Prediction of survival of advanced dementia patients using the advanced dementia prognostic tool: a 2-year prospective study

doi:10.21203/rs.3.rs-2604364/v1

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Prediction of survival of advanced dementia patients using the advanced dementia prognostic tool: a 2-year prospective study

https://doi.org/10.21203/rs.3.rs-2604364/v1

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Background

There is a lack of research on life expectancy estimation in advanced dementia patients. In this prospective study, we evaluated the usefulness of the advanced dementia prognostic tool (ADEPT) for estimating the 2-year survival of patients in China.

Methods

Patients were recruited from nursing homes and hospitals in Chongqing, China, and followed up for 2 years. The usefulness of the ADEPT score for predicting the 2-year survival rate was evaluated using the area under the receiver operating characteristic (AUROC) curve.

Results

In total, 115 patients were included in the study. Of these patients, 48 died. The mean ADEPT score was 13.0. The AUROC for the prediction of the 2-year mortality rate using the ADEPT score was 0.62. The optimal threshold of ADEPT score was 11.2, which had an AUROC of 0.63, specificity of 41.8, and sensitivity of 83.3.

Conclusions

The ADEPT score based on a threshold of 11.2 was useful to determine the 2-year survival rate of patients with advanced dementia in Chongqing, China. The survival estimation may be used to improve the treatment of patients.

ADEPT

advanced dementia prognostic tool

advanced dementia

prediction

survival

Advanced dementia is defined as the final stage of dementia, a syndrome characterized by acquired and persistent cognitive impairments caused by brain dysfunction. The most common cause of dementia is Alzheimer’s disease (AD) [1]. Advanced dementia is defined as stage 7 of the global deterioration scale (GDS; ranging from 1 to 7, with higher stages indicating more severe dementia). GDS provides a useful description of the features of advanced dementia [2]. Patients with advanced dementia are often bedridden and have a poor quality of life as well as many complications that lead to high mortality. This disease places a great burden on families and society, and has become a significant public health problem worldwide [3].

In total, 44 million people had dementia worldwide in 2013; this figure is estimated to reach approximately 135 million by 2050. In the United States, between 2000 and 2010, the death rate from AD increased by 39%, and AD became the fourth-leading cause of death for people older than 65 years in 2010 [4, 5]. Medical and care costs for people with advanced dementia range from $157–215 billion annually and is expected to more than double by 2040 [6].

In 2020, a model predicted that there will be 16.25 million (95% confidence interval [CI], 11.55−21.18) persons with dementia in China. By 2050, this number would increase by approximately three-fold to 48.98 million (38.02−61.73). According to the data simulation, if the incidence of dementia decreased by 10% every 10 years from 2020 due to various interventions and prevention strategies, the number of dementia cases would be reduced by 11.96 million by 2050. This would reduce the economic burden by US $639.04 billion [7].

The challenge of accurately estimating life expectancy in advanced dementia is a barrier to providing palliative care or active treatment to patients with advanced dementia. The original ADEPT study was conducted to assist in the identification of U.S. Medicare patients who may be eligible for hospice care and determine the interrater reliability of ADEPT scores. However, studies of survival of advanced dementia patients have typically been restricted to 6 months due to time limitations [8–11]. Furthermore, there is a lack of studies and data collection for life expectancy estimations of advanced dementia patients in China. Therefore, additional surveys are needed to evaluate the usefulness of the ADEPT score in China.

In this survey, we conducted a 2-year follow-up to test the effect of the internationally used advanced dementia prognostic tool (ADEPT) for the estimation of life expectancy in patients with advanced dementia in China.

Study participants

Patients were recruited between March 12, 2018, and January 21, 2020; 53 patients were recruited from three hospitals and 89 patients were recruited from five nursing homes in Chongqing, China. The study eligibility criteria included a diagnosis of dementia, age older than 60 years, a mini-mental state examination (MMSE) score of < 10, clinical dementia rating (CDR) score of three, and a GDS score of six or seven [2]. Each patient had an onsite assessment to collect data, and previous dementia records were not used.

The sample size was calculated using the area under the relative operating characteristic (ROC) curve-Medcalc version 20. Based on a type I error (alpha, significance) of 0.05 and type II error (beta, 1-power) of 0.20 for the area under the ROC curve (AUROC), the minimum acceptable AUROC was established to be 0.65, similar to a previous study [10, 11]. The null hypothesis value refers to an AUROC of 0.5 when the index has no diagnostic value under the null hypothesis. For the ratio of sample sizes in the negative/positive groups, the ratio of negative to positive groups was one. The estimated sample size was 115 samples.

The patient proxies were contacted to provide oral informed consent for the patients’ and their own participation. The study protocol was approved by the ethics review committee of Chongqing Medical University and the other participating institutions.

Adept Score

The ADEPT score was designed using the minimum data set (MDS) data collected from all licensed nursing homes in the United States. It included 12 items; the total score ranged from 1.0 to 32.5, with higher points indicating a greater risk of death (eFigure, available at http://www.jama.com) [10]. In our survey, researchers collected primary data from the patients’ daily situations and conducted interviews of nurses to calculate the scores. Previous assessments were not used. The obtained data included the date of nursing home admission, age, sex, shortness of breath, ≥ 1 pressure ulcers of ≥ stage 2, activities of daily living score = 28 (complete functional dependence), bedbound for most of the day, insufficient oral intake, bowel incontinence, body mass index (BMI) < 18.5 kg/m², recent weight loss, and congestive heart failure.

The weights and heights of the residents were used to determine whether the BMI (calculated as weight in kilograms divided by height in meters squared) was < 18.5 kg/m² (threshold of underweight) [12] and whether they had experienced recent weight loss (> 5% of the body weight in last 30 days or > 10% in the last 180 days). Total functional dependence was defined as a score of 28 on the activities of daily living scale (range, 0−28) [13] as assessed by a carer interview. The carer also determined whether the residents were bedbound (in a bed or recliner > 22 hours/d) for at least 4 days a week; had bowel incontinence at least once a week during the prior 14 days; were dyspneic during the past 7 days; had poor oral intake in the past 3 days (ate < 75% of food in at least two out of three daily meals or did not consume all or nearly all liquids); and had at least one pressure ulcer that was worse than stage 2. Tube-fed residents were considered not to have poor oral intake. Dyspnea was considered present when documented in the residents’ records or reported by their nurses. A time limit of 90 days was selected to distinguish between short and long nursing home stays [11, 14, 15].

Procedures

After patient recruitment, we calculated the ADEPT, MMSE, CDR, GDS, and movement disorder society-activities of daily living (MDS-ADL) scores.

Two years later, we contacted the proxies and nurses of the patients to check whether the patient was alive. If a patient had died, we confirmed the date of death. Accordingly, we excluded 27 patients who were lost to follow-up.

Outcomes

We recorded the ADEPT scores and survival of the enrolled patients to calculate the ratio of the ADEPT score to predict the 2-year survival of patients with advanced dementia. We compared the ratio between hospitals and nursing homes.

Statistical analysis

The frequencies of all patient characteristics and ADEPT score items were calculated. The total ADEPT score was calculated for each resident, and the mean (standard deviation) was determined for the cohort.

The ADEPT score for the life expectancy prediction of the 2-year survival was assessed using logistic regression analysis and AUROC. To determine the optimal threshold of the ADEPT score for the 2-year survival prediction, 95% confidence intervals (CIs) were calculated for the sensitivity, specificity, positive and negative predictive values, and the observed mortality rates using the AUROC Yorden index. The optimal threshold value of the ADEPT score that exerted a predictable reference value was filtered out (Table 1).

Table 1

Operating characteristics of risk score cut-offs to predict the 2-year mortality for advanced dementia patients
Risk score cut-off	Sensitivity	Specificity	Positive predictive value	Negative predictive value
> 6.4	97.9 (88.9–99.9)	6.06 (1.7–14.8)	43.1 (41.3–44.9)	80.0 (31.6–97.2)
> 7.9	93.8 (82.8–98.7)	12.1 (5.4–22.5)	43.7 (40.9–46.6)	72.7 (42.7–90.5)
> 8.9	93.8 (82.8–98.7)	22.7 (8.6–27.9)	46.9 (43.2–50.6)	83.3 (60.5–94.2)
> 9.7	93.8 (82.8–98.7)	25.8 (15.8–38.0)	47.9 (43.9–51.9)	85.0 (63.8–94.8)
> 10.5	87.5 (74.8–95.3)	31.8 (20.9–44.4)	48.3 (43.4–53.2)	77.8 (60.5–88.9)
> 11.5	79.2 (65.0–89.5)	43.9 (31.7–56.7)	50.7 (44.2–57.1)	74.4 (61.1–84.3)
> 12.5	62.5 (47.4–76.0)	59.1 (46.3–71.0)	52.6 (43.6–61.5)	68.4 (58.8–76.7)
> 14.0	37.5 (24.5–53.6)	66.7 (58.5–83.0)	45.0 (33.2–57.4)	59.5 (52.6–65.9)
> 16.1	27.1 (15.3–41.8)	84.9 (73.9–92.5)	56.5 (38.4–73.1)	61.5 (56.7–66.2)

In addition, the AUROC was used to examine whether there was a difference in the ratios of usefulness of the ADEPT score to predict the 2-year survival of patients with advanced dementia between hospitals and nursing homes.

Study sample

Among the 142 recruited advanced dementia patients, 115 (80.3%) were included in the final analysis (48 from the hospital and 67 from the nursing home); 27 were excluded due to loss during follow-up. Only five patients died in 6 months, 15 patients died in the next 6 months, 28 patients died in the second year, and 67 were still alive after 2 years. Their ADEPT scores are shown in Table 2.

Table 2

ADEPT score for nursing home and hospital residents with advanced dementia (N = 115)
Characteristic	No. (%) of nursing home residents	Points of risk score
Nursing home stay < 90 d	3 (2.6)	3.3
Age, y (per 5-y increment)	-	-
< 65	2 (1.7)	0.0
65–69	4 (3.5)	1.0
70–74	7 (6.1)	2.0
75–79	14 (12.2)	3.0
80–84	24 (20.9)	4.0
85–89	34 (29.6)	5.0
90–94	22 (19.1)	6.0
95–99	8 (6.9)	7.0
≥ 100	0 (0)	8.0
Sex, male	41 (36.0)	3.3
Shortness of breath	16 (14.0)	2.7
≥ 1 Pressure ulcers at ≥ stage 2	2 9 (7.9)	2.2
Activity of daily living score = 28^a	84 (73.7)	2.1
Bedbound for most of the day	95 (83.3)	2.1
Insufficient oral intake^b	46 (40.4)	2.0
Bowel incontinence^c	92 (80.7)	1.9
BMI < 18.5 kg/m^2d	53 (46.5)	1.8
Recent weight loss^{d, e}	9 (7.9)	1.6
Congestive heart failure	8 (7.0)	1.5
Abbreviations: ADEPT advanced dementia prognostic tool, BMI body mass index
^a Activities of daily living score (range, 0–28) is the sum of scores in seven domains of function, including bed mobility, dressing, toileting, transfer, eating, grooming, and locomotion. Each domain is scored on a 5-point scale (0 = independent; 1 = requires supervision; 2 = requires limited assistance; 3 = requires extensive assistance; and 4 = total dependence). A score of 28 represents complete functional dependence
^b Not consuming almost all liquids in the previous 3 days or at least 25% of food uneaten at most meals
^c Occasionally, frequently, or always (vs rarely or never)
^d BMI and recent weight loss are calculated with a sample size of 580 because a recent weight was not available for 26 nursing home residents
^e Recent weight loss is defined as more than 5% body weight in prior 30 days or more than 10% in prior 180 days

A total of 59 nursing home residents (51.7%) were aged 80–90 years; three (2.6%) had resided in the nursing home for < 90 days. A total of 84 residents (73.7%) were completely functionally dependent (activity of daily living score = 28), and 95 (83.3%) were bedbound for most of the day. Dyspnea was experienced by 16 residents (14.0%), and eight (7.0%) had congestive heart failure. In terms of nutritional markers, 46 residents (40.4%) had an insufficient oral intake, 53 (46.5%) had a BMI < 18.5 kg/m², and nine (7.9%) had recent weight loss. There were 92 residents (80.7%) with bowel incontinence and nine (7.9%) with at least one pressure ulcer (≥ stage 2).

Adept Score

The mean (SD) ADEPT score of the residents was 13.0 (3.9). The results suggest that patients from Chongqing, China tended to have a longer life expectancy, despite a greater ADEPT score (Table 2).

Further statistical analysis showed that the ADEPT score was not useful for the life expectancy prediction of the 6-month and 1-year survival because only five and 20 patients, respectively, among 115 patients died.

The AUROC for the usefulness of the ADEPT score for the prediction of the 2-year mortality was 0.62 (95% CI, 0.53−0.71) (Fig. 1). Table 1 shows the operating characteristics of the ADEPT risk score at various cut-off points. A cut-off point > 11.2 achieved the highest AUROC value of 0.63 (95% CI, 0.53−0.72), a sensitivity of 83.3 (95% CI, 50.7−79.1), and a specificity of 41.8 (95% CI, 51.1−77.1). Figure 2 displays the survival curves for the entire cohort and residents with ADEPT scores > 11.2 (n = 36 [31.3%]) and ≤ 11.2 (n = 79 [68.7%]).

The AUROC for the use of the ADEPT score for the prediction of the 2-year mortality in hospitals was 0.58 (95% CI, 0.43−0.71) and in nursing homes was 0.66 (95% CI, 0.53−0.77). However, p > 0.05 (Fig. 3) indicated the lack of statistical difference in the ADEPT score prediction for the 2-year mortality between the hospitals and nursing homes.

Among the 142 recruited patients, 118 (83.1%) reported their monthly costs over the past year, the average of which was ¥9,727. The cost was mainly covered by patients’ offspring and pension.

To the best of our knowledge, the use of the ADEPT survey for the prediction of survival in patients with advanced dementia is rare in China, and our findings fill several knowledge gaps regarding its use. First, patients with advanced dementia in our cohort generally displayed a longer survival than the 6-month survival period, indicates that the commonly used survival time period of 6 months is not suitable in China [8–11]. Second, using the 2-year period as the survival time limit, the ADEPT risk score assisted in the prediction of the outcomes for advanced dementia patients. Third, there was no statistical difference in the ADEPT score prediction for the 2-year mortality between hospitals and nursing homes.

In addition to the physical condition, the survival prediction for dementia patients is influenced by many other factors, including treatment, disease type, medical insurance, nursing condition, race, national development, and natural environment [16–23]. The survival prediction tools for advanced dementia should take these factors into consideration and set appropriate criteria for different countries and possibly even districts [24, 25]. This survey evaluated the usefulness of ADEPT for estimating the survival of advanced dementia patients in Chongqing, China.

The ADEPT risk score displayed modest calibration and discrimination for the 2-year survival prediction when applied as a continuous measure (AUROC = 0.62). It may be used for both hospital patients and nursing home residents. Furthermore, we found that an ADEPT cutoff score of 11.2 could be used as a diagnostic reference for the 2-year survival prediction (AUROC = 0.63).

The discrimination of the ADEPT score to predict survival in patients with advanced dementia between this study and previous studies was remarkable. Previous research regarding survival prediction in patients with advanced dementia has focused on the 6-month period and has rarely targeted Chinese patients [8–11]. In our study, patients with advanced dementia had a mean ADEPT score of 13.0, but death occurred within 6 months in only five (4.3%) patients and within 2 years in 48 (41.7%) patients. The most representative international research has shown a mean ADEPT score of 10.1 and 6-month mortality of 18.3% [11]. Compared to other studies in North America, the patients in our study had higher mean ADEPT scores but lower mortality, indicating a better survival for advanced dementia patients in Chongqing, China [8–11].

The primary reason for the difference in the survival prediction of advanced dementia patients between this study and previous international studies may be the positive attitude toward treatment and the highly developed aged care system [26]. Due to a lack of death education in China and the essential pursuit of longevity in traditional culture, both the patients and their family members prefer active, and sometimes excessive, treatment to prolong life. The abovementioned viewpoints are supported by the lack of euthanasia acceptance [27, 28] and the development of the health products industry and caring professions for the elderly compared with little publicity for hospice services [29]. Furthermore, under the influence of Confucian filial piety that “Filial piety is the foundation of all virtues”, children face great social and mental stress when they end the active treatment of a parent, which may be misunderstood as irresponsible behavior in the viewpoint of the parent [30–32]. In our study, the offspring’s support for the medical and care costs of patients support the abovementioned opinion. In conclusion, palliative care and quality of life are increasingly emphasized in Western countries [33, 34], while in China, the survival period is still the paramount consideration, followed by quality of life. A positive treatment attitude explains the outcome in this study, i.e., longer survival of patients with advanced dementia in China compared to other countries.

This study demonstrated that there was no statistical difference in the prediction of the 2-year mortality by the ADEPT score between the hospitals and nursing homes. Therefore, our results do not support the viewpoint that living in a hospital prolongs survival. The family of an advanced dementia patient may select the appropriate therapeutic regimen based on the will of the patient and other conditions.

The study has several advantages that provide evidence regarding the accuracy of data. First, the data were collected onsite or from the caregivers. Second, the study follow-up lasted 2 years, while previous studies mainly followed patients for 6 months. Third, participants were willing to cooperate because the study only involved data collection and did not involve the use of placebo, which might influence the treatment outcomes.

In clinical practice, asymptomatic patients and patients with low ADEPT scores are less likely to develop dementia and visit a doctor. To reduce wastage of medical resources and the panic associated with misdiagnosis, we prefer to select sensitive diagnostic tests and cut-off points. In this case, the sensitivity indices had a definite influence on the overall accuracy of the diagnostic tests. The diagnostic tests were selected based on only a portion of the ROC curve (areas of high sensitivity), rather than the entire AUROC. The potential advantage of the ADEPT score is that it is a continuous measure and offers physicians and other primary care clinicians caring for these patients (e.g., nurse practitioners) the flexibility to select cutoff values with different operating characteristics (i.e., a trade-off between sensitivity and specificity).

Notably, there were several limitations to our study. First, the study enrolled a relatively small number of patients (i.e., 115). Future studies should enroll a larger sample size. Second, the ADEPT score was calculated at a single random time point in the disease course, and the clinical events were not recorded. In practice, hospice referrals are often initiated when care preferences shift toward comfort following a clinical setback. Third, our prospective cohort was predominantly based on patients who lived in Chongqing, China, potentially limiting the generalizability of our findings. In addition, the ADEPT score was derived and validated in nursing home residents. Although a large number of patients with dementia die in nursing homes and hospitals, the ADEPT score has not been validated for use in patients living in the community.

In summary, this study emphasized the challenge of prognostication in advanced dementia patients. The ADEPT score based on a threshold of 11.2 was useful to determine the 2-year survival rate of patients with advanced dementia in Chongqing, China (AUROC = 0.63). As such, the determination of the life expectancy of patients with advanced dementia and limits of the provision of supportive care hospice service, especially for patients in China, requires more research. We found that the treatment attitude of a patient’s family had a non-negligible effect on the allocation of medical resources. Furthermore, a generally longer survival period was observed for patients in Chongqing, China. These results could help to better coordinate therapies—including the survival period and quality of life—and allocate medical resources more rationally [35]. Further research on the survival rates and related treatment schedules of Chinese patients with advanced dementia is required.

ADEPT	advanced dementia prognostic tool
AD	Alzheimer’s disease
AUROC	area under the receiver operating characteristic
BMI	body mass index
CDR	clinical dementia rating
CIs	confidence intervals
GDS	global deterioration scale
MMSE	mini-mental state examination
MDS	minimum data set
MDS-ADL	movement disorder society-activities of daily living
ROC	relative operating characteristic
SD	standard deviation

Acknowledgment

We thank the following organizations for their assistance: the Chongqing General Hospital, Chongqing Qinggang Senior Care Center, Chongqing Mental Health Center, Second Social Welfare Institute of Chongqing, Yunyang Health Care Home of Chongqing, Yunyang Xingjiawan Elder Service Center of Chongqing, and Sunset Elder Care Center of Chongqing.

Author contributions

Xuebing Li, Weihua Yu, and Yang Lü designed the study. Xuebing Li, Bei Liu, Wuhan Yu, Wenbo Zhang, Cheng Hu, Zhangjin Qin, and Yu Chen collected the data. Junjin Liu performed the follow-up, analyzed the data, and wrote the manuscript. Junjin Liu, Weihua Yu, and Yang Lü revised the manuscript.

Funding

This study was supported by grants from the Chongqing Talent Plan (grant number cstc2022ycjh-bgzxm0184); the Key Project of Technological Innovation and Application Development of Chongqing Science & Technology Bureau (grant number CSTC2021jscx-gksb-N0020); the Science Innovation Programs Led by the Academicians in Chongqing (grant number cstc2020yszx-jscxX0006); and the Intelligent Medicine Program of Chongqing Medical University (grant numbers ZHYX2019008 and ZHYX202110).

Availability of data and materials

Anonymized data not published within this article will be made available by request from any qualified investigator.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University and was performed in accordance with the ethical standards laid down in the Declaration of Helsinki and its later amendments.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no potential competing interests.

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Prediction of survival of advanced dementia patients using the advanced dementia prognostic tool: a 2-year prospective study

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