Disability is common in the elderly and is a major public health concern because it is associated with reduced quality of life and increased service utilization. Alzheimer's Disease (AD) is a major cause of disability. Despite its importance, relatively little research has been done to understand the course of functional decline in AD, or the mechanisms that drive individual trajectories of declines in everyday function. The loss of everyday abilities in the setting of a developing degenerative dementia such as AD is a progressive process. That is, functional abilities decline along a continuum, similar to cognition, reflecting progression of the underlying disease. A major emphasis of the proposed study is to better understand the full continuum of functional decline, particularly early and subtle problems that precede and predict disability (disability being defined as dependency in major life domains such as instrumental and basic activities of daily living). The development of disability results from a complex interplay between numerous factors. In AD, clearly cognitive decline is a major determinant;a focus of this project is to better understand how specific cognitive impairments contribute to deficits in specific domains of everyday function. In addition to cognition, however, there are likely a large number of other factors that further contribute to and help explain individual variability in rates and patterns of decline. With previous NIA support (AG021511) we developed a novel and sensitive approach to measuring `functional limitations'- functional problems that likely precede the development of frank disability. Using this approach we have demonstrated that Mild Cognitive Impairment (MCI) is associated with functional limitations intermediate to normal aging and dementia. Using a prospective, longitudinal research design, Aim 1 of this project focuses on characterizing the intermediate stages and transition points between normal function and disability.
Aims 2 -4 seek to understand the heterogeneity we see in individual functional trajectories by examining potential sources of this variability. Specifically, we will examine how neuropsychological, neuropsychiatric, and motor impairments influence the disability pathway. In addition, we will examine how associated risk factors, such as general health status and education, modify the trajectories of functional decline. An improved understanding of trajectories of functional decline, and the factors that contribute to individual rates and patterns of decline, will have important clinical relevance for: early diagnosis and prognosis;treatment development and the early implementation of supportive services and care planning;and the measurement of disease progression and the effects of potential disease modifying treatments.

Public Health Relevance

Alzheimer's Disease (AD) is a major cause of disability (declines in real-world abilities such as manage one's finances or medications, driving, etc.), which directly reduced quality of life for patients and their caregivers, and lead to increased economic burden. Despite their importance, we do not clearly understand how functional problems develop and progress in association with AD, nor do we understand the specific factors that contribute to progressive disability. Understanding how disability develops in AD will have far reaching applications to public health, preventative medicine, and treatment development, and will also have important implications for the individualized care of patients.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG031252-05
Application #
8314006
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Silverberg, Nina B
Project Start
2008-09-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$296,516
Indirect Cost
$101,440
Name
University of California Davis
Department
Neurology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Rueda, Alicia D; Lau, Karen M; Saito, Naomi et al. (2015) Self-rated and informant-rated everyday function in comparison to objective markers of Alzheimer's disease. Alzheimers Dement 11:1080-9
Rog, Lauren A; Park, Lovingly Quitania; Harvey, Danielle J et al. (2014) The independent contributions of cognitive impairment and neuropsychiatric symptoms to everyday function in older adults. Clin Neuropsychol 28:215-36
Maillard, P; Carmichael, O; Harvey, D et al. (2013) FLAIR and diffusion MRI signals are independent predictors of white matter hyperintensities. AJNR Am J Neuroradiol 34:54-61
Farias, Sarah Tomaszewski; Park, Lovingly Quitania; Harvey, Danielle J et al. (2013) Everyday cognition in older adults: associations with neuropsychological performance and structural brain imaging. J Int Neuropsychol Soc 19:430-41
Carmichael, Owen; Mungas, Dan; Beckett, Laurel et al. (2012) MRI predictors of cognitive change in a diverse and carefully characterized elderly population. Neurobiol Aging 33:83-95
Tomaszewski Farias, Sarah; Mungas, Dan; Harvey, Danielle J et al. (2011) The measurement of everyday cognition: development and validation of a short form of the Everyday Cognition scales. Alzheimers Dement 7:593-601
Farias, Sarah Tomaszewski; Mungas, Dan; Hinton, Ladson et al. (2011) Demographic, neuropsychological, and functional predictors of rate of longitudinal cognitive decline in Hispanic older adults. Am J Geriatr Psychiatry 19:440-50
Landau, S M; Harvey, D; Madison, C M et al. (2010) Comparing predictors of conversion and decline in mild cognitive impairment. Neurology 75:230-8
Petersen, R C; Aisen, P S; Beckett, L A et al. (2010) Alzheimer's Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology 74:201-9
Perneczky, R; Wagenpfeil, S; Lunetta, K L et al. (2010) Head circumference, atrophy, and cognition: implications for brain reserve in Alzheimer disease. Neurology 75:137-42

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