- Email: [email protected]
EDUCATION AND THE PREVALENCE OF AMYLOID PATHOLOGY
P232
Oral Sessions: O3-11: Epidemiology: Cognitive Reserve, Resilience, and Traumatic Injury
study that enrolls consenting randomly selected non-demented people aged 65 from a healthcare delivery system. Participants were asked at enrollment and biennially regarding injuries leading to loss of consciousness (LOC), including TBI. Those endorsing TBI were asked about age at time of TBI and duration of loss of consciousness. Autopsy consent rates are 25-30%. We evaluated the following outcomes: Braak stage; CERAD grade; amyloid angiopathy; presence of cystic infarcts; presence of any microinfarcts, cerebral microinfarcts, and deep microinfarcts; atrophy ascertained by lateral ventricle diameter at the temporal pole; presence of any Lewy bodies and Lewy bodies in the substantia nigra or locus ceruleus, frontal or temporal cortex, and in the amygdala. We performed loglinear regression for each outcome, controlling for age, education, and sex. We used inverse probability weighting to account for factors associated with dying and coming to autopsy; resulting estimates are weighted back to the parent ACT study, thus giving population-relevant relative risks. Results: 529 decedents came to autopsy by 9/2013, 2 families withdrew consent and 2 had no TBI data. Of the remaining 525, 107 (20.4%) reported 1 TBI. For the 94 decedents with LOC length data, 14 (15%) had LOC >1 hour. Regression results are summarized in the Table. The most notable finding was the strong association between TBI with LOC >1 hour with Lewy bodies, especially in frontal or temporal cortex or in substantia nigra or locus ceruleus. Conclusions: We found large associations between TBI with LOC >1 hour and Lewy bodies. There was no particular relationship between TBI exposures and neuropathological indices used to characterize Alzheimer’s disease pathology, vascular pathology, or atrophy. Further assessments are warranted to determine whether tau pathologies characteristic of chronic traumatic encephalopathy seen in athletes with multiple concussions are also seen following single or multiple TBIs in a community-based cohort, and also to determine whether gene expression may be altered in brains of people who survived to older age despite TBI.
O3-11-05
EDUCATION AND THE PREVALENCE OF AMYLOID PATHOLOGY
Willemijn J. Jansen1, Rik Ossenkoppele2, Frans R. J. Verhey1, Pieter Jelle Visser3, 1Maastricht University/Alzheimer Center Limburg/School for Mental Health and Neuroscience, Maastricht, Netherlands; 2VU Medical Center, Maastricht, Netherlands; 3VU Medical Center/Maastricht University/Alzheimer Center Limburg/School for Mental Health and Neuroscience, Maastricht, Netherlands. Contact e-mail: [email protected] Background: Amyloid pathology is thought to be the earliest pathological event in Alzheimer’s disease. Biomarkers can detect amyloid up to 20 years before the onset of symptoms. Education, a proxy for cognitive reserve, might modify the impact amyloid pathology has on cognition. We aimed to estimate the relation between education and amyloid prevalence in healthy controls, and subjects with MCI and dementia. We also tested whether education influenced the relation between amyloid pathology and cognitive functioning. Methods: We selected 2349 healthy controls, 2296 subjects with MCI and 1340 subjects with dementia from 57 centers that participated in a multicenter collaborative project on the prevalence of amyloid pathology. As a measure of amyloid pathology we used amyloid-PET retention or CSF Ab42 concentration. Amyloid was dichotomized using center-specific cutoffs for abnormality. Education in years was divided into high ( 14y) and low (<14y) education groups. Generalized linear models were used to predict probabilities for abnormal amyloid in the high and low education groups. Mixed models were used to examine the effect of amyloid by education on MMSE score. All analyses were adjusted for age, APOE- ε4 status and clinical diagnosis. Results: Highly educated subjects more often had amyloid pathology than lowly educated subjects in cognitively normal subjects (24% vs. 20%) and MCI subjects (53% vs. 48%, both p ¼ 0.001) but not in the dementia group. Education did not
interact with the relation between amyloid status and MMSE score in controls, MCI subjects and dementia patients. Conclusions: The observation that amyloid prevalence is increased in controls and MCI subjects with a high level of education could suggest that high education protects against cognitive deterioration. This protective effect of education in the presence of amyloid pathology is however not reflected in MMSE score. These results could help to improve success of preventive strategies as well as our understanding of the disease.
O3-11-06
RELATIONSHIP OF LIFE SPACE AND ACTIVITY IN LATE LIFE WITH NEUROPATHOLOGY
Bryan David James1, Patricia Boyle2, Aron S. Buchman1, Lisa L. Barnes1, Robert S. Wilson1, David A. Bennett2, Julie A. Schneider1, 1Rush Alzheimer’s Disease Center, Chicago, Illinois, United States; 2Rush University Medical Center, Chicago, Illinois, United States. Contact e-mail: [email protected] Background: Physical, cognitive, and social activities are related to better cognitive outcomes in later life. We previously have demonstrated that persons with a larger life space, the extent of movement from the home, have lowered risk for Alzheimer’s disease (AD). Multiple pathologies including cerebrovascular underlie the clinical manifestation of Alzheimer’s disease and other dementias. We now examine the relationship between life space and activity types with common neuropathologies of dementia. Methods: Clinical and neuropathologic data were available from 482 persons aged 65-106 (mean age¼89.2, SD¼6.1) at death from the Rush Memory and Aging Project. As part of annual evaluation, participants reported life space (ranging from bedroom to outside of town) and late-life physical (five items), cognitive (seven items), and social activities (six items). At death (mean 5.2 years from first clinical evaluation), autopsied brains were examined for AD pathology (NIA-Reagan criteria), Lewy Bodies (LB), chronic and micro-infarcts, cerebral atherosclerosis, and arteriolosclerosis. Each pathology was regressed on each behavior (from baseline or earliest visit available) in models adjusted for age at death, sex, and education. Results: Larger life space was consistently associated with less cerebrovascular pathology: total chronic infarcts (p<0.003), as well as gross (p¼0.028) and microinfarcts (p¼0.033), cerebral atherosclerosis (p¼0.005), and arteriolosclerosis (p<0.001). Social activity was associated with gross chronic infarcts only (p¼0.048). Physical and cognitive activity were not associated with any pathology. None of the behaviors examined were associated with AD or LB pathology. In models that included terms for all behaviors, life space remained associated with cerebrovascular pathology. Conclusions: Larger life space is associated with less cerebrovascular pathology. Though life space was measured an average of 5 years before death, it is not
Oral Sessions: O3-11: Epidemiology: Cognitive Reserve, Resilience, and Traumatic Injury
study that enrolls consenting randomly selected non-demented people aged 65 from a healthcare delivery system. Participants were asked at enrollment and biennially regarding injuries leading to loss of consciousness (LOC), including TBI. Those endorsing TBI were asked about age at time of TBI and duration of loss of consciousness. Autopsy consent rates are 25-30%. We evaluated the following outcomes: Braak stage; CERAD grade; amyloid angiopathy; presence of cystic infarcts; presence of any microinfarcts, cerebral microinfarcts, and deep microinfarcts; atrophy ascertained by lateral ventricle diameter at the temporal pole; presence of any Lewy bodies and Lewy bodies in the substantia nigra or locus ceruleus, frontal or temporal cortex, and in the amygdala. We performed loglinear regression for each outcome, controlling for age, education, and sex. We used inverse probability weighting to account for factors associated with dying and coming to autopsy; resulting estimates are weighted back to the parent ACT study, thus giving population-relevant relative risks. Results: 529 decedents came to autopsy by 9/2013, 2 families withdrew consent and 2 had no TBI data. Of the remaining 525, 107 (20.4%) reported 1 TBI. For the 94 decedents with LOC length data, 14 (15%) had LOC >1 hour. Regression results are summarized in the Table. The most notable finding was the strong association between TBI with LOC >1 hour with Lewy bodies, especially in frontal or temporal cortex or in substantia nigra or locus ceruleus. Conclusions: We found large associations between TBI with LOC >1 hour and Lewy bodies. There was no particular relationship between TBI exposures and neuropathological indices used to characterize Alzheimer’s disease pathology, vascular pathology, or atrophy. Further assessments are warranted to determine whether tau pathologies characteristic of chronic traumatic encephalopathy seen in athletes with multiple concussions are also seen following single or multiple TBIs in a community-based cohort, and also to determine whether gene expression may be altered in brains of people who survived to older age despite TBI.
O3-11-05
EDUCATION AND THE PREVALENCE OF AMYLOID PATHOLOGY
Willemijn J. Jansen1, Rik Ossenkoppele2, Frans R. J. Verhey1, Pieter Jelle Visser3, 1Maastricht University/Alzheimer Center Limburg/School for Mental Health and Neuroscience, Maastricht, Netherlands; 2VU Medical Center, Maastricht, Netherlands; 3VU Medical Center/Maastricht University/Alzheimer Center Limburg/School for Mental Health and Neuroscience, Maastricht, Netherlands. Contact e-mail: [email protected] Background: Amyloid pathology is thought to be the earliest pathological event in Alzheimer’s disease. Biomarkers can detect amyloid up to 20 years before the onset of symptoms. Education, a proxy for cognitive reserve, might modify the impact amyloid pathology has on cognition. We aimed to estimate the relation between education and amyloid prevalence in healthy controls, and subjects with MCI and dementia. We also tested whether education influenced the relation between amyloid pathology and cognitive functioning. Methods: We selected 2349 healthy controls, 2296 subjects with MCI and 1340 subjects with dementia from 57 centers that participated in a multicenter collaborative project on the prevalence of amyloid pathology. As a measure of amyloid pathology we used amyloid-PET retention or CSF Ab42 concentration. Amyloid was dichotomized using center-specific cutoffs for abnormality. Education in years was divided into high ( 14y) and low (<14y) education groups. Generalized linear models were used to predict probabilities for abnormal amyloid in the high and low education groups. Mixed models were used to examine the effect of amyloid by education on MMSE score. All analyses were adjusted for age, APOE- ε4 status and clinical diagnosis. Results: Highly educated subjects more often had amyloid pathology than lowly educated subjects in cognitively normal subjects (24% vs. 20%) and MCI subjects (53% vs. 48%, both p ¼ 0.001) but not in the dementia group. Education did not
interact with the relation between amyloid status and MMSE score in controls, MCI subjects and dementia patients. Conclusions: The observation that amyloid prevalence is increased in controls and MCI subjects with a high level of education could suggest that high education protects against cognitive deterioration. This protective effect of education in the presence of amyloid pathology is however not reflected in MMSE score. These results could help to improve success of preventive strategies as well as our understanding of the disease.
O3-11-06
RELATIONSHIP OF LIFE SPACE AND ACTIVITY IN LATE LIFE WITH NEUROPATHOLOGY
Bryan David James1, Patricia Boyle2, Aron S. Buchman1, Lisa L. Barnes1, Robert S. Wilson1, David A. Bennett2, Julie A. Schneider1, 1Rush Alzheimer’s Disease Center, Chicago, Illinois, United States; 2Rush University Medical Center, Chicago, Illinois, United States. Contact e-mail: [email protected] Background: Physical, cognitive, and social activities are related to better cognitive outcomes in later life. We previously have demonstrated that persons with a larger life space, the extent of movement from the home, have lowered risk for Alzheimer’s disease (AD). Multiple pathologies including cerebrovascular underlie the clinical manifestation of Alzheimer’s disease and other dementias. We now examine the relationship between life space and activity types with common neuropathologies of dementia. Methods: Clinical and neuropathologic data were available from 482 persons aged 65-106 (mean age¼89.2, SD¼6.1) at death from the Rush Memory and Aging Project. As part of annual evaluation, participants reported life space (ranging from bedroom to outside of town) and late-life physical (five items), cognitive (seven items), and social activities (six items). At death (mean 5.2 years from first clinical evaluation), autopsied brains were examined for AD pathology (NIA-Reagan criteria), Lewy Bodies (LB), chronic and micro-infarcts, cerebral atherosclerosis, and arteriolosclerosis. Each pathology was regressed on each behavior (from baseline or earliest visit available) in models adjusted for age at death, sex, and education. Results: Larger life space was consistently associated with less cerebrovascular pathology: total chronic infarcts (p<0.003), as well as gross (p¼0.028) and microinfarcts (p¼0.033), cerebral atherosclerosis (p¼0.005), and arteriolosclerosis (p<0.001). Social activity was associated with gross chronic infarcts only (p¼0.048). Physical and cognitive activity were not associated with any pathology. None of the behaviors examined were associated with AD or LB pathology. In models that included terms for all behaviors, life space remained associated with cerebrovascular pathology. Conclusions: Larger life space is associated with less cerebrovascular pathology. Though life space was measured an average of 5 years before death, it is not