Metabolic and Neurocognitive Changes Following Lifestyle Modification: Examination of Biomarkers from the ENLIGHTEN Randomized Clinical Trial

Article type: Research Article

Authors: Smith, Patrick J.^{a; *} | Mabe, Stephanie M.^a | Sherwood, Andrew^a | Doraiswamy, P. Murali^a | Welsh-Bohmer, Kathleen A.^a | Burke, James R.^b | Kraus, William E.^c | Lin, Pao-Hwa^c | Browndyke, Jeffrey N.^a | Babyak, Michael A.^a | Hinderliter, Alan L.^d | Blumenthal, James A.^a

Affiliations: [a] Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA | [b] Department of Neurology, Duke University Medical Center, Durham, NC, USA | [c] Department of Medicine, Duke University Medical Center, Durham, NC, USA | [d] Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Correspondence: [*] Correspondence to: Patrick J. Smith, PhD, MPH, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. Tel.: +1 919 684 3006; Fax: +1 919 684 8629; E-mail: patrick.j.smith@dm.duke.edu.

Abstract: Background:Previous studies have demonstrated that aerobic exercise (AE) and the Dietary Approaches to Stop Hypertension (DASH) diet can improve neurocognition. However, the mechanisms by which lifestyle improves neurocognition have not been widely studied. We examined the associations between changes in metabolic, neurotrophic, and inflammatory biomarkers with executive functioning among participants from the Exercise and Nutritional Interventions for Neurocognitive Health Enhancement (ENLIGHTEN) trial. Objective:To examine the association between changes in metabolic function and neurocognition among older adults with cognitive impairment, but without dementia (CIND) participating in a comprehensive lifestyle intervention. Methods:ENLIGHTEN participants were randomized using a 2×2 factorial design to receive AE, DASH, both AE+DASH, or a health education control condition (HE) for six months. Metabolic biomarkers included insulin resistance (homeostatic model assessment [HOMA-IR]), leptin, and insulin-like growth factor (IGF-1); neurotrophic biomarkers included brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF); and inflammatory biomarkers included interleukin-6 (IL-6) and C-Reactive Protein (CRP). Results:Participants included 132 sedentary older adults (mean age = 65 [SD = 7]) with CIND. Results demonstrated that both AE (d = 0.48, p = 0.015) and DASH improved metabolic function (d = 0.37, p = 0.039), without comparable improvements in neurotrophic or inflammatory biomarkers. Greater improvements in metabolic function, including reduced HOMA-IR (B = –2.3 [–4.3, –0.2], p = 0.033) and increased IGF-1 (B = 3.4 [1.2, 5.7], p = 0.004), associated with increases in Executive Function. Conclusion:Changes in neurocognition after lifestyle modification are associated with improved metabolic function.

Keywords: Aerobic exercise, CIND, DASH diet, executive function, lifestyle modification, metabolic function, vascular risk factors

DOI: 10.3233/JAD-200374

Journal: Journal of Alzheimer's Disease, vol. 77, no. 4, pp. 1793-1803, 2020