Subproject 2 will be a direct extension of our ongoing work and will develop objective and quantitative criteria for classifying mild cognitive impairment (MCI) in adults with Down Syndrome (DS) based upon the assessment methods we have been employing in our current studies. Alzheimer's disease (AD) in adults with DS represents a very real and highly significant public health concern. The current increase in the number of aged individuals with DS warrants dependable strategies to improve early detection of cognitive impairment and for identifying individuals at high risk for developing frank dementia. There is increasing evidence that subtle losses in cognitive functions may be symptomatic of a transition to early AD. This suggests that we may be able to identify such individuals prospectively and as therapeutic interventions become available, clinicians can intervene to halt or slow the progress towards severe dementia. The construct of Mild Cognitive Impairment (MCI) has been used to describe this intermediate state between cognitively normal aging and dementia. Identifying MCI in adults with DS can be difficult because of their lifelong cognitive deficits and variability in baseline level-of-functioning. Despite these difficulties, recent longitudinal studies have shown that measures of memory and other cognitive functions that are appropriate for use with adults with DS are sensitive to relatively subtle decline. Recent research also suggests that neuropsychiatric symptomatology may be indicative of MCI and may predict progression to AD. Based upon a substantial body of data collected during our current funding period, we have generated sets of criteria referenced to baseline IQ that appear to differentiate cognitively normal individuals and those exhibiting MCI with moderately good sensitivity and specificity. However, because these criteria have been generated from our obtained data, original estimates of their accuracy may be overly optimistic. We now need to confirm that our methods are valid and that they have prognostic value. We are confident that this validation will prove successful. We will then have a cognitive and functional assessment battery with standardized procedures and objective classification criteria that can inform clinical judgment regarding whether an individual with DS is showing declines in functioning that are consistent with current conceptions of MCI.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD035897-24
Application #
8376127
Study Section
Special Emphasis Panel (ZHD1-MRG-C)
Project Start
Project End
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
24
Fiscal Year
2012
Total Cost
$130,838
Indirect Cost
$11,547
Name
Hugo W. Moser Research Institute Kennedy Krieger
Department
Type
DUNS #
155342439
City
Baltimore
State
MD
Country
United States
Zip Code
21205
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Esbensen, Anna J; Mailick, Marsha R; Silverman, Wayne (2013) Long-term impact of parental well-being on adult outcomes and dementia status in individuals with Down syndrome. Am J Intellect Dev Disabil 118:294-309
Janicki, S C; Park, N; Cheng, R et al. (2013) Aromatase variants modify risk for Alzheimer's disease in a multiethnic female cohort. Dement Geriatr Cogn Disord 35:340-6
Xing, Luzhou; Salas, Martha; Zhang, Hong et al. (2013) Creation and characterization of BAC-transgenic mice with physiological overexpression of epitope-tagged RCAN1 (DSCR1). Mamm Genome 24:30-43

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