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Cited by 68Down syndrome and intellectual disability researchDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatments

Association of biological sex with clinical outcomes and biomarkers of Alzheimer’s disease in adults with Down syndrome

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Iulita, M Florencia, Bejanin, Alexandre, Vilaplana, Eduard, Carmona-Iragui, Maria, Benejam, Bessy, Videla, Laura, Barroeta, Isabel, Fernández, Susana +28 more·2023·Brain Communications
DOI 10.1093/braincomms/fcad074PMC PMC10088472
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Abstract

The study of sex differences in Alzheimer’s disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer’s disease (>90% in the 7th decade). Yet, sex differences in Alzheimer’s disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials. In this double-centre, cross-sectional study of 628 adults with Down syndrome [46% female, 44.4 (34.6; 50.7) years], we compared Alzheimer’s disease prevalence, as well as cognitive outcomes and AT(N) biomarkers across age and sex. Participants were recruited from a population-based health plan in Barcelona, Spain, and from a convenience sample recruited via services for people with intellectual disabilities in England and Scotland. They underwent assessment with the Cambridge Cognitive Examination for Older Adults with Down Syndrome, modified cued recall test and determinations of brain amyloidosis (CSF amyloid-β 42 / 40 and amyloid-PET), tau pathology (CSF and plasma phosphorylated-tau181) and neurodegeneration biomarkers (CSF and plasma neurofilament light, total-tau, fluorodeoxyglucose-PET and MRI). We used within-group locally estimated scatterplot smoothing models to compare the trajectory of biomarker changes with age in females versus males, as well as by apolipoprotein ɛ4 carriership. Our work revealed similar prevalence, age at diagnosis and Cambridge Cognitive Examination for Older Adults with Down Syndrome scores by sex, but males showed lower modified cued recall test scores from age 45 compared with females. AT(N) biomarkers were comparable in males and females. When considering apolipoprotein ɛ4, female ɛ4 carriers showed a 3-year earlier age at diagnosis compared with female non-carriers (50.5 versus 53.2 years, P = 0.01). This difference was not seen in males (52.2 versus 52.5 years, P = 0.76). Our exploratory analyses considering sex, apolipoprotein ɛ4 and biomarkers showed that female ɛ4 carriers tended to exhibit lower CSF amyloid-β 42/amyloid-β 40 ratios and lower hippocampal volume compared with females without this allele, in line with the clinical difference. This work showed that biological sex did not influence clinical and biomarker profiles of Alzheimer’s disease in adults with Down syndrome. Consideration of apolipoprotein ɛ4 haplotype, particularly in females, may be important for clinical research and clinical trials that consider this population. Accounting for, reporting and publishing sex-stratified data, even when no sex differences are found, is central to helping advance precision medicine.

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  • In DSAD, the effect of APOEε4 genotype on the age of onset of clinical features of disease and AD biomarkers is significant, but relatively modest compared with the effect of the genotype in LOAD, and may be limited to females.

    “Notably, recent work has indicated that in DSAD, the effect of APOEε4 genotype on the age of onset of clinical features of disease and AD biomarkers is significant, but relatively modest compared with the effect of the genotype in LOAD, and may be limited to females [5, 20, 32].”

    From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [32]

    The Results section reports that female APOE ε4 carriers with Down syndrome were diagnosed about three years earlier than female non-carriers (P = 0.01), with no corresponding difference in males. It also reports exploratory biomarker differences, but does not establish a significant effect on the age of onset of biomarkers or compare the magnitude of the effect with LOAD. The biomarker results include trends in males, so they do not establish that the effect is limited to females. Page numbers were not provided in our copy. (LLM, conf=0.86)

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  1. [1]Hentzen NB, Ferretti MT, Santuccione A, et al Mapping of European activities on the integration of sex and gender factors in neurology and neuroscience. Eur J Neurol. 2022; 29(9): 2572– 2579. 35673956
  2. [2]Spires-Jones TL. Let's talk about sex (in translational neuroscience). Brain Commun. 2022; 4(2): fcac028. PMC8896755 35261975
  3. [4]Ferretti MT, Iulita MF, Cavedo E, et al Sex differences in Alzheimer disease—The gateway to precision medicine. Nat Rev Neurol. 2018; 14(8): 457– 469. 29985474
  4. [5]Nebel RA, Aggarwal NT, Barnes LL, et al Understanding the impact of sex and gender in Alzheimer's disease: A call to action. Alzheimers Dement. 2018; 14(9): 1171– 1183. 29907423 PMC6400070
  5. [6]McCarrey AC, An Y, Kitner-Triolo MH, Ferrucci L, Resnick SM. Sex differences in cognitive trajectories in clinically normal older adults. Psychol Aging. 2016; 31(2): 166– 175. 26796792 PMC4783196
  6. [7]Sundermann EE, Maki P, Biegon A, et al Sex-specific norms for verbal memory tests may improve diagnostic accuracy of amnestic MCI. Neurology. 2019; 93(20): e1881– e1889. 31597708 PMC6946472
  7. [8]Digma LA, Madsen JR, Rissman RA, et al Women can bear a bigger burden: Ante- and post-mortem evidence for reserve in the face of tau. Brain Commun. 2020; 2(1): fcaa025. PMC7166251 32337508
  8. [10]Sohn D, Shpanskaya K, Lucas JE, et al Sex differences in cognitive decline in subjects with high likelihood of mild cognitive impairment due to Alzheimer's disease. Sci Rep. 2018; 8(1): 7490. 29748598 PMC5945611
  9. [11]Lin KA, Choudhury KR, Rathakrishnan BG, et al Marked gender differences in progression of mild cognitive impairment over 8 years. Alzheimers Dement (N Y). 2015; 1(2): 103– 110. 26451386 PMC4593067
  10. [12]Mielke MM. Consideration of sex differences in the measurement and interpretation of Alzheimer disease-related biofluid-based biomarkers. J Appl Lab Med. 2020; 5(1): 158– 169. 31811073 PMC7246149
  11. [14]Buckley RF, Scott MR, Jacobs HIL, et al Sex mediates relationships between regional tau pathology and cognitive decline. Ann Neurol. 2020; 88(5): 921– 932. 32799367 PMC7581543
  12. [15]Edwards L, La Joie R, Iaccarino L, et al Multimodal neuroimaging of sex differences in cognitively impaired patients on the Alzheimer's continuum: Greater tau-PET retention in females. Neurobiol Aging. 2021; 105: 86– 98. 34049062 PMC8820163
  13. [16]Liesinger AM, Graff-Radford NR, Duara R, et al Sex and age interact to determine clinicopathologic differences in Alzheimer's disease. Acta Neuropathol. 2018; 136(6): 873– 885. 30219939 PMC6280837
  14. [20]Sampedro F, Vilaplana E, de Leon MJ, et al APOE-by-sex interactions on brain structure and metabolism in healthy elderly controls. Oncotarget. 2015; 6(29): 26663– 26674. 26397226 PMC4694943
  15. [21]Hohman TJ, Dumitrescu L, Barnes LL, et al Sex-specific association of apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol. 2018; 75(8): 989– 998. 29801024 PMC6142927
  16. [22]Wang YT, Pascoal TA, Therriault J, et al Interactive rather than independent effect of APOE and sex potentiates tau deposition in women. Brain Commun. 2021; 3(2): fcab126. PMC8226193 34189460
  17. [23]Yan S, Zheng C, Paranjpe MD, et al Sex modifies APOE epsilon4 dose effect on brain tau deposition in cognitively impaired individuals. Brain. 2021; 144(10): 3201– 3211. 33876815 PMC8634082
  18. [24]McCarron M, McCallion P, Reilly E, Dunne P, Carroll R, Mulryan N. A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome. J Intellect Disabil Res. 2017; 61(9): 843– 852. 28664561
  19. [25]Fortea J, Vilaplana E, Carmona-Iragui M, et al Clinical and biomarker changes of Alzheimer's disease in adults with Down syndrome: A cross-sectional study. Lancet. 2020; 395(10242): 1988– 1997. 32593336 PMC7322523
  20. [26]Snyder HM, Bain LJ, Brickman AM, et al Further understanding the connection between Alzheimer's disease and Down syndrome. Alzheimers Dement. 2020; 16(7): 1065– 1077. 32544310 PMC8865308
  21. [28]Wisniewski KE, Wisniewski HM, Wen GY. Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol. 1985; 17(3): 278– 282. 3158266
  22. [30]Bateman RJ, Xiong C, Benzinger TL, et al Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012; 367(9): 795– 804. 22784036 PMC3474597
  23. [31]Rafii MS, Ances BM, Schupf N, et al The AT(N) framework for Alzheimer's disease in adults with Down syndrome. Alzheimers Dement (Amst). 2020; 12(1): e12062. PMC7588820 33134477
  24. [32]Schupf N, Kapell D, Nightingale B, Rodriguez A, Tycko B, Mayeux R. Earlier onset of Alzheimer's disease in men with Down syndrome. Neurology. 1998; 50(4): 991– 995. 9566384
  25. [33]Lai F, Kammann E, Rebeck GW, Anderson A, Chen Y, Nixon RA. APOE genotype and gender effects on Alzheimer disease in 100 adults with Down syndrome. Neurology. 1999; 53(2): 331– 336. 10430422
  26. [34]Sinai A, Mokrysz C, Bernal J, et al Predictors of age of diagnosis and survival of Alzheimer's disease in Down syndrome. J Alzheimers Dis. 2018; 61(2): 717– 728. 29226868 PMC6004911
  27. [35]Lai F, Mhatre PG, Yang Y, Wang MC, Schupf N, Rosas HD. Sex differences in risk of Alzheimer's disease in adults with Down syndrome. Alzheimers Dement (Amst). 2020; 12(1): e12084. PMC7507514 32995462
  28. [36]Mhatre PG, Lee JH, Pang D, et al The association between sex and risk of Alzheimer's disease in adults with Down syndrome. J Clin Med. 2021; 10(13): 2966. 34279450 PMC8268850
  29. [37]Rafii MS, Zaman S, Handen BL. Integrating biomarker outcomes into clinical trials for Alzheimer's disease in Down syndrome. J Prev Alzheimers Dis. 2021; 8(1): 48– 51. 33336224 PMC8279390
  30. [38]Annus T, Wilson LR, Hong YT, et al The pattern of amyloid accumulation in the brains of adults with Down syndrome. Alzheimers Dementia. 2016; 12(5): 538– 545. PMC4867786 26362596
  31. [39]Alcolea D, Clarimon J, Carmona-Iragui M, et al The Sant Pau initiative on neurodegeneration (SPIN) cohort: A data set for biomarker discovery and validation in neurodegenerative disorders. Alzheimers Dement (N Y). 2019; 5: 597– 609. 31650016 PMC6804606
  32. [40]Aylward EH, Burt DB, Thorpe LU, Lai F, Dalton A. Diagnosis of dementia in individuals with intellectual disability. J Intellect Disabil Res. 1997; 41(Pt 2): 152– 164. 9161927
  33. [41]Esteba-Castillo S, Dalmau-Bueno A, Ribas-Vidal N, Vila-Alsina M, Novell-Alsina R, Garcia-Alba J. [Adaptation and validation of CAMDEX-DS (Cambridge examination for mental disorders of older people with Down's syndrome and others with intellectual disabilities) in Spanish population with intellectual disabilities]. Rev Neurol. 2013; 57(8): 337– 346. Adaptacion y validacion del Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) en poblacion espanola con discapacidad intelectual. 24081888
  34. [42]Benejam B, Videla L, Vilaplana E, et al Diagnosis of prodromal and Alzheimer's disease dementia in adults with Down syndrome using neuropsychological tests. Alzheimers Dement (Amst). 2020; 12(1): e12047. PMC7322242 32613076
  35. [43]Fortea J, Carmona-Iragui M, Benejam B, et al Plasma and CSF biomarkers for the diagnosis of Alzheimer's disease in adults with Down syndrome: A cross-sectional study. Lancet Neurol. 2018; 17(10): 860– 869. 30172624
  36. [45]Delaby C, Estelles T, Zhu N, et al The Abeta1–42/Abeta1–40 ratio in CSF is more strongly associated to tau markers and clinical progression than Abeta1–42 alone. Alzheimers Res Ther. 2022; 14(1): 20. 35105351 PMC8809019
  37. [46]Lleo A, Zetterberg H, Pegueroles J, et al Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer's disease in adults with Down syndrome. Nat Commun. 2021; 12(1): 4304. 34262030 PMC8280160
  38. [47]Landau SM, Harvey D, Madison CM, et al Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol Aging. 2011; 32(7): 1207– 1218. 19660834 PMC2891865
  39. [48]Avants BB, Tustison NJ, Song G, Cook PA, Klein A, Gee JC. A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage. 2011; 54(3): 2033– 2044. 20851191 PMC3065962
  40. [49]Zammit MD, Laymon CM, Betthauser TJ, et al Amyloid accumulation in Down syndrome measured with amyloid load. Alzheimers Dement (Amst). 2020; 12(1): e12020. PMC7233422 32435686
  41. [50]Klunk WE, Koeppe RA, Price JC, et al The Centiloid project: Standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2015; 11(1): 1– 15 e1–4. 25443857 PMC4300247
  42. [51]Hastie TJ. Generalized additive models. In: Chambers JM, Hastie TJ, eds. Statistical models in S. Wadsworth & Brooks; 1992: 309– 376.
  43. [52]Ferretti MT, Martinkova J, Biskup E, et al Sex and gender differences in Alzheimer's disease: Current challenges and implications for clinical practice: Position paper of the Dementia and Cognitive Disorders Panel of the European Academy of Neurology. Eur J Neurol. 2020; 27(6): 928– 943. 32056347
  44. [53]Raghavan R, Khin-Nu C, Brown AG, et al Gender differences in the phenotypic expression of Alzheimer's disease in Down's syndrome (trisomy 21). Neuroreport. 1994; 5(11): 1393– 1396. 7919207
  45. [54]Schupf N, Pang D, Patel BN, et al Onset of dementia is associated with age at menopause in women with Down's syndrome. Ann Neurol. 2003; 54(4): 433– 438. 14520653
  46. [55]Jansen WJ, Ossenkoppele R, Knol DL, et al Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis. JAMA. 2015; 313(19): 1924– 1938. 25988462 PMC4486209
  47. [56]Buckley RF, Mormino EC, Amariglio RE, et al Sex, amyloid, and APOE epsilon4 and risk of cognitive decline in preclinical Alzheimer's disease: Findings from three well-characterized cohorts. Alzheimers Dement. 2018; 14(9): 1193– 1203. 29803541 PMC6131023
  48. [58]Wisniewski KE, Dalton AJ, McLachlan C, Wen GY, Wisniewski HM. Alzheimer's disease in Down's syndrome: Clinicopathologic studies. Neurology. 1985; 35(7): 957– 961. 3159974
  49. [59]Mann DM. The pathological association between Down syndrome and Alzheimer disease. Mech Ageing Dev. 1988; 43(2): 99– 136. 2969441
  50. [60]Ball MJ, Nuttall K. Topography of neurofibrillary tangles and granulovacuoles in hippocampi of patients with Down's syndrome: Quantitative comparison with normal ageing and Alzheimer's disease. Neuropathol Appl Neurobiol. 1981; 7(1): 13– 20. 6453301
  51. [61]Motte J, Williams RS. Age-related changes in the density and morphology of plaques and neurofibrillary tangles in Down syndrome brain. Acta Neuropathol. 1989; 77(5): 535– 546. 2524150
  52. [62]Vila-Castelar C, Guzman-Velez E, Pardilla-Delgado E, et al Examining sex differences in markers of cognition and neurodegeneration in autosomal dominant Alzheimer's disease: Preliminary findings from the Colombian Alzheimer's prevention initiative biomarker study. J Alzheimers Dis. 2020; 77(4): 1743– 1753. 32925067 PMC8075106
  53. [65]Cacciaglia R, Salvado G, Molinuevo JL, et al Age, sex and APOE-epsilon4 modify the balance between soluble and fibrillar beta-amyloid in non-demented individuals: Topographical patterns across two independent cohorts. Mol Psychiatry. 2022; 27(4): 2010– 2018. 35236958 PMC9126807
  54. [66]Cho SH, Woo S, Kim C, et al Disease progression modelling from preclinical Alzheimer's disease (AD) to AD dementia. Sci Rep. 2021; 11(1): 4168. 33603015 PMC7893024
  55. [67]Mathys H, Davila-Velderrain J, Peng Z, et al Single-cell transcriptomic analysis of Alzheimer's disease. Nature. 2019; 570(7761): 332– 337. 31042697 PMC6865822
  56. [68]Andrews EJ, Martini AC, Head E. Exploring the role of sex differences in Alzheimer's disease pathogenesis in Down syndrome. Front Neurosci. 2022; 16: 954999. PMC9411995 36033603
  57. [69]Schupf N, Zigman W, Kapell D, Lee JH, Kline J, Levin B. Early menopause in women with Down's syndrome. J Intellect Disabil Res. 1997; 41(Pt 3): 264– 267. 9219076
  58. [70]Coppus A, Evenhuis H, Verberne GJ, et al Early age at menopause is associated with increased risk of dementia and mortality in Down syndrome. J Appl Res Intellect Disabil. 2010; 23(5): 408– 408.
  59. [71]Almey A, Milner TA, Brake WG. Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females. Horm Behav. 2015; 74: 125– 138. 26122294 PMC4820286
  60. [72]Spampinato SF, Molinaro G, Merlo S, et al Estrogen receptors and type 1 metabotropic glutamate receptors are interdependent in protecting cortical neurons against beta-amyloid toxicity. Mol Pharmacol. 2012; 81(1): 12– 20. 21984253
  61. [73]Liang K, Yang L, Yin C, et al Estrogen stimulates degradation of beta-amyloid peptide by up-regulating neprilysin. J Biol Chem. 2010; 285(2): 935– 942. 19897485 PMC2801294
  62. [74]Amtul Z, Wang L, Westaway D, Rozmahel RF. Neuroprotective mechanism conferred by 17beta-estradiol on the biochemical basis of Alzheimer's disease. Neuroscience. 2010; 169(2): 781– 786. 20493928
  63. [75]Batallan Burrowes AA, Olajide OJ, Iasenza IA, Shams WM, Carter F, Chapman CA. Ovariectomy reduces cholinergic modulation of excitatory synaptic transmission in the rat entorhinal cortex. PLoS One. 2022; 17(8): e0271131. PMC9359571 35939438
  64. [76]Taxier LR, Philippi SM, Fleischer AW, York JM, LaDu MJ, Frick KM. APOE4 homozygote females are resistant to the beneficial effects of 17beta-estradiol on memory and CA1 dendritic spine density in the EFAD mouse model of Alzheimer's disease. Neurobiol Aging. 2022; 118: 13– 24. 35843109 PMC10756028
  65. [77]Brinton RD. Cellular and molecular mechanisms of estrogen regulation of memory function and neuroprotection against Alzheimer's disease: Recent insights and remaining challenges. Learn Mem. 2001; 8(3): 121– 133. 11390632
  66. [78]Garcia-Segura LM, Azcoitia I, DonCarlos LL. Neuroprotection by estradiol. Prog Neurobiol. 2001; 63(1): 29– 60. 11040417
  67. [79]Cosgrave MP, Tyrrell J, McCarron M, Gill M, Lawlor BA. Age at onset of dementia and age of menopause in women with Down's syndrome. J Intellect Disabil Res. 1999; 43(Pt 6): 461– 465. 10622361
  68. [80]Schupf N, Winsten S, Patel B, et al Bioavailable estradiol and age at onset of Alzheimer's disease in postmenopausal women with Down syndrome. Neurosci Lett. 2006; 406(3): 298– 302. 16926067
  69. [81]Schupf N, Lee JH, Wei M, et al Estrogen receptor-alpha variants increase risk of Alzheimer's disease in women with Down syndrome. Dement Geriatr Cogn Disord. 2008; 25(5): 476– 482. 18408366 PMC2430887
  70. [82]de Gonzalo-Calvo D, Barroeta I, Nan MN, et al Evaluation of biochemical and hematological parameters in adults with Down syndrome. Sci Rep. 2020; 10(1): 13755. 32792619 PMC7426851
  71. [83]Startin CM, D'Souza H, Ball G, et al Health comorbidities and cognitive abilities across the lifespan in Down syndrome. J Neurodev Disord. 2020; 12(1): 4. 31973697 PMC6979347
  72. [85]Patel BN, Seltzer GB, Wu HS, Schupf N. Effect of menopause on cognitive performance in women with Down syndrome. Neuroreport. 2001; 12(12): 2659– 2662. 11522943
  73. [86]Coppus AMW, Evenhuis HM, Verberne GJ, et al Early age at menopause is associated with increased risk of dementia and mortality in women with Down syndrome. J Alzheimers Dis. 2010; 19(2): 545– 550. 20110600

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Authors
Iulita, M. F., Bejanin, A., Vilaplana, E., Carmona-Iragui, M., Benejam, B., Videla, L., Barroeta, I., Fernández, S., Altuna, M., Pegueroles, J., Montal, V., Valldeneu, S., Giménez, S., González-Ortiz, S., Torres, S., El Bounasri El Bennadi, S., Padilla, C., Rozalem Aranha, M., Estellés, T., Illán-Gala, I., Belbin, O., Valle-Tamayo, N., Camacho, V., Blessing, E., Osorio, R. S., Videla, S., Lehmann, S., Holland, A. J., Zetterberg, H., Blennow, K., Alcolea, D., Clarimón, J., Zaman, S. H., Blesa, R., Lleó, A., & Fortea, J.
Affiliations
  • Universitat Autònoma de Barcelona (ES)
  • Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona , Barcelona 08025 , Spain
  • Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
  • Barcelona Down Medical Center, Fundació Catalana Síndrome de Down , Barcelona 08029 , Spain
  • Hospital de Sant Pau (ES)
  • Hospital del Mar , Barcelona 08003 , Spain
  • New York University (US)
  • Clinical Research Support Unit, Bellvitge Biomedical Research Institute (IDIBELL), Department of Clinical Pharmacology, University of Barcelona , Barcelona 08908 , Spain
  • Inserm (FR)
  • University of Cambridge (GB)
  • Sahlgrenska University Hospital (SE)
Corresponding author
  • Iulita, M Florencia
  • Fortea, Juan
ORCID
Venue
Brain Communications
Publisher
Oxford University Press (OUP)
Published
2023-03-02
Volume
5
Issue
2
Pages
fcad074-fcad074
ISSN
2632-1297 (ISSN-L)
DOI
10.1093/braincomms/fcad074
PMC
PMC10088472
OpenAlex
W4327724279
Cited by
68
References
12
Citations by year
2026: 19 · 2025: 29 · 2024: 16 · 2023: 4
FWCI
17.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
  • UCL Discovery (University College London) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
Funders
  • Fondo de Investigaciones Sanitario, Carlos III Health Institute (PI14/01126, PI17/01019, PI20/01473, PI13/01532, PI16/01825, PI18/00335, PI18/00435, PI14/1561, PI20/01330, P21/00791)
  • Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
  • National Institutes of Health (1R01AG056850-01A1; R21AG056974 and R01AG061566, #1R01AG068398-01)
  • Department de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca i Innovació en Salut (SLT002/16/00408)
  • Fundació La Marató de TV3 (20141210, 044412)
  • Wallenberg Scholar
  • Swedish Research Council (2018-02532, #2017-00915)
  • European Research Council (#681712)
  • Swedish State Support for Clinical Research (#ALFGBG-720931)
  • Alzheimer Drug Discovery Foundation (#201809-2016862, #RDAPB-201809-2016615)
  • Alzheimer’s Disease Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C)
  • Olav Thon Stiftelsen
  • Erling-Persson Family Foundation
  • Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228)
  • European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie (860197)
  • EU Joint Programme Neurodegenerative Disease Research (JPND2021-00694, JPND2019-466-236)
  • UK Dementia Research Institute at University College London
  • Swedish Alzheimerfonden (#AF-742881, #FO2017-0243, #ALFGBG-715986)
  • Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495)
  • Medical Research Council (#98480)
  • NIHR Cambridge Biomedical Research Centre
  • National Institute for Health and Care Research Collaborations
  • National Institute for Health and Care Research Cambridge Dementia Biomedical Research Unit
  • Down Syndrome Association
  • Health Foundation
  • Applied Health Research and Care East of England
  • Cambridgeshire and Peterborough National Health Service Foundation Trust
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Alzheimer's disease, Down syndrome, sex differences, amyloid-beta, tau pathology, neurodegeneration biomarkers, neurofilament light chain, hippocampal volume, cognitive decline, age at diagnosis, adults with intellectual disabilities

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