Affiliations: [a] VA San Diego Healthcare System, San Diego, CA, USA
| [b] Department of Psychiatry, UC San Diego, La Jolla, CA, USA
| [c] Department of Radiology, UC San Diego, La Jolla, CA, USA
| [d] Department of Neurosciences, UC San Diego, La Jolla, CA, USA
| [e] SDSU/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA
Correspondence:
[*]
Correspondence to: Christina E. Wierenga, PhD, VA San Diego Healthcare System, 3350 La Jolla Village Dr., MC
151B, San Diego, CA 92161, USA. Tel.: +1 858 534 8047; Fax: +1 858 642 1218; E-mail: cwierenga@ucsd.edu.
Abstract: Evidence suggests the ɛ4 allele of the apolipoprotein E (APOE) gene may accelerate an age-related process of cortical thickening and cerebral blood flow (CBF) reduction in the anterior cingulate cortex (ACC). Although the neural basis of this association remains unclear, evidence suggests it might reflect early neurodegenerative processes. However, to date, associations between cerebrospinal fluid (CSF) biomarkers of neurodegeneration, such as CSF tau, and APOE-related alterations in ACC cortical thickness (CTH) and CBF have yet to be explored. The current study explored the interaction of CSF tau and APOE genotype (ɛ4+, ɛ4–) on FreeSurfer-derived CTH and arterial spin labeling MRI-measured resting CBF in the ACC (caudal ACC [cACC] and rostral ACC [rACC]) among a sample of 45 cognitively normal older adults. Secondary analyses also examined associations between APOE, CTH/CBF, and cognitive performance. In the cACC, higher CSF tau was associated with higher CTH and lower CBF in ɛ4+, whereas these relationships were not evident in ɛ4–. In the rACC, higher CSF tau was associated with higher CTH for both ɛ4+ and ɛ4–, and with lower CBF only in ɛ4+. Significant interactions of CSF tau and APOE on CTH/CBF were not observed in two posterior reference regions implicated in Alzheimer’s disease. Secondary analyses revealed a negative relationship between cACC CTH and executive functioning in ɛ4+ and a positive relationship in ɛ4–. Findings suggest the presence of an ɛ4–related pattern of increased CTH and reduced CBF in the ACC that is associated with biomarkers of neurodegeneration and subtle decrements in cognition.
Keywords: Aging, Alzheimer’s disease, APOE
, cerebral blood flow, cognition, cognitive decline, grey matter, magnetic resonance imaging, tau proteins
