Costs During the Last Five Years of Life for Patients with Clinical and Pathological Confirmed Diagnosis of Lewy Body Dementia and Alzheimer’s Disease

2.1 Study participants and sample selection

The participants of the current study were from the Predictors 2 study, a cohort of patients who were clinically diagnosed with mild dementia-predominantly AD but also DLB [33]. Recruitment of this cohort was initiated in 1997 at three sites: Columbia University, Johns Hopkins University, and Massachusetts General Hospital. Participants were then followed up every 6 months with repeated clinical measurements including medical, neuropsychological, functional, and dependence measures. AD was clinically diagnosed according to NINCDS-ADRDA criteria (n = 221) [34] and DLB was diagnosed according to the 1996 Consensus Guidelines (n = 28) [35]. 78 patients donated brains and have pathological data available. Of these 78, 62 participants had autopsy-confirmed diagnosis of AD (n = 34), mixed AD+LB (n = 17), or LB (n = 11). Sixteen participants who did not have α-synuclein immunohistochemistry staining to confirm the presence of Lewy body disease/synucleinopathy, seven participants who did not have pathological features required for AD or DLB diagnosis, and one participant who had no follow-up visits to assess clinical trajectory were excluded from the current analysis. Pathological categorization for each case into AD, DLB, or AD-DLB was based on review of neuropathologic reports and slides if necessary and staging of AD and Lewy body pathology as outlined in the National Institute on Aging-Alzheimer’s Association (NIA-AA) pathologic assessment of AD and Lewy body disease [36]. Details of clinical and pathological diagnosis procedures were reported previously [15]. We further excluded four participants who did not have Medicare claims. Differences in participants’ age, sex, education, and clinical symptoms at study enrollment between excluded and included samples were not statistically significantly different. The project was approved by the Institutional Review Board at each study site. All patients and their proxy decision makers provided written informed consent.

2.2 Medicare claims

Individuals were matched to Medicare Beneficiary Summary files using social security number and Medicare beneficiary ID. Medicare expenditures data were obtained from Medicare Standard Analytic Files (SAFs) and included all covered services (inpatient, outpatient, professional, emergency department, physician office visits, hospital outpatient visits, hospice, skilled nursing facility, home health, and durable medical supplies) in 6-month intervals from date of death to 5 years prior to death. Total expenditures in the last 5 years of life and average annual expenditures were summed. Expenditures were adjusted to 2021$ using the medical care component of the Consumer Price Index [37].

2.3 Patient characteristics

Participants underwent detailed cognitive and clinical assessment at baseline and at approximately 6-month intervals until drop out or death. Global cognitive status was assessed with the Folstein Mini-Mental State Examination (MMSE) (0–30, a higher score indicating better cognitive performance). Functional capacity was reported by the patient’s reliable informant using the Blessed Dementia Rating Scale (BDRS) Activities of Daily Living (ADL) sub-score [38], including seven instrumental ADL (IADL) items and three basic ADL items. Total ADL score was the sum of scores on all 10 items (range: 0–16), with higher scores indicating worse functional capacity. The ADL scale has good reliability and validity, with reliability coefficients reported to be between 0.60 and 0.80 [38]. Columbia University Scale for Psychopathology in Alzheimer’s Disease (CUSPAD) was used to measure patients’ psychotic, behavioral, and depressive symptoms [39]. The Unified Parkinson’s Disease Rating Scale (UPDRS) [40] was used to measure extrapyramidal signs (EPS) and treated as a binary variable with 1 indicating severity rating of mild-to-moderate or greater on any item [41]. Patients’ age at death, sex, and highest level of education were recorded. An Elixhauser comorbidities index was constructed using all ICD-9-CM diagnosis codes in all Medicare SAFs for the last 5 years of life [42, 43].

2.4 Statistical analyses

Demographic and clinical characteristics were summarized by mean and standard deviation (SD) for continuous variables and by frequency and proportions for categorical variables. The measures were compared among clinical diagnosis and autopsy-confirmed diagnosis groups using Kruskal-Wallis test for continuous variables and Chi-square test for categorical variables.

We estimated the association between average Medicare costs per year during the last 5 years of life and clinical and pathological diagnosis using generalized linear models (GLM). The main independent variables were the clinical diagnosis (AD versus DLB), confirmed pathology (pure AD, pure LB, and mixed AD+LB), and their interaction terms. We also estimated models adjusted for 1) demographics including age at death, sex, number of comorbidities, 2) demographics, MMSE, and BDRS 5 years prior to death, and 3) demographics, MMSE, BDRS, and extrapyramidal signs and psychotic symptoms 5 years prior to death. The Modified Park test (i.e., GLM family test), was used to identify the appropriate distribution, and the Pregibon Link test used to examine linearity of response on scale of estimation. The Modified Park test suggested that the normal (Gaussian) distribution with an identity link (i.e. ordinary linear regression models) function provided the best fit for the data.

All analyses were conducted using Stata 16.0. Due to the exploratory nature of this analysis, statistical significance level was defined as p < 0.05 a priori without corrections for multiple comparisons.

3.1 Patient characteristics

Half of the participants in the current study were female. Age at death was 80.2±8.8 (mean±SD) years, and years of education was 15±2.9 (Table 2). Five years prior to death, participants had an average of 2±1.9 comorbid conditions, average MMSE was 18.3±6.4, and BDRS was 10.9±4.5. Most had extrapyramidal signs (83%), and 52% had psychotic symptoms.

44 participants had a clinical diagnosis of AD (75.9%) and 14 (14.1%) had a clinical diagnosis of DLB (Table 1). At autopsy, 32 (55.2%) were confirmed to have AD pathology, 11 (19%) were confirmed to have DLB pathology, and 15 (25.9%) had mixed AD+LB pathology. Of the 44 participants with a clinical diagnosis of AD, 30 (68.2%) were confirmed to have pure AD pathology, 4 (9.1%) were confirmed to have pure LB pathology, and 10 (22.7%) had both AD and LB. Of the 14 participants with a clinical diagnosis of DLB, 7 (50%) were found to have pure LB neuropathologic changes in the autopsy, 2 were confirmed to have pure AD pathology, and 5 (35.7%) had both AD and LB pathology.

Compared to patients clinically diagnosed with AD, those clinically diagnosed with DLB died younger (DLB: 76.2±9.6, AD: 81.5±8.3, p = 0.05), and were marginally more likely to have extrapyramidal symptoms (DLB: 100%, AD: 78.6%, p < 0.10) and psychiatric symptoms (DLB: 75.0%, AD: 45.2%, p = 0.07) five years prior to death. Hallucinations (DLB: 667%, AD 11.9%, p < 0.001) and illusions (DLB 25.0% AD: 4.9%, p = 0.04) were higher in DLB than AD patients.

Looking at pathology confirmed diagnosis, those with AD pathology were older at death (pure AD: 81.8±8.7, pure LB: 77.2±8.4; mixed AD+LB: 78.9±8.9, p = 0.04). Five years prior to death, hallucinations (pure AD: 20%, pure LB: 56%; mixed AD+LB: 13%, p = 0.04) were significant higher in those with DLB pathology.

During the last 5 years of life, unadjusted annualized total Medicare expenditures were higher in patients clinically diagnosed DLB ($11,780±9,415) than in those clinically diagnosed with AD ($7,216±7,583, p = 0.06). Unadjusted annualized total Medicare expenditures during the last 5 years of life were higher in patients with mixed AD+LB pathology ($11,341±11,239) than in those with pure AD ($7,065±7,280) and pure LB ($7,839±4,949) pathologies, but these differences were not statistically significant (Table 2, also Table 3, Models 1 and 2).

We computed total Medicare expenditures in 6-month intervals for the last 5 years of life by clinical and pathology diagnosis. For 8 of the 10 6-month intervals, Medicare expenditures for clinically diagnosed DLB patients were higher than those for AD patients. However, because there were substantial variations in expenditures during each 6-month intervals, differences between DLB and AD groups were not statistically significant in any individual 6-month interval. Cumulative Medicare expenditures during the last 5 years of life in 6-month increments are presented by clinical diagnosis (Fig. 1) and pathology confirmed diagnosis (Fig. 2).

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Fig. 1

Unadjusted cumulative Medicare expenditures during the last 5 years of life, by clinical diagnosis. Medicare expenditures data were obtained from Medicare Standard Analytic Files (SAFs) and included all covered services (inpatient, outpatient, professional, emergency department, physician office visits, hospital outpatient visits, hospice, skilled nursing facility, home health, and durable medical supplies) in 6-month intervals from date of death to 5 years prior to death. Expenditures were adjusted to 2021$ using the medical care component of the Consumer Price Index.

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Fig. 2

Unadjusted cumulative Medicare A + B Payment, last 5 years of life, by pathology confirmed diagnosis. Medicare expenditures data were obtained from Medicare Standard Analytic Files (SAFs) and included all covered services (inpatient, outpatient, professional, emergency department, physician office visits, hospital outpatient visits, hospice, skilled nursing facility, home health, and durable medical supplies) in 6-month intervals from date of death to 5 years prior to death. Expenditures were adjusted to 2021$ using the medical care component of the Consumer Price Index.

Models 3–6 in Table 3 show estimated relationships between Medicare expenditures when both clinical and pathology-confirmed diagnoses are considered. Model 3 did not include any additional control variables, Model 4–6 additional controlled for demographics, dementia severity measures, and DLB specific clinical characteristics. Although the magnitude of the estimated coefficients varied across models, the directions of the estimates were consistent.

In the fully adjusted model (Table 3, model 6), the negative coefficient estimate (beta±SE = –8134±3166, p < 0.05) on clinical DLB suggests that in patients with pure AD (reference group), expenditures were lower in those clinically diagnosed as DLB than those clinically diagnosed with AD. However, such lower expenditures in clinically diagnosed DLB versus AD among pure AD cases was offset substantially if the patients carried mixed AD+LB pathologies rather than pure AD, as reflected by the significant positive coefficient on the interaction term ‘pathology confirmed mixed AD+LB ^* clinical DLB’ (beta±SE = 20,623±8,499, p < 0.05), suggesting that expenditures were higher for those clinically diagnosed with DLB than for those clinically diagnosed with AD among those with mixed AD+LB pathology. The coefficient on the interaction term “pathology confirmed pure LB ^* clinical DLB” (beta±SE = 2,727±3,728) was not statistically significant, suggesting that the lower expenditure of clinical DLB compared to clinical AD was similar in pure LB patients as in pure AD patients.

None of the coefficient estimates on the pathology diagnoses were statistically significant, suggesting that in patients clinically diagnosed with AD (reference group), differences in expenditures by pathology diagnosis were not statistically significant. The coefficient estimates on the interaction term on pathology confirmed mixed AD+LB and clinical DLB were statistically significant for all models, suggesting that for those clinically diagnosed with DLB, expenditures were substantially higher in those with mixed AD+LB pathology than in those with pure AD or pure LB.

Tables 4 shows predicted Medicare expenditures from Model 4, which includes clinical and pathology diagnosis and their interactions and demographic characteristics, but does not adjust for the subject’s clinical features that might drive costs of care (e.g., BDRS, MMSE, EPS, any psychotic symptoms), and the fully adjusted model (Model 6). Results show that, when pathology diagnoses were not considered, predicted expenditures were similar between clinically diagnosed AD ($7,465±1,098) and DLB ($7,783±1,803). When clinical diagnoses were not considered, predicted expenditures were substantially higher in patients with pathology confirmed mixed AD+LB ($12,005±2,455) than either pure AD ($6,173±941) or pure LB ($4,629±1,968) cases. Considering clinical and pathology diagnosis together, expenditures for patients with clinical DLB and pathology mixed AD+LB ($23,592±3,679) dwarfed other groups.

Results from models 4–6 which additionally controlled for demographics, dementia severity measures, and DLB specific clinical characteristics showed that number of comorbidities was associated with higher Medicare expenditures. Being female was associated with lower expenditures, but the estimates were no longer statistically significant once dementia severity and DLB specific clinical characteristics were controlled for.