2002 — 2008 |
Tschanz, Joann T |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Progression of Dementia: a Population
DESCRIPTION (provided by applicant): Dementia is a major public health problem with several unanswered questions. Limited data exist on the trajectory of cognitive, functional, and behavioral decline, their longitudinal interaction, and the variables that modify their expression. Population-based incident cohorts of dementia can best answer these questions. The Cache County Study on Memory in Aging (The Cache County Study) provides such cases for study. Established in 1994, the Cache County Study is a population-based longitudinal investigation of the risk factors for dementia. The entire cohort has been followed for six years, with careful identification of prevalent and incident cases of dementia, and characterization of genetic and environmental risk factors for each individual. Not an aim of the original or recently submitted renewal applications, the present application intends to follow the incident cases of dementia until death. Using existing and new data, we will characterize the clinical trajectories of three important domains in dementia: cognitive, functional, and behavioral. The role of genetic and environmental variables on these trajectories and on survival will be examined. With this unique cohort of incident cases of dementia, available in few other settings worldwide, we will build upon the rich antecedent information gathered prior to the onset of dementia. The cohort is ideal for study as cases are population-based (and not subject to referral bias), have lower rates of medical co-morbidities, and, on average, are longer lived. There are three major specific aims of the project, which are as follows: 1. In a population panel of incident cases of dementia, model the cognitive, functional, and behavioral trajectories to characterize the natural progression of dementia as a continuum from its prodrome to end-stage disease. Models will examine the inter-relatedness of the individual domains. 2. Test in this same cohort a series of hypotheses regarding genetic and environmental variables that modify decline in each trajectory. Along with environmental risk factors such as medical history, key features of the care environment will also be studied. 3. Test in this same cohort a series of hypotheses regarding genetic, social, and environmental variables that modify survival in dementia.
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2009 — 2010 |
Lyketsos, Constantine G Tschanz, Joann T |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Progression of Dementia: a Population Study
The Cache County Dementia Progression Study (CC-DPS) has followed one of a few population based samples of incident dementia, consisting of individuals characterized before their dementia onset. The project utilizes pre-morbid health and genetic and environmental risk factor information to determine their effects on the progression of cognitive, functional and behavioral trajectories. Key discoveries include: a) 30% of cases are "slow decliners," b) neuropsychiatric symptoms occur in clusters, c) vascular factors, their treatments, and the care environment modify progression, and d) the APOE e4 allele modifies the effects of other factors. In its next phase, CC-DPS proposes to examine hypothesized mechanisms underlying some of the above observations, clarify the role of APOE e4 on the course of dementia progression, examine how medical co-morbidities as well as the use of medications and supplements affects the rate of progression and disease duration, and to expand understanding of the interrelated nature of the cognitive, functional and behavioral trajectories of dementia. The specific aims are to: 1) Clarify whether the association between APOE e4 and dementia progression varies according to dementia severity and duration; 2) Examine whether lifetime medical co-morbidities and exposure to antioxidant and anti-inflammatory compounds accelerate or attenuate dementia progression and whether their effects are modified by APOE genotype; 3) Examine whether strategies to build cognitive reserve after the onset of dementia are associated with slower progression; 4) Examine the effects of modifiable factors on the emergence and persistence of behavioral symptoms and symptom clusters; 5) Examine putative mechanisms underlying the relationship between the care environment and dementia progression;and 6) Characterize the interacting nature of domain trajectories in dementia. To support these aims, the study will continue to follow the remaining participants and their caregivers for an additional 1.5 years to increase person years of observation. Principal measures of progression include: a cognitive battery, Clinical Dementia Rating Scale, Neuropsychiatric Inventory, Cornell Scale for Depression in Dementia, time to institutionalization, quality of life ratings, and mortality. This project is the first population-based study of caregiving effects on dementia progression, and with the examination of a rich array of modifiable risk factors, the study has the potential to advance our understanding of the epidemiology of behavioral symptoms in dementia and the factors that contribute to clinical variation in disease course. At CC-DPS completion, we will 1) advance understanding of dementia progression and prognosis;2) discover factors that modify its course;and 3) identify potential new avenues for effective interventions.
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