Effect of cognitive fluctuation on neuropsychological performance in aging and dementia

Cognitive fluctuations are spontaneous alterations in cognition, attention, and arousal. Fluctuations are a core feature of dementia with Lewy bodies, but the impact of fluctuations in healthy brain aging and Alzheimer disease (AD) are unknown. Research participants (n = 511, age 78.1 +/- 8 years, education 14.9 +/- 3 years) enrolled in a longitudinal study of memory and aging at the Washington University Alzheimer Disease Research Center were assessed for the presence and severity of dementia with the Clinical Dementia Rating (CDR) and a neuropsychological test battery. Informant assessments of fluctuations with the Mayo Fluctuations Questionnaire and daytime level of alertness with the Mayo Sleep Questionnaire were completed. After controlling for age and alertness level, participants with cognitive fluctuations (3 or 4 individual symptoms) were 4.6 times more likely to have dementia (95% confidence interval: 2.05, 10.40). Participants who presented with disorganized, illogical thinking were 7.8 times more likely to be rated CDR >0. The risk of being rated CDR 0.5 among those with fluctuations was 13.4 times higher than among those without fluctuations. The risk of being rated CDR 1 increased 34-fold among participants with fluctuations. Compared with participants without fluctuations, the presence of cognitive fluctuations corresponds to a decrease in performance across individual neuropsychological tests as well as composite scores. Cognitive fluctuations occur in Alzheimer disease and, when present, significantly affect both clinical rating of dementia severity and neuropsychological performance. Assessment of fluctuations should be considered in the evaluation of patients for cognitive disorders.