Challenges in Predicting Cognitive Decline in Dementia with Lewy Bodies

Abstract

Despite being the second most common form of neurodegenerative dementia, dementia with Lewy bodies (DLB) is under-recognized and carries a worse prognosis than other subtypes of the condition. Cognitive impairment is a cardinal feature of all types of dementia and DLB presents with a distinct profile with deficits in attention, executive function, and visuoperceptual abilities. This difference from Alzheimer’s disease and the common presence of neuropsychiatric symptoms may lead to challenges in predicting cognitive decline in this patient population. Firstly, the diagnosis of DLB is often delayed in clinical practice leading to variability from which time point in the disease course cognitive decline is measured. Secondly, the most frequently used measurement tools for cognitive difficulties focus on memory and naming rather than the domains affected by DLB. While there is now largely a consensus which tools are useful in diagnosing DLB, their validity in assessing deteriorating cognition is less clear. Thirdly, the presence of fluctuating cognition, the propensity to develop delirium episodes, as well as difficulties in distinguishing the two entities in clinical practice make it difficult to predict the disease course. Sleep disturbances are likely to influence cognitive decline but require further study in patients within established DLB. Fourthly, as in most cases of dementia, neuropathological comorbidities are frequently present in DLB. While the influence of Alzheimer’s pathology on cognitive decline in DLB is comparatively well understood, the impact of other pathologies remains unclear. The recent definition of research criteria for mild cognitive impairment in DLB could facilitate earlier diagnosis and more structured follow-up. Assessment tools measuring cognitive domains predominantly affected in DLB need to be more consistently used in longitudinal studies and clinical practice, as well as concurrent measures of fluctuations in cognition. Greater availability of biomarkers and digital healthcare solutions can play an important role in enabling more accurate monitoring and prediction of cognitive decline in DLB.

Optimizing cCOG, a Web‐based tool, to detect dementia with Lewy Bodies

“…Generally, this finding is in line with recent literature on the ability of neuropsychological testing to differentiate DLB from AD. 6,35 One explanation for this finding in our study could be that memory impairment in DLB patients was secondary to attentional impairment. It might also be due to the visual function of our memory test (reading a word with a picture) and DLB patients performing worse on visual memory than verbal memory.…”

“…In addition to core features, DLB is associated with several supportive clinical features, such as autonomic disturbances causing constipation, urinary incontinence, and orthostatic hypotension. Standard cognitive screeners usually focus on detecting memory impairment and lack sensitivity to detect DLB‐specific impairment, such as impaired visuospatial functioning 6 . Still, even with elaborate neuropsychological testing across multiple cognitive domains, the sensitivity to discriminate DLB from AD remains limited 7 .…”

“…Still, even with elaborate neuropsychological testing across multiple cognitive domains, the sensitivity to discriminate DLB from AD remains limited 7 . This is likely because cognitive tests do not consider non‐cognitive clinical symptomatology, while this plays a critical role in DLB 6,8 . As a result, diagnosing DLB and discriminating DLB from Alzheimer's disease (AD) remains challenging 6 …”

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

“…When looking at individual cognitive domains, we found prominent decline on tests that address attention and processing speed. Most previous studies evaluating cognitive decline in DLB were limited by the use of screening tools that are particularly sensitive for memory impairment, while such tools might fail to capture decline in cognitive domains that are most affected in DLB 38 . The trajectories of the MMSE might be an underrepresentation of the actual decline in cognitive functioning.…”

“…A last limitation to be mentioned is that the findings are dependent on the measurements that were used, but it is not clear whether all measures are equally responsiveness to change. There is no consensus on how to measure DLB specific symptomatology and progression 38 . A DLB‐specific, standardized set of outcomes would highly improve evaluation of disease progression and would enhance the potential of comparison with other studies.…”