Cognitive and Functional Decline Occurs Faster in Lewy Body Dementia vs Pure Alzheimer Disease

Yian Gu, MD, MS, PhD

Using autopsy-confirmed cases of pure Alzheimer disease (AD), mixed AD and dementia with Lewy bodies (AD+DLB), or pure DLB, findings of a recent study showed different disease trajectories prior to death, with the pure DLB group experiencing nearly double the rate of both cognitive and functional decline than pure AD.¹

"The findings of this autopsy-based study have great implications for clinical management, future clinical study design, and research on pathology-specific biomarkers,” lead author Yian Gu, MD, MS, PhD, assistant professor of neurological sciences, Columbia University, and colleagues concluded.

The retrospective longitudinal study included 62 participants from the Predictors 2 study, a cohort of patients with dementia clinically diagnosed with predominantly AD but also DLB. Recruitment for the study began in 1997 and patients were followed up every 6 months with repeated clinical measurements including medical, neuropsychological, functional, and dependence measures. The study used Mini-Mental State Examination (MMSE) to examine the trajectory of cognition and Blessed Dementia Rating Scale (BDRS) Activities of Daily Living (ADL) to assess function. The dependence scale (DS), the third measure observed, was developed to evaluate the amount of assistance patients with AD require to fulfill daily functions.

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There were 34 patients with pure AD, 17 with mixed AD+DLB, and 11 with pure DLB. At the time of recruitment, the participants of the study were 73.5 years old (±7.9), had 15 years (±2.9) of education, scored 20.8 (±4.3) on MMSE, 4.68 (±3.0) on ADL, and 4.48 (±2.6) on DS. The majority (87%) of the participants had mild dementia with the other 13% having moderate dementia, demonstrated by Clinical Dementia Rating scores of at least 2. Overall, the participants received an average of 9.4 assessments (±4.6) at 6-month intervals during a mean 5.4 years (±2.9) of follow-up time.

Among all subjects, MMSE declined 0.74 points (SE, 0.17; P <.0001), ADL increased 0.66 points (SE, 0.14; P <.0001), and DS increased 0.47 points (SE, 0.09; P <.0001) per year. In a fully adjusted model, the pure-DLB group experienced a faster decline in MMSE (b = –1.02; SE, 0.39; P = .010) and faster deterioration in DS (b = 0.41; SE, 0.17; P = .015) relative to the pure-AD group.

For a patient with pure AD who experienced 0.61 points decline in MMSE in 1 year, a patient with pure DLB who has similar characteristics would decline an additional 1.02 points, or a total of 1.63 points per year. This equated to approximately 2.7 times of the rate in patients with pure AD.

Compared with the pure AD group, the AD+DLB group experienced a faster deterioration in ADL (b = 0.48; SE, 0.21; P = .026). Furthermore, the annual change of ADL in patients with AD+DLB was similar to the change typically seen in a patient with pure AD of similar characteristics in approximately 1.9 years. Between the AD+DLB and pure DLB groups, there were no difference in the trajectory of MMSE, ADL, or DS.

On supplementary analysis, which limited the assessments to the 5 years preceding death, the results were similar, even with larger effect sizes, but were no longer significant. Specifically, compared with the AD group, the DLB group experienced a non-significant faster deterioration in MMSE (b = 0.81; SE, 0.96; P = 0.120), DS (b = 0.53; SE, 0.32; P = .096), and ADL (b = 0.81; SE, 0.50; P = 0.106).

REFERENCE
1. Gu Y, Kociolek A, Fernandez KK, et al. Clinical trajectories at the end of life in dementia patients with Alzheimer disease and Lewy body neuropathologic changes. Neurology. Published online April 4, 2022. doi:10.1212/WNL.0000000000200259