**5. Conclusions**

The cognitive abilities of individuals with atypical brain development, early onset of AD pathology, and accelerated rates of amyloid accumulation may be characterized by the same cognitive domains described for neurotypical populations. However, the complex pathobiology of DS leads to both physical deficits and biochemical changes that can lead to

multiple comorbid medical conditions, genetic and epigenetic variation, environmental factors, and stochastic events [14], all contributing to considerable heterogeneity in this population. Just as there are multiple cognitive phenotypes of MCI in the neurotypical population, there may also be more than one cognitive phenotype of MCI-DS.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/10 .3390/brainsci11091220/s1, Figure S1: Effects of aging on cognitive tests by Alzheimer's disease status.

**Author Contributions:** Conceptualization, C.L.H. and D.B.K.; methodology, S.J.K.-M. and W.S.; validation, S.J.K.-M. and M.B.P.; formal analysis, K.A.K. and J.R.-O.; investigation, C.L.H., S.J.K.-M. and M.B.P.; writing—original draft preparation, C.L.H.; writing—review and editing, J.R.-O., D.B.K., W.S., S.J.K.-M. and N.S.; visualization, K.A.K.; supervision, W.S.; project administration, H.D.R., F.L., N.S. and I.T.L.; funding acquisition, N.S., I.T.L. and W.S. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the National Institute on Aging and the Eunice Kennedy Shriver National Institute for Child Health and Human Development, grant number U01 AG051412.

**Institutional Review Board Statement:** The study was approved by the Institutional Review Boards of New York State Institute for Basic Research in Developmental Disabilities (protocol #7259, 04/20/2021-04/19/2022), Columbia University Irving Medical Center (protocol #AAAR0398, 02/10/2021-02/09/2022 and protocol #AAAS1197, 08/25/2021-08/24/2022), Massachusetts General Hospital (protocol #2016P000419, 02/08/2021-02/02/2022), the University of California at Irvine (protocol #2016-2690, 01/08/2021-01/07/2022), and the University of North Texas Health Science Center (protocol #2015-171, 09/02/2021-09/02/2022).

**Informed Consent Statement:** Informed consent was obtained from participants or their legally authorized representatives along with participant assent.

**Data Availability Statement:** The data presented in this study are openly available in the LONI Image and Data Archive (IDA) repository at https://ida.loni.usc.edu/login.jsp?project=ABCDS (accessed on 28 October 2020).

**Acknowledgments:** The authors would like to thank the adults with Down syndrome who volunteered as participants in this study for their invaluable contributions to this work, as well as their families and care providers for their generous support. We would also like to thank Deborah Pang, Eric Doran, and Courtney Jordan for their coordination of data collection.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
