Blossom Stephan | Newcastle University (original) (raw)
Papers by Blossom Stephan
Journals of Gerontology Series A-biological Sciences and Medical Sciences, Jan 1, 2010
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Free Radical Biology and Medicine, Jan 1, 2011
Stable isotopic methods are considered the “gold standard” for the measurement of rates of in viv... more Stable isotopic methods are considered the “gold standard” for the measurement of rates of in vivo NO production. However, values reported for healthy human individuals differ by more than 1 order of magnitude. The reason for the apparent variability in NO production is unclear. The primary aim of this review was to evaluate and compare the rates of in vivo NO production in health and disease using stable isotope methods. Articles were retrieved using the PubMed electronic database. Information on concentrations, isotopic enrichments of fluxes, and conversion rates of molecules involved in the NO metabolic pathway was extracted from selected articles; 35 articles were included in the final analysis. Three protocols were identified, including the arginine–citrulline, the arginine–nitrate, and the oxygen–nitrate protocols. The arginine–citrulline protocol showed a wider variability compared to the arginine–nitrate and oxygen–nitrate protocols. The direction of the association between disease state and rate of NO production was essentially determined by the etiopathogenesis of the disorder (inflammatory, metabolic, vascular). Considerable variation in methodologies used to assess whole-body NO synthesis in humans exists. The precision of several aspects of the techniques and the validity of some assumptions made remain unknown, and there is a paucity of information about physiological rates of NO production from childhood over adolescence to old age.
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American Journal of Geriatric Psychiatry, Jan 1, 2010
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Journal of Internal Medicine, Jan 1, 2010
Abstract. Siervo M, Ruggiero D, Sorice R, Nutile T, Aversano M, Stephan BCM, Ciullo M. (Address:... more Abstract. Siervo M, Ruggiero D, Sorice R, Nutile T, Aversano M, Stephan BCM, Ciullo M. (Address: Human Nutrition and Physiology, Department of Neuroscience, University “Federico II”, Faculty of Medicine, Napoli; Institute of Genetics and Biophysics “A. Buzzati-Traverso”, CNR, Napoli, Italy; and Institute of Public Health, University of Cambridge, UK). Angiogenesis and biomarkers of cardiovascular risk in adults with metabolic syndrome. J Intern Med 2010; 268: 338–347.Objectives. Metabolic syndrome (MetSyn) is associated with an increased risk of atherosclerosis and fatal cardiovascular events. Angiogenesis is thought to contribute to this risk as it might be involved in the progression of atherosclerotic plaques. We investigated the levels of circulating biomarkers of angiogenesis and cardiovascular risk in adults with MetSyn and assessed their association with established metabolic risk factors.Design. The Genetic Park project is a highly inclusive cross-sectional survey (about 80% of residents) conducted in three isolated populations in Southern Italy. A total of 1000 men and women (age range: 18–98 years) were included in the analysis. Anthropometric and blood pressure measurements were recorded. Metabolic and cardiovascular biomarkers included glucose, triglycerides, total cholesterol, HDL, vascular endothelial growth factor, placental growth factor (PlGF), soluble fms-like tyrosine kinase-1, high-sensitivity C-reactive protein, high-sensitivity troponin T (hs-TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP).Result. Subjects with MetSyn had higher levels of PlGF and NT-proBNP after adjustment for age, smoking and body mass index. Circulating levels of PlGF, hs-TnT and NT-proBNP were directly related to the number of criteria of MetSyn, and this association interacted with gender. There was a strong correlation between ageing and cardiovascular risk.Conclusions. The increase in circulating levels of biomarkers of angiogenesis and cardiac function in subjects with MetSyn mirrors the pathophysiological changes occurring in the cardiovascular system. Over time, these changes might accelerate the formation and progression of atherosclerotic plaques and contribute significantly to cardiovascular morbidity and mortality risk.
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BMC Geriatrics, Jan 1, 2010
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Journal of Clinical Epidemiology, Jan 1, 2011
To determine whether the full Mini Mental State Examination (MMSE) scale range can be derived fro... more To determine whether the full Mini Mental State Examination (MMSE) scale range can be derived from an abbreviated 11-item version that was designed for testing general cognitive function in a cohort where only a small proportion were expected to be severely impaired or demented. Using simple computation and multiple imputation, the properties of the abbreviated MMSE were compared with the full MMSE score using data from the Medical Research Council Cognitive Function and Ageing Study. Full MMSE scores can be generated for the abbreviated version by assuming high functioning on excluded items. Of the imputed scores, 88.8% were within 1 point of their true value. When the sample was restricted to individuals with normal cognitive functioning (MMSE total score ≥ 24/30), 96.7% of individuals were classified within 1 point of their true total score. The model worked best at predicting cognitive level when cutoff scores were used to classify individuals into impaired vs. not nonimpaired. Full-scale MMSE scores can be reasonably accurately derived from an 11-item abbreviated version. This reduced version can be applied within other frameworks that require reduced test length but need results that are comparable to studies where the full version has been administered.
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Perception, Jan 1, 2007
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Nature Reviews Neurology, Jan 1, 2010
Early identification of individuals at risk of dementia will become crucial when effective preven... more Early identification of individuals at risk of dementia will become crucial when effective preventative strategies for this condition are developed. Various dementia prediction models have been proposed, including clinic-based criteria for mild cognitive impairment, and more-broadly constructed algorithms, which synthesize information from known dementia risk factors, such as poor cognition and health. Knowledge of the predictive accuracy of such models will be important if they are to be used in daily clinical practice or to screen the entire older population (individuals aged >or=65 years). This article presents an overview of recent progress in the development of dementia prediction models for use in population screening. In total, 25 articles relating to dementia risk screening met our inclusion criteria for review. Our evaluation of the predictive accuracy of each model shows that most are poor at discriminating at-risk individuals from not-at-risk cases. The best models incorporate diverse sources of information across multiple risk factors. Typically, poor accuracy is associated with single-factor models, long follow-up intervals and the outcome measure of all-cause dementia. A parsimonious and cost-effective consensus model needs to be developed that accurately identifies individuals with a high risk of future dementia.
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Alzheimer's Research & Therapy, Jan 1, 2009
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Brain and Cognition, Jan 1, 2009
Visual scanpath recording was used to investigate the information processing strategies used by a... more Visual scanpath recording was used to investigate the information processing strategies used by a prosopagnosic patient, SC, when viewing faces. Compared to controls, SC showed an aberrant pattern of scanning, directing attention away from the internal configuration of facial features (eyes, nose) towards peripheral regions (hair, forehead) of the face. The results suggest that SC’s face recognition deficit can be linked to an inability to assemble an accurate and unified face percept due to an abnormal allocation of attention away from the internal face region. Extraction of stimulus attributes necessary for face identity recognition is compromised by an aberrant face scanning pattern.
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International Review of Psychiatry, Jan 1, 2008
The identification of modifiable risk factors that prevent dementia or slow its progression is a ... more The identification of modifiable risk factors that prevent dementia or slow its progression is a major public health priority. Vascular disease and its risk factors have been linked with cognitive decline and dementia, although the degree of association varies depending on differences in vulnerability related to age, ethnicity, disease co-morbidity and possibly brain reserve. Here we review current dementia prevention strategies linked to vascular modification to identify whether any approach exists that will reduce the population burden of dementia, and whether any exist that show evidence of being cost effective and safe for populations. As yet, there is no compelling evidence that dementia can be prevented through vascular manipulation by pharmacological or non-pharmacological trials. To date, no intervention can be recommended for dementia prevention at the population level including Alzheimer's Disease or Vascular Dementia. Advances in the prevention of dementia will be gained, it is argued, from a more complete understanding of the pathophysiology of disease and its causes, particularly in early life, within and across different populations and age groups. Furthermore, a more complete understanding of the earliest pre-clinical stage of disease is required for effective risk factor modification. Although the current state of knowledge cannot support public health policy for vascular manipulation for dementia prevention at the population level, this does not undermine the importance of vascular manipulation in its own right to promote healthier ageing.
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Biochemical Pharmacology, Jan 1, 2011
The change in the world’s age demographics and the predicted rise in the incidence of age-related... more The change in the world’s age demographics and the predicted rise in the incidence of age-related diseases, including dementia, is a source of major public health concern. Major research effort in both the United States and Europe has been targeted toward understanding the pathogenesis and epidemiology of dementia. This article presents a general overview of the history of dementia research in Europe and how it compares with that in the United States. The review highlights the common issues which both U.S. and European researchers have identified and attempted to tackle. To maximize information gained from studies across the world, better harmonization of methodology is needed, as informed from current research practice.
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Journal of The International Neuropsychological Society, Jan 1, 2006
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Stroke, Jan 1, 2010
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International Journal of Geriatric Psychiatry, Jan 1, 2008
ObjectivesClassifications of mild cognitive impairment (MCI) vary in the precision of the definin... more ObjectivesClassifications of mild cognitive impairment (MCI) vary in the precision of the defining criteria. Their value in clinical settings is different from population settings. This difference depending on setting is to be expected, but must be well understood if population screening for dementia and pre-dementia states is to be considered. Of importance is the impact of missed diagnosis. The magnitude of missed ‘at-risk’ cases in the application of different MCI criteria in the population is unknown.Classifications of mild cognitive impairment (MCI) vary in the precision of the defining criteria. Their value in clinical settings is different from population settings. This difference depending on setting is to be expected, but must be well understood if population screening for dementia and pre-dementia states is to be considered. Of importance is the impact of missed diagnosis. The magnitude of missed ‘at-risk’ cases in the application of different MCI criteria in the population is unknown.MethodsData were from the Medical Research Council Cognitive Function and Ageing Study, a large population based study of older aged individuals in the UK. Prevalence and two-year progression to dementia in individuals whose impairment failed to fulfil published criteria for MCI was evaluated.Data were from the Medical Research Council Cognitive Function and Ageing Study, a large population based study of older aged individuals in the UK. Prevalence and two-year progression to dementia in individuals whose impairment failed to fulfil published criteria for MCI was evaluated.ResultsPrevalence estimates of individuals not classified from current MCI definitions were extremely variable (range 2.5–41.0%). Rates of progression to dementia in these non-classified groups were also very variable (3.7–30.0%), reflecting heterogeneity in MCI classification requirements.Prevalence estimates of individuals not classified from current MCI definitions were extremely variable (range 2.5–41.0%). Rates of progression to dementia in these non-classified groups were also very variable (3.7–30.0%), reflecting heterogeneity in MCI classification requirements.ConclusionsNarrow definitions of MCI developed for clinical settings when applied in the population result in a large proportion of individuals who progress to dementia being excluded from MCI classifications. More broadly defined criteria would be better for selection of individuals at risk of dementia in population settings, but at the possibility of high false positive rates. While exclusion may be a good thing in the population since most people are presumably ‘normal’, over-inclusion is more likely to be harmful. Further work needs to investigate the best classification system for application in the population. Copyright © 2008 John Wiley & Sons, Ltd.Narrow definitions of MCI developed for clinical settings when applied in the population result in a large proportion of individuals who progress to dementia being excluded from MCI classifications. More broadly defined criteria would be better for selection of individuals at risk of dementia in population settings, but at the possibility of high false positive rates. While exclusion may be a good thing in the population since most people are presumably ‘normal’, over-inclusion is more likely to be harmful. Further work needs to investigate the best classification system for application in the population. Copyright © 2008 John Wiley & Sons, Ltd.
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Journal of The American Geriatrics Society, Jan 1, 2007
OBJECTIVES: To explore the application of existing classifications of mild cognitive impairment (... more OBJECTIVES: To explore the application of existing classifications of mild cognitive impairment (MCI) and associated states in a large population sample.DESIGN: Prospective cohort study, baseline phase (cross-sectional analysis).SETTING: Large-scale multicenter study in the United Kingdom.PARTICIPANTS: Thirteen thousand four individuals aged 65 and older from the Medical Research Council Cognitive Function and Aging Study. From this, a subsample of 2,640 individuals was selected and completed a more-detailed cognitive assessment.MEASUREMENTS: Information on sociodemographic status, general health, cognitive impairment (measured using the Mini-Mental State Examination), and functional ability was collected in a structured interview at baseline. The Geriatric Mental State Automated Geriatric Examination for Computer-Assisted Taxonomy and the Cambridge Cognitive Examination were used in assessment to determine cognitive status. Using a systematic literature review to collect all symptom classifications for nonnormal dementia states, these were then operationalized retrospectively. Each participant was classified according to each.RESULTS: Population prevalence estimates were variable (range 0.1–42%), reflecting differences in the focus and content of each state. Limited overlap existed between states such that many individuals were concurrently classified as normal and impaired. This highlights the heterogeneity in classification as captured using different definitions.CONCLUSION: Classification of cognitively impaired and cognitively normal individuals is dependent on the way criteria are defined and operationalized. Each classification captures a unique group of individuals, with little concordance. Given the importance of early detection of dementia and the calls for screening, and recruitment into pharmacological trials of cognitively impaired individuals, there is an urgent need for an agreed-upon standard MCI case definition to use as a criterion standard.
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Journal of The American Geriatrics Society, Jan 1, 2008
OBJECTIVES: To determine the 2-year outcome from 16 different current classifications of mild cog... more OBJECTIVES: To determine the 2-year outcome from 16 different current classifications of mild cognitive impairment (MCI) in a population-based sample.DESIGN: Prospective cohort study: baseline and 2-year follow-up phases.SETTING: Large-scale multicenter study, United Kingdom.PARTICIPANTS:: Thirteen thousand four individuals aged 65 and older from the Medical Research Council Cognitive Function and Ageing Study. From this, a subsample of 2,640 individuals was selected and completed a more-detailed cognitive assessment. Individuals who underwent further assessment were asked to complete annual or 2-year follow-ups.MEASUREMENTS: Information on sociodemographic status, general health, cognitive impairment and functional ability were collected using a structured interview. Individuals were classified according to 16 different definitions of MCI. These were applied retrospectively.RESULTS: The dominant outcome across definitions was an impairment that was not classifiable or reversion to normality. Progression to dementia was variable and generally poor. Overall progression was highest in classifications in which impairment extended to memory and nonmemory domains. Predictability was age dependent in some but not all classifications.CONCLUSION: Current classifications of MCI have variable outcomes in population-based samples. Progression to dementia is relatively rare and is dependent on age and definition. Selection criteria developed for the clinic are based on a “high risk” approach that leads to exclusion of a large percentage of the impaired population who are neither normal nor demented and for whom no intervention options are currently available. A refined definition of this construct is urgently needed if MCI is to be used to predict dementia in population-based studies.
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Plos Medicine, Jan 1, 2007
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Journals of Gerontology Series A-biological Sciences and Medical Sciences, Jan 1, 2010
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Free Radical Biology and Medicine, Jan 1, 2011
Stable isotopic methods are considered the “gold standard” for the measurement of rates of in viv... more Stable isotopic methods are considered the “gold standard” for the measurement of rates of in vivo NO production. However, values reported for healthy human individuals differ by more than 1 order of magnitude. The reason for the apparent variability in NO production is unclear. The primary aim of this review was to evaluate and compare the rates of in vivo NO production in health and disease using stable isotope methods. Articles were retrieved using the PubMed electronic database. Information on concentrations, isotopic enrichments of fluxes, and conversion rates of molecules involved in the NO metabolic pathway was extracted from selected articles; 35 articles were included in the final analysis. Three protocols were identified, including the arginine–citrulline, the arginine–nitrate, and the oxygen–nitrate protocols. The arginine–citrulline protocol showed a wider variability compared to the arginine–nitrate and oxygen–nitrate protocols. The direction of the association between disease state and rate of NO production was essentially determined by the etiopathogenesis of the disorder (inflammatory, metabolic, vascular). Considerable variation in methodologies used to assess whole-body NO synthesis in humans exists. The precision of several aspects of the techniques and the validity of some assumptions made remain unknown, and there is a paucity of information about physiological rates of NO production from childhood over adolescence to old age.
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American Journal of Geriatric Psychiatry, Jan 1, 2010
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Journal of Internal Medicine, Jan 1, 2010
Abstract. Siervo M, Ruggiero D, Sorice R, Nutile T, Aversano M, Stephan BCM, Ciullo M. (Address:... more Abstract. Siervo M, Ruggiero D, Sorice R, Nutile T, Aversano M, Stephan BCM, Ciullo M. (Address: Human Nutrition and Physiology, Department of Neuroscience, University “Federico II”, Faculty of Medicine, Napoli; Institute of Genetics and Biophysics “A. Buzzati-Traverso”, CNR, Napoli, Italy; and Institute of Public Health, University of Cambridge, UK). Angiogenesis and biomarkers of cardiovascular risk in adults with metabolic syndrome. J Intern Med 2010; 268: 338–347.Objectives. Metabolic syndrome (MetSyn) is associated with an increased risk of atherosclerosis and fatal cardiovascular events. Angiogenesis is thought to contribute to this risk as it might be involved in the progression of atherosclerotic plaques. We investigated the levels of circulating biomarkers of angiogenesis and cardiovascular risk in adults with MetSyn and assessed their association with established metabolic risk factors.Design. The Genetic Park project is a highly inclusive cross-sectional survey (about 80% of residents) conducted in three isolated populations in Southern Italy. A total of 1000 men and women (age range: 18–98 years) were included in the analysis. Anthropometric and blood pressure measurements were recorded. Metabolic and cardiovascular biomarkers included glucose, triglycerides, total cholesterol, HDL, vascular endothelial growth factor, placental growth factor (PlGF), soluble fms-like tyrosine kinase-1, high-sensitivity C-reactive protein, high-sensitivity troponin T (hs-TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP).Result. Subjects with MetSyn had higher levels of PlGF and NT-proBNP after adjustment for age, smoking and body mass index. Circulating levels of PlGF, hs-TnT and NT-proBNP were directly related to the number of criteria of MetSyn, and this association interacted with gender. There was a strong correlation between ageing and cardiovascular risk.Conclusions. The increase in circulating levels of biomarkers of angiogenesis and cardiac function in subjects with MetSyn mirrors the pathophysiological changes occurring in the cardiovascular system. Over time, these changes might accelerate the formation and progression of atherosclerotic plaques and contribute significantly to cardiovascular morbidity and mortality risk.
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BMC Geriatrics, Jan 1, 2010
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Journal of Clinical Epidemiology, Jan 1, 2011
To determine whether the full Mini Mental State Examination (MMSE) scale range can be derived fro... more To determine whether the full Mini Mental State Examination (MMSE) scale range can be derived from an abbreviated 11-item version that was designed for testing general cognitive function in a cohort where only a small proportion were expected to be severely impaired or demented. Using simple computation and multiple imputation, the properties of the abbreviated MMSE were compared with the full MMSE score using data from the Medical Research Council Cognitive Function and Ageing Study. Full MMSE scores can be generated for the abbreviated version by assuming high functioning on excluded items. Of the imputed scores, 88.8% were within 1 point of their true value. When the sample was restricted to individuals with normal cognitive functioning (MMSE total score ≥ 24/30), 96.7% of individuals were classified within 1 point of their true total score. The model worked best at predicting cognitive level when cutoff scores were used to classify individuals into impaired vs. not nonimpaired. Full-scale MMSE scores can be reasonably accurately derived from an 11-item abbreviated version. This reduced version can be applied within other frameworks that require reduced test length but need results that are comparable to studies where the full version has been administered.
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Perception, Jan 1, 2007
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Nature Reviews Neurology, Jan 1, 2010
Early identification of individuals at risk of dementia will become crucial when effective preven... more Early identification of individuals at risk of dementia will become crucial when effective preventative strategies for this condition are developed. Various dementia prediction models have been proposed, including clinic-based criteria for mild cognitive impairment, and more-broadly constructed algorithms, which synthesize information from known dementia risk factors, such as poor cognition and health. Knowledge of the predictive accuracy of such models will be important if they are to be used in daily clinical practice or to screen the entire older population (individuals aged >or=65 years). This article presents an overview of recent progress in the development of dementia prediction models for use in population screening. In total, 25 articles relating to dementia risk screening met our inclusion criteria for review. Our evaluation of the predictive accuracy of each model shows that most are poor at discriminating at-risk individuals from not-at-risk cases. The best models incorporate diverse sources of information across multiple risk factors. Typically, poor accuracy is associated with single-factor models, long follow-up intervals and the outcome measure of all-cause dementia. A parsimonious and cost-effective consensus model needs to be developed that accurately identifies individuals with a high risk of future dementia.
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Alzheimer's Research & Therapy, Jan 1, 2009
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Brain and Cognition, Jan 1, 2009
Visual scanpath recording was used to investigate the information processing strategies used by a... more Visual scanpath recording was used to investigate the information processing strategies used by a prosopagnosic patient, SC, when viewing faces. Compared to controls, SC showed an aberrant pattern of scanning, directing attention away from the internal configuration of facial features (eyes, nose) towards peripheral regions (hair, forehead) of the face. The results suggest that SC’s face recognition deficit can be linked to an inability to assemble an accurate and unified face percept due to an abnormal allocation of attention away from the internal face region. Extraction of stimulus attributes necessary for face identity recognition is compromised by an aberrant face scanning pattern.
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International Review of Psychiatry, Jan 1, 2008
The identification of modifiable risk factors that prevent dementia or slow its progression is a ... more The identification of modifiable risk factors that prevent dementia or slow its progression is a major public health priority. Vascular disease and its risk factors have been linked with cognitive decline and dementia, although the degree of association varies depending on differences in vulnerability related to age, ethnicity, disease co-morbidity and possibly brain reserve. Here we review current dementia prevention strategies linked to vascular modification to identify whether any approach exists that will reduce the population burden of dementia, and whether any exist that show evidence of being cost effective and safe for populations. As yet, there is no compelling evidence that dementia can be prevented through vascular manipulation by pharmacological or non-pharmacological trials. To date, no intervention can be recommended for dementia prevention at the population level including Alzheimer's Disease or Vascular Dementia. Advances in the prevention of dementia will be gained, it is argued, from a more complete understanding of the pathophysiology of disease and its causes, particularly in early life, within and across different populations and age groups. Furthermore, a more complete understanding of the earliest pre-clinical stage of disease is required for effective risk factor modification. Although the current state of knowledge cannot support public health policy for vascular manipulation for dementia prevention at the population level, this does not undermine the importance of vascular manipulation in its own right to promote healthier ageing.
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Biochemical Pharmacology, Jan 1, 2011
The change in the world’s age demographics and the predicted rise in the incidence of age-related... more The change in the world’s age demographics and the predicted rise in the incidence of age-related diseases, including dementia, is a source of major public health concern. Major research effort in both the United States and Europe has been targeted toward understanding the pathogenesis and epidemiology of dementia. This article presents a general overview of the history of dementia research in Europe and how it compares with that in the United States. The review highlights the common issues which both U.S. and European researchers have identified and attempted to tackle. To maximize information gained from studies across the world, better harmonization of methodology is needed, as informed from current research practice.
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Journal of The International Neuropsychological Society, Jan 1, 2006
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Stroke, Jan 1, 2010
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International Journal of Geriatric Psychiatry, Jan 1, 2008
ObjectivesClassifications of mild cognitive impairment (MCI) vary in the precision of the definin... more ObjectivesClassifications of mild cognitive impairment (MCI) vary in the precision of the defining criteria. Their value in clinical settings is different from population settings. This difference depending on setting is to be expected, but must be well understood if population screening for dementia and pre-dementia states is to be considered. Of importance is the impact of missed diagnosis. The magnitude of missed ‘at-risk’ cases in the application of different MCI criteria in the population is unknown.Classifications of mild cognitive impairment (MCI) vary in the precision of the defining criteria. Their value in clinical settings is different from population settings. This difference depending on setting is to be expected, but must be well understood if population screening for dementia and pre-dementia states is to be considered. Of importance is the impact of missed diagnosis. The magnitude of missed ‘at-risk’ cases in the application of different MCI criteria in the population is unknown.MethodsData were from the Medical Research Council Cognitive Function and Ageing Study, a large population based study of older aged individuals in the UK. Prevalence and two-year progression to dementia in individuals whose impairment failed to fulfil published criteria for MCI was evaluated.Data were from the Medical Research Council Cognitive Function and Ageing Study, a large population based study of older aged individuals in the UK. Prevalence and two-year progression to dementia in individuals whose impairment failed to fulfil published criteria for MCI was evaluated.ResultsPrevalence estimates of individuals not classified from current MCI definitions were extremely variable (range 2.5–41.0%). Rates of progression to dementia in these non-classified groups were also very variable (3.7–30.0%), reflecting heterogeneity in MCI classification requirements.Prevalence estimates of individuals not classified from current MCI definitions were extremely variable (range 2.5–41.0%). Rates of progression to dementia in these non-classified groups were also very variable (3.7–30.0%), reflecting heterogeneity in MCI classification requirements.ConclusionsNarrow definitions of MCI developed for clinical settings when applied in the population result in a large proportion of individuals who progress to dementia being excluded from MCI classifications. More broadly defined criteria would be better for selection of individuals at risk of dementia in population settings, but at the possibility of high false positive rates. While exclusion may be a good thing in the population since most people are presumably ‘normal’, over-inclusion is more likely to be harmful. Further work needs to investigate the best classification system for application in the population. Copyright © 2008 John Wiley & Sons, Ltd.Narrow definitions of MCI developed for clinical settings when applied in the population result in a large proportion of individuals who progress to dementia being excluded from MCI classifications. More broadly defined criteria would be better for selection of individuals at risk of dementia in population settings, but at the possibility of high false positive rates. While exclusion may be a good thing in the population since most people are presumably ‘normal’, over-inclusion is more likely to be harmful. Further work needs to investigate the best classification system for application in the population. Copyright © 2008 John Wiley & Sons, Ltd.
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Journal of The American Geriatrics Society, Jan 1, 2007
OBJECTIVES: To explore the application of existing classifications of mild cognitive impairment (... more OBJECTIVES: To explore the application of existing classifications of mild cognitive impairment (MCI) and associated states in a large population sample.DESIGN: Prospective cohort study, baseline phase (cross-sectional analysis).SETTING: Large-scale multicenter study in the United Kingdom.PARTICIPANTS: Thirteen thousand four individuals aged 65 and older from the Medical Research Council Cognitive Function and Aging Study. From this, a subsample of 2,640 individuals was selected and completed a more-detailed cognitive assessment.MEASUREMENTS: Information on sociodemographic status, general health, cognitive impairment (measured using the Mini-Mental State Examination), and functional ability was collected in a structured interview at baseline. The Geriatric Mental State Automated Geriatric Examination for Computer-Assisted Taxonomy and the Cambridge Cognitive Examination were used in assessment to determine cognitive status. Using a systematic literature review to collect all symptom classifications for nonnormal dementia states, these were then operationalized retrospectively. Each participant was classified according to each.RESULTS: Population prevalence estimates were variable (range 0.1–42%), reflecting differences in the focus and content of each state. Limited overlap existed between states such that many individuals were concurrently classified as normal and impaired. This highlights the heterogeneity in classification as captured using different definitions.CONCLUSION: Classification of cognitively impaired and cognitively normal individuals is dependent on the way criteria are defined and operationalized. Each classification captures a unique group of individuals, with little concordance. Given the importance of early detection of dementia and the calls for screening, and recruitment into pharmacological trials of cognitively impaired individuals, there is an urgent need for an agreed-upon standard MCI case definition to use as a criterion standard.
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Journal of The American Geriatrics Society, Jan 1, 2008
OBJECTIVES: To determine the 2-year outcome from 16 different current classifications of mild cog... more OBJECTIVES: To determine the 2-year outcome from 16 different current classifications of mild cognitive impairment (MCI) in a population-based sample.DESIGN: Prospective cohort study: baseline and 2-year follow-up phases.SETTING: Large-scale multicenter study, United Kingdom.PARTICIPANTS:: Thirteen thousand four individuals aged 65 and older from the Medical Research Council Cognitive Function and Ageing Study. From this, a subsample of 2,640 individuals was selected and completed a more-detailed cognitive assessment. Individuals who underwent further assessment were asked to complete annual or 2-year follow-ups.MEASUREMENTS: Information on sociodemographic status, general health, cognitive impairment and functional ability were collected using a structured interview. Individuals were classified according to 16 different definitions of MCI. These were applied retrospectively.RESULTS: The dominant outcome across definitions was an impairment that was not classifiable or reversion to normality. Progression to dementia was variable and generally poor. Overall progression was highest in classifications in which impairment extended to memory and nonmemory domains. Predictability was age dependent in some but not all classifications.CONCLUSION: Current classifications of MCI have variable outcomes in population-based samples. Progression to dementia is relatively rare and is dependent on age and definition. Selection criteria developed for the clinic are based on a “high risk” approach that leads to exclusion of a large percentage of the impaired population who are neither normal nor demented and for whom no intervention options are currently available. A refined definition of this construct is urgently needed if MCI is to be used to predict dementia in population-based studies.
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Plos Medicine, Jan 1, 2007
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