Affiliations: [a]
Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
| [b]
Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
| [c] Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA
| [d] Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA
Correspondence:
[*]
Correspondence to: Dr. Ira Driscoll, Department of Psychology, University of Wisconsin-Milwaukee, 2441 E Hartford Ave, Milwaukee, WI 53211, USA. Tel.: +1 414 229 6665; E-mail: driscoli@uwm.edu.
Abstract: Background:Disease-modifying treatments for Alzheimer’s disease (AD) may be more successful if interventions occur early, prior to significant neurodegeneration and subsequent to the onset of clinical symptoms, potentially during middle age. Polymorphisms within BDNF, COMT, and KIBRA have been implicated in AD and relate to episodic memory and executive functioning, two domains that decline early in AD. Objective:The purpose of the current study was to use an endophenotype approach to examine in healthy, non-demented middle-aged adults the association between polymorphisms in BDNF, COMT, and KIBRA and functional connectivity within networks related to episodic memory and executive function (i.e., default mode network (DMN), executive control network (ECN), and frontoparietal network (FPN)). Methods:Resting state networks were identified using independent component analysis and spatial maps with associated time courses were extracted using a dual regression approach. Results:Functional connectivity within the DMN was associated with polymorphisms in BDNF (rs11030096, rs1491850) and KIBRA (rs1030182, rs6555791, rs6555802) (ps < 0.05), ECN connectivity was associated with polymorphisms in KIBRA (rs10475878, rs6555791) (ps < 0.05), and FPN connectivity was associated with KIBRA rs6555791 (p < 0.05). There were no COMT-related differences in functional connectivity of any of the three networks investigated (ps > 0.05). Conclusion:Our study demonstrates that in middle age, polymorphisms in BDNF and KIBRA are associated with altered functional connectivity in networks that are affected early in AD. Future preclinical work should consider these polymorphisms to further elucidate their role in pathological aging and to aid in the identification of biomarkers.
