Initiated in 2003, the goal of The 90+Study is to perform prospective clinical, pathological, and genetic investigations in a population based sample of people aged 90 years and older. With a wealth of cognitive tests, laboratory studies, physical performance measures, genetic and other data in The 90+ Study, plus survey information collected on these individuals since 1981 as part of the Leisure World Cohort Study, we will estimate incidence rates and evaluate risk and protective factors for dementia (Aim 1), functional disability and frailty (Aim 2), as well as cognitive and functional decline in the oldest old (Aim 3). Our studies emphasize potentially modifiable factors (oxygen saturation, anemia, and physical performance) as risk factors for dementia and disability in this age group, and could potentially provide the basis for future intervention studies in the oldest old. Based on our preliminary studies, we hypothesize that poor arterial oxygen saturation is a risk factor for cognitive decline and dementia, while anemia and physical performance measures (such as walk speed and handgrip) are risk factors for the development of disability, frailty, and functional decline in demented and non demented individuals. Half of all demented subjects in this age range do not have significant classical AD or other pathologies to explain cognitive loss. In this application, new collaborations enhance our clinical pathological studies investigating the biological correlates of cognition in the oldest old (Aim 4). Brain tissues from our well characterized subjects will be studied by investigators at the University of California, Irvine, University of Pennsylvania, and Johns Hopkins School of Medicine as we test our hypotheses that soluble, rather than insoluble, oligomeric species of A2, tau and 1 synuclein may be responsible for cognitive loss in 90+ year olds (Aim 4b) and that non AD pathologies, relevant to neuronal integrity and circuits, may contribute to cognitive loss through other age related mechanisms (Aim 4c). Finally, we will develop our clinical data and biological samples (brain tissues and DNA) as a resource to be actively shared with scientists worldwide. Project Narrative Understanding factors that influence the cognitive and functional status of the most senior members of our society is a major goal of this proposal. In our prospective studies of dementia, disability, and frailty in the oldest old, we will investigate the relationship to dementia, disability, and frailty of arterial O2 saturation, anemia, physical performance measures, and other factors that might be amenable to intervention. Ultimately our goal is to find ways to extend life without disability in nonagenarians and centenarians. If low O2 saturation, anemia or poor physical performance is associated with increased risk of dementia or disability in exceptionally long life, it would provide the basis for experimental studies to determine if oxygen therapy, treatment of anemia, or exercise could prevent or delay the loss of cognition and activities of daily living in the oldest old. The potential public health implications are enormous for the fastest growing segment of our population.

Public Health Relevance

Understanding factors that influence the cognitive and functional status of the most senior members of our society is a major goal of this proposal. In our prospective studies of dementia, disability, and frailty in the oldest-old, we will investigate the relationship to dementia, disability, and frailty of arterial O2 saturation, anemia, physical performance measures, and other factors that might be amenable to intervention. Ultimately our goal is to find ways to extend life without disability in nonagenarians and centenarians. If low O2 saturation, anemia or poor physical performance is associated with increased risk of dementia or disability in exceptionally long life, it would provide the basis for experimental studies to determine if oxygen therapy, treatment of anemia, or exercise could prevent or delay the loss of cognition and activities of daily living in the oldest-old. The potential public health implications are enormous for the fastest growing segment of our population.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG021055-10
Application #
8230622
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Anderson, Dallas
Project Start
2002-09-15
Project End
2013-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
10
Fiscal Year
2012
Total Cost
$1,369,210
Indirect Cost
$215,216
Name
University of California Irvine
Department
Neurology
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Robinson, John L; Molina-Porcel, Laura; Corrada, Maria M et al. (2014) Perforant path synaptic loss correlates with cognitive impairment and Alzheimer's disease in the oldest-old. Brain 137:2578-87
Pensalfini, Anna; Albay 3rd, Ricardo; Rasool, Suhail et al. (2014) Intracellular amyloid and the neuronal origin of Alzheimer neuritic plaques. Neurobiol Dis 71:53-61
Guay, Manon; Dubois, Marie-France; Corrada, MarĂ­a et al. (2014) Exponential increases in the prevalence of disability in the oldest old: a Canadian national survey. Gerontology 60:395-401
Nelson, Peter T; Estus, Steven; Abner, Erin L et al. (2014) ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology. Acta Neuropathol 127:825-43
Yasar, Sevil; Xia, Jin; Yao, Wenliang et al. (2013) Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of Memory Study. Neurology 81:896-903
Corrada, Maria M; Paganini-Hill, Annlia; Berlau, Daniel J et al. (2013) Apolipoprotein E genotype, dementia, and mortality in the oldest old: the 90+ Study. Alzheimers Dement 9:12-8
Berlau, Daniel J; Corrada, Maria M; Robinson, John L et al. (2013) Neocortical *-amyloid area is associated with dementia and APOE in the oldest-old. Alzheimers Dement 9:699-705
Kawas, Claudia H; Greenia, Dana E; Bullain, Szofia S et al. (2013) Amyloid imaging and cognitive decline in nondemented oldest-old: the 90+ Study. Alzheimers Dement 9:199-203
Bullain, Szofia S; Corrada, Maria M; Shah, Barbara Agee et al. (2013) Poor physical performance and dementia in the oldest old: the 90+ study. JAMA Neurol 70:107-13
Berlau, Daniel J; Corrada, Maria M; Peltz, Carrie B et al. (2012) Disability in the oldest-old: incidence and risk factors in the 90+ study. Am J Geriatr Psychiatry 20:159-68

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