepines also increased slightly from 11.7% in February to 13 .7% in May and decreased to 11.2% in June. Remarkably, as needed prescriptions afterwards increased again to 13.7% August (Table S4) . However, these changes over time are all non-significant. The prescription rate of anti-dementia drugs was very low throughout the study period ( Previous studies on the effect of the COVID-19 induced restrictions on NPS in patients with dementia living at home, [17] [18] [19] [20] 22 reported that except for psychotic behavior, all NPS increased during the pandemic compared to before the pandemic. The data collection in our study started during severe restrictions in social contact. If these restrictions would induce an increase in NPS, one would expect a high prevalence of NPS during the severe restrictions and a decrease in prevalence when lifting the restrictions. For agitated behavior, we indeed observed a high prevalence of all agitation subscales in May, during severe restrictions in social contact. This prevalence appears to be higher than reported in two previous studies in the Dutch NH setting before the COVID-19 pandemic. 1, 30 Furthermore, overall agitation significantly decreased when the restrictions in social contact were lifted whereas under normal circumstances, the overall prevalence of agitation tends to increase over time. 1 Therefore, our results suggest that the lockdown negatively affected agitated behavior in NH residents with dementia. However, in the majority of individual residents, agitation still persisted, similarly to patterns in pre-COVID studies. 1,31 Furthermore, we observed that for some NH residents, agitation developed when the restrictions in social contact were relieved, as reflected in the incidence of agitation in June, July and August (16%-21%). Possibly, these are the residents described by professionals who benefitted from the restrictions during the lockdown. 24 In line with our agitation results, the prevalence of depressive symptoms significantly decreased over time. This also may be attrib- with dementia also tend to decrease somewhat over time. 1, 32 For anxiety, psychotic behavior, and apathy we found no significant change over time. Conversely, at all timepoints the prevalence of anxiety was relatively high compared to pre-pandemic studies. 1, 30 Possibly, symptoms of anxiety are less related to the restrictions in social contact but more a result of the threat of a pandemic as a whole. 33 Still, symptoms of anxiety fluctuated; in 26%-33% of the residents, anxiety resolved during each interval. The overall prevalence of psychotic behavior and apathy appeared to stay in a narrow range whereas resolution and incidence showed an intermittent course. Taken together, the specific NPS scores at group level can provide a comprehensive overview of effects over time, but may mask individual variability. Our results underscore the findings by Leontjevas et al. 24 who reported that the effect of the restrictions in social contact on NPS differed per individual. As psychotropic drugs in residents with dementia are often prescribed to treat NPS, an increase in NPS could also induce an increase in PDU. Interestingly, we found that PDU remained largely stable in NH throughout the whole first wave of COVID-19 induced restrictions in social contact and the prevalence of PDU is in line with a recent study in Dutch NH conducted before the pandemic. 5 These results differ from findings in community-dwelling patients with dementia in other countries reporting an increase in PDU. 21, 22 Apparently, the high prevalence of NPS did not induce an increase in psychotropic drug prescriptions in NH residents. We consider this a positive result, in line with the recommendations in guidelines to prefer non-pharmacological interventions over PDU. 2, 3 The strength of this study is that, despite the high workload in NHs during the first wave of COVID-19, we were able to prospectively collect data on NPS using a validated questionnaire on a monthly basis in a large cohort of NH residents with dementia. Moreover, we were able to retrieve data on PDU throughout the whole first wave of the pandemic. The proportion of residents with complete data at each This study showed that NPS manifest and develop heterogeneously in residents with dementia during a period of time with a continuously changing environment. Some residents will suffer from the social isolation and the changing environment. Others might even benefit from less external stimuli due to restrictions in social contact. In case of new restrictions, nursing home professionals need to be alert for changes in NPS of residents. Policy makers should take the effects on NPS in residents with dementia into consideration when imposing restrictions in social contact on NH residents. Course of neuropsychiatric symptoms in residents with dementia in nursing homes over 2-year period Multidisciplinary Guideline Problem Behavior in Dementia. NIP Dementia: Assessment, Management and Support for People Living with Dementia and Their Carers Determinants of quality of life in nursing home residents with dementia Psychotropic drug prescription for nursing home residents with dementia: prevalence and associations with non-resident-related factors The impact of COVID-19 on long-term care in the Netherlands. Long-Term Care Policy Network. CPEC-LSE COVID-19 in verpleeghuizen: Een studie naar de diagnostiek, de ziektepresentatie en het ziektebeloopNTVG Clinical presentation of COVID19 in dementia patients Op advies van Verenso scherpt kabinet bezoekregeling verpleeghuizen aan. Dutch Organisation for Elderly Care Physicians (Verenso); 2020 Dilemmas with restrictive visiting policies in Dutch nursing homes during the COVID-19 pandemic: a qualitative analysis of an openended questionnaire with elderly care physicians Reopening the doors of Dutch nursing homes during the COVID-19 crisis: results of an indepth monitoring The impact of COVID-19 measures on well-being of older long-term care facility residents in the Netherlands Influencers on quality of life as reported by people living with dementia in long-term care: a descriptive exploratory approach Quality of life of institutionalized older adults by dementia severity The impact of COVID-19 infection and enforced prolonged social isolation on neuropsychiatric symptoms in older adults with and without dementia: a Review Neuropsychiatric symptoms in elderly with dementia during COVID-19 pandemic: definition, treatment, and future directions Neuropsychiatric symptoms and quality of life in Spanish patients with alzheimer's disease during the COVID-19 lockdown The effects of confinement on neuropsychiatric symptoms in alzheimer's disease during the COVID-19 crisis Behavioral and psychological effects of coronavirus disease-19 quarantine in patients with dementia High depression and anxiety in people with alzheimer's disease living in retirement homes during the Covid-19 crisis Antipsychotic prescribing to people with dementia during COVID-19 COVID-19 epidemic in Argentina: worsening of behavioral symptoms in elderly subjects with dementia living in the community Burden of behavioral and psychiatric symptoms in people screened positive for dementia in primary care: results of the delpHi-study Challenging behavior of nursing home residents during COVID-19 measures in the Netherlands The Dutch move beyond the concept of nursing home physician specialists The Global Deterioration Scale for assessment of primary degenerative dementia Validation of the NPI-Q, a brief clinical form of the neuropsychiatric inventory Stability of the factor structure of the neuropsychiatric inventory in a 31-month follow-up study of a large sample of nursing-home patients with dementia The course of neuropsychiatric symptoms in dementia. Part I: findings from the two-year longitudinal Maasbed Study Prevalence of neuropsychiatric symptoms in a large sample of Dutch nursing home patients with dementia The course of psychiatric and behavioral symptoms and the use of psychotropic medication in patients with dementia in Norwegian nursing homes--a 12-month follow-up study The course of depressive symptoms as measured by the Cornell Scale for depression in dementia over 74 months in 1158 nursing home residents Impact of social isolation on people with dementia and their family caregivers The Hawthorne effect: a fresh examination The authors thank all ECPs in training who participated in the data The authors have no conflicts of interest to declare. The Dutch METC of the UMC in Amsterdam UMC, location VUmc approved the study protocol. Due to the nature of this research, residents included in this study did not agree for their data to be shared publicly, so supporting data is not available. -9