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.

Public Health Relevance

The project entitled, Progression of Dementia: A Population Study is one of a few population-based studies of dementia progression in the world. With over 80 million to be afflicted with this condition in the coming decades, and no effective means of prevention or treatment, increasing numbers of individuals will be living with AD or other dementias. To meet the increasing demands for effective clinical care, greater understanding of the clinical progression of dementia, and course modifying factors, is an urgent public health priority. This project will examine these factors to further knowledge and to identify potential avenues for intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG021136-06A2
Application #
7655051
Study Section
Special Emphasis Panel (ZRG1-HOP-J (02))
Program Officer
Anderson, Dallas
Project Start
2002-09-15
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
6
Fiscal Year
2009
Total Cost
$1,555,326
Indirect Cost
Name
Utah State University
Department
Psychology
Type
Schools of Education
DUNS #
072983455
City
Logan
State
UT
Country
United States
Zip Code
84322
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Sims, Rebecca (see original citation for additional authors) (2017) Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet 49:1373-1384
Sanders, Chelsea; Behrens, Stephanie; Schwartz, Sarah et al. (2016) Nutritional Status is Associated with Faster Cognitive Decline and Worse Functional Impairment in the Progression of Dementia: The Cache County Dementia Progression Study1. J Alzheimers Dis 52:33-42
Rattinger, Gail B; Fauth, Elizabeth B; Behrens, Stephanie et al. (2016) Closer caregiver and care-recipient relationships predict lower informal costs of dementia care: The Cache County Dementia Progression Study. Alzheimers Dement 12:917-24
Ebbert, Mark T W; Boehme, Kevin L; Wadsworth, Mark E et al. (2016) Interaction between variants in CLU and MS4A4E modulates Alzheimer's disease risk. Alzheimers Dement 12:121-129
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Rattinger, Gail B; Schwartz, Sarah; Mullins, C Daniel et al. (2015) Dementia severity and the longitudinal costs of informal care in the Cache County population. Alzheimers Dement 11:946-54
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Lythgoe, Caitlin; Perkes, Ammon; Peterson, Michael et al. (2015) Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline: the Cache County Study. Neurobiol Aging 36:547.e1-3
Leoutsakos, Jeannie-Marie S; Forrester, Sarah N; Corcoran, Christopher D et al. (2015) Latent classes of course in Alzheimer's disease and predictors: the Cache County Dementia Progression Study. Int J Geriatr Psychiatry 30:824-32

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