Sílvia Valldeneu, Spain
Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas CIBERNEDAuthor Of 2 Presentations
EFFECT OF BIOLOGICAL SEX ON CLINICAL, BIOCHEMICAL AND NEUROIMAGING BIOMARKERS OF ALZHEIMER’S DISEASE IN ADULTS WITH DOWN SYNDROME: A CROSS-SECTIONAL STUDY
Abstract
Aims
Biological sex is increasingly recognized as a modifier of Alzheimer’s disease (AD) pathophysiology and disease progression. We aimed to assess the effect of sex on cognitive and biomarker measures of AD in adults with Down syndrome, who have an ultra-high risk for developing AD dementia.
Methods
Cross-sectional study of 494 adults with Down syndrome recruited from two sites. We compared clinical characteristics and AD biomarkers between men (n=268) and women (n=226). Participants had at least one biomarker assessment among plasma NfL, Aβ1-42/1-40, p-Tau-181, tau and NfL in CSF, PET with amyloid tracers or 18F-fluorodeoxyglucose and/or MRI. We compared age at symptom onset and used within-group local regression models with confidence intervals to compare the trajectory of biomarker changes with age.
Results
The mean age at which women were diagnosed with dementia was 53 years vs. 53.6 for men (p=0.46). Women with Down syndrome showed earlier decreases in CSF Aß1-42, however no differences were found when comparing the Aß1-42/Aß1-40 ratio. The biomarker trajectories of plasma NfL and CSF NfL, p-Tau-181 and tau were similar across ages between men and women. Women had smaller head sizes and hippocampal volumes, but there were no differences in hippocampal volumes when adjusted for differences in head size. There were no differences in age-associated changes in cerebral amyloid deposition (Centiloid) or glucose metabolism (FDG-PET).
Conclusions
In adults with Down syndrome, sex does not modify the age at diagnosis of dementia or the trajectories of plasma, CSF and imaging biomarkers. Reporting of negative results is important to avoid publication bias.
PROGRESSION ALONG THE ALZHEIMER DISEASE CONTINUUM AND LONGITUDINAL COGNITIVE DECLINE IN ADULTS WITH DOWN SYNDROME.
Abstract
Aims
Down syndrome(DS) is a genetically determined form of Alzheimer’s disease(AD). Objective: to describe the clinical progression along the ADcontinuum and the associated cognitive decline in a cohort of adults with DS.
Methods
Single-centre longitudinal study. We included adults with DS with at least one follow-up. Participants were clinically classified as: asymptomatic (aDS), prodromalAD (pDS) or ADdementia (dDS). For prognostic evaluation, aDS and pDS were also classified as “progressors” and “non-progressors” based on clincal criteria. We performed KaplanMeier regression analyses to study progression across diagnostic categories and linear mixed effect models to estimate the longitudinal cognitive decline. For cognitive measures we used CAMCOG-DS and CRT.
Results
From February'14 to May'20 we assessed 540 adults with DS (19.1%mild, 50.6%moderate, 21.9%severe, 8.3%profound intellectual disability), 69.7% were aDS, 10.9% pDS and 19.4% dDS. aDS were younger than pDS and dDS (mean age 38, 51, 53 respectively; p=0.001). aDS had a median time to progression to symptomatic AD of 5.4 years. When stratifying by baseline age, we observed a clear age-dependence risk for progression in the aDS group, but not in pDS. Progressors had higher annual cognitive decline in neuropsychological test than non-progressors, 0.25 points and 0.05 respectively (p<0.05). There were no differences in the longitudinal performance in neuropsychological testing when stratifying by intellectual disability (0.005 and -0.017 points/year for CAMCOG and CRT respectively, (p>0.05)).
Conclusions
This longitudinal study confirms the ultra-high risk to develop symptomatic AD in DS. The rate of progression in aDS confirms that a preventive trial would have high statistical power in this population.