Cortical thickness relates to later dementia symptoms in middle-aged adults with Down syndrome
Poster No:
117
Submission Type:
Abstract Submission
Authors:
Katherine Koenig1, Pallab Bhattacharyya1
Institutions:
1The Cleveland Clinic, Cleveland, OH
First Author:
Co-Author:
Introduction:
Down syndrome (DS) is associated with intellectual disability and early onset Alzheimer's disease (DSAD). Nearly half of adults with DS show dementia symptoms by age 60, with some AD-associated biomarkers showing differences in those with DS by age 30.1 Varying levels of intellectual disability complicate the diagnosis of DSAD, highlighting the need for measures that are associated with dementia risk or disease progression.
Those with DSAD show a pattern of cortical atrophy similar to the general population,2 although developmental differences in DS like regionally increased cortical thickness (CT)3-5 may complicate the association of cortical atrophy and dementia symptoms. An understanding of the interaction between developmental differences in DS and changes that are the consequence of dementia could identify early diseased-related changes that may be suitable for biomarker development.
We previously assessed CT in a sample of young adults with DS (mean age 31.4, all showing no symptoms of dementia), finding that thicker cortex at baseline was related to an increase in dementia-related symptoms after 4.6 years.6 Here, we assess CT in a sample of slightly older adults with DS, hypothesizing that CT will relate to later dementia symptoms even after accounting for baseline full-scale IQ (FSIQ).
Those with DSAD show a pattern of cortical atrophy similar to the general population,2 although developmental differences in DS like regionally increased cortical thickness (CT)3-5 may complicate the association of cortical atrophy and dementia symptoms. An understanding of the interaction between developmental differences in DS and changes that are the consequence of dementia could identify early diseased-related changes that may be suitable for biomarker development.
We previously assessed CT in a sample of young adults with DS (mean age 31.4, all showing no symptoms of dementia), finding that thicker cortex at baseline was related to an increase in dementia-related symptoms after 4.6 years.6 Here, we assess CT in a sample of slightly older adults with DS, hypothesizing that CT will relate to later dementia symptoms even after accounting for baseline full-scale IQ (FSIQ).
Methods:
Sixteen adults with DS (mean age (years) 44.1 ± 6.5, range 29-56; 7 males) with baseline and follow-up visits after six months. None of the participants were diagnosed with DSAD.
MRI acquisition: Siemens TIM Trio 3 Tesla scanner (Siemens Healthineers, Erlangen, Germany) with a 12-channel head coil. T1-weighted MPRAGE: 120 axial slices at 1.2 mm thickness; field-of-view (FOV) 256 mm×256 mm; matrix = 256×256; voxel size 1×1×1.2 mm3; inversion time (TI)/echo time (TE)/repetition time (TR)/flip angle (FA)=900 ms/1.71 ms/1900 ms/8°; bandwidth (BW)=62 kHz; time 4:03. For each participant, the MPRAGE was segmented using the Desikan-Killiany atlas in Freesufer 7.4.1 and mean cortical thickness (CT) was extracted for 34 regions.
Figure 1 details all measures used in the analysis. Relationships between CT and measures of dementia symptoms (DLD scores) were assessed using partial correlations including FSIQ as a covariate.
MRI acquisition: Siemens TIM Trio 3 Tesla scanner (Siemens Healthineers, Erlangen, Germany) with a 12-channel head coil. T1-weighted MPRAGE: 120 axial slices at 1.2 mm thickness; field-of-view (FOV) 256 mm×256 mm; matrix = 256×256; voxel size 1×1×1.2 mm3; inversion time (TI)/echo time (TE)/repetition time (TR)/flip angle (FA)=900 ms/1.71 ms/1900 ms/8°; bandwidth (BW)=62 kHz; time 4:03. For each participant, the MPRAGE was segmented using the Desikan-Killiany atlas in Freesufer 7.4.1 and mean cortical thickness (CT) was extracted for 34 regions.
Figure 1 details all measures used in the analysis. Relationships between CT and measures of dementia symptoms (DLD scores) were assessed using partial correlations including FSIQ as a covariate.
·Figure 1. Measures used in this analysis.
Results:
FSIQ was not significantly related to CT. After accounting for baseline FSIQ, follow-up DLD-SCS and DLD-SOC scores were largely negatively related to baseline CT, primarily in temporal and frontal regions (Figure 2A), so that thinner cortex at baseline was associate with more dementia symptoms at follow-up. Further, those with thinner cortex at baseline in regions such as the parahippocampal gyrus were more likely to show an increase in DLD-SCS score at follow-up (Figure 2B). Interestingly, those with thicker cortex in the cuneus, pericalcarine fissure, and rostral anterior cingulate were more likely to show an increase in DLD-SOS score at follow-up.
·Figure 2.
Conclusions:
In a sample of middle-aged adults with DS, we found that thinner cortex in temporal and frontal lobe regions was associated with more cognitive and social domain dementia symptoms after six months, even after accounting for baseline cognitive ability. The change in dementia symptoms over time was also related to CT, although the direction and location of the relationships differed for the cognitive and social domain scores. Thicker cortex was associated with an increase in social domain dementia symptoms. This echoes our findings in a separate, younger sample,6 although the widespread association between more social domain symptoms and thinner cortex in the temporal and frontal lobes in this older sample suggests that possible impacts of thicker cortex is mitigated as dementia onset approaches. Still, this analysis suggests that DSAD biomarker development may benefit from a greater understanding of developmental differences (i.e. thicker cortex) and their causative mechanisms.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Neurodevelopmental/ Early Life (eg. ADHD, autism)
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Cortical Anatomy and Brain Mapping 2
Keywords:
Aging
Cortex
Degenerative Disease
Development
MRI
Segmentation
STRUCTURAL MRI
Other - Down Syndrome
1|2Indicates the priority used for review
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2. Dickerson, B.C. et al. The Cortical Signature of Alzheimer’s Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals. Cerebral Cortex. 2009; 19(3):497–510.
3. Levman, J. et al. Structural Magnetic Resonance Imaging Demonstrates Abnormal Cortical Thickness in Down Syndrome: Newborns to Young Adults. Neuroimage Clin. 2019; 23(101874):1-8.
4. Lee, N.R. et al. Dissociations in Cortical Morphometry in Youth with Down Syndrome: Evidence for Reduced Surface Area but Increased Thickness. Cereb Cortex. 2016; 26(7):2982-90.
5. Bletsch, A. et al. Down syndrome is accompanied by significantly reduced cortical grey–white matter tissue contrast. Human Brain Mapping. 2018; 39(10):4043-4054.
6. Koenig, K.A. et al. (2023, June) Cortical thickness related to future score on the Dementia Questionnaire for People with Learning Disabilities in adults with Down syndrome. Poster presented at the International Society for Magnetic Resonance in Medicine Annual Meeting, Toronto, CA.
7. Wechsler, D. WAIS-III/WMS-III Technical Manual; The Psychological Corporation: San Antonio, TX, 1997.
8. Evenhuis, H.M. Further evaluation of the Dementia Questionnaire for Persons with Mental Retardation. J Intellectual Disabilities Res 1996, 40, 369-373.