Associations Between Brainstem Volume and Alzheimer’s Disease Pathology in Middle-Aged Individuals of the Framingham Heart Study

Article type: Short Communication

Authors: Jacobs, Heidi I.L.^{a; b; c; d} | O’Donnell, Adrienne^{e; f} | Satizabal, Claudia L.^{f; g; h} | Lois, Cristina^{a; b; d} | Kojis, Daniel^{e; f} | Hanseeuw, Bernard J.^{a; d; i} | Thibault, Emma^{a; d} | Sanchez, Justin S.^{a; d} | Buckley, Rachel F.^{a; b; j} | Yang, Qiong^e | DeCarli, Charles^k | Killiany, Ron^g | Sargurupremraj, Muralidharan^h | Sperling, Reisa A.^{a; b; l} | Johnson, Keith A.^{a; b; d; l} | Beiser, Alexa S.^{e; f; g} | Seshadri, Sudha^{f; g; h}

Affiliations: [a] Massachusetts General Hospital, Boston, MA, USA | [b] Harvard Medical School, Boston, MA, USA | [c] School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, Netherlands | [d] Gordon Center for Medical Imaging, Boston, MA, USA | [e] Boston University School of Public Health, Boston, MA, USA | [f] The Framingham Heart Study, Framingham, MA, USA | [g] Boston University School of Medicine, Boston, MA, USA | [h] Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA | [i] Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium | [j] Melbourne School of Psychological Sciences, University of Melbourne, Victoria, Australia | [k] University of California, Davis, Davis, CA, USA | [l] Brigham and Women’s Hospital, Boston, MA, USA

Correspondence: [*] Correspondence to: Dr. Heidi Jacobs, PhD, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston MA 02114, USA. E-mail: hjacobs@mgh.harvard.edu.

Abstract: The brainstem is among the first regions to accumulate Alzheimer’s disease (AD)-related hyperphosphorylated tau pathology during aging. We aimed to examine associations between brainstem volume and neocortical amyloid-β or tau pathology in 271 middle-aged clinically normal individuals of the Framingham Heart Study who underwent MRI and PET imaging. Lower volume of the medulla, pons, or midbrain was associated with greater neocortical amyloid burden. No associations were detected between brainstem volumes and tau deposition. Our results support the hypothesis that lower brainstem volumes are associated with initial AD-related processes and may signal preclinical AD pathology.

Keywords: Aging, amyloid, brainstem, tau

DOI: 10.3233/JAD-215372

Journal: Journal of Alzheimer's Disease, vol. 86, no. 4, pp. 1603-1609, 2022