%0 Journal Article %J J Alzheimers Dis %D 2021 %T Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer's Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome. %A Petersen, Melissa E %A Rafii, Michael S %A Zhang, Fan %A Hall, James %A Julovich, David %A Ances, Beau M %A Schupf, Nicole %A Krinsky-McHale, Sharon J %A Mapstone, Mark %A Silverman, Wayne %A Lott, Ira %A Klunk, William %A Head, Elizabeth %A Christian, Brad %A Foroud, Tatiana %A Lai, Florence %A Diana Rosas, H %A Zaman, Shahid %A Wang, Mei-Cheng %A Tycko, Benjamin %A Lee, Joseph %A Handen, Benjamin %A Hartley, Sigan %A Fortea, Juan %A O'Bryant, Sid %X

BACKGROUND: The need for diagnostic biomarkers of cognitive decline is particularly important among aging adults with Down syndrome (DS). Growing empirical support has identified the utility of plasma derived biomarkers among neurotypical adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD); however, the application of such biomarkers has been limited among the DS population.

OBJECTIVE: This study aimed to investigate the cross-sectional diagnostic performance of plasma neurofilament light chain (Nf-L) and total-tau, individually and in combination among a cohort of DS adults.

METHODS: Plasma samples were analyzed from n = 305 (n = 225 cognitively stable (CS); n = 44 MCI-DS; n = 36 DS-AD) participants enrolled in the Alzheimer's Biomarker Consortium -Down Syndrome.

RESULTS: In distinguishing DS-AD participants from CS, Nf-L alone produced an AUC of 90%, total-tau alone reached 74%, and combined reached an AUC of 86%. When age and gender were included, AUC increased to 93%. Higher values of Nf-L, total-tau, and age were all shown to be associated with increased risk for DS-AD. When distinguishing MCI-DS participants from CS, Nf-L alone produced an AUC of 65%, while total-tau alone reached 56%. A combined model with Nf-L, total-tau, age, and gender produced an AUC of 87%. Both higher values in age and total-tau were found to increase risk for MCI-DS; Nf-L levels were not associated with increased risk for MCI-DS.

CONCLUSION: Advanced assay techniques make total-tau and particularly Nf-L useful biomarkers of both AD pathology and clinical status in DS and have the potential to serve as outcome measures in clinical trials for future disease-modifying drugs.

%B J Alzheimers Dis %V 79 %P 671-681 %8 2021 Jan 19 %G eng %N 2 %& 671 %R 10.3233/JAD-201167 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Secular Trends in the Incidence of Dementia in a Multi-Ethnic Community. %A Noble, James M %A Schupf, Nicole %A Manly, Jennifer J %A Andrews, Howard %A Tang, Ming-Xin %A Mayeux, Richard %X

BACKGROUND: Determination of secular trends in cognitive aging is important for prioritization of resources, services, and research in aging populations. Prior studies have identified declining dementia incidence associated with changes in cardiovascular risk factors and increased educational attainment. However, few studies have examined these factors in multi-ethnic cohorts.

OBJECTIVE: To identify secular trends in the incidence rate of dementia in an elderly population.

METHODS: Participants in this study were drawn from the Washington Heights-Inwood Columbia Aging Project, a multi-ethnic cohort study of northern Manhattan residents aged 65 years and older. Cox proportional hazards models were used to examine differences in the incidence of dementia in cohorts recruited in 1992 and 1999, with age at dementia or age at last follow-up visit as the "time-to-event" variable.

RESULTS: Overall, there was a 41% reduction in the hazard ratio for dementia among participants in the 1999 cohort compared with those in the 1992 cohort, adjusting for age, sex, race, and baseline memory complaints (HR = 0.59). The reduction in incidence was greatest among non-Hispanic Whites and African-Americans and lowest among Hispanic participants (HRs = 0.60, 0.52 and 0.64, respectively), and was associated with increases in level of educational attainment, especially among African-Americans. Reduction in incidence of dementia was also greater among persons 75 years or older than among younger participants (HR = 0.52 versus HR = 0.69).

CONCLUSIONS: Our results support previous findings that secular trends in dementia incidence are changing, including in aging minority populations.

%B J Alzheimers Dis %V 60 %P 1065-1075 %8 2017 Oct 03 %G eng %N 3 %R 10.3233/JAD-170300 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Dementia Risk and Protective Factors Differ in the Context of Memory Trajectory Groups. %A Zahodne, Laura B %A Schupf, Nicole %A Brickman, Adam M %A Mayeux, Richard %A Wall, Melanie M %A Stern, Yaakov %A Manly, Jennifer J %X

BACKGROUND: Previous research has identified multiple risk and protective factors for late onset Alzheimer's disease (LOAD). However, it is not known whether these risk and protective factors differ for individuals who are cognitively stable versus those already experiencing declines.

OBJECTIVE: This study examined how dementia risk factors differ across subgroups of older adults defined by memory trajectory. This line of research may lead to more individualized risk profiles.

METHODS: Risk factors for incident LOAD were compared across previously-validated groups of older adults exhibiting different memory trajectories ("Stable-High," "Stable-Low," "Decliner," "Rapid Decliner") using stratified Cox regressions. Participants included 2,593 racially/ethnically diverse older adults (mean age of 76 at study entry) in the Washington Heights-Inwood Columbia Aging Project.

RESULTS: Predictors of incident dementia differed across trajectory groups: older age only incurred independent risk in stable groups, education did not incur independent protection in the rapidly declining group, depression only incurred independent risk in the stable-low group, stroke incurred independent risk in the two extreme groups, and APOE-ɛ4 only incurred independent risk in the rapidly declining group.

CONCLUSION: The finding that different risk factors for LOAD were associated with specific memory trajectories may reflect the existence of resilience or vulnerability factors that modify the individual influences of risk/protective factors. This study highlights the utility of considering interactions between dementia risk factors and a patient's unique cognitive history.

%B J Alzheimers Dis %V 52 %P 1013-20 %8 2016 Apr 12 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/27079709?dopt=Abstract %R 10.3233/JAD-151114