Predictors and outcomes of fluctuations in the clinical dementia rating scale

• Published in: Alzheimer's & dementia 2024-03, Vol.20 (3), p.2080-2088
• Main Authors: Wilks, Hannah, Benzinger, Tammie L. S., Schindler, Suzanne E., Cruchaga, Carlos, Morris, John C., Hassenstab, Jason
• Format: Article
• Language: English
• Subjects: Aging; Alzheimer disease; Alzheimer Disease - diagnosis; Alzheimer Disease - genetics; Alzheimer Disease - psychology; Alzheimer's disease; Apolipoproteins; Asymptomatic; Biological markers; Biomarkers; Candidates; clinical dementia rating scale; clinical reversion; Clinical trials; Cognition; Cognition & reasoning; Cognitive ability; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - genetics; Cognitive Dysfunction - psychology; Cognitive impairment; Dementia; Disease Progression; Humans; Longitudinal studies; Memory; Mental Status and Dementia Tests; Normality; Older people; Ratings & rankings; Secondary prevention; Systematic review
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1002/alz.13679

INTRODUCTION Reversion, or change in cognitive status from impaired to normal, is common in aging and dementia studies, but it remains unclear what factors predict reversion. METHODS We investigated whether reverters, defined as those who revert from a Clinical Dementia Rating® (CDR®) scale score of 0.5 to CDR 0) differed on cognition and biomarkers from unimpaired participants (always CDR 0) and impaired participants (converted to CDR > 0 and had no reversion events). Models evaluated relationships between biomarker status, apolipoprotein E (APOE) ε4 status, and cognition. Additional models described predictors of reversion and predictors of eventual progression to CDR > 0. RESULTS CDR reversion was associated with younger age, better cognition, and negative amyloid biomarker status. Reverters that eventually progressed to CDR > 0 had more visits, were older, and were more likely to have an APOE ε4 allele. DISCUSSION CDR reversion occupies a transitional phase in disease progression between cognitive normality and overt dementia. Reverters may be ideal candidates for secondary prevention Alzheimer's disease (AD) trials. Highlights Reverters had more longitudinal cognitive decline than those who remained cognitively normal. Predictors of reversion: younger age, better cognition, and negative amyloid biomarker status. Reverting from CDR 0.5 to 0 is a risk factor for future conversion to CDR > 0. CDR reversion may be a transitional phase in Alzheimer's Disease progression. CDR reverters may be ideal for Alzheimer's disease secondary prevention trials.