In vivo cholinergic system integrity and cognition using [18F]‐FEOBV PET in healthy postmenopausal women: a pilot study

Abstract Background Women are at a higher risk of developing Alzheimer’s disease (AD), and a possible reason for this may be the effects of estrogen depletion and cholinergic system activity following menopause. The investigational radiotracer [18F]‐fluoroethoxybenzovesamicol (FEOBV) can assess in vivo cholinergic integrity, as the tracer binds to the vesicular cholinergic transporter at the synapse. FEOBV has previously shown cholinergic system decline in AD patients. The present study is an investigation of cholinergic system integrity in a sample of cognitively normal postmenopausal women, aged 50‐70 years that were part of a larger study examining cholinergic compensation following menopause. We predicted that higher FEOBV standardized uptake value ratios (SUVR) would be associated with larger basal forebrain cholinergic volumes, lower levels of amyloid SUVR, and better cognitive performance as measured by the RBANS. Methods Ten postmenopausal women (mean age: 57.3 ± 5.1 years) completed an FEOBV PET scan (6.5 mCi dose), MRI and cognitive assessments. The FEOBV PET images were co‐registered to the participant’s structural MRI data. FEOBV SUVR was normalized in reference to the supraventricular white matter to avoid partial volume effects from ventricular tissue. Preliminary analyses focused on associations between FEOBV SUVR and the key outcome variables. Results Preliminary analyses showed a positive relationship between FEOBV SUVR and the gray‐matter volume of the cholinergic basal forebrain of both hemispheres (L: r =0.51, R: r =0.65). Two participants were amyloid positive, and their FEOBV SUVR values were lower compared to the amyloid negative participants. A positive relationship was also seen between FEOBV SUVR and the RBANS total score, with higher SUVR associated with better cognitive performance ( r =0.43). Conclusions In a small sample of cognitively normal postmenopausal women, greater FEOBV uptake was positively associated with both basal forebrain volume and cognitive performance. The results of this pilot sample show the importance of cholinergic system integrity in cognitive performance following menopause, supporting the idea that cholinergic integrity may be linearly related to performance and amyloid aggregation. Deterioration of cholinergic integrity post‐menopause may increase the risk of future cognitive decline and development of AD.