Worsening Cognitive Impairment and Neurodegenerative Pathology Progressively Increase Risk for Delirium.
Item Type:Journal Article
Citation:Davis DH, Skelly DT, Murray C, Hennessy E, Bowen J, Norton S, Brayne C, Rahkonen T, Sulkava R, Sanderson DJ, Rawlins JN, Bannerman DM, MacLullich AM, Cunningham C, Worsening Cognitive Impairment and Neurodegenerative Pathology Progressively Increase Risk for Delirium., The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 23, 4, 2015, 403 415
Davis-Worsening Cognitive Impairment and Neuro.pdf (Accepted for publication (author's copy) - Peer Reviewed) 2.181Mb
Background Delirium is a profound neuropsychiatric disturbance precipitated by acute illness. Although dementia is the major risk factor this has typically been considered a binary quantity (i.e., cognitively impaired versus cognitively normal) with respect to delirium risk. We used humans and mice to address the hypothesis that the severity of underlying neurodegenerative changes and/or cognitive impairment progressively alters delirium risk. Methods Humans in a population-based longitudinal study, Vantaa 85+, were followed for incident delirium. Odds for reporting delirium at follow-up (outcome) were modeled using random-effects logistic regression, where prior cognitive impairment measured by Mini-Mental State Exam (MMSE) (exposure) was considered. To address whether underlying neurodegenerative pathology increased susceptibility to acute cognitive change, mice at three stages of neurodegenerative disease progression (ME7 model of neurodegeneration: controls, 12 weeks, and 16 weeks) were assessed for acute cognitive dysfunction upon systemic inflammation induced by bacterial lipopolysaccharide (LPS; 100 μg/kg). Synaptic and axonal correlates of susceptibility to acute dysfunction were assessed using immunohistochemistry. Results In the Vantaa cohort, 465 persons (88.4 ± 2.8 years) completed MMSE at baseline. For every MMSE point lost, risk of incident delirium increased by 5% (p = 0.02). LPS precipitated severe and fluctuating cognitive deficits in 16-week ME7 mice but lower incidence or no deficits in 12-week ME7 and controls, respectively. This was associated with progressive thalamic synaptic loss and axonal pathology. Conclusions A human population-based cohort with graded severity of existing cognitive impairment and a mouse model with progressing neurodegeneration both indicate that the risk of delirium increases with greater severity of pre-existing cognitive impairment and neuropathology.
Type of material:Journal Article
Series/Report no:The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
Availability:Full text available
Keywords:neuroinflammation, susceptibility, Delirium, dementia, neurodegeneration, neuropathology, synaptic, axonal, hippocampus, basal, forebrain, ageing, cognitive, decline, systemic, inflammation