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Background: Mild cognitive impairment (MCI) may gradually worsen to dementia, but often remains stable for extended periods of time. Little is known about the predictors of decline to help explain this variation. We aimed to explore whether this heterogeneous course of MCI may be predicted by the presence of Lewy body (LB) symptoms in a prospectively-recruited longitudinal cohort of MCI with Lewy bodies (MCI-LB) and Alzheimer's disease (MCI-AD)., Methods: A prospective cohort (n = 76) aged ⩾60 years underwent detailed assessment after recent MCI diagnosis, and were followed up annually with repeated neuropsychological testing and clinical review of cognitive status and LB symptoms. Latent class mixture modelling identified data-driven sub-groups with distinct trajectories of global cognitive function., Results: Three distinct trajectories were identified in the full cohort: slow/stable progression (46%), intermediate progressive decline (41%) and a small group with a much faster decline (13%). The presence of LB symptomology, and visual hallucinations in particular, predicted decline v. a stable cognitive trajectory. With time zeroed on study end (death, dementia or withdrawal) where available (n = 39), the same subgroups were identified. Adjustment for baseline functioning obscured the presence of any latent classes, suggesting that baseline function is an important parameter in prospective decline., Conclusions: These results highlight some potential signals for impending decline in MCI; poorer baseline function and the presence of probable LB symptoms - particularly visual hallucinations. Identifying people with a rapid decline is important but our findings are preliminary given the modest cohort size.

Objective: We explored whether the mild cognitive impairment (MCI) stages of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) differ in their cognitive profiles, and longitudinal progression., Design: A prospective, longitudinal design was utilized with annual follow-up (Max 5 years, Mean 1.9, standard deviation 1.1) after diagnosis. Participants underwent repeated cognitive testing, and review of their clinical diagnosis and symptoms, including evaluation of core features of DLB., Setting: This was an observational study of independently living individuals, recruited from local healthcare trusts in North East England, UK., Participants: An MCI cohort (n = 76) aged ≥60 years was utilized, differentially diagnosed with MCI due to AD (MCI-AD), or possible/probable MCI with Lewy bodies (MCI-LB)., Measurements: A comprehensive clinical and neuropsychological testing battery was administered, including ACE-R, trailmaking tests, FAS verbal fluency, and computerized battery of attention and perception tasks., Results: Probable MCI-LB presented with less impaired recognition memory than MCI-AD, greater initial impairments in verbal fluency and perception of line orientation, and thereafter demonstrated an expedited decline in visuo-constructional functions in the ACE-R compared to MCI-AD. No clear diagnostic group differences were found in deterioration speeds for global cognition, language, overall memory, attention or other executive functions., Conclusion: These findings provide further evidence for differences in severity and decline of visuospatial dysfunctions in DLB compared with AD; further exploration is required to clarify when and how differences in attention, executive, and memory functions emerge, as well as speed of decline to dementia., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: We conducted a prospective longitudinal study of plasma cytokines during the Mild Cognitive Impairment (MCI) stage of Lewy body disease and Alzheimer's disease, hypothesizing that cytokine levels would decrease over time and that this would be correlated with decline in cognition., Methods: Older (≥60) people with MCI were recruited from memory services in healthcare trusts in North East England, UK. MCI was diagnosed as due to Alzheimer's disease (MCI-AD) or Lewy body disease (MCI-LB). Baseline and repeat annual clinical and cognitive assessments were undertaken and plasma samples were obtained at the same time. Cytokine assays were performed on all samples using the Meso Scale Discovery V-Plex Plus Proinflammatory Panel 1, which included IFNγ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13 and TNFα., Results: Fifty-six patients (21 MCI-AD, 35 MCI-LB) completed prospective evaluations and provided samples up to 3 years after baseline. Six cytokines (IFNγ, IL-1β, IL-2, IL-4, IL-6 and IL-10) showed highly significant (P < .002) decreases over time. AD and LB did not differ in rate of decrease nor were there any effects related to age or general morbidity. Decrease in five of these cytokines (IFNγ, IL-1β, IL-2, IL-4, and IL-10) was highly correlated with decrease in cognition (P < .003)., Conclusions: Peripheral inflammation decreased in both disease groups during MCI suggesting this may be a therapeutic window for future anti-inflammatory agents., (© 2020 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Objective: Significant amyloid deposition is present in approximately half of all cases of dementia with Lewy bodies (DLB). We sought to determine whether amyloid deposition was associated with more rapid clinical decline over 1 year., Methods: Twenty-eight participants had a baseline clinical assessment and amyloid PET scan, followed by a further clinical assessment after 1 year. Changes in clinical measures were compared with amyloid deposition assessed by visual rating and cortical standardized uptake value ratio., Results: Amyloid deposition on visual rating was associated with greater decline in Mini-Mental State Examination and daily function over 1 year. There was no correlation between cortical standardized uptake value ratio and clinical measures., Conclusions: This study provides further evidence for a link between amyloid deposition and clinical progression in DLB. Pathologies such as amyloid, and their interaction with α-synuclein, remain possible treatment targets in DLB., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Amyloid deposition is common in dementia with Lewy bodies, but its pathophysiological significance is unclear., Objective: The objective of this study was to investigate the relationship between amyloid deposition and clinical profile, gray matter volume, and brain perfusion in dementia with Lewy bodies., Methods: Dementia with Lewy bodies (n = 37), Alzheimer's disease (n = 20), and controls (n = 20) underwent a thorough clinical assessment, 3T MRI, and early- and late-phase 18 F-Florbetapir PET-CT to assess cortical perfusion and amyloid deposition, respectively. Amyloid scans were visually categorized as positive or negative. Image analysis was carried out using statistical parametric mapping (SPM) 8., Results: There were no significant differences between amyloid-positive and amyloid-negative dementia with Lewy bodies cases in age (P = .78), overall cognitive impairment (P = .83), level of functional impairment (P = .80), or any other clinical or cognitive scale. There were also no significant differences in hippocampal or gray matter volumes. However, amyloid-positive dementia with Lewy bodies cases had lower medial temporal lobe perfusion (P = .03) than amyloid-negative cases, although a combination of medial temporal lobe perfusion, hippocampal volume, and cognitive measures was unable to accurately predict amyloid status in dementia with Lewy bodies., Conclusions: Amyloid deposition was not associated with differences in clinical or neuropsychological profiles in dementia with Lewy bodies, but was associated with imaging evidence of medial temporal lobe dysfunction. The presence of amyloid in dementia with Lewy bodies cannot be identified on the basis of clinical and other imaging features and will require direct assessment via PET imaging or CSF. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society., (© 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)