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.
| Schupf, Nicole; Lee, Joseph H; Pang, Deborah et al. (2018) Epidemiology of estrogen and dementia in women with Down syndrome. Free Radic Biol Med 114:62-68 |
| Babulal, Ganesh M; Quiroz, Yakeel T; Albensi, Benedict C et al. (2018) Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need. Alzheimers Dement : |
| Esbensen, Anna J; Hooper, Stephen R; Fidler, Deborah et al. (2017) Outcome Measures for Clinical Trials in Down Syndrome. Am J Intellect Dev Disabil 122:247-281 |
| Do, Catherine; Xing, Zhuo; Yu, Y Eugene et al. (2017) Trans-acting epigenetic effects of chromosomal aneuploidies: lessons from Down syndrome and mouse models. Epigenomics 9:189-207 |
| Lee, Joseph H; Lee, Annie J; Dang, Lam-Ha et al. (2017) Candidate gene analysis for Alzheimer's disease in adults with Down syndrome. Neurobiol Aging 56:150-158 |
| Jenkins, Edmund C; Ye, Lingling; Krinsky-McHale, Sharon J et al. (2016) Telomere longitudinal shortening as a biomarker for dementia status of adults with Down syndrome. Am J Med Genet B Neuropsychiatr Genet 171B:169-74 |
| Mendioroz, Maite; Do, Catherine; Jiang, Xiaoling et al. (2015) Trans effects of chromosome aneuploidies on DNA methylation patterns in human Down syndrome and mouse models. Genome Biol 16:263 |
| Schupf, Nicole; Lee, Annie; Park, Naeun et al. (2015) Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome. Neurobiol Aging 36:2907.e1-10 |
| 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 |
| Hobbs, Charlotte A; Chowdhury, Shimul; Cleves, Mario A et al. (2014) Genetic epidemiology and nonsyndromic structural birth defects: from candidate genes to epigenetics. JAMA Pediatr 168:371-7 |
Showing the most recent 10 out of 73 publications
