Characterizing the Behavior Profile of Healthy Cognitive Aging

Summary

Principal Investigator: Patricia A Boyle,
Affiliation: Rush University Medical Center
Country: USA
Abstract: DESCRIPTION (provided by applicant): Cognitive decline is nearly universal in older persons and its prevention is one of the most important public health challenges of the 21st century. Despite considerable progress in identifying the causes of cognitive decline in older persons, surprisingly little is known about the profile of healthy cognitive aging. Most of the available studies of healthy cognitive aging have examined cognitive change in persons without clinical dementia. However, the vast majority of persons without dementia who come to autopsy have extensive neuropathologic evidence of the diseases commonly known to cause cognitive impairment in old age, particularly Alzheimer's disease, cerebral infarcts, and Lewy bodies, and the exclusion of persons without clinical dementia does not account for the effect of accumulating neuropathology on the trajectory of cognitive aging. Moreover, most older persons exhibit a precipitous decline in cognition in the years just prior to death, a phenomenon referred to as terminal decline, and this also contributes to cognitive aging. Thus, a substantial portion of the cognitive decline currently attributed to healthy cognitive aging likely is due to the influence of accumulating neuropathology and terminal decline. We propose to use innovative statistical approaches to characterize the profile of healthy cognitive aging defined as age-related cognitive change not accounted for by the presence of common neuropathologies (i.e., Alzheimer's disease, cerebral infarcts, and the Lewy body diseases) or terminal decline. The proposed study will capitalize on the unique longitudinal cognitive and neuropathologic data available from two ongoing epidemiologic studies, the Religious Orders Study (P30AG10161), which will serve as the exploratory cohort, and the Rush Memory and Aging Project (R01AG17917), which will serve as the confirmatory cohort. These studies perform comparable and detailed annual cognitive evaluations on more than 2,300 persons in total, all of whom have agreed to brain donation. By the end of the funding period of the proposed study, more than 23,000 cognitive data points will be available from more than 2,500 persons with up to 20 years of annual follow-up. In addition, detailed post-mortem data will be available from more than 1,200 persons. Data from these studies will be used to model the trajectory of cognitive change as a function of accumulating neuropathology and terminal decline in order to elucidate the trajectory of healthy cognitive aging (i.e., age-related cognitive change not accounted for by common neuropathologies or terminal decline). The proposed study offers a novel, timely, and potentially powerful approach to identify the profile of healthy cognitive aging. Knowledge of the trajectory of healthy cognitive aging is essential for the identification of persons who might benefit from interventions to prevent age-related cognitive decline and, ultimately, for the identification of factors associated with successful aging. PUBLIC HEALTH RELEVANCE: Cognitive decline is nearly universal in older persons and its prevention is one of the most important public health challenges of the 21st century. First, knowledge of the profile of healthy cognitive aging will allow for identification of persons exhibiting the earliest signs of pathologic cognitive aging who are most likely to benefit from the available therapies and disease modifying agents as they become available. Second, the proposed study will elucidate the extent to which common neuropathologies underlie age-related cognitive change and will directly inform on the public health burden associated with the diseases commonly known to cause cognitive impairment in old age;if common neuropathologies account for most of cognitive change seen in older persons, then these data would suggest that the public health burden posed by these diseases is greater than currently recognized and that a much larger group of persons, including those without overt dementia, ultimately may benefit from effective treatment and prevention strategies developed for cognitive impairment and dementia.
Funding Period: 2009-08-15 - 2014-07-31
more information: NIH RePORT

Top Publications

  1. pmc Correlates of susceptibility to scams in older adults without dementia
    Bryan D James
    a Department of Internal Medicine, Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, Illinois, USA
    J Elder Abuse Negl 26:107-22. 2014
  2. pmc Neural reserve, neuronal density in the locus ceruleus, and cognitive decline
    Robert S Wilson
    Rush Alzheimer s Disease Center and Departments of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
    Neurology 80:1202-8. 2013
  3. pmc The influence of cognitive decline on well-being in old age
    Robert S Wilson
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
    Psychol Aging 28:304-13. 2013
  4. pmc Poor decision making is associated with an increased risk of mortality among community-dwelling older persons without dementia
    Patricia A Boyle
    Rush Alzheimer s Disease Center 600 S Paulina, Suite 1020B, Chicago, IL 60612, USA Patricia_Boyle rush edu
    Neuroepidemiology 40:247-52. 2013
  5. pmc Neuroticism, extraversion, and motor function in community-dwelling older persons
    Aron S Buchman
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
    Am J Geriatr Psychiatry 21:145-54. 2013
  6. pmc Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies
    J A Schneider
    Rush Alzheimer s Disease Centre, Rush University Medical Centre, Chicago, IL 60612, USA
    Brain 135:3005-14. 2012
  7. pmc Emotional neglect in childhood and cerebral infarction in older age
    Robert S Wilson
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL, USA
    Neurology 79:1534-9. 2012
  8. pmc The natural history of cognitive decline in Alzheimer's disease
    Robert S Wilson
    Rush Alzheimer s Disease Center, Chicago, IL 60612, USA
    Psychol Aging 27:1008-17. 2012
  9. pmc Association of cognition with temporal discounting in community based older persons
    Patricia A Boyle
    Rush University Medical Center, Rush Alzheimer s Disease Center, 600 S, Paulina, Suite 1020B, Chicago, IL 60612, USA
    BMC Geriatr 12:48. 2012
  10. pmc Poor decision making is a consequence of cognitive decline among older persons without Alzheimer's disease or mild cognitive impairment
    Patricia A Boyle
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, Illinois, USA
    PLoS ONE 7:e43647. 2012

Scientific Experts

  • Robert Wilson
  • Patricia A Boyle,
  • Liesi Hebert
  • Bryan D James
  • Aron Buchman
  • Patricia A Boyle
  • David A Bennett
  • Lei Yu
  • Julie A Schneider
  • Eisuke Segawa
  • Sue Leurgans
  • Lisa L Barnes
  • Kumar B Rajan
  • Debra A Fleischman
  • Zoe Arvanitakis
  • Patricia Boyle
  • J A Schneider
  • Jarred S Bennett
  • David I Laibson
  • Carlos F Mendes de Leon
  • Kimberly A Skarupski
  • Denis A Evans
  • LEYLA DE TOLEDO-MORRELL
  • William G Honer
  • Konstantinos Arfanakis
  • S Duke Han
  • Alasdair M Barr
  • P A Boyle
  • S E Leurgans
  • L Yu
  • Z Arvanitakis
  • Philip L De Jager
  • D A Bennett
  • Keith Gamble
  • Sue E Leurgans

Detail Information

Publications48

  1. pmc Correlates of susceptibility to scams in older adults without dementia
    Bryan D James
    a Department of Internal Medicine, Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, Illinois, USA
    J Elder Abuse Negl 26:107-22. 2014
    ..Fully adjusted models indicated that older age and lower levels of cognitive function, decreased psychological well-being, and lower literacy in particular may be markers of susceptibility to financial victimization in old age. ..
  2. pmc Neural reserve, neuronal density in the locus ceruleus, and cognitive decline
    Robert S Wilson
    Rush Alzheimer s Disease Center and Departments of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
    Neurology 80:1202-8. 2013
    ..To test the hypothesis that higher neuronal density in brainstem aminergic nuclei contributes to neural reserve...
  3. pmc The influence of cognitive decline on well-being in old age
    Robert S Wilson
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
    Psychol Aging 28:304-13. 2013
    ..The results support the hypothesis that cognitive aging leads to diminished well-being, particularly aspects such as purpose in life that involve behavioral regulation...
  4. pmc Poor decision making is associated with an increased risk of mortality among community-dwelling older persons without dementia
    Patricia A Boyle
    Rush Alzheimer s Disease Center 600 S Paulina, Suite 1020B, Chicago, IL 60612, USA Patricia_Boyle rush edu
    Neuroepidemiology 40:247-52. 2013
    ..Decision making is thought to be an important determinant of health and well-being across the lifespan, but little is known about the association of decision making with mortality...
  5. pmc Neuroticism, extraversion, and motor function in community-dwelling older persons
    Aron S Buchman
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
    Am J Geriatr Psychiatry 21:145-54. 2013
    ..Personality traits are associated with adverse health outcomes in old age, but their association with motor function is unclear. We tested the hypothesis that neuroticism and extraversion are associated with motor decline in older persons...
  6. pmc Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies
    J A Schneider
    Rush Alzheimer s Disease Centre, Rush University Medical Centre, Chicago, IL 60612, USA
    Brain 135:3005-14. 2012
    ..Limbic-type Lewy body pathology is specifically associated with lower and more rapid decline in visuospatial skills. The effect of Lewy body pathology on cognition appears to be independent of Alzheimer's disease pathology...
  7. pmc Emotional neglect in childhood and cerebral infarction in older age
    Robert S Wilson
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL, USA
    Neurology 79:1534-9. 2012
    ..The purpose of the study was to test the hypothesis that a higher level of childhood adversity is associated with increased risk of cerebral infarction in old age...
  8. pmc The natural history of cognitive decline in Alzheimer's disease
    Robert S Wilson
    Rush Alzheimer s Disease Center, Chicago, IL 60612, USA
    Psychol Aging 27:1008-17. 2012
    ..The results indicate that cognitive decline in AD begins many years before dementia is diagnosed and accelerates during the course of the disease...
  9. pmc Association of cognition with temporal discounting in community based older persons
    Patricia A Boyle
    Rush University Medical Center, Rush Alzheimer s Disease Center, 600 S, Paulina, Suite 1020B, Chicago, IL 60612, USA
    BMC Geriatr 12:48. 2012
    ..The objective of this study was to test the hypothesis that cognitive function is negatively associated with temporal discounting in old age...
  10. pmc Poor decision making is a consequence of cognitive decline among older persons without Alzheimer's disease or mild cognitive impairment
    Patricia A Boyle
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, Illinois, USA
    PLoS ONE 7:e43647. 2012
    ..The objective of this study was to test the hypothesis that poor decision making is a consequence of cognitive decline among older persons without Alzheimer's disease or mild cognitive impairment...
  11. pmc APOE ε4, Alzheimer's disease pathology, cerebrovascular disease, and cognitive change over the years prior to death
    Lei Yu
    Rush Alzheimer s Disease Center, Rush University Medical Center
    Psychol Aging 28:1015-23. 2013
    ..The APOE ε4 allele is an important determinant of late-life change in cognition, including terminal decline, and works primarily through AD pathology...
  12. pmc Faster cognitive decline in the years prior to MR imaging is associated with smaller hippocampal volumes in cognitively healthy older persons
    Debra A Fleischman
    Rush Alzheimer s Disease Center, Rush University Medical Center Chicago, IL, USA Department of Neurological Sciences, Rush University Medical Center Chicago, IL, USA Department of Behavioral Sciences, Rush University Medical Center Chicago, IL, USA
    Front Aging Neurosci 5:21. 2013
    ..The results emphasize the importance of closely examining cognitive change and its association with brain structure during the years in which older persons are considered cognitively healthy...
  13. pmc Much of late life cognitive decline is not due to common neurodegenerative pathologies
    Patricia A Boyle
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL
    Ann Neurol 74:478-89. 2013
    ..We tested the hypothesis that these pathologic indices account for the majority of late life cognitive decline...
  14. pmc Gene-behavior interaction of depressive symptoms and the apolipoprotein E {varepsilon}4 allele on cognitive decline
    Kumar B Rajan
    PH, 1645 W Jackson Blvd, Suite 675, Chicago IL 60612
    Psychosom Med 76:101-8. 2014
    ..However, it is not clear whether the presence of both depressive symptoms and the APOE ε4 allele increases cognitive decline...
  15. pmc Harm avoidance and cerebral infarction
    Robert S Wilson
    Rush Alzheimer s Disease Center
    Neuropsychology 28:305-11. 2014
    ..We test the hypothesis that higher level of harm avoidance is associated with increased likelihood of cerebral infarction...
  16. pmc Disentangling the effects of age and APOE on neuropathology and late life cognitive decline
    Lei Yu
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL, USA Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA Electronic address
    Neurobiol Aging 35:819-26. 2014
    ..There were no direct effects of age and APOE on decline after accounting for these pathologic pathways. ..
  17. pmc Brainstem aminergic nuclei and late-life depressive symptoms
    Robert S Wilson
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, Illinois2Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois3Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois
    JAMA Psychiatry 70:1320-8. 2013
    ..The neurobiologic basis of late-life depressive symptoms is not well understood...
  18. pmc TDP-43 pathology, cognitive decline, and dementia in old age
    Robert S Wilson
    Department of Neurological Sciences, Behavioral Sciences, and Pathology, Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, Illinois
    JAMA Neurol 70:1418-24. 2013
    ..Cognitive decline is a leading cause of disability and death in old age but its neurobiological bases are not well understood...
  19. pmc Cognitive decline impairs financial and health literacy among community-based older persons without dementia
    Patricia A Boyle
    Rush Alzheimer s Disease Center, Rush University Medical Center
    Psychol Aging 28:614-24. 2013
    ..These findings suggest that diverse individual resources contribute to financial and health literacy and lower literacy in old age is partially due to declines in executive function and episodic memory...
  20. pmc Life-span cognitive activity, neuropathologic burden, and cognitive aging
    Robert S Wilson
    Rush Alzheimer s Disease Center and Departments of Neurological Sciences, Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA
    Neurology 81:314-21. 2013
    ..To test the hypothesis that cognitive activity across the life span is related to late-life cognitive decline not linked to common neuropathologic disorders...
  21. pmc A random change point model for cognitive decline in Alzheimer's disease and mild cognitive impairment
    Lei Yu
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA lei_yu rush edu
    Neuroepidemiology 39:73-83. 2012
    ....
  22. pmc The impact of health and financial literacy on decision making in community-based older adults
    Bryan D James
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
    Gerontology 58:531-9. 2012
    ....
  23. pmc Correlates of health and financial literacy in older adults without dementia
    Jarred S Bennett
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL, USA
    BMC Geriatr 12:30. 2012
    ..Our study examines the relation of health and financial literacy with health promoting behaviors and health status among community-based older persons...
  24. pmc Harm avoidance and risk of Alzheimer's disease
    Robert S Wilson
    Rush Alzheimer s Disease Center, Rush University Medical Center, 600 S Paulina, Suite 1038, Chicago, IL 60612, USA
    Psychosom Med 73:690-6. 2011
    ..To test the hypothesis that harm avoidance, a trait associated with behavioral inhibition, is associated with the risk of developing Alzheimer's disease (AD)...
  25. pmc Life space and risk of Alzheimer disease, mild cognitive impairment, and cognitive decline in old age
    Bryan D James
    Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA
    Am J Geriatr Psychiatry 19:961-9. 2011
    ....
  26. pmc Total daily activity measured with actigraphy and motor function in community-dwelling older persons with and without dementia
    Bryan D James
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
    Alzheimer Dis Assoc Disord 26:238-45. 2012
    ..These associations did not vary by dementia status. Actigraphy may provide a means to more fully explicate the nature and course of motor impairment in old age...
  27. pmc Overview and findings from the rush Memory and Aging Project
    David A Bennett
    Rush Alzheimer s Disease Center, Rush University Medical Center, 600 S Paulina, Suite 1028, Chicago, IL 60612, USA
    Curr Alzheimer Res 9:646-63. 2012
    ..The findings are discussed and contextualized...
  28. pmc Physical frailty is associated with incident mild cognitive impairment in community-based older persons
    Patricia A Boyle
    Rush Alzheimer s Disease Center, Rush University Medical Center, Armour Academic Facility, Suite 1020B, 600 South Paulina Street, Chicago, IL 60612, USA
    J Am Geriatr Soc 58:248-55. 2010
    ..To test the hypothesis that physical frailty is associated with risk of mild cognitive impairment (MCI)...
  29. pmc Selected findings from the Religious Orders Study and Rush Memory and Aging Project
    David A Bennett
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA David A
    J Alzheimers Dis 33:S397-403. 2013
    ..The findings illustrate the range of insights that can be gained into cognitive aging by incorporating neuropathologic indices into well designed, prospective cohort studies...
  30. pmc Effect of purpose in life on the relation between Alzheimer disease pathologic changes on cognitive function in advanced age
    Patricia A Boyle
    Rush Alzheimer s Disease Center, 600 S Paulina Ave, Ste 1020B, Chicago, IL 60612, USA
    Arch Gen Psychiatry 69:499-505. 2012
    ..Purpose in life is associated with a substantially reduced risk of Alzheimer disease (AD), but the neurobiologic basis of this protective effect remains unknown...
  31. pmc Terminal decline in motor function
    Robert S Wilson
    Rush Alzheimer s Disease Center, Chicago, IL 60612, USA
    Psychol Aging 27:998-1007. 2012
    ..The results demonstrate that motor and cognitive functions both undergo a period of accelerated decline in the last few years of life...
  32. pmc Relation of neuropathology to cognition in persons without cognitive impairment
    David A Bennett
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
    Ann Neurol 72:599-609. 2012
    ..A study was undertaken to examine the relation of Alzheimer disease (AD) pathology, cerebral infarcts, and Lewy body (LB) pathology to cognition in persons without cognitive impairment...
  33. pmc Association between life space and risk of mortality in advanced age
    Patricia A Boyle
    Rush Alzheimer s Disease Center, Chicago, Illinois 60612, USA
    J Am Geriatr Soc 58:1925-30. 2010
    ..To examine the association between life space, a measure of functional status that describes the range of movement through the environment covered during daily functioning, and the risk of mortality in older community-based persons...
  34. pmc Loneliness and the rate of motor decline in old age: the Rush Memory and Aging Project, a community-based cohort study
    Aron S Buchman
    Department of Neurological Sciences, Rush Alzheimer s Disease Center, Rush University Medical Center, 600 S, Paulina, Chicago, Illinois 60612, USA
    BMC Geriatr 10:77. 2010
    ..We tested the hypothesis that feeling alone is associated with the rate of motor decline in community-dwelling older persons...
  35. pmc Cognitive activity and the cognitive morbidity of Alzheimer disease
    R S Wilson
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
    Neurology 75:990-6. 2010
    ..To test the hypothesis that frequent cognitive activity predicts slower cognitive decline before dementia onset in Alzheimer disease (AD) and faster decline thereafter...
  36. pmc Change in risk of Alzheimer disease over time
    L E Hebert
    Rush Institute for Healthy Aging, 1645 W Jackson Blvd Suite 675, Chicago, IL 60612, USA
    Neurology 75:786-91. 2010
    ..The increase in numbers of people at the oldest ages in the population will bring an increase in the number of people with AD. Projections of the size of the increase assume the risk of AD is constant...
  37. pmc Neurodegenerative basis of age-related cognitive decline
    R S Wilson
    Rush Alzheimer s Disease Center, Rush University Medical Center, 600 South Paulina Ave, Suite 1038, Chicago, IL 60612, USA
    Neurology 75:1070-8. 2010
    ..To assess the contribution of dementia-related neuropathologic lesions to age-related and disease-related change in cognitive function...
  38. pmc Combinations of motor measures more strongly predict adverse health outcomes in old age: the rush memory and aging project, a community-based cohort study
    Aron S Buchman
    Department of Neurological Sciences, Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, Illinois 60612, USA
    BMC Med 9:42. 2011
    ..We tested the hypothesis that combinations of motor constructs more strongly predict adverse health outcomes in older people...
  39. pmc Cognitive function is associated with the development of mobility impairments in community-dwelling elders
    Aron S Buchman
    Rush Alzheimer s Disease Center, Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA
    Am J Geriatr Psychiatry 19:571-80. 2011
    ..To examine the association of cognitive function with the risk of incident mobility impairments and the rate of declining mobility in older adults...
  40. pmc Cognitive function is associated with risk aversion in community-based older persons
    Patricia A Boyle
    Rush University Medical Center, Rush Alzheimer s Disease Center, 600 S Paulina, Chicago, IL 60612, USA
    BMC Geriatr 11:53. 2011
    ....
  41. pmc Relation of late-life social activity with incident disability among community-dwelling older adults
    Bryan D James
    Rush University Medical Center, Room 1038, 600 South Paulina Street, Chicago, IL 60612, USA
    J Gerontol A Biol Sci Med Sci 66:467-73. 2011
    ..We tested the hypothesis that a higher level of social activity was associated with decreased risk of incident disability in older adults...
  42. pmc Terminal dedifferentiation of cognitive abilities
    R S Wilson
    Rush Alzheimer s Disease Center and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
    Neurology 78:1116-22. 2012
    ..To test the cognitive dedifferentiation hypothesis that cognitive abilities become increasingly correlated in late life...
  43. pmc Influence of late-life cognitive activity on cognitive health
    Robert S Wilson
    Rush Alzheimer s Disease Center and Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
    Neurology 78:1123-9. 2012
    ..To test the hypothesis that late-life participation in mentally stimulating activities affects subsequent cognitive health...
  44. pmc Total daily physical activity and the risk of AD and cognitive decline in older adults
    A S Buchman
    Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL, USA
    Neurology 78:1323-9. 2012
    ..We tested the hypothesis that an objective measure of total daily physical activity predicts incident AD and cognitive decline...