Exploring the relationship between patient-relevant outcomes and Alzheimer's disease progression assessed using the clinical dementia rating scale: a systematic literature review

Abstract

Background: People with Alzheimer's disease (AD) have difficulties in performing activities of daily living (ADLs) as the disease progresses, commonly experience neuropsychiatric symptoms (NPS), and often have comorbidities such as cardiovascular disease. These factors all contribute to a requirement for care and considerable healthcare costs in AD. The Clinical Dementia Rating (CDR) scale is a widely used measure of dementia staging, but the correlations between scores on this scale and patient-/care partner-relevant outcomes have not been characterized fully. We conducted a systematic literature review to address this evidence gap.

Methods: Embase, MEDLINE, and the Cochrane Library were searched September 13, 2022, to identify published studies (no restriction by date or country) in populations with mild cognitive impairment due to AD or AD dementia. Studies of interest reported data on the relationships between CDR Global or CDR-Sum of Boxes (CDR-SB) scores and outcomes including NPS, comorbidities, ADLs, nursing home placement, healthcare costs, and resource use.

Results: Overall, 58 studies met the inclusion criteria (42 focusing on comorbidities, 14 on ADLs or dependence, five on nursing home placement, and six on economic outcomes). CDR/CDR-SB scores were correlated with the frequency of multiple NPS and with total scores on the Neuropsychiatric Inventory. For cardiovascular comorbidities, no single risk factor was consistently linked to AD progression. Increasing CDR/CDR-SB scores were correlated with decline in multiple different measures of ADLs and were also associated with nursing home placement and increasing costs of care.

Conclusion: NPS, ADLs, and costs of care are clearly linked to AD progression, as measured using CDR Global or CDR-SB scores, from the earliest stages of disease. This indicates that scores derived from the CDR are a meaningful way to describe the severity and burden of AD for patients and care partners across disease stages.

Keywords: Alzheimer’s disease; activities of daily living; clinical dementia rating (CDR); comorbidity; healthcare costs; healthcare resource use; neuropsychiatric inventory (NPI); nursing home placement.

Figure 1

PRISMA diagram for the SLR. AD, Alzheimer’s disease; CDR, Clinical Dementia Rating; CDR-SB, Clinical Dementia Rating–Sum of Boxes; MCI, mild cognitive impairment; SLR, systematic literature review.

Figure 2

NPS frequency by AD stage. Panels (A–L) show data for each individual NPS (see labels on y-axes). Where p values are not shown, statistical tests were not conducted. p values across multiple categories represent tests of linear trends. Zhang et al. (74) used the CDR to determine disease severity, but did not specify exactly how each AD stage was defined (74). AD, Alzheimer’s disease; CDR, Clinical Dementia Rating; CI, confidence interval; MMSE, Mini Mental State Examination; NPS, neuropsychiatric symptom(s); NR, not reported; OR, odds ratio.

Figure 2

NPS frequency by AD stage. Panels (A–L) show data for each individual NPS (see labels on y-axes). Where p values are not shown, statistical tests were not conducted. p values across multiple categories represent tests of linear trends. Zhang et al. (74) used the CDR to determine disease severity, but did not specify exactly how each AD stage was defined (74). AD, Alzheimer’s disease; CDR, Clinical Dementia Rating; CI, confidence interval; MMSE, Mini Mental State Examination; NPS, neuropsychiatric symptom(s); NR, not reported; OR, odds ratio.

Figure 2

NPS frequency by AD stage. Panels (A–L) show data for each individual NPS (see labels on y-axes). Where p values are not shown, statistical tests were not conducted. p values across multiple categories represent tests of linear trends. Zhang et al. (74) used the CDR to determine disease severity, but did not specify exactly how each AD stage was defined (74). AD, Alzheimer’s disease; CDR, Clinical Dementia Rating; CI, confidence interval; MMSE, Mini Mental State Examination; NPS, neuropsychiatric symptom(s); NR, not reported; OR, odds ratio.

Figure 2

NPS frequency by AD stage. Panels (A–L) show data for each individual NPS (see labels on y-axes). Where p values are not shown, statistical tests were not conducted. p values across multiple categories represent tests of linear trends. Zhang et al. (74) used the CDR to determine disease severity, but did not specify exactly how each AD stage was defined (74). AD, Alzheimer’s disease; CDR, Clinical Dementia Rating; CI, confidence interval; MMSE, Mini Mental State Examination; NPS, neuropsychiatric symptom(s); NR, not reported; OR, odds ratio.

Figure 3

Prevalence of comorbidities by AD stage in Ton et al. (68) and Eldholm et al. (50) (A) and Yang et al. (72) (B). p values across multiple categories represent tests of linear trends. Tests of statistical significance in Ton et al. (68) also include a group with normal cognition (data not shown). AD, Alzheimer’s disease; CDR, Clinical Dementia Rating; CDR-SB, Clinical Dementia Rating–Sum of Boxes; TIA, transient ischemic attack.

Figure 4

Economic costs associated with CDR score categories in Darba et al. (85) (A,B) and Ikeda et al. (87) (C). Statistical significance in Darba et al. (85). Direct medical costs: p = 0.02 (CDR 1.0 and CDR 3.0). Social care costs p < 0.001 (CDR 1.0 and CDR 2.0; CDR 1.0 and CDR 3.0). Indirect costs: p = 0.9. Informal care costs and total care costs: p < 0.001 (CDR 0.5 and CDR 2.0, CDR 0.5 and CDR 3.0, CDR 1.0 and CDR 2.0, CDR 1.0 and CDR 3.0, and CDR 2.0 and CDR 3.0). Sample sizes in Ikeda et al. (87) refer to estimated patient numbers for the whole of Japan. Statistical significance was not tested. Estimated per-person costs are also included in the study publication but are not presented here because an estimate for total per-person healthcare costs for CDR 0.5 was not available. ADD, Alzheimer’s disease dementia; CDR, Clinical Dementia Rating; JPY, Japanese Yen.