Tracy Tholanikunnel1, Brian Labarre1, Kaitlin Sovich1, Zhigang Li1, James Galvin2, Henry Paulson3, Susan Maixner3, Carol Manning4, Julie Fields5, Angela Lunde5, Bradley Boeve5, Leah Forsberg5, Angela Taylor6, Melissa Armstrong7
1University of Florida, 2University of Miami, 3University of Michigan, 4University of Virginia, 5Mayo Clinic, 6Lewy Body Dementia Association, 7UF Department of Neurology
Objective:
To assess correlates of fluctuations in moderate-advanced dementia with Lewy bodies [DLB].
Background:
Cognitive fluctuations (spontaneous episodic deficits in attention, arousal, cognition, and behavior) are a core DLB feature, but remain poorly understood.
Design/Methods:
The PACE-DLB study collected measures of Lewy body disease, demographics, and patient and caregiver experiences from moderate-advanced DLB individual-caregiver dyads. Fluctuations were assessed via the Mayo Fluctuations Scale (MFS, range 0-4) and Clinician Assessment of Fluctuation (CAF, range 0-16). Concordance was assessed using Spearman correlation for raw scores and Cohen’s Kappa for assessing scores above/below the cut-off. Nonparametric methods including Spearman correlation, two-sample Wilcoxon test, and odds ratios assessed factors associated with fluctuations. The FDR method corrected raw scores for multiple testing.
Results:
Patients (n=137) identified as white non-Hispanic (94.9%) and male (79.6%); mean age 75.0 (SD 8.0), disease duration 3.0 years (SD 2.4). Caregivers were typically wives (72.3%) and daughters (13.1%). On the MFS, 116 participants (84.7%) had fluctuations (score ≥3) (mean 3.3, SD 0.8) versus 116 (84.7%) on the CAF (score >0) (correlation: 0.2, p<0.001; fluctuations absent/present: 0.3, p=0.002). The mean CAF score was 8.8 (SD 6.6). Variables associated with a positive MFS included higher sleepiness scores (p=0.02), lower QoL-AD scores (p=0.02), and parkinsonism (p=0.02). No variables associated with a positive CAF. Higher MFS scores associated with higher sleepiness scores (p<0.001), lower QoL-AD, and more autonomic symptoms (p=0.03). Higher CAF scores associated with higher Neuropsychiatric Inventory severity scores (p<0.0001), hallucinations (p=0.045), orthostatic hypotension (p=0.02), more comorbidities (p=0.04), and higher sleepiness scores (p=0.045). Fluctuations associated with worse patient and caregiver quality of life and higher caregiver burden and depression.
Conclusions:
The MFS and CAF correlated weakly. Fluctuations associated with sleepiness, autonomic symptoms, parkinsonism, and neuropsychiatric symptoms. Given the impact of fluctuations on quality of life and caregiver burden and depression, fluctuations are an important target for future pharmacologic therapies.