Greater Variability in Cognitive Decline in Lewy Body Dementia Compared to Alzheimer's Disease

Abstract

Studies indicate more rapid cognitive decline in patients with Lewy body dementia (LBD) compared to Alzheimer's disease (AD). However, there has been less focus on any difference in the variability of cognitive decline. We assessed Mini-Mental State Examination (MMSE) test performance at baseline and annually for 5 years in 222 patients with mild dementia in the DemVest study who had either AD (137) or LBD (85). We used linear mixed models (LMMs) with random intercepts (variability in MMSE at baseline) and slopes (variability in MMSE decline), with years in study, age, gender, and diagnosis as independent variables. A non-linear (quadratic) trajectory was selected, interacting with age and diagnosis. To study differences in variance, we compared a regular LMM (i.e., a homoscedastic model), which assumes equal variance across groups, to a heteroscedastic model, assuming unequal intercept and slope variance based on diagnosis. The heteroscedastic model gave a better fit (Likelihood ratio test: χ2 = 30.3, p < 0.001), showing overall more variability in LBD. Further, the differences in intercept and slope variances were tested using a modified Wald test. The MMSE intercept variance (AD: 2.78, LBD: 7.75, difference: 4.97, p = 0.021) and slope variance (AD: 2.62, LBD 7.81, difference: 5.19, p = 0.004) were both higher in LBD. In conclusion, patients with LBD in the DemVest study have a higher variability in MMSE scores at study inclusion, and in MMSE decline compared to AD. Accordingly, clinical trials on LBD may need a larger sample size compared to AD.

Keywords: Alzheimer’s disease; Lewy body dementia; Lewy body disease; MMSE decline; cognitive decline; dementia with Lewy bodies; heteroscedastic; random effects; trajectory; variability; variance.