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.

National Institute of Health (NIH)
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Special Emphasis Panel (ZHD1)
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Hugo W. Moser Research Institute Kennedy Krieger
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Krinsky-McHale, Sharon J; Silverman, Wayne; Gordon, James et al. (2014) Vision deficits in adults with Down syndrome. J Appl Res Intellect Disabil 27:247-63
Janicki, S C; Park, N; Cheng, R et al. (2014) Estrogen receptor ? variants affect age at onset of Alzheimer's disease in a multiethnic female cohort. Dement Geriatr Cogn Disord 38:200-13
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
Krinsky-McHale, Sharon J; Silverman, Wayne (2013) Dementia and mild cognitive impairment in adults with intellectual disability: issues of diagnosis. Dev Disabil Res Rev 18:31-42
Silverman, Wayne P; Zigman, Warren B; Krinsky-McHale, Sharon J et al. (2013) Intellectual Disability, Mild Cognitive Impairment, and Risk for Dementia. J Policy Pract Intellect Disabil 10:
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
Zigman, Warren B (2013) Atypical aging in Down syndrome. Dev Disabil Res Rev 18:51-67
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
Chace, Constance; Pang, Deborah; Weng, Catherine et al. (2012) Variants in CYP17 and CYP19 cytochrome P450 genes are associated with onset of Alzheimer's disease in women with down syndrome. J Alzheimers Dis 28:601-12
Prasher, V P; Sajith, S G; Mehta, P et al. (2010) Plasma beta-amyloid and duration of Alzheimer's disease in adults with Down syndrome. Int J Geriatr Psychiatry 25:202-7

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