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      Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study

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          Abstract

          Recent studies suggest that delirium is associated with risk of dementia and also acceleration of decline in existing dementia. However, previous studies may have been confounded by incomplete ascertainment of cognitive status at baseline. Herein, we used a true population sample to determine if delirium is a risk factor for incident dementia and cognitive decline. We also examined the effect of delirium at the pathological level by determining associations between dementia and neuropathological markers of dementia in patients with and without a history of delirium. The Vantaa 85+ study examined 553 individuals (92% of those eligible) aged ≥85 years at baseline, 3, 5, 8 and 10 years. Brain autopsy was performed in 52%. Fixed and random-effects regression models were used to assess associations between (i) delirium and incident dementia and (ii) decline in Mini-Mental State Examination scores in the whole group. The relationship between dementia and common neuropathological markers (Alzheimer-type, infarcts and Lewy-body) was modelled, stratified by history of delirium. Delirium increased the risk of incident dementia (odds ratio 8.7, 95% confidence interval 2.1–35). Delirium was also associated with worsening dementia severity (odds ratio 3.1, 95% confidence interval 1.5–6.3) as well as deterioration in global function score (odds ratio 2.8, 95% confidence interval 1.4–5.5). In the whole study population, delirium was associated with loss of 1.0 more Mini-Mental State Examination points per year (95% confidence interval 0.11–1.89) than those with no history of delirium. In individuals with dementia and no history of delirium ( n = 232), all pathologies were significantly associated with dementia. However, in individuals with delirium and dementia ( n = 58), no relationship between dementia and these markers was found. For example, higher Braak stage was associated with dementia when no history of delirium (odds ratio 2.0, 95% confidence interval 1.1–3.5, P = 0.02), but in those with a history of delirium, there was no significant relationship (odds ratio 1.2, 95% confidence interval 0.2–6.7, P = 0.85). This trend for odds ratios to be closer to unity in the delirium and dementia group was observed for neuritic amyloid, apolipoprotein ε status, presence of infarcts, α-synucleinopathy and neuronal loss in substantia nigra. These findings are the first to demonstrate in a true population study that delirium is a strong risk factor for incident dementia and cognitive decline in the oldest-old. However, in this study, the relationship did not appear to be mediated by classical neuropathologies associated with dementia.

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          Most cited references26

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          Diagnostic and statistical manual of mental disorders.

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            Delirium in older persons.

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              Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.

              Criteria for the diagnosis of vascular dementia (VaD) that are reliable, valid, and readily applicable in a variety of settings are urgently needed for both clinical and research purposes. To address this need, the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), resulting in research criteria for the diagnosis of VaD. Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features. These criteria are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible). They await testing and validation and will be revised as more information becomes available.
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                Author and article information

                Journal
                Brain
                Brain
                brainj
                brain
                Brain
                Oxford University Press
                0006-8950
                1460-2156
                September 2012
                9 August 2012
                9 August 2012
                : 135
                : 9
                : 2809-2816
                Affiliations
                1 Department of Public Health and Primary Care, University of Cambridge, UK
                2 Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK
                3 Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, UK
                4 School of Psychology, Social Work and Social Policy, University of South Australia
                5 Department of Geriatrics, Jämsä District Municipal Federation of Health Care, Jämsä, Finland
                6 Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
                7 Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland
                8 School of Biochemistry and CNS Inflammation, Trinity College, Dublin, Ireland
                9 Institute for Ageing and Health, Newcastle University, UK
                10 School of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
                11 Edinburgh Delirium Research Group, Geriatric Medicine Unit, University of Edinburgh, UK
                Author notes
                Correspondence to: Daniel Davis, MB ChB, Institute of Public Health, University of Cambridge, Robinson Way, Cambridge, UK CB2 0SR E-mail: dhjd2@ 123456cam.ac.uk
                Article
                aws190
                10.1093/brain/aws190
                3437024
                22879644
                e3f0207b-ecf9-4edd-854e-890887f3949d
                © The Author 2012. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 March 2012
                : 16 May 2012
                : 10 June 2012
                Page count
                Pages: 8
                Categories
                Original Articles

                Neurosciences
                neuropathology,epidemiology,dementia,delirium,population-based
                Neurosciences
                neuropathology, epidemiology, dementia, delirium, population-based

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