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David A. Snowdon - One of the best experts on this subject based on the ideXlab platform.
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p1 393 hypertrophy of ca1 hippocampal neurons and apoe frequency in asymptomatic alzheimer s disease findings from the Nun Study
Alzheimers & Dementia, 2008Co-Authors: Diego Iacono, William R Markesbery, Olga Pletnikova, Peter P Zandi, Juan C Troncoso, Ela Patel, Dianna Tudor, David A. SnowdonAbstract:subjects, 28 with MCI and 24 with dementia (17 mild), aged 82.2 5.0 years, 56% female and with educational level of 2.9 2.4 years. No correlation was found between apathy scores and any global or executive cognitive measure. This finding were observed in the whole sample and where replicated in the MCI, mildly demented and demented sub-samples. Apathy scores inversely correlated with DAD scores in the demented subjects (r -0.698; p 0.0011). Conclusions: In this community based sample of low-literacy cognitively impaired oldest old elderly, no correlation was found between executive measures and apathy scores. However, higher apathy scores correlated with worse functional performance in the demented patients.
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healthy ageing in the Nun Study definition and neuropathologic correlates
Age and Ageing, 2007Co-Authors: Suzanne L Tyas, David A. Snowdon, Mark F Desrosiers, Kathryn P Riley, William R MarkesberyAbstract:Background although the concept of healthy ageing has stimulated considerable interest, no generally accepted definition has been developed nor has its biological basis been determined. Objective to develop a definition of healthy ageing and investigate its association with longevity and neuropathology. Methods analyses were based on cognitive, physical, and post-mortem assessments from 1991 to 1998 in the Nun Study, a longitudinal Study of ageing in participants 75+ years at baseline. We defined three mutually exclusive levels of healthy ageing (excellent, very good, and good) based on measures of global cognitive function, short-term memory, basic and instrumental activities of daily living, and self-rated function. Mortality analyses were based on 636 participants; neuropathologic analyses were restricted to 221 who had died and were autopsied. Results only 11% of those meeting criteria for the excellent level of healthy ageing at baseline subsequently died, compared with 24% for the very good, 39% for the good, and 60% for the remaining participants. Survival curves showed significantly greater longevity with higher levels of healthy ageing. The risk of not attaining healthy ageing, adjusted for age, increased two-fold in participants with brain infarcts alone, six-fold in those with Alzheimer neuropathology alone, and more than thirteen-fold in those with both brain infarcts and Alzheimer neuropathology. Conclusions the biological validity of our definition of healthy ageing is supported by its strong association with mortality and longevity. Avoiding Alzheimer and stroke neuropathology is critical to the maintenance of healthy ageing, and the presence of both pathologies dramatically decreases the likelihood of healthy ageing.
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neuropathological findings processed by artificial neural networks anns can perfectly distinguish alzheimer s patients from controls in the Nun Study
BMC Neurology, 2007Co-Authors: Enzo Grossi, David A. Snowdon, Massimo Buscema, Piero AntuonoAbstract:Background Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this Study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs) analysis
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transitions to mild cognitive impairments dementia and death findings from the Nun Study
American Journal of Epidemiology, 2007Co-Authors: Suzanne L Tyas, David A. Snowdon, Mark F Desrosiers, Kathryn P Riley, Juan C Salazar, Marta S Mendiondo, Richard J KryscioAbstract:The potential of early interventions for dementia has increased interest in cognitive impairments less severe than dementia. However, predictors of the trajectory from intact cognition to dementia have not yet been clearly identified. The purpose of this Study was to determine whether known risk factors for dementia increased the risk of mild cognitive impairments or progression from mild cognitive impairments to dementia. A polytomous logistic regression model was used, with parameters governing transitions within transient states (intact cognition, mild cognitive impairments, global impairment) estimated separately from parameters governing the transition from transient to absorbing state (dementia or death). Analyses were based on seven annual examinations (1991–2002) of 470 Nun Study participants aged � 75 years at baseline and living in the United States. Odds of developing dementia increased with age primarily for those with low educational levels. In these women, presence of an apolipoprotein E gene *E4 allele increased the odds more than fourfold by age 95 years. Age, education, and the apolipoprotein E gene were all significantly associated with mild cognitive impairments. Only age, however, was associated with progression to dementia. Thus, risk factors for dementia may operate primarily by predisposing individuals to develop mild cognitive impairments; subsequent progression to dementia then depends on only time and competing mortality. aged, 80 and over; apolipoproteins E; cognition disorders; cohort studies; dementia; disease progression; Markov chains; risk factors
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early life linguistic ability late life cognitive function and neuropathology findings from the Nun Study
Neurobiology of Aging, 2005Co-Authors: Kathryn P Riley, David A. Snowdon, Mark F Desrosiers, William R MarkesberyAbstract:The relationships between early life variables, cognitive function, and neuropathology were examined in participants in the Nun Study who were between the ages of 75 and 95. Our early life variable was idea density, which is a measure of linguistic ability, derived from autobiographies written at a mean age of 22 years. Six discrete categories of cognitive function, including mild cognitive impairments, were evaluated, using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Neuropathologic data included Braak staging, neurofibrillary tangle and senile plaque counts, brain weight, degree of cerebral atrophy, severity of atherosclerosis, and the presence of brain infarcts. Early-life idea density was significantly related to the categories of late-life cognitive function, including mild cognitive impairments: low idea density was associated with greater impairment. Low idea density also was significantly associated with lower brain weight, higher degree of cerebral atrophy, more severe neurofibrillary pathology, and the likelihood of meeting neuropathologic criteria for Alzheimer's disease.
William R Markesbery - One of the best experts on this subject based on the ideXlab platform.
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apoe2 and education in cognitively normal older subjects with high levels of ad pathology at autopsy findings from the Nun Study
Oncotarget, 2015Co-Authors: Diego Iacono, Myron D Gross, William R Markesbery, Olga Pletnikova, Peter P Zandi, Juan C TroncosoAbstract:Asymptomatic Alzheimer’s disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOe4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE could be associated with the different clinical outcomes between ASYMAD and MCI subjects despite equivalent AD pathology. A total of 523 brains from the Nun Study were screened for this investigation. The results showed higher APOe2 frequency (p < 0.001) in ASYMAD (19.2%) vs. MCI (0%) and vs. AD (4.7%). Furthermore, higher education in ASYMAD vs. MCI and AD (p < 0.05) was found. These novel autopsy-verified findings support the hypothesis of the beneficial effect of APOe2 and education, both which seem to act as contributing factors in delaying or forestalling the clinical manifestations of AD despite consistent levels of AD pathology.
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the Nun Study clinically silent ad neuronal hypertrophy and linguistic skills in early life
Neurology, 2009Co-Authors: Diego Iacono, Myron D Gross, William R Markesbery, Olga Pletnikova, G Rudow, Peter P Zandi, Juan C TroncosoAbstract:Background: It is common to find substantial Alzheimer disease (AD) lesions, i.e., neuritic β-amyloid plaques and neurofibrillary tangles, in the autopsied brains of elderly subjects with normal cognition assessed shortly before death. We have termed this status asymptomatic AD (ASYMAD). We assessed the morphologic substrate of ASYMAD compared to mild cognitive impairment (MCI) in subjects from the Nun Study. In addition, possible correlations between linguistic abilities in early life and the presence of AD pathology with and without clinical manifestations in late life were considered. Methods: Design-based stereology was used to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in the CA1 region of hippocampus (CA1). Four groups of subjects were compared: ASYMAD (n = 10), MCI (n = 5), AD (n = 10), and age-matched controls (n = 13). Linguistic ability assessed in early life was compared among all groups. Results: A significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and nucleoli (+80.2%) in the CA1 neurons was found in ASYMAD compared with MCI. Similar differences were observed with controls. Furthermore, significant higher idea density scores in early life were observed in controls and ASYMAD group compared to MCI and AD groups. Conclusions: 1) Neuronal hypertrophy may constitute an early cellular response to Alzheimer disease (AD) pathology or reflect compensatory mechanisms that prevent cognitive impairment despite substantial AD lesions; 2) higher idea density scores in early life are associated with intact cognition in late life despite the presence of AD lesions.
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p1 393 hypertrophy of ca1 hippocampal neurons and apoe frequency in asymptomatic alzheimer s disease findings from the Nun Study
Alzheimers & Dementia, 2008Co-Authors: Diego Iacono, William R Markesbery, Olga Pletnikova, Peter P Zandi, Juan C Troncoso, Ela Patel, Dianna Tudor, David A. SnowdonAbstract:subjects, 28 with MCI and 24 with dementia (17 mild), aged 82.2 5.0 years, 56% female and with educational level of 2.9 2.4 years. No correlation was found between apathy scores and any global or executive cognitive measure. This finding were observed in the whole sample and where replicated in the MCI, mildly demented and demented sub-samples. Apathy scores inversely correlated with DAD scores in the demented subjects (r -0.698; p 0.0011). Conclusions: In this community based sample of low-literacy cognitively impaired oldest old elderly, no correlation was found between executive measures and apathy scores. However, higher apathy scores correlated with worse functional performance in the demented patients.
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healthy ageing in the Nun Study definition and neuropathologic correlates
Age and Ageing, 2007Co-Authors: Suzanne L Tyas, David A. Snowdon, Mark F Desrosiers, Kathryn P Riley, William R MarkesberyAbstract:Background although the concept of healthy ageing has stimulated considerable interest, no generally accepted definition has been developed nor has its biological basis been determined. Objective to develop a definition of healthy ageing and investigate its association with longevity and neuropathology. Methods analyses were based on cognitive, physical, and post-mortem assessments from 1991 to 1998 in the Nun Study, a longitudinal Study of ageing in participants 75+ years at baseline. We defined three mutually exclusive levels of healthy ageing (excellent, very good, and good) based on measures of global cognitive function, short-term memory, basic and instrumental activities of daily living, and self-rated function. Mortality analyses were based on 636 participants; neuropathologic analyses were restricted to 221 who had died and were autopsied. Results only 11% of those meeting criteria for the excellent level of healthy ageing at baseline subsequently died, compared with 24% for the very good, 39% for the good, and 60% for the remaining participants. Survival curves showed significantly greater longevity with higher levels of healthy ageing. The risk of not attaining healthy ageing, adjusted for age, increased two-fold in participants with brain infarcts alone, six-fold in those with Alzheimer neuropathology alone, and more than thirteen-fold in those with both brain infarcts and Alzheimer neuropathology. Conclusions the biological validity of our definition of healthy ageing is supported by its strong association with mortality and longevity. Avoiding Alzheimer and stroke neuropathology is critical to the maintenance of healthy ageing, and the presence of both pathologies dramatically decreases the likelihood of healthy ageing.
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early life linguistic ability late life cognitive function and neuropathology findings from the Nun Study
Neurobiology of Aging, 2005Co-Authors: Kathryn P Riley, David A. Snowdon, Mark F Desrosiers, William R MarkesberyAbstract:The relationships between early life variables, cognitive function, and neuropathology were examined in participants in the Nun Study who were between the ages of 75 and 95. Our early life variable was idea density, which is a measure of linguistic ability, derived from autobiographies written at a mean age of 22 years. Six discrete categories of cognitive function, including mild cognitive impairments, were evaluated, using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Neuropathologic data included Braak staging, neurofibrillary tangle and senile plaque counts, brain weight, degree of cerebral atrophy, severity of atherosclerosis, and the presence of brain infarcts. Early-life idea density was significantly related to the categories of late-life cognitive function, including mild cognitive impairments: low idea density was associated with greater impairment. Low idea density also was significantly associated with lower brain weight, higher degree of cerebral atrophy, more severe neurofibrillary pathology, and the likelihood of meeting neuropathologic criteria for Alzheimer's disease.
Myron D Gross - One of the best experts on this subject based on the ideXlab platform.
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apoe2 and education in cognitively normal older subjects with high levels of ad pathology at autopsy findings from the Nun Study
Oncotarget, 2015Co-Authors: Diego Iacono, Myron D Gross, William R Markesbery, Olga Pletnikova, Peter P Zandi, Juan C TroncosoAbstract:Asymptomatic Alzheimer’s disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOe4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE could be associated with the different clinical outcomes between ASYMAD and MCI subjects despite equivalent AD pathology. A total of 523 brains from the Nun Study were screened for this investigation. The results showed higher APOe2 frequency (p < 0.001) in ASYMAD (19.2%) vs. MCI (0%) and vs. AD (4.7%). Furthermore, higher education in ASYMAD vs. MCI and AD (p < 0.05) was found. These novel autopsy-verified findings support the hypothesis of the beneficial effect of APOe2 and education, both which seem to act as contributing factors in delaying or forestalling the clinical manifestations of AD despite consistent levels of AD pathology.
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blood folate is associated with asymptomatic or partially symptomatic alzheimer s disease in the Nun Study
Journal of Alzheimer's Disease, 2012Co-Authors: Huifen Wang, Suzanne L Tyas, Andrew O Odegaard, Bharat Thyagarajan, Jennifer Hayes, Karen Santa Cruz, Mark F Derosiers, Myron D GrossAbstract:Asymptomatic and partially symptomatic Alzheimer's disease (APSYMAD) are a series of cognitive states wherein subjects have substantial Alzheimer's disease (AD) pathology (classification B or C by the Consortium to Establish a Registry for AD criteria), but have normal or only partially impaired cognitive function; all of these subjects are non-demented. These cognitive states may arise from the prevention or delay of clinical symptom expression by exposure to certain nutritional factors. This Study examined blood levels of folate and antioxidants (i.e., carotenoids) in relation to APSYMAD, nested in the Nun Study, a longitudinal Study of aging and AD. Sixty elderly female subjects, who had AD on the basis of neuropathology exams, were included. Following adjustment for APOE4 status, education level, and age at blood draw, subjects with the highest blood folate levels had a higher likelihood of being in the APSYMAD group as compared to the demented (AD) group (odds ratio = 1.09, 95% CI = 1.00-1.18. p < 0.06). This association was not significantly influenced by additional adjustment for blood concentrations of carotenoids. Restriction of the population to subjects with near normal cognition on the cognitive state score (score = 1-3) indicated an elevated association with blood folate (odds ratio = 1.12, 95% CI = 1.01-1.25, p < 0.04). Blood carotenoids were not associated with APSYMAD. Thus, folate status may influence the expression of clinical symptoms of AD disease and aid in the delay or prevention of dementia.
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association between gene expression of peripheral blood oxidative stress markers and alzheimer s disease the Nun Study
Alzheimers & Dementia, 2010Co-Authors: Jon D Wilson, Bharat Thyragarajan, Myron D GrossAbstract:Background: A definite diagnosis of Alzheimer’s disease (AD) is determined following brain autopsy by detection of hallmark pathologies of the disease: an extracellular aggregates of amyloid-b (Ab) peptides, termed as Ab plaques, and an intracellular neurofibrillary tangles. Presently, noninvasive monitoring of Ab plaques in the brains of living patients is, however, inadequate due to restricted resolution and specificity. We, thus, hypothesized that the eyes can serve as a window to the brain for direct and noninvasive imaging of AD. Methods: To this end, we used APPswe/PS1dE9 double-transgenic AD mice, which faithfully represent some of the key pathologies found in the human disease. We investigated presence and formation of amyloid plaques in retinas from these AD mice, as well as estimated the correlation between retinal amyloid plaques and the plaque pathology in the brain. Lastly, we evaluated responsiveness of retinal plaques to an immune-based therapy and the ability to image them in live mice. Results: Here, we detected Ab plaques in retinal samples of AD mice, and found that Ab plaques appear in the retina significantly earlier than in the brain. Retinal plaques accumulated during disease progression, and in good correlation with brain pathology. Moreover, retinal Ab plaque number and size were significantly reduced following an immune-based therapy, which we found to be effective in reducing plaques in the brain. Systemic administration of a natural compound that binds and labels Ab plaques, allowed in vivo noninvasive visualization of retinal Ab plaques in live AD mice, with high resolution and specificity. Conclusions: These studies establish the potential of direct retinal Ab plaque imaging in live subjects as a promising tool for early AD diagnosis, prognosis and assessment of therapies.
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the Nun Study clinically silent ad neuronal hypertrophy and linguistic skills in early life
Neurology, 2009Co-Authors: Diego Iacono, Myron D Gross, William R Markesbery, Olga Pletnikova, G Rudow, Peter P Zandi, Juan C TroncosoAbstract:Background: It is common to find substantial Alzheimer disease (AD) lesions, i.e., neuritic β-amyloid plaques and neurofibrillary tangles, in the autopsied brains of elderly subjects with normal cognition assessed shortly before death. We have termed this status asymptomatic AD (ASYMAD). We assessed the morphologic substrate of ASYMAD compared to mild cognitive impairment (MCI) in subjects from the Nun Study. In addition, possible correlations between linguistic abilities in early life and the presence of AD pathology with and without clinical manifestations in late life were considered. Methods: Design-based stereology was used to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in the CA1 region of hippocampus (CA1). Four groups of subjects were compared: ASYMAD (n = 10), MCI (n = 5), AD (n = 10), and age-matched controls (n = 13). Linguistic ability assessed in early life was compared among all groups. Results: A significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and nucleoli (+80.2%) in the CA1 neurons was found in ASYMAD compared with MCI. Similar differences were observed with controls. Furthermore, significant higher idea density scores in early life were observed in controls and ASYMAD group compared to MCI and AD groups. Conclusions: 1) Neuronal hypertrophy may constitute an early cellular response to Alzheimer disease (AD) pathology or reflect compensatory mechanisms that prevent cognitive impairment despite substantial AD lesions; 2) higher idea density scores in early life are associated with intact cognition in late life despite the presence of AD lesions.
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plasma antioxidant concentrations in a population of elderly women findings from the Nun Study
Nutrition Research, 1996Co-Authors: Myron D Gross, David A. SnowdonAbstract:Abstract Low plasma alpha-tocopherol and beta-carotene concentrations have been associated with an increased risk of numerous degenerative diseases, including cancer. Several characteristics that accompany aging, including changes in dietary habits and physiologic capacity, may place elderly populations at a high risk of low plasma antioxidant concentrations. Thus, the present Study was undertaken to characterize plasma concentrations of alpha-tocopherol, beta-carotene and several other carotenoids in elderly subjects, to describe the relationship between age and plasma antioxidant concentrations in this population and to compare the concentrations of plasma antioxidants in middle-aged and elderly individuals. The Study recruited 94 participants from the Nun Study, a longitudinal Study of aging and Alzheimer disease. Women in this population were unique for their advanced age, 77–99 years old, and their comparability across age groups due to the absence of several potential confounders of plasma antioxidant concentrations. The population mean and standard deviation of several plasma carotenoids and alpha-tocopherol concentrations (μg/dl) were as follows: lycopene, 15.0+− 10.0; beta-carotene, 30.0+− 19.7; alpha-carotene, 15.0 +− 9.6; zeaxanthin plus lutein, 22.0+− 7.4; beta-cryptoxanthin, 14.0 +− 8.6 and alpha-tocopherol, 980 +− 310. Concentrations of all analytes, except lycopene, were similar to or higher than those reported for several middle-aged American populations. Lycopene concentrations were significantly lower in the population of sisters as compared with the middle-aged populations and tended to decrease across age groups within the population of sisters. Age appeared to be a relatively minor determinant of plasma alpha-tocopherol and the concentrations of carotenoids, other than lycopene, in this population. Importantly, the plasma concentrations of most carotenoids and alpha-tocopherol in this population of independent elderly women were apparently adequate on the basis of population comparisons. Further studies of this population may define determinants essential for the maintenance of antioxidant status in elderly populations.
James A Mortimer - One of the best experts on this subject based on the ideXlab platform.
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the Nun Study risk factors for pathology and clinical pathologic correlations
Current Alzheimer Research, 2012Co-Authors: James A MortimerAbstract:The Nun Study was the first cohort Study to enroll and follow a large, well-defined population that included demented and non-demented participants, all of whom agreed to donate their brains for research. The inclusion of systematic neuropathologic analysis in this Study has resulted in a greater understanding of the role of Alzheimer and vascular pathology in the expression of memory deficits and dementia and has provided data showing that biomarkers for the pathology may be evident many decades earlier in adult life. Findings related to neuropathology in this Study have included the following: (1) Although clinical outcomes were strongly correlated with Alzheimer neuropathology, about one-third of the participants fulfilling criteria for neuropathologic Alzheimer's disease (AD) were not demented at the time of death. (2) Brain infarcts by themselves had little effect on cognitive status, but played an important role in increasing the risk of dementia associated with Alzheimer pathology. (3) Hippocampal volume was strongly correlated with Braak neurofibrillary stage even in participants with normal cognitive function. (4) A linguistic characteristic of essays written in early adult life, idea density, had a strong association with not only clinical outcomes in late life, but the severity of Alzheimer neuropathology as well. (5) The effect of apolipoprotein E-e4 on dementia was mediated through Alzheimer, but not vascular pathology.
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delayed recall hippocampal volume and alzheimer neuropathology findings from the Nun Study
Neurology, 2004Co-Authors: James A Mortimer, William R Markesbery, Kathryn P Riley, Karen M Gosche, David A. SnowdonAbstract:Objective: To examine the associations of hippocampal volume and the severity of neurofibrillary lesions determined at autopsy with delayed verbal recall performance evaluated an average of 1 year prior to death. Methods: Hippocampal volumes were computed using postmortem brain MRI from the first 56 scanned participants of the Nun Study. Quantitative neuropathologic studies included lesion counts, Braak staging, and determination of whether neuropathologic criteria for Alzheimer disease (AD) were met. Multiple regression was used to assess the association of hippocampal volume and neuropathologic lesions with the number of words (out of 10) recalled on the Consortium to Establish a Registry for Alzheimer’s Disease Delayed Word Recall Test administered an average of 1 year prior to death. Results: When entered separately, hippocampal volume, Braak stage, and the mean neurofibrillary tangle counts in the CA-1 region of the hippocampus and the subiculum were strongly associated with the number of words recalled after a delay, adjusting for age and education. When hippocampal volume was entered together with each neuropathologic index, only hippocampal volume retained a significant association with the delayed recall measure. The association between hippocampal volume and the number of words recalled was present in both demented and nondemented individuals as well as in those with and without substantial AD neurofibrillary pathology. Conclusions: The association of neurofibrillary tangles with delayed verbal recall may reflect associated hippocampal atrophy.
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head circumference education and risk of dementia findings from the Nun Study
Journal of Clinical and Experimental Neuropsychology, 2003Co-Authors: James A Mortimer, David A. Snowdon, William R MarkesberyAbstract:To examine the prevalence of dementia associated with having a smaller brain, lower education or both of these characteristics, 294 Catholic sisters were assessed annually for dementia. Sixty participants died and their brains were evaluated to determine fulfillment of neuropathological criteria for Alzheimer‘s disease (AD). Lower educational attainment and the interaction of smaller head circumference with lower education were associated with the presence of dementia, controlling for age and the presence of one or more apolipoprotein E-e4 alleles. By contrast, neither low educational attainment nor head circumference was significantly associated with fulfillment of neuropathological criteria for AD. Individuals having both low education and small head circumference were four times as likely to be demented as the rest of the sample. The findings suggest that higher education and larger head size, alone or in combination, may reduce the risk of expressing dementia in late life.
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hippocampal volume as an index of alzheimer neuropathology findings from the Nun Study
Neurology, 2002Co-Authors: Karen M Gosche, James A Mortimer, William R Markesbery, Charles D Smith, David A. SnowdonAbstract:Objective: To determine whether hippocampal volume is a sensitive and specific indicator of Alzheimer neuropathology, regardless of the presence or absence of cognitive and memory impairment. Methods: Postmortem MRI scans were obtained for the first 56 participants of the Nun Study who were scanned. The area under receiver operating characteristic curves, sensitivity, specificity, and positive and negative predictive values were used to assess the diagnostic accuracy of hippocampal volume in predicting fulfillment of Alzheimer neuropathologic criteria and differences in Braak staging. Results: Hippocampal volume predicted fulfillment of neuropathologic criteria for AD for all 56 participants ( p p = 0.036); 32 sisters who remained nondemented ( p p p = 0.003). In individuals who remained nondemented, hippocampal volume was a better indicator of AD neuropathology than a delayed memory measure. Among nondemented sisters, Braak stages III and VI were distinguishable from Braak stages II or lower ( p = 0.001). Among cognitively intact individuals, those in Braak stage II could be distinguished from those in stage I or less ( p = 0.025). Conclusion: Volumetric measures of the hippocampus may be useful in identifying nondemented individuals who satisfy neuropathologic criteria for AD as well as pathologic stages of AD that may be present decades before initial clinical expression.
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cognitive function and apolipoprotein e in very old adults findings from the Nun Study
Journals of Gerontology Series B-psychological Sciences and Social Sciences, 2000Co-Authors: Kathryn P Riley, David A. Snowdon, James A Mortimer, Ann M Saunders, Allen D Roses, Nuwan NanayakkaraAbstract:OBJECTIVES The epsilon4 allele of apolipoprotein E (APOE) has been associated with Alzheimer' s disease and with milder forms of cognitive impairment. We investigated the possibility that the absence of the epsilon4 allele may predict the maintenance of high cognitive function among very old individuals. METHODS Our data are from the Nun Study, a longitudinal Study of aging and Alzheimer's disease in 678 Catholic sisters. All sisters participate in annual functional exams that include the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. High cognitive function was defined as intact scores on five of the CERAD tests. A total of 241 participants aged 75 to 98 met this criterion at the first exam. RESULTS Findings showed that 62% of the 241 participants maintained intact scores on the five CERAD tests throughout their participation in the Study. Life table analyses indicated that those without the APOE epsilon4 allele spent more time with intact cognitive function than those with the epsilon4 allele (p = .007). Cox regression analyses indicated that those without the epsilon4 allele had half the risk of losing their intact status during the Study when compared with those with the epsilon4 allele (p < .01). DISCUSSION Our findings suggest that the APOE epsilon4 allele may be included among the variables that predict high cognitive function in cognitively intact, very old adults. Although the presence or absence of the epsilon4 allele is known to be related to the risk of dementia, it also appears to be related to maintaining high levels of cognitive function in old age.
Christine L. Tully - One of the best experts on this subject based on the ideXlab platform.
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serum folate and the severity of atrophy of the neocortex in alzheimer disease findings from the Nun Study
The American Journal of Clinical Nutrition, 2000Co-Authors: David A. Snowdon, Christine L. Tully, Kathryn P Riley, Charles D Smith, William R MarkesberyAbstract:Background: Previous studies suggested that low concentrations of folate in the blood are related to poor cognitive function, dementia, and Alzheimer disease-related neurodegeneration of the brain. Objective: Our aim was to determine whether serum folate is inversely associated with the severity of atrophy of the neocortex. Design: Nutrients, lipoproteins, and nutritional markers were measured in the blood of 30 participants in the Nun Study from one convent who later died when they were 78-101 y old (x: 91 y). At autopsy, several neuropathologic indicators of Alzheimer disease were determined, including the degree of atrophy of 3 lobes of the neocortex (frontal, temporal, and parietal) and the number of neocortical Alzheimer disease lesions (ie, senile plaques and neurofibrillary tangles) as assessed by a neuropathologist. Results: The correlation between serum folate and the severity of atrophy of the neocortex was -0.40 (P = 0.03). Among a subset of 15 participants with significant numbers of Alzheimer disease lesions in the neocortex, the correlation between folate and atrophy was -0.80 (P = 0.0006). Atrophy may be specific to low folate because none of the 18 other nutrients, lipoproteins, or nutritional markers measured in the blood had significant negative correlations with atrophy. Conclusions: Among elderly Catholic sisters who lived in one convent, ate from the same kitchen, and were highly comparable for a wide range of environmental and lifestyle factors, low serum folate was strongly associated with atrophy of the cerebral cortex. Definitive evidence for this relation and its temporal sequence awaits the findings of other studies.
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Acute phase response and plasma carotenoid concentrations in older women: Findings from the Nun Study
Nutrition, 1996Co-Authors: Boosalis Mg, David A. Snowdon, Christine L. Tully, Myron D GrossAbstract:Abstract This cross-sectional Study investigated whether the acute phase response was associated with suppressed circulating levels of antioxidants in a population of 85 Catholic sisters (Nuns) ages 77–99 y. Fasting blood was drawn to determine the presence of an acute phase response, as defined by an elevation in the serum concentration of C-reactive protein. Serum concentrations of albumin, thyroxine-binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma concentrations of carotenoids and alpha tocopherol. Results showed that the presence of an acute phase response was associated with ( 1 ) an expected significant decrease in the serum concentrations of albumin ( p p 2 ) an expected significant increase in copper ( p p = 0.003); and ( 3 ) a significant decrease in the plasma concentrations of lycopene ( p = 0.03), alpha carotene ( p = 0.02), beta carotene ( p = 0.02), and total carotenoids ( p = 0.01). The acute phase response was associated with decreased plasma levels of the antioxidants lycopene, alpha carotene, and beta carotene. This decrease in circulating antioxidants may further compromise antioxidant status and increase oxidative stress and damage in elders.
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Acute phase response and plasma carotenoid concentrations in older women: findings from the Nun Study.
Nutrition (Burbank Los Angeles County Calif.), 1996Co-Authors: M G Boosalis, David A. Snowdon, Christine L. Tully, Myron D GrossAbstract:This cross-sectional Study investigated whether the acute phase response was associated with suppressed circulating levels of antioxidants in a population of 85 Catholic sisters (Nuns) ages 77-99 y. Fasting blood was drawn to determine the presence of an acute phase response, as defined by an elevation in the serum concentration of C-reactive protein. Serum concentrations of albumin, thyroxine-binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma concentrations of carotenoids and alpha tocopherol. Results showed that the presence of an acute phase response was associated with (1) an expected significant decrease in the serum concentrations of albumin (p < 0.001) and thyroxine-binding prealbumin (p < 0.001); (2) an expected significant increase in copper (p < 0.001) and fibrinogen (p = 0.003); and (3) a significant decrease in the plasma concentrations of lycopene (p = 0.03), alpha carotene (p = 0.02), beta carotene (p = 0.02), and total carotenoids (p = 0.01). The acute phase response was associated with decreased plasma levels of the antioxidants lycopene, alpha carotene, and beta carotene. This decrease in circulating antioxidants may further compromise antioxidant status and increase oxidative stress and damage in elders.
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serum zinc and plasma lipoproteins in elderly women findings from the Nun Study
Journal of Trace Elements in Experimental Medicine, 1996Co-Authors: Christine L. Tully, David A. Snowdon, John D BelcherAbstract:Supplementation with zinc has been associated with changes in lipoprotein levels in prior studies. The purpose of this Study was to define further the relationship between serum zinc and plasma total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides. This Study was conducted in a homogeneous population of elderly women who were not taking zinc supplements. Fasting blood samples were drawn from 87 women, 77–99 years old. Serum zinc concentrations were significantly positively correlated with total cholesterol (r = 0.37, P = <0.01) and with LDL-cholesterol (r = 0.41, P = <0.001). In 77–84-year-old women (N = 47), a normal serum zinc level (70–150 μg/dl) was associated with a 27 mg/dl higher mean LDL-cholesterol (P = 0.06) compared to low serum zinc (<70 μg/dl). In 85–99-year-old women (N = 40), a normal serum zinc was associated with a 49 mg-dl higher mean LDL-cholesterol (P = 0.002) compared to low serum zinc. These associations were not materially affected by the potential confounding effects of weight, weight change over 8 years, triceps skinfold, or serum C-reactive protein. Overall, serum zinc concentration had a strong positive association with plasma LDL-cholesterol and to a lesser extent, with total plasma cholesterol in this population. The association between serum zinc and plasma cholesterol may be due to a third factor, such as red meat consumption, which is a significant source of zinc and saturated fat. Alternatively, zinc may play a role in cholesterol metabolism. © 1995 Wiley-Liss, Inc.
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weight change and physical function in older women findings from the Nun Study
Journal of the American Geriatrics Society, 1995Co-Authors: Christine L. Tully, David A. SnowdonAbstract:OBJECTIVE: To investigate the association between change in weight and decline in physical function in older women. DESIGN: Longitudinal Study of a defined population of Catholic sisters (Nuns) whose weight and function were assessed twice, an average of 584 days apart. SETTING: Unique life communities (convents) located throughout the United States. PARTICIPANTS: 475 Catholic sisters who were 75 to 99 years of age (M = 82.1, SD = 4.8) and were independent in at least one Activity of Daily Living (ADL) at the first assessment of weight and function. INTERVENTIONS: None. MEASUREMENTS: At each assessment, weight, ADLs, and cognitive function were evaluated as part of the Nun Study-a longitudinal Study of aging and Alzheimer's disease. Annual percent weight change was calculated using weights from the two assessments, as well as the number of days that elapsed between assessments. RESULTS: Mean weight at first assessment was 140 pounds (range 78 to 232, SD = 27). The mean annual percent weight change was 0.1% (range 22% loss to 16% gain, SD = 3.8). Age- and initial weight-adjusted findings indicated that those participants with an annual percent weight loss of 3% or greater had 2.7 to 3.9 times the risk of becoming dependent in each ADL, compared to the sisters with no weight change. The elevated risk persisted in those who were mentally intact or were independent in their eating habits. CONCLUSION: Monitoring of weight may be an easy and inexpensive method of identifying older individuals at increased risk of disability.
