%0 Journal Article %J J Alzheimers Dis %D 2023 %T Timing of Alzheimer's Disease by Intellectual Disability Level in Down Syndrome. %A Hartley, Sigan L %A Fleming, Victoria %A Schworer, Emily K %A Peven, Jamie %A Handen, Benjamin L %A Krinsky-McHale, Sharon %A Hom, Christy %A Lee, Laisze %A Tudorascu, Dana L %A Laymon, Charles %A Minhas, Davneet %A Luo, Weiquan %A Cohen, Annie %A Zaman, Shahid %A Ances, Beau M %A Mapstone, Mark %A Head, Elizabeth %A Lai, Florence %A Rosas, H Diana %A Klunk, William %A Christian, Bradley %X

BACKGROUND: Trisomy 21 causes Down syndrome (DS) and is a recognized cause of early-onset Alzheimer's disease (AD).

OBJECTIVE: The current study sought to determine if premorbid intellectual disability level (ID) was associated with variability in age-trajectories of AD biomarkers and cognitive impairments. General linear mixed models compared the age-trajectory of the AD biomarkers PET Aβ and tau and cognitive decline across premorbid ID levels (mild, moderate, and severe/profound), in models controlling trisomy type, APOE status, biological sex, and site.

METHODS: Analyses involved adults with DS from the Alzheimer's Biomarkers Consortium-Down Syndrome. Participants completed measures of memory, mental status, and visuospatial ability. Premorbid ID level was based on IQ or mental age scores prior to dementia concerns. PET was acquired using [11C] PiB for Aβ, and [18F] AV-1451 for tau.

RESULTS: Cognitive data was available for 361 participants with a mean age of 45.22 (SD = 9.92) and PET biomarker data was available for 154 participants. There was not a significant effect of premorbid ID level by age on cognitive outcomes. There was not a significant effect of premorbid ID by age on PET Aβ or on tau PET. There was not a significant difference in age at time of study visit of those with mild cognitive impairment-DS or dementia by premorbid ID level.

CONCLUSION: Findings provide robust evidence of a similar time course in AD trajectory across premorbid ID levels, laying the groundwork for the inclusion of individuals with DS with a variety of IQ levels in clinical AD trials.

%B J Alzheimers Dis %V 95 %P 213-225 %8 2023 Aug 29 %G eng %N 1 %R 10.3233/JAD-230200 %0 Journal Article %J J Alzheimers Dis %D 2022 %T Weight Loss and Alzheimer's Disease in Down Syndrome. %A Fleming, Victoria %A Helsel, Brian C %A Ptomey, Lauren T %A Rosas, H Diana %A Handen, Benjamin %A Laymon, Charles %A Christian, Bradley T %A Head, Elizabeth %A Mapstone, Mark %A Lai, Florence %A Krinsky-McHale, Sharon %A Zaman, Shahid %A Ances, Beau M %A Lee, Joseph H %A Hartley, Sigan L %X

BACKGROUND: Virtually all adults with Down syndrome (DS) develop Alzheimer's disease (AD) pathology, but research gaps remain in understanding early signs of AD in DS.

OBJECTIVE: The goal of the present study was to determine if unintentional weight loss is part of AD in DS. The specific aims were to: 1) examine relation between chronological age, weight, AD pathology, and AD-related cognitive decline were assessed in a large cohort of adults with DS, and 2) determine if baseline PET amyloid-β (Aβ) and tau PET status (-versus+) and/or decline in memory and mental status were associated with weight loss prior to AD progression.

METHODS: Analyses included 261 adults with DS. PET data were acquired using [11C] PiB for Aβ and [18F] AV-1451 for tau. Body mass index (BMI) was calculated from weight and height. Direct measures assessed dementia and memory. Clinical AD status was determined using a case consensus process. Percent weight decline across 16-20 months was assessed in a subset of participants (n = 77).

RESULTS: Polynomial regressions indicated an 0.23 kg/m2 decrease in BMI per year beginning at age 36.5 years, which occurs alongside the period during which Aβ and tau increase and memory and mental status decline. At a within-person level, elevated Aβ, decline in memory and mental status were associated with higher percent weight loss across 16-20 months.

CONCLUSION: Unintentional weight loss occurs alongside Aβ deposition and prior to onset of AD dementia, and thus may be a useful sign of AD in DS.

%B J Alzheimers Dis %V 91 %P 1215-1227 %8 2023 Jan 31 %G eng %N 3 %R 10.3233/JAD-220865 %0 Journal Article %J J Alzheimers Dis %D 2016 %T White Matter Changes are Associated with Ventricular Expansion in Aging, Mild Cognitive Impairment, and Alzheimer's Disease. %A Coutu, Jean-Philippe %A Goldblatt, Alison %A Rosas, H Diana %A Salat, David H %K Aged %K Aging %K Alzheimer Disease %K Cognitive Dysfunction %K Diffusion Tensor Imaging %K Factor Analysis, Statistical %K Female %K Hippocampus %K Humans %K Imaging, Three-Dimensional %K Male %K Mental Status Schedule %K Neuropsychological Tests %K White Matter %X

White matter lesions are highly prevalent in individuals with Alzheimer's disease (AD). Although these lesions are presumed to be of vascular origin and linked to small vessel disease in older adults, little information exists about their relationship to markers of classical AD neurodegeneration. Thus, we examined the link between these white matter changes (WMC) segmented on T1-weighted MRI and imaging markers presumed to be altered due to primary AD neurodegenerative processes. Tissue microstructure of WMC was quantified using diffusion tensor imaging and the relationship of WMC properties and volume to neuroimaging markers was examined in 219 cognitively healthy older adults and individuals with mild cognitive impairment and AD using data from the Alzheimer's Disease Neuroimaging Initiative. No significant group differences in WMC properties were found. However, there were strong associations between diffusivity of WMC and ventricular volume, volume of WMC and total WM volume. In comparison, group differences in parahippocampal white matter microstructure were found for all diffusion metrics and were largely explained by hippocampal volume. Factor analysis on neuroimaging markers suggested two independent sets of covarying degenerative changes, with potentially age- and vascular-mediated tissue damage contributing to one factor and classical neurodegenerative changes associated with AD contributing to a second factor. These data demonstrate two potentially distinct classes of degenerative change in AD, with one factor strongly linked to aging, ventricular expansion, and both volume and tissue properties of white matter lesions, while the other factor related to classical patterns of cortical and hippocampal neurodegeneration in AD.

%B J Alzheimers Dis %V 49 %P 329-42 %8 2016 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/26444767?dopt=Abstract %R 10.3233/JAD-150306