A real-world assessment of healthcare costs associated with agitation in Alzheimer’s dementia

Figures & data

Figure 1. Sample selection flow chart. Abbreviations. AD, Alzheimer’s dementia; ICD-10-CM, International classification of diseases, Tenth revision, Clinical Modification. Note: 1. Patients who were identified as having agitation based solely on neuropsychiatric symptoms (i.e. hallucinations, delirium, paranoia) were excluded, as the true agitation state was not identifiable based on the information collected (i.e. unclear whether their charts had additional information to denote agitation or whether these symptoms were misclassified).

Table 1. Patient characteristics.

Patient characteristics	Before weighting			After weighting^1
	Agitation cohort	No agitation cohort	Std. diff.	Agitation cohort	No agitation cohort	Std. diff.
Number of patients, N	N = 240	N = 471		N = 240	N = 471
At the index date
Age, mean ± SD [median]	84.9 ± 7.7 [86.0]	84.9 ± 7.8 [86.0]	0.00	84.9 ± 7.7 [86.0]	84.8 ± 7.7 [86.0]	0.01
Female gender, n (%)	160 (66.7%)	359 (76.2%)	0.21*	160 (66.7%)	314 (66.7%)	0.00
Race, n (%)
White	203 (84.6%)	395 (83.9%)	0.02	203 (84.6%)	398 (84.5%)	0.00
African American or Black	1 (0.4%)	6 (1.3%)	0.09	1 (0.4%)	11 (2.3%)	0.16*
Asian	2 (0.8%)	4 (0.8%)	0.00	2 (0.8%)	4 (0.8%)	0.01
Native American or Alaskan Native	3 (1.3%)	2 (0.4%)	0.09	3 (1.3%)	4 (0.8%)	0.04
Unknown	31 (12.9%)	64 (13.6%)	0.02	31 (12.9%)	55 (11.7%)	0.04
Ethnicity, n (%)
Non-hispanic	185 (77.1%)	342 (72.6%)	0.10*	185 (77.1%)	363 (77.1%)	0.00
Hispanic	1 (0.4%)	7 (1.5%)	0.11*	1 (0.4%)	5 (1.1%)	0.08
Unknown	54 (22.5%)	122 (25.9%)	0.08	54 (22.5%)	103 (21.9%)	0.02
Calendar year, n (%)
2016	71 (29.6%)	139 (29.5%)	0.00	71 (29.6%)	139 (29.5%)	0.00
2017	58 (24.2%)	126 (26.8%)	0.06	58 (24.2%)	114 (24.2%)	0.00
2018	81 (33.8%)	155 (32.9%)	0.02	81 (33.8%)	159 (33.8%)	0.00
2019	30 (12.5%)	51 (10.8%)	0.05	30 (12.5%)	59 (12.5%)	0.00
Primary residence, n (%)
Single- or multi-family private residence (apartment, condo, house)	111 (46.3%)	216 (45.9%)	0.01	111 (46.3%)	218 (46.3%)	0.00
Skilled nursing facility, nursing home, hospital, or hospice	95 (39.6%)	120 (25.5%)	0.31*	95 (39.6%)	186 (39.5%)	0.00
Assisted living, adult family home, or boarding home	23 (9.6%)	62 (13.2%)	0.11*	23 (9.6%)	45 (9.6%)	0.00
Retirement community or independent group living	3 (1.3%)	11 (2.3%)	0.08	3 (1.3%)	6 (1.3%)	0.01
Unknown	8 (3.3%)	62 (13.2%)	0.36*	8 (3.3%)	16 (3.4%)	0.00
Living situation, n (%)
Lives in a group home (e.g. assisted living, nursing home, convent)	118 (49.2%)	183 (38.9%)	0.21*	118 (49.2%)	231 (49.0%)	0.00
Lives with one other person	74 (30.8%)	146 (31.0%)	0.00	74 (30.8%)	145 (30.8%)	0.00
Spouse or partner	48 (64.9%)	97 (66.4%)	0.03	48 (64.9%)	104 (71.7%)	0.15*
Relative, friend, or roommate	26 (35.1%)	49 (33.6%)	0.03	26 (35.1%)	41 (39.4%)	0.15*
Lives alone	22 (9.2%)	54 (11.5%)	0.08	22 (9.2%)	43 (9.1%)	0.00
Lives with a group (related or not related) in a private residence	16 (6.7%)	23 (4.9%)	0.08	16 (6.7%)	31 (6.6%)	0.00
Lives with a caregiver who is not spouse, relative, or friend	3 (1.3%)	4 (0.8%)	0.04	3 (1.3%)	6 (1.3%)	0.01
Unknown	7 (2.9%)	61 (13.0%)	0.38*	7 (2.9%)	14 (3.0%)	0.00
Smoking history, n (%)
Current smoker	6 (2.5%)	5 (1.1%)	0.11*	6 (2.5%)	12 (2.5%)	0.00
Former smoker	78 (32.5%)	171 (36.3%)	0.08	78 (32.5%)	153 (32.5%)	0.00
Never smoker	91 (37.9%)	162 (34.4%)	0.07	91 (37.9%)	179 (38.0%)	0.00
Unknown	65 (27.1%)	133 (28.2%)	0.03	65 (27.1%)	127 (27.0%)	0.00
Severity of AD, n (%)
Mild	19 (7.9%)	61 (13.0%)	0.17*	19 (7.9%)	37 (7.9%)	0.00
Moderate	23 (9.6%)	53 (11.3%)	0.06	23 (9.6%)	45 (9.6%)	0.00
Severe	79 (32.9%)	88 (18.7%)	0.33*	79 (32.9%)	155 (32.9%)	0.00
Unknown	119 (49.6%)	269 (57.1%)	0.15*	119 (49.6%)	233 (49.5%)	0.00
At any time
Year of AD diagnosis, n (%)
≤ 2015	129 (53.8%)	254 (53.9%)	0.00	129 (53.8%)	265 (56.3%)	0.05
2016	50 (20.8%)	81 (17.2%)	0.09	50 (20.8%)	74 (15.7%)	0.14*
2017	26 (10.8%)	65 (13.8%)	0.09	26 (10.8%)	62 (13.2%)	0.07
2018	24 (10.0%)	49 (10.4%)	0.01	24 (10.0%)	49 (10.4%)	0.02
2019	5 (2.1%)	9 (1.9%)	0.01	5 (2.1%)	9 (1.9%)	0.02
Unknown	6 (2.5%)	13 (2.8%)	0.02	6 (2.5%)	12 (2.5%)	0.00
Time from first onset of AD symptoms to diagnosis (years)^2, mean ± SD [median]	2.5 ± 2.7 [2.0]	2.0 ± 2.2 [1.5]	0.19*	2.5 ± 2.7 [2.0]	2.3 ± 2.3 [2.0]	0.08
Time from AD diagnosis to index date (years)^2, mean ± SD [median]	2.8 ± 2.5 [2.0]	2.8 ± 2.8 [2.0]	0.02	2.8 ± 2.5 [2.0]	2.8 ± 2.7 [2.0]	0.02
Time from first onset of AD symptoms to index date (years)^2, mean ± SD [median]	5.2 ± 3.6 [5.0]	4.5 ± 3.3 [4.0]	0.20*	5.2 ± 3.6 [5.0]	4.8 ± 3.2 [4.0]	0.11*
During the 6-month period prior to the index date
CCI score, mean ± SD [median]	3.4 ± 1.8 [3.0]	3.2 ± 2.0 [3.0]	0.13*	3.4 ± 1.8 [3.0]	3.4 ± 1.8 [3.0]	0.00

Abbreviations. AD, Alzheimer’s dementia; CCI, Charlson comorbidity index; N, number; SD, standard deviation; std. diff, standardized difference.

* Standardized difference > 0.1.

Notes:

1. Entropy balancing was used to balance key characteristics that may have an impact on the outcomes of interest between the agitation cohort and the no agitation cohort (i.e. age, gender, race, ethnicity, calendar year of index date, smoking history, time from first onset of AD symptoms to diagnosis, time from AD diagnosis to index date, time from first onset of AD symptoms to index date, severity of AD, primary residence, living situation, and CCI score). Patients in the no agitation cohort were assigned weights such that the distribution of key characteristics had the same mean and SD as the agitation cohort. Subject to rounding exceptions, weights were normalized so that the sum of weights was equal to the number of patients in each cohort.

2. The amount of time was calculated using the year of AD diagnosis (rather than the exact date).

Table 2. Comorbidities and treatments during the study period.

Number of patients, N	Before weighting			After weighting
	Agitation cohort	No agitation cohort	Std. diff.	Agitation cohort	No agitation cohort	Std. diff.
	N = 240	N = 471		N = 240	N = 471
Selected comorbidities^1, n (%)
Infection	132 (55.0%)	192 (40.8%)	0.29*	132 (55.0%)	206 (43.7%)	0.23*
Urinary tract infection	98 (40.8%)	114 (24.2%)	0.36*	98 (40.8%)	132 (28.0%)	0.27*
Pneumonia	38 (15.8%)	62 (13.2%)	0.08	38 (15.8%)	63 (13.4%)	0.07
Other	132 (55.0%)	192 (40.8%)	0.29*	132 (55.0%)	206 (43.7%)	0.23*
Depression	138 (57.5%)	171 (36.3%)	0.44*	138 (57.5%)	175 (37.2%)	0.42*
Osteoarthritis	102 (42.5%)	187 (39.7%)	0.06	102 (42.5%)	203 (43.1%)	0.01
Altered mental status	103 (42.9%)	109 (23.1%)	0.43*	103 (42.9%)	133 (28.2%)	0.31*
Osteoporosis	60 (25.0%)	138 (29.3%)	0.10	60 (25.0%)	129 (27.4%)	0.06
Fracture	79 (32.9%)	111 (23.6%)	0.21*	79 (32.9%)	133 (28.2%)	0.10*
Anxiety	70 (29.2%)	116 (24.6%)	0.10*	70 (29.2%)	125 (26.5%)	0.06
Falls	51 (21.3%)	54 (11.5%)	0.27*	51 (21.3%)	70 (14.9%)	0.17*
Delirium	52 (21.7%)	38 (8.1%)	0.39*	52 (21.7%)	44 (9.3%)	0.34*
Selected treatments^1, n (%)
Antidepressant	129 (53.8%)	180 (38.2%)	0.32*	129 (53.8%)	191 (40.6%)	0.27*
Antidementia	105 (43.8%)	199 (42.3%)	0.03	105 (43.8%)	208 (44.2%)	0.01
Cholinesterase inhibitor	89 (37.1%)	159 (33.8%)	0.07	89 (37.1%)	162 (34.4%)	0.05
Memantine	47 (19.6%)	98 (20.8%)	0.03	47 (19.6%)	100 (21.2%)	0.04
Anticonvulsant	65 (27.1%)	76 (16.1%)	0.27*	65 (27.1%)	86 (18.3%)	0.21*
Antipsychotic	71 (29.6%)	46 (9.8%)	0.52*	71 (29.6%)	45 (9.6%)	0.52*
Atypical antipsychotic	69 (28.8%)	44 (9.3%)	0.51*	69 (28.8%)	42 (8.9%)	0.52*
Antianxiety	21 (8.8%)	32 (6.8%)	0.07	21 (8.8%)	24 (5.1%)	0.14*
Benzodiazepines	20 (8.3%)	28 (5.9%)	0.09	20 (8.3%)	22 (4.7%)	0.15*

Abbreviations. AD, Alzheimer’s dementia; N, number; std. diff., standardized difference.

*Standardized difference > 0.1.

Note: 1. More than one option could have been selected (i.e. responses were not mutually exclusive).

Figure 2. Agitation characteristics during the study period.

Figure 3. Healthcare costs incurred during the study period. Abbreviations. AD, Alzheimer’s dementia; CI, confidence interval; PPPY, per-patient-per-year. *Significant at the 5% level. Notes: 1. IP costs includes admissions in hospital settings and skilled nursing facilities. 2. For AD-related healthcare costs, pharmacy costs represented only those associated with use of antidementia, antidepressant, antipsychotic, and antianxiety medications.

Table 3. Death and institutionalization characteristics at any time.

Number of patients, N	Before weighting			After weighting
	Agitation cohort	No agitation cohort	Std. diff.	Agitation cohort	No agitation cohort	Std. diff.
	N = 240	N = 471		N = 240	N = 471
At any time
Death status
Died, n (%)	155 (64.6%)	240 (51.0%)	0.28*	155 (64.6%)	270 (57.3%)	0.15*
Unknown	0 (0.0%)	0 (0.0%)	–	0 (0.0%)	0 (0.0%)	–
Time from AD diagnosis to death (years), mean ± SD [median]	4.7 ± 2.5 [4.0]	5.1 ± 2.8 [5.0]	0.15*	4.7 ± 2.5 [4.0]	5.0 ± 2.8 [4.0]	0.09
< 2 years, n (%)	5 (3.2%)	11 (4.6%)	0.07	5 (3.2%)	10 (3.7%)	0.03
2 - 4 years, n (%)	47 (30.3%)	65 (27.1%)	0.07	47 (30.3%)	88 (32.6%)	0.05
≥ 4 years, n (%)	100 (64.5%)	156 (65.0%)	0.01	100 (64.5%)	164 (60.7%)	0.08
Unknown, n (%)	3 (1.9%)	8 (3.3%)	0.09	3 (1.9%)	7 (2.6%)	0.05
Time from index date to death (years), mean ± SD [median]	1.8 ± 0.9 [1.6]	2.1 ± 0.9 [1.9]	0.30*	1.8 ± 0.9 [1.6]	2.0 ± 0.9 [1.7]	0.14*
< 1 year, n (%)	0 (0.0%)	0 (0.0%)	–	0 (0.0%)	0 (0.0%)	0.00
1– 2 years, n (%)	105 (67.7%)	127 (52.9%)	0.31*	105 (67.7%)	170 (63.0%)	0.10*
2 – 4 years, n (%)	48 (31.0%)	105 (43.8%)	0.27*	48 (31.0%)	92 (34.1%)	0.07
≥ 4 years, n (%)	2 (1.3%)	8 (3.3%)	0.14*	2 (1.3%)	8 (3.0%)	0.12*
Unknown, n (%)	0 (0.0%)	0 (0.0%)	–	0 (0.0%)	0 (0.0%)	–
Institutionalization
Lived in a private or group residence, n (%)	114 (47.5%)	227 (48.2%)	0.01	114 (47.5%)	224 (47.6%)	0.00
Moved from private home to an institutionalized setting (i.e. nursing home,  dementia-specific facility, other long-term care facility), n (%)	45 (39.5%)	62 (27.3%)	0.26*	45 (39.5%)	59 (26.3%)	0.29*
Time from index date to institutionalization (years), mean ± SD [median]	1.3 ± 0.9 [1.0]	1.8 ± 1.2 [1.5]	0.54*	1.3 ± 0.9 [1.0]	1.8 ± 1.2 [1.5]	0.53*
< 1 year, n (%)	22 (48.9%)	22 (35.5%)	0.27*	22 (48.9%)	24 (40.7%)	0.16*
1 - 2 years, n (%)	13 (28.9%)	15 (24.2%)	0.11*	13 (28.9%)	13 (22.0%)	0.16*
2 - 4 years, n (%)	10 (22.2%)	22 (35.5%)	0.30*	10 (22.2%)	19 (32.2%)	0.25*
≥ 4 years, n (%)	0 (0.0%)	3 (4.8%)	0.32*	0 (0.0%)	2 (3.4%)	0.28*
Unknown, n (%)	0 (0.0%)	0 (0.0%)	–	0 (0.0%)	0 (0.0%)	–
Time from AD diagnosis to institutionalization (years), mean ± SD [median]	3.8 ± 2.2 [3.5]	4.2 ± 2.7 [4.0]	0.18*	3.8 ± 2.2 [3.5]	3.8 ± 2.4 [3.0]	0.01
< 2 years, n (%)	6 (13.3%)	8 (12.9%)	0.01	6 (13.3%)	7 (11.9%)	0.02
2 - 4 years, n (%)	16 (35.6%)	20 (32.3%)	0.07	16 (35.6%)	22 (37.3%)	0.06
≥ 4 years, n (%)	22 (48.9%)	34 (54.8%)	0.12*	22 (48.9%)	29 (49.2%)	0.00
Unknown, n (%)	1 (2.2%)	0 (0.0%)	0.21*	1 (2.2%)	0 (0.0%)	0.21*
Time from first onset of agitated behaviors to institutionalization (years),  mean ± SD [median]	1.7 ± 1.5 [1.3]	–	–	1.7 ± 1.5 [1.3]	–	–
Institutionalized prior to the first onset of agitated behaviors, n (%)	4 (8.9%)	–	–	4 (8.9%)	–	–
< 1 year, n (%)	15 (33.3%)	–	–	15 (33.3%)	–	–
1 - 2 years, n (%)	10 (22.2%)	–	–	10 (22.2%)	–	–
2 - 4 years, n (%)	11 (24.4%)	–	–	11 (24.4%)	–	–
≥ 4 years, n (%)	5 (11.1%)	–	–	5 (11.1%)	–	–
Unknown, n (%)	0 (0.0%)	–	–	0 (0.0%)	–	–

Abbreviations. AD, Alzheimer’s dementia; N, number; SD, standard deviation; std. diff., standardized difference.

* Standardized difference > 0.1.

Data availability statement

Data is not available due to legal restrictions. Due to the nature of this research, participants of this study did not agree for their data to be shared publicly, so supporting data is not available. Therefore, restrictions apply to the availability of these data, which are not publicly available.