Mild Cognitive Impairment: a Prospective Community Study. Mild Cognitive Impairment (MCI) is the cognitive state intermediate between normal aging and dementia. Multiple terms, definitions, and criterion sets exist for MCI. In specialty clinical settings, MCI almost uniformly progresses to dementia at a high rate, and is assumed to represent prodromal dementia. In community studies, MCI is a more heterogeneous state with less elevated risk of progression to dementia, and with substantial proportions remaining only mildly impaired or even reverting to normal cognition. A better understanding is needed of who will and will not progress from MCI to dementia, so that diagnostic criteria can be based on predictive validity in the community at large, and so that individuals can be more appropriately targeted for prevention and early intervention. This application is for renewal of a new study of a cohort randomly selected from a community in Western PA. In 2008, the cohort completed recruitment of 2036 individuals aged 65+, and the majority of them have had APOE genotyping. We conduct annual followup assessments in overlapping 2-year cycles. This study was designed de novo to focus on MCI rather than on the more severe impairments typical of dementia. The assessment protocol allows the application of many extant classification systems and criterion sets for MCI, thus allowing their predictive values for dementia to be compared during followup. Besides the standard criteria, we have also developed reliable cognitive classifications relative to normative data from our cohort, and a novel web-based approach to expert diagnostic consensus. Relevant clinical and biological measures are assessed as covariates and predictors. The primary outcome measure is progression to dementia;we also examine longitudinal change measures in clinical dementia rating, individual cognitive domains, functional impairment, and other assessments. We now propose to follow the cohort for a further five years, so that sufficient individuals will undergo these changes to power the key analyses predicting progression to dementia from MCI. New measures include structural MRI brain imaging in 250 individuals to determine the extent to which measures of cortical and regional atrophy and white matter hyperintensities improve prediction of dementia in this community sample;assays of 6 vascular and inflammatory markers in stored serum, and genotyping for 13 new SNPs associated with Alzheimer's disease and stroke in all stored DNA. These new measures reflect an expanded emphasis on vascular risk factors. Continued followup of this well- characterized aging cohort will improve understanding of the heterogeneity of MCI in the population at large, and help identify reliable predictors of the outcomes of MCI.

Public Health Relevance

A community-based cohort of over 2,000 adults aged 65+ years, assembled between 2006 and 2008, has been carefully assessed on their cognitive abilities, everyday functioning, and on several clinical and biological measures. By following them annually to determine their risk of developing Alzheimer's and other dementias, the study will provide critical information to help identify those at risk of dementia outside specialty clinic settings. This knowledge is needed so that individuals in the larger community can be appropriately targeted for prevention and early intervention strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG023651-08
Application #
8310959
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Anderson, Dallas
Project Start
2004-04-01
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
8
Fiscal Year
2012
Total Cost
$1,543,906
Indirect Cost
$524,342
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Li, Dalin; Achkar, Jean-Paul; Haritunians, Talin et al. (2016) A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn's Disease and Human Gut Microbiome Composition. Gastroenterology 151:724-32
McDade, Eric; Sun, Zhaowen; Lee, Ching-Wen et al. (2016) The association between pulse pressure change and cognition in late life: Age and where you start matters. Alzheimers Dement (Amst) 4:56-66
Ganguli, Mary; Lee, Ching-Wen; Snitz, Beth E et al. (2015) Rates and risk factors for progression to incident dementia vary by age in a population cohort. Neurology 84:72-80
Rabin, Laura A; Smart, Colette M; Crane, Paul K et al. (2015) Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies. J Alzheimers Dis 48 Suppl 1:S63-86
Hughes, Tiffany F; Becker, James T; Lee, Ching-Wen et al. (2015) Independent and combined effects of cognitive and physical activity on incident MCI. Alzheimers Dement 11:1377-84
Chaudhry, Mamoonah; Wang, Xingbin; Bamne, Mikhil N et al. (2015) Genetic variation in imprinted genes is associated with risk of late-onset Alzheimer's disease. J Alzheimers Dis 44:989-94
Snitz, Beth E; Small, Brent J; Wang, Tianxiu et al. (2015) Do Subjective Memory Complaints Lead or Follow Objective Cognitive Change? A Five-Year Population Study of Temporal Influence. J Int Neuropsychol Soc 21:732-42
Ganguli, Mary; Lee, Ching-Wen; Hughes, Tiffany et al. (2015) Who wants a free brain scan? Assessing and correcting for recruitment biases in a population-based sMRI pilot study. Brain Imaging Behav 9:204-12
Nimgaonkar, Vishwajit L; Yolken, Robert H; Wang, Tianxiu et al. (2015) Temporal Cognitive Decline Associated With Exposure to Infectious Agents in a Population-based, Aging Cohort. Alzheimer Dis Assoc Disord :
Andreescu, Carmen; Teverovsky, Esther; Fu, Bo et al. (2014) Old worries and new anxieties: behavioral symptoms and mild cognitive impairment in a population study. Am J Geriatr Psychiatry 22:274-84

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