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Prospective predictors of decline versus stability in mild cognitive impairment with Lewy bodies or Alzheimer’s disease

Lookup NU author(s): Dr Calum Hamilton, Professor Fiona MatthewsORCiD, Dr Paul Donaghy, Professor John-Paul TaylorORCiD, Professor John O'Brien, Nicola Barnett, Kirsty OlsenORCiD, Professor Ian McKeith, Professor Alan ThomasORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Background Mild cognitive impairment (MCI) may gradually worsen to dementia, but often remains stable for extended periods of time. Little is known about 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 Lewy body 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 much faster decline (13%). The presence of Lewy body symptomology, and visual hallucinations in particular, predicted decline versus 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.

Publication metadata

Author(s): Hamilton CA, Matthews FE, Donaghy PC, Taylor JP, O'Brien JT, Barnett N, Olsen K, McKeith IG, Thomas AJ

Publication type: Article

Publication status: Published

Journal: Psychological Medicine

Year: 2020

Volume: 51

Issue: 15

Pages: 2590-2598

Print publication date: 01/11/2021

Online publication date: 05/05/2020

Acceptance date: 07/04/2020

Date deposited: 08/04/2020

ISSN (print): 0033-2917

ISSN (electronic): 1469-8978

Publisher: Cambridge University Press


DOI: 10.1017/S0033291720001130


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Funder referenceFunder name
Alzheimer’s Research UK (ARUK-PG2015-13).
NIHR Newcastle Biomedical Research Unit (grant numbers BH120812 and BH120878)