Sum of boxes of the clinical dementia rating scale highly predicts conversion or reversion in predementia stages

Abstract

Background: The clinical dementia rating (CDR) scale is commonly used to diagnose dementia due to Alzheimer's disease (AD). The sum of boxes of the CDR (CDR-SB) has recently been emphasized and applied to interventional trials for tracing the progression of cognitive impairment (CI) in the early stages of AD. We aimed to study the influence of baseline CDR-SB on disease progression to dementia or reversion to normal cognition (NC).

Materials and methods: The baseline CDR < 1 cohort registered from September 2015 to August 2020 with longitudinal follow-up in the History-based Artificial Intelligence Clinical Dementia Diagnostic System (HAICDDS) database was retrospectively analyzed for the rates of conversion to CDR ≥ 1. A Cox regression model was applied to study the influence of CDR-SB levels on progression, adjusting for age, education, sex, neuropsychological tests, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors.

Results: A total of 1,827 participants were analyzed, including 1,258 (68.9%) non-converters, and 569 (31.1%) converters with mean follow-up of 2.1 (range 0.4-5.5) and 1.8 (range 0.3-5.0) years, respectively. Conversion rates increased with increasing CDR-SB scores. Compared to a CDR-SB score of 0, the hazard ratios (HR) for conversion to dementia were 1.51, 1.91, 2.58, 2.13, 3.46, 3.85, 3.19, 5.12, and 5.22 for CDR-SB scores of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, and ≥4.5, respectively (all p < 0.05 except for CDR-SB score = 0.5). In addition, older age, lower education, lower cognitive performance, and a history of diabetes also increased conversion rates. Furthermore, reversions to NC were 12.5, 5.6, 0.9, and 0% for CDR-SB scores of 0.5, 1.0-2.0, 2.5-3.5 and ≥4.0, respectively (p < 0.001).

Conclusion: CDR-SB in predementia or very mild dementia (VMD) stages highly predicts progression to dementia or reversion to NC. Therefore, CDR-SB could be a good candidate for tracing the effectiveness of pharmacological and non-pharmacological interventions in populations without dementia.

Keywords: Alzheimer’s disease; history-based artificial intelligence clinical dementia diagnostic system; predementia; sum of boxes of the clinical dementia rating; the clinical dementia rating.

FIGURE 1

Flow chart for participant selection.

FIGURE 2

Cox regression model of the clinical dementia rating (CDR) < 1 cohort was adopted for investigating the contribution of sum of boxes of the CDR (CDR-SB) levels to conversion to CDR ≥ 1. Hazard ratios (HRs) were adjusted for age, gender, education, cerebrovascular disease (CVD), parkinsonism, diabetes, hypertension, dyslipidemia, coronary artery disease, arrhythmias, and congestive heart failure.

FIGURE 3

Cox regression model of the clinical dementia rating (CDR) < 1 cohort was adopted for investigating the contribution of cognitive impairment (CI) groups determined with the sum of boxes of the CDR (CDR-SB) levels to conversion to CDR ≥ 1. Hazard ratios (HRs) were adjusted for age, gender, education, cerebrovascular diseases (CVD), parkinsonism, diabetes, hypertension, dyslipidemia, and coronary artery diseases.

FIGURE 4

Percentage frequency of reversion to normal cognition (NC), stable, and conversion to clinical dementia rating (CDR) ≥ 1 among different cognitive impairment (CI) groups determined with the sum of boxes of the CDR (CDR-SB) levels.