This Project builds on recent observations from the EAS and elsewhere indicating that both stress and pain are Important risk factors for cognitive decline and dementia. Although pain contributes to stress and stress to pain, we recognize that these exposures are distinct. We propose to assess them together because they are associated at a behavioral level, have overlapping effects on the hypothalamic-pituitary-adrenal (HPA) axis and on cognitive function. In addtion they share similar psychosocial and genetic moderators, and present measurement challenges that can be addressed using similar intensive measurement strategies. The overall goal of this project is to examine the Influence of experiential (e.g., daily and chronic pain, daily stressors and life events) and biological factors (e.g., glucocorticoid dysregulation) on cognitive decline and dementia risk in the elderly. This Project will use annual assessments as well as an intensive measurement burst to provide precise measurements ofthe experience of pain and stress as well as their physiologic consequences. The measurement burst consists of an 8-day telephone diary assessing pain, daily stressors, mood, and activity limitations; participants also provide multiple salivary samples per day over 4 days for analysis of diurnal Cortisol profiles to assess the HPA axis dysfunction. We will assess the Influence of pain, stress and glucocorticoids on measures of microvascular disease (retinal photography and reactivity to carbon dioxide as assessed by transcranial doppler) from Project 2. With Project 3, we will access the influence of pain, stress, and glucocorticoids on locomotion. Participants will complete in-lab annual cognitive assessment of episodic memory, working memory, executive function and processing speed because deficits In these domains have been linked to pain and stress in older adults. This design will allow us to determine how daily pain and stress as well as related processes (e.g., blunted morning Cortisol response, heightened emotional reactivity to daily stress) influence neuro-imaging as well as cognitive decline and dementia risk. We will also examine the influence of selected candidate genes, personality (e.g. neuroticism) and psychosocial factors (e.g., social support) on these pathways.

Public Health Relevance

Pain and stress are common in late adult life and powerfully Influence brain structure and function. Yet they remain understudied as risk factors for cognitive decline. This study will yield insights into early behavioral and biological indicators of dementia, improving preclinical detection of disease and facilitating the development of novel preventive strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG003949-30
Application #
8850737
Study Section
Special Emphasis Panel (ZAG1-ZIJ-1)
Project Start
Project End
2015-08-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
30
Fiscal Year
2015
Total Cost
$355,889
Indirect Cost
$122,757
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Blumen, Helena M; Brown, Lucy L; Habeck, Christian et al. (2018) Gray matter volume covariance patterns associated with gait speed in older adults: a multi-cohort MRI study. Brain Imaging Behav :
Kidana, Kiwami; Tatebe, Takuya; Ito, Kaori et al. (2018) Loss of kallikrein-related peptidase 7 exacerbates amyloid pathology in Alzheimer's disease model mice. EMBO Mol Med 10:
Sanchez-Contreras, Monica Y; Kouri, Naomi; Cook, Casey N et al. (2018) Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci. Mol Neurodegener 13:37
Kasanuki, Koji; Ross, Owen A; DeTure, Michael A et al. (2018) Relationships between lewy and tau pathologies in 375 consecutive non-Alzheimer's olfactory bulbs. Mov Disord 33:333-334
Ogaki, Kotaro; Martens, Yuka A; Heckman, Michael G et al. (2018) Multiple system atrophy and apolipoprotein E. Mov Disord 33:647-650
Hyun, Jinshil; Sliwinski, Martin J; Almeida, David M et al. (2018) The moderating effects of aging and cognitive abilities on the association between work stress and negative affect. Aging Ment Health 22:611-618
Fleysher, Roman; Lipton, Michael L; Noskin, Olga et al. (2018) White matter structural integrity and transcranial Doppler blood flow pulsatility in normal aging. Magn Reson Imaging 47:97-102
Sliwinski, Martin J; Mogle, Jacqueline A; Hyun, Jinshil et al. (2018) Reliability and Validity of Ambulatory Cognitive Assessments. Assessment 25:14-30
Zammit, Andrea R; Robitaille, Annie; Piccinin, Andrea et al. (2018) Associations between aging-related changes in grip strength and cognitive function in older adults: A systematic review. J Gerontol A Biol Sci Med Sci :
Graham-Engeland, Jennifer E; Sin, Nancy L; Smyth, Joshua M et al. (2018) Negative and positive affect as predictors of inflammation: Timing matters. Brain Behav Immun 74:222-230

Showing the most recent 10 out of 319 publications