Disease progression in dementia with Lewy bodies: A longitudinal study on clinical symptoms, quality of life and functional impairment

Abstract

Background and Objectives Dementia with Lewy Bodies (DLB) is a heterogeneous disease, with variable signs and symptoms across multiple domains. We aimed to identify associations with rate of change in cognition, everyday functioning (IADL) and quality of life (QoL). Methods We included 121 DLB patients (69 ± 6 yrs, 14%F, MMSE: 25 ± 3) in our prospective cohort (follow‐up 2 ± 1 yrs). We described progression of symptoms and cognitive decline over time. Mixed models were used to investigate whether changes in symptoms were associated to changes in IADL (FAQ), QoL (QoL‐AD) and caregiver burden (ZBI). Last, we investigated whether baseline symptoms and biomarkers predicted decline in cognition (MMSE), IADL (FAQ) and QoL (QoL‐AD). Results Parkinsonism and RBD were most frequently present early in the disease course, while hallucinations were more likely to develop in a later stage. MMSE (annual change β ± SE = −2.06 ± 0.23), QoL‐AD (−1.03 ± 0.20), and FAQ (3.04 ± 0.30) declined over time. Increasing severity of clinical symptoms was associated to increases in FAQ, QoL‐AD and caregiver burden. Baseline clinical symptoms were not predictive for decline in these outcomes. By contrast, AD co‐pathology (CSF pTau/Aβ42 ratio) was associated to steeper decline in MMSE (−1.23 ± 0.54). Medial temporal atrophy (−0.81 ± 0.26) and global cortical atrophy (−0.73 ± 0.36) predisposed for decline in QoL‐AD. Conclusions Our findings imply that underlying disease processes, rather than clinical symptomatology aid in predicting decline. These findings are relevant for treatment strategies and the development of DLB specific outcome measures.

Patient‐ and proxy‐reported quality of life in advanced dementia with Lewy bodies

“…Using this composite score, hallucinations, constipation, depressive symptoms, and higher IADL dependency were related to lower QoL in univariate analyses, but hallucinations were no longer significant in the multivariable model 5 . In a subsequent longitudinal analysis with a larger cohort, declining QoL (rater not specified) correlated with changes in depressive symptoms, but this was not significant after adjustment for multiple comparisons 6 . In the other study including both patient‐ and proxy‐rated QoL, regression analyses were only performed using proxy‐rated scores 1 .…”

“…Three prior studies specifically queried patient-reported QoL in individuals with DLB, one of which was reported in two publications. 1,[4][5][6] In a study of correlates of patient-reported QoL in early DLB (mean Mini-Mental State Examination [MMSE] score 25, range [22][23][24][25][26][27], worse QoL correlated with more depressive symptoms and higher dependency in instrumental activities of daily living (IADLs). 4 In the DEvELOP cohort including individuals with both mild cognitive impairment and dementia (mean MMSE 25 ± 3), analyses of QoL used a weighted Quality of Life in Alzheimer's Disease (QoL-AD) composite score calculated by combining patient-and caregiver-rated QoL-AD scores, weighting the patient-rated score twice as much.…”

“…Three prior studies specifically queried patient‐reported QoL in individuals with DLB, one of which was reported in two publications 1,4–6 . In a study of correlates of patient‐reported QoL in early DLB (mean Mini‐Mental State Examination [MMSE] score 25, range 22–27), worse QoL correlated with more depressive symptoms and higher dependency in instrumental activities of daily living (IADLs) 4 .…”

“… 5 In a subsequent longitudinal analysis with a larger cohort, declining QoL (rater not specified) correlated with changes in depressive symptoms, but this was not significant after adjustment for multiple comparisons. 6 In the other study including both patient‐ and proxy‐rated QoL, regression analyses were only performed using proxy‐rated scores. 1 Features associated with proxy‐reported QoL for individuals with DLB included neuropsychiatric symptoms, IADL dependence, and whether the person with DLB lived with the primary caregiver.…”

Specific neuropsychiatric symptoms are associated with functional decline trajectories in Alzheimer’s disease and Lewy body dementia: a five-year follow-up study

“…However, our results also exhibited relevant differences between functional impairment in AD and LBD, with a constant and more pronounced decline in the latter ( 7 ). Current evidence about the impact of specific NPS on activities of daily living (ADL) decline is scarce, especially in those diagnosed with LBD ( 10–12 ). Previous studies on AD have reported an association between apathy, psychotic symptoms, and functional decline, but the reproducibility of these conclusions should be further examined in external samples ( 13 ).…”