How Does Dementia Begin to Manifest in Bipolar Disorder? A Description of Prodromal Clinical and Cognitive Changes.

BackgroundThis study aims to identify longitudinal cognitive changes that may signal early dementia in bipolar disorder.MethodsParticipants were 114 adults with bipolar disorder, all initially non-demented, who underwent annual neuropsychological assessment up to ten years (47.3 months average follow-up). A small subset (n=12) also had available structural neuroimaging data. Longitudinal features associated with future dementia status were examined with linear mixed-effects models, and yearly differences between incident dementia and controls cases were examined in the six years prior to diagnosis.ResultsTwenty-six participants (22.8%) developed dementia over the follow-up period (‘incident cases’), and the remaining 88 (77.2%) remained dementia-free (‘controls’). Alzheimer’s disease was the most common presumed etiology in the incident cases, and this aligned with findings of smaller hippocampal volumes relative to controls. The incident cases showed clearly declining trajectories in episodic memory, verbal fluency and attention. Story recall and digit symbol substitution showed the earliest decline, four and five years before diagnosis respectively. Digit symbol substitution was most accurate at distinguishing cases from controls: impaired performance (<-1.5 SD) at any time during the follow-up period was associated with 54% sensitivity and 87% specificity of future dementia.ConclusionsProdromal dementia in bipolar disorder can be detected up to five years before onset using the same cognitive tests used in psychiatrically-healthy older adults. Cognition in the natural course of bipolar disorder is generally stable, and impairment or marked decline on measures of memory, fluency or attention may indicate an early neurodegenerative process.