A Pilot Study Assessing Central Cholinergic Integrity in Individuals with Down Syndrome Using [18F]‐FEOBV PET and Basal Forebrain Cholinergic Anatomy
Jason K Russell, Alexander C Conley, Brian Boyd, Rachel Schlossberg, Adam J Rosenberg, Lealani Mae Y. Acosta, Sepideh Shokouhi, Paul A Newhouse- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Down Syndrome (DS) individuals express an extra copy of chromosome 21, which contains the gene for APP, producing a higher risk of developing Alzheimer’s Disease (AD). By 40 years old, amyloid plaques and tau neurofibrillary tangles are present in most individuals with DS, with AD progression risk being greater than 90%. In AD, the cholinergic basal forebrain projections degenerate and are known to play a significant role in cognitive deficits. We assess the integrity of the cholinergic system directly in individuals with DS utilizing [18F]‐FEOBV PET imaging.
Method
Seven individuals (19‐50 years old) with DS, not exhibiting AD symptoms on neuropsychiatric assessment, completed a FEOBV PET scan (6.5mCi dose) and MRI. Participants over 25 years old were recruited from the TRC‐DS study, where individuals undergo multimodal imaging assessment, including brain amyloid and tau PET imaging. A Brodmann area (BA) atlas from MRIcron and Freesurfer cortical and subcortical parcellations were registered to participants’ MRI scans and transformed to native PET space. Regional FEOBV uptake was normalized to supraventricular white matter generating standard uptake value ratios (SUVRs). Initial analysis assessed uncorrected associations between FEOBV SUVR, cholinergic basal forebrain volumes, Ch1‐3 (medial septum, vertical and horizontal limbs of the diagonal band of Broca and Ch4 (basal nucleus of Meynert), and age.
Result
Individuals with DS displayed region‐specific uptake comparable to FEOBV data in normal non‐DS individuals published by other groups. FEOBV SUVRs in the posterior cingulate cortex positively correlated with left and right Ch1‐3 and right Ch4 volumes (r>0.79, p<0.05), with a trend observed with left Ch4 volumes (r = 0.73, p = 0.064), while FEOBV SUVR in the posterior cingulate cortex displayed a trend towards a negative association with age (r = ‐0.73, p = 0.063). Additionally, trends to positive correlations were observed between basal forebrain cholinergic nuclei volume and BA5, 24, and 44. (r>0.67 and p<0.1).
Conclusion
Given comparable results to previously published data in normal non‐DS individuals, FEOBV PET imaging appears a valid modality for assessing cholinergic integrity in individuals with DS. Initial analysis suggests associations between specific cortical regions, cholinergic basal forebrain volumes, and age. Ongoing assessments will investigate associations between FEOBV uptake, cognition, and amyloid deposition.