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

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.

Neurocognition in treatment-resistant hypertension: profile and associations with cardiovascular biomarkers.

BACKGROUND: Hypertension in midlife has been associated with increased risk of stroke and neurocognitive decline. Few studies, however, have examined neurocognition among individuals with treatment-resistant hypertension or potential mechanisms by which treatment-resistant hypertension may impair neurocognition. METHODS: We examined the pattern of neurocognitive impairment and potential mechanisms in a sample of 96 overweight adults with treatment-resistant hypertension, aged 41-81 years. Neurocognitive function was assessed using a 45-min test battery consisting of executive function and memory. Vascular and metabolic mechanisms examined included cerebrovascular risk factors (CVRFs: Framingham Stroke Risk Profile), insulin sensitivity (homeostatic model assessment of insulin resistance), waist-to-hip ratio, microvascular function (hyperemic response), and peak oxygen consumption from an exercise treadmill test. Simple path analyses were used to assess the association between potential vascular and metabolic mechanisms and neurocognition. RESULTS: Neurocognitive impairments were common, with 70% of the sample exhibiting impaired performance on at least one executive function subtest and 38% on at least one measure of memory. Higher levels of aerobic fitness, greater insulin sensitivity, and better microvascular function, as well as lower CVRFs and waist-to-hip ratio were associated with better neurocognition. In path analyses, aerobic fitness, microvascular function, and CVRFs all were independently associated with neurocognitive performance. Insulin resistance associated with worse executive function but better memory performance among older participants. CONCLUSION: Neurocognitive impairments are common in adults with treatment-resistant hypertension, particularly on tests of executive function. Better neurocognition is independently associated with aerobic fitness, microvascular function, and CVRFs.