lewy body dementia
Latest
Attending to the ups and downs of Lewy body dementia: An exploration of cognitive fluctuations
Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) share similarities in pathology and clinical presentation and come under the umbrella term of Lewy body dementias (LBD). Fluctuating cognition is a key symptom in LBD and manifests as altered levels of alertness and attention, with a marked difference between best and worst performance. Cognition and alertness can change over seconds or minutes to hours and days of obtundation. Cognitive fluctuations can have significant impacts on the quality of life of people with LBD as well as potentially contribute to the exacerbation of other transient symptoms including, for example, hallucinations and psychosis as well as making it difficult to measure cognitive effect size benefits in clinical trials of LBD. However, this significant symptom in LBD is poorly understood. In my presentation I will discuss the phenomenology of cognitive fluctuations, how we can measure it clinically and limitations of these approaches. I will then outline the work of our group and others which has been focussed on unpicking the aetiological basis of cognitive fluctuations in LBD using a variety of imaging approaches (e.g. SPECT, sMRI, fMRI and EEG). I will then briefly explore future research directions.
Multimorbidity in the ageing human brain: lessons from neuropathological assessment
Age-associated dementias are neuropathologically characterized by the identification of hallmark intracellular and extracellular deposition of proteins, i.e., hyperphosphorylated-tau, amyloid-β, and α-synuclein, or cerebrovascular lesions. The neuropathological assessment and staging of these pathologies allows for a diagnosis of a distinct disease, e.g., amyloid-β plaques and hyperphosphorylated tau pathology in Alzheimer's disease. Neuropathological assessment in large scale cohorts, such as the UK’s Brains for Dementia Research (BDR) programme, has made it increasingly clear that the ageing brain is characterized by the presence of multiple age-associated pathologies rather than just the ‘pure’ hallmark lesion as commonly perceived. These additional pathologies can range from low/intermediate levels, that are assumed to have little if any clinical significance, to a full-blown mixed disease where there is the presence of two distinct diseases. In our recent paper (McAleese et al. 2021 Concomitant neurodegenerative pathologies contribute to the transition from mild cognitive impairment to dementia, https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12291, Alzheimer's & Dementia), using the BDR cohort, we investigated the frequency of multimorbidity and specifically investigated the impact of additional low-level pathology on cognition. In this study, of 670 donated post-mortem brains, we found that almost 70% of cases exhibited multimorbidity and only 22% were considered a pure diagnosis. Importantly, no case of Lewy Body dementia or vascular dementia was considered pure. A key finding is that the presence of low levels of additional pathology increased the likelihood of having mild dementia vs mild cognitive impairment by almost 20-fold, indicating low levels of additional pathology do impact the clinical progression of a distinct disease. Given the high prevalence and the potential clinical impact, cerebral multimorbidity should be at the forefront of consideration in dementia research.
lewy body dementia coverage
2 items