| Autor: |
Fleming, Victoria L, Hartley, Sigan, Handen, Benjamin L., Tudorascu, Dana, Lee, Laise, Krinsky‐McHale, Sharon J, Hom, Christy, Cohen, Annie, Schworer, Emily K, Peven, Jamie C, Zammit, Matthew D, Klunk, William E, Laymon, Charles M, Zaman, Shahid, Ances, Beau, Christian, Bradley T. |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2023 Supplement 15, Vol. 19, p1-2, 2p |
| Abstrakt: |
Background: Trisomy 21 causes Down syndrome (DS) and is a recognized cause of Alzheimer's disease (AD). The triplication of the amyloid precursor protein gene leads to an overexpression of amyloid‐beta (Aβ), which accumulates into extracellular plaques, followed by intracellular neurofibrillary tau tangles (Lott & Head, 2019). However, variability in the age of AD onset in DS spans 25+ years (Iulita et al., 2022). As the DS field moves to AD clinical trials, it is important to identify factors related to this variability, such as premorbid severity of intellectual disability (ID). We compared the age‐trajectory of the AD biomarkers Aβ and tau and cognitive decline across premorbid ID levels (mild, moderate, and severe/profound), in models controlling trisomy type (full, mosaic, translocation) and APOE status Method: Analyses involved 361 adults with DS (M = 45.22 years, SD = 9.92) from the Alzheimer's Biomarkers Consortium‐Down Syndrome. Participants completed measures of memory, mental status, and visuospatial ability. Premorbid ID level was recorded. PET was acquired using [11C] PiB for Aβ, and [18F] AV‐1451 for tau in 162 participants. Aβ was quantified using the centiloid method and tau was quantified as SUVR (reference: cerebellar cortex) in a composite region determined as the volume‐weighted average of select FreeSurfer 5.3, T1 MR‐based components. Results: General linear models controlling for site, age, trisomy type and APOE status indicated no significant effect of premorbid ID level by age on the cognitive outcomes (Figure 1a‐e). There was not a significant effect of premorbid ID by age on PET Aβ or on tau PET (Figure 2a‐b). There was not a significant difference in age of those with mild cognitive impairment‐DS (MCI‐DS) or dementia by premorbid ID level (Figure 3). Conclusion: This study adds to the characterization of the time course of AD pathology and clinical symptomology in DS. Findings provide robust evidence of a similar time course in AD trajectory across severity of ID, laying the groundwork for the inclusion of individuals with DS with a variety of IQ levels in clinical AD trials. Premorbid IQ may have little effect on AD biomarkers in DS in contrast to findings in neurotypical populations. [ABSTRACT FROM AUTHOR] |
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