Journals of Gerontology Series A-biological Sciences and Medical Sciences, Jan 1, 2010
The transition in the world age demographic toward older age is associated with an increased risk... more The transition in the world age demographic toward older age is associated with an increased risk of neurodegenerative diseases, such as Alzheimer's disease. Risk profiles for dementia may also be changing. Obesity and type 2 diabetes have increased in prevalence in the last half-century and have been associated with increased dementia risk. Specific changes in nutrition may also represent a direct risk. A diet transition in the United States has occurred in the intake of refined sugar, particularly high-fructose corn syrup (HFCS) from a yearly estimate of 8.1 kg/person at the beginning of the XIX century to a current estimate of 65 kg/person. This article considers the association between refined sugar intake, markers of cardiovascular disease risk, and the possible promotion of the development of dementia.
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.
American Journal of Geriatric Psychiatry, Jan 1, 2010
Background Criteria for Mild Cognitive Impairment (MCI) predict dementia risk in the clinic. Deme... more Background Criteria for Mild Cognitive Impairment (MCI) predict dementia risk in the clinic. Dementia risk in the population is different and whether there is an optimal MCI derived threshold for discriminating at-risk from not-at-risk cases in the general older population is not known. Data were from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Two risk thresholds were derived from each of seven different concepts of MCI including: Mayo Clinic defined amnestic, non-amnestic, multiple and revised MCI, MCI based on Mini Mental State Examination (MMSE) derived categories, and the definitions of Cognitive Impairment No Dementia (CIND) and Age Related Cognitive Decline (ARCD). Receiver Operating Characteristic (ROC) analysis was used to compare the predictive validity of two-year incident dementia for each risk threshold across the different MCI definitions. Findings MCI derived risk thresholds varied in their ability to predict dementia. MCI thresholds were accurate in identifying individuals not-at-risk of dementia progression (False Negative range, 0-3.4%). No MCI derived threshold accurately identified an at-risk group with a two year progression rate greater than 20%. Criteria for ARCD defined the threshold with the highest sensitivity and specificity for dementia conversion. Interpretation MCI derived thresholds do not reliably identify individuals at-risk of incident dementia at two years when applied in the general population. A large subpopulation of individuals not-at-risk was more reliably identified. What is considered a sufficient level of accuracy for identification of individuals at increased risk of dementia depends on the motivation for screening and on the safety and efficacy of available interventions.
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.
Background: Behavioural and psychological symptoms are associated with dementia, but are also pre... more Background: Behavioural and psychological symptoms are associated with dementia, but are also present in a significant number of the older population without dementia. Here we explore the distribution of behavioural and psychological symptoms in the population without dementia, and their relationship with domains and severity of health and cognitive impairment. Methods: The Medical Research Council Cognitive Function and Ageing Study is a two-phase longitudinal study of ageing representative of the population aged 65 and over of England and Wales. A subsample of 1781 participants without a study diagnosis of dementia was included in this study. Information on symptoms including depression, apathy, anxiety, feelings of persecution, hallucination, agitated behaviour, elation, irritability, sleep problems, wandering, confabulation and misidentification, cognitive function, health related factors and socio-demographic information was extracted from interviews with participants and knowledgeable informants. Participants were classified according to the Mini-Mental State Examination and by criteria for subtypes of mild cognitive impairment (MCI). The prevalence of behavioural and psychological symptoms and associations with cognitive function, health and socio-demographics was examined. Co-occurrence of symptoms was tested using factor analysis.
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.
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.
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.
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.
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.
Journal of The International Neuropsychological Society, Jan 1, 2006
Prosopagnosia is currently viewed within the constraints of two competing theories of face recogn... more Prosopagnosia is currently viewed within the constraints of two competing theories of face recognition, one highlighting the analysis of features, the other focusing on configural processing of the whole face. This study investigated the role of feature analysis versus whole face configural processing in the recognition of facial expression. A prosopagnosic patient, SC made expression decisions from whole and incomplete (eyes-only and mouth-only) faces where features had been obscured. SC was impaired at recognizing some (e.g., anger, sadness, and fear), but not all (e.g., happiness) emotional expressions from the whole face. Analyses of his performance on incomplete faces indicated that his recognition of some expressions actually improved relative to his performance on the whole face condition. We argue that in SC interference from damaged configural processes seem to override an intact ability to utilize part-based or local feature cues. (JINS, 2006, 12, 884-895.
Background and Purpose-Stroke is implicated in the incidence of dementia, and the risk of poststr... more Background and Purpose-Stroke is implicated in the incidence of dementia, and the risk of poststroke dementia is well characterized, but the excess risk of dementia in those with stroke compared with those without stroke is not well known. Methods-We conducted a systematic review of the excess risk of incident dementia conferred by stroke. Studies of the risk of incident dementia in the population with stroke compared with the population without stroke were identified and compared. Results-Sixteen studies were identified with all but one conducted in a community setting. A history of stroke doubles the risk of incident dementia in the older population. This increase is not explained by demographic or cardiovascular risk factors or by prestroke cognitive decline. The excess risk of incident dementia diminishes with time after stroke and may be higher in those without an APOE ⑀4 allele. There is no excess risk of incident dementia in those aged Ͼ85 years with a history of stroke compared to those aged Ͼ85 years without stroke. Conclusions-The effect of stroke on dementia incidence in the population is not explained by common risk factors. At this time of population aging and increased stroke survival, more research is needed to determine to what extent efforts to reduce the incidence of stroke will affect the incidence of dementia. (Stroke. 2010;41:e41-e46.)
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.
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.
rTMS over the DLPFC combined with tomographic neurofeedback of the sgACC as a tailored antidepres... more rTMS over the DLPFC combined with tomographic neurofeedback of the sgACC as a tailored antidepressant intervention with enduring effects View project RDoC Anxiety and Depression ("RAD") Project: Developing a clinical translational neuroscience taxonomy for anxiety and mood disorder View project New treatments for Alzheimer's disease require early detection of cognitive decline. Most studies seeking to identify markers of early cognitive decline have focused on a limited number of measures. We sought to establish the profile of brain function measures which best define early neuropsychological decline. We compared subjects with subjective memory complaints to normative controls on a wide range of EEG derived measures, including a new measure of event-related spatio-temporal waves and biophysical modeling, which derives anatomical and physiological parameters based on subject's EEG measurements. Measures that distinguished the groups were then related to cognitive performance on a variety of learning and executive function tasks. The EEG measures include standard power measures, peak alpha frequency, EEG desynchronization to eyes-opening, and global phase synchrony. The most prominent differences in subjective memory complaint subjects were elevated alpha power and an increased number of spatio-temporal wave events. Higher alpha power and changes in wave activity related most strongly to a decline in verbal memory performance in subjects with subjective memory complaints, and also declines in maze performance and working memory reaction time. Interestingly, higher alpha power and wave activity were correlated with improved performance in reverse digit span in the subjective memory complaint group. The modeling results suggest that differences in the subjective memory complaint subjects were due to a decrease in cortical and thalamic inhibitory gains and slowed dendritic time-constants. The complementary profile that emerges from the variety of measures and analyses points to a nonlinear progression in electrophysiological changes from early neuropsychological decline to late-stage dementia, and electrophysiological changes in subjective memory complaint that vary in their relationships to a range of memory-related tasks.
Journals of Gerontology Series A-biological Sciences and Medical Sciences, Jan 1, 2010
The transition in the world age demographic toward older age is associated with an increased risk... more The transition in the world age demographic toward older age is associated with an increased risk of neurodegenerative diseases, such as Alzheimer's disease. Risk profiles for dementia may also be changing. Obesity and type 2 diabetes have increased in prevalence in the last half-century and have been associated with increased dementia risk. Specific changes in nutrition may also represent a direct risk. A diet transition in the United States has occurred in the intake of refined sugar, particularly high-fructose corn syrup (HFCS) from a yearly estimate of 8.1 kg/person at the beginning of the XIX century to a current estimate of 65 kg/person. This article considers the association between refined sugar intake, markers of cardiovascular disease risk, and the possible promotion of the development of dementia.
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.
American Journal of Geriatric Psychiatry, Jan 1, 2010
Background Criteria for Mild Cognitive Impairment (MCI) predict dementia risk in the clinic. Deme... more Background Criteria for Mild Cognitive Impairment (MCI) predict dementia risk in the clinic. Dementia risk in the population is different and whether there is an optimal MCI derived threshold for discriminating at-risk from not-at-risk cases in the general older population is not known. Data were from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Two risk thresholds were derived from each of seven different concepts of MCI including: Mayo Clinic defined amnestic, non-amnestic, multiple and revised MCI, MCI based on Mini Mental State Examination (MMSE) derived categories, and the definitions of Cognitive Impairment No Dementia (CIND) and Age Related Cognitive Decline (ARCD). Receiver Operating Characteristic (ROC) analysis was used to compare the predictive validity of two-year incident dementia for each risk threshold across the different MCI definitions. Findings MCI derived risk thresholds varied in their ability to predict dementia. MCI thresholds were accurate in identifying individuals not-at-risk of dementia progression (False Negative range, 0-3.4%). No MCI derived threshold accurately identified an at-risk group with a two year progression rate greater than 20%. Criteria for ARCD defined the threshold with the highest sensitivity and specificity for dementia conversion. Interpretation MCI derived thresholds do not reliably identify individuals at-risk of incident dementia at two years when applied in the general population. A large subpopulation of individuals not-at-risk was more reliably identified. What is considered a sufficient level of accuracy for identification of individuals at increased risk of dementia depends on the motivation for screening and on the safety and efficacy of available interventions.
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.
Background: Behavioural and psychological symptoms are associated with dementia, but are also pre... more Background: Behavioural and psychological symptoms are associated with dementia, but are also present in a significant number of the older population without dementia. Here we explore the distribution of behavioural and psychological symptoms in the population without dementia, and their relationship with domains and severity of health and cognitive impairment. Methods: The Medical Research Council Cognitive Function and Ageing Study is a two-phase longitudinal study of ageing representative of the population aged 65 and over of England and Wales. A subsample of 1781 participants without a study diagnosis of dementia was included in this study. Information on symptoms including depression, apathy, anxiety, feelings of persecution, hallucination, agitated behaviour, elation, irritability, sleep problems, wandering, confabulation and misidentification, cognitive function, health related factors and socio-demographic information was extracted from interviews with participants and knowledgeable informants. Participants were classified according to the Mini-Mental State Examination and by criteria for subtypes of mild cognitive impairment (MCI). The prevalence of behavioural and psychological symptoms and associations with cognitive function, health and socio-demographics was examined. Co-occurrence of symptoms was tested using factor analysis.
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.
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.
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.
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.
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.
Journal of The International Neuropsychological Society, Jan 1, 2006
Prosopagnosia is currently viewed within the constraints of two competing theories of face recogn... more Prosopagnosia is currently viewed within the constraints of two competing theories of face recognition, one highlighting the analysis of features, the other focusing on configural processing of the whole face. This study investigated the role of feature analysis versus whole face configural processing in the recognition of facial expression. A prosopagnosic patient, SC made expression decisions from whole and incomplete (eyes-only and mouth-only) faces where features had been obscured. SC was impaired at recognizing some (e.g., anger, sadness, and fear), but not all (e.g., happiness) emotional expressions from the whole face. Analyses of his performance on incomplete faces indicated that his recognition of some expressions actually improved relative to his performance on the whole face condition. We argue that in SC interference from damaged configural processes seem to override an intact ability to utilize part-based or local feature cues. (JINS, 2006, 12, 884-895.
Background and Purpose-Stroke is implicated in the incidence of dementia, and the risk of poststr... more Background and Purpose-Stroke is implicated in the incidence of dementia, and the risk of poststroke dementia is well characterized, but the excess risk of dementia in those with stroke compared with those without stroke is not well known. Methods-We conducted a systematic review of the excess risk of incident dementia conferred by stroke. Studies of the risk of incident dementia in the population with stroke compared with the population without stroke were identified and compared. Results-Sixteen studies were identified with all but one conducted in a community setting. A history of stroke doubles the risk of incident dementia in the older population. This increase is not explained by demographic or cardiovascular risk factors or by prestroke cognitive decline. The excess risk of incident dementia diminishes with time after stroke and may be higher in those without an APOE ⑀4 allele. There is no excess risk of incident dementia in those aged Ͼ85 years with a history of stroke compared to those aged Ͼ85 years without stroke. Conclusions-The effect of stroke on dementia incidence in the population is not explained by common risk factors. At this time of population aging and increased stroke survival, more research is needed to determine to what extent efforts to reduce the incidence of stroke will affect the incidence of dementia. (Stroke. 2010;41:e41-e46.)
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.
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.
rTMS over the DLPFC combined with tomographic neurofeedback of the sgACC as a tailored antidepres... more rTMS over the DLPFC combined with tomographic neurofeedback of the sgACC as a tailored antidepressant intervention with enduring effects View project RDoC Anxiety and Depression ("RAD") Project: Developing a clinical translational neuroscience taxonomy for anxiety and mood disorder View project New treatments for Alzheimer's disease require early detection of cognitive decline. Most studies seeking to identify markers of early cognitive decline have focused on a limited number of measures. We sought to establish the profile of brain function measures which best define early neuropsychological decline. We compared subjects with subjective memory complaints to normative controls on a wide range of EEG derived measures, including a new measure of event-related spatio-temporal waves and biophysical modeling, which derives anatomical and physiological parameters based on subject's EEG measurements. Measures that distinguished the groups were then related to cognitive performance on a variety of learning and executive function tasks. The EEG measures include standard power measures, peak alpha frequency, EEG desynchronization to eyes-opening, and global phase synchrony. The most prominent differences in subjective memory complaint subjects were elevated alpha power and an increased number of spatio-temporal wave events. Higher alpha power and changes in wave activity related most strongly to a decline in verbal memory performance in subjects with subjective memory complaints, and also declines in maze performance and working memory reaction time. Interestingly, higher alpha power and wave activity were correlated with improved performance in reverse digit span in the subjective memory complaint group. The modeling results suggest that differences in the subjective memory complaint subjects were due to a decrease in cortical and thalamic inhibitory gains and slowed dendritic time-constants. The complementary profile that emerges from the variety of measures and analyses points to a nonlinear progression in electrophysiological changes from early neuropsychological decline to late-stage dementia, and electrophysiological changes in subjective memory complaint that vary in their relationships to a range of memory-related tasks.
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Papers by Blossom Stephan