Authors: Shinto, Lynne | Lahna, David | Murchison, Charles F. | Dodge, Hiroko | Hagen, Kirsten | David, Jason | Kaye, Jeffrey | Quinn, Joseph F. | Wall, Rachel | Silbert, Lisa C.
Article Type: Research Article
Abstract: Background: Cerebrovascular disease is a common cause of dementia in older adults, and potentially preventable with early intervention. Oxylipins are produced from the oxidation of long-chain polyunsaturated fatty acids (PUFA) possessing potent vascular effects. Oxylipins generated from the cytochrome P450 pathway are enzymatically converted to diols by soluble epoxide hydrolase (sEH); sEH products have been associated with small vessel ischemic disease. Little is known about oxylipins’ impact on markers of dementia risk. Objective: An exploratory examination of the association between omega-6 and omega-3 derived oxylipins, brain MRI, and cognition. Methods: Thirty-seven non-demented participants with controlled hypertension (mean age 65.6 years) …were enrolled in a dementia prevention study investigating fish oil and lipoic acid on preserving cognitive function. Baseline associations between plasma oxylipins, white matter hyperintensity (WMH), and Trails-B were examined using linear regression. P450-derived diol/epoxide ratio was an indirect measure of sEH activity. Results: Omega-6 derived 9-HODE was associated with increased WMH (p = 0.017) and reduced grey matter volume (p = 0.02). Omega-6 P450-derived diol/epoxide ratio 9,10-DiHOME/9,10-EpOME was associated with increased WMH (p = 0.035) and poorer performance on Trails-B (p = 0.05); ratio14,15-DHET/14,15-EET was associated with increased WMH (p = 0.045). Omega-3 P450-derived diol/epoxide ratio 19,20-DiHDPE/19,20-EpDPE was associated with increased WMH (p = 0.04) and poorer performance on Trails-B (p = 0.04). Arachidonic acid was associated with better performance on Trails-B (p = 0.012); Omega-3 derived 16,17-EpDPE was associated with decreased WMH (p = 0.005). Conclusions: With the exception of arachidonic acid, it was specific oxylipin products, not their parent PUFAs, that were associated with unfavorable and favorable MRI and cognitive markers of dementia risk. Show more
Keywords: Alzheimer’s disease, cross-sectional studies, fatty acids, humans, oxylipins, vascular dementia
DOI: 10.3233/JAD-191197
Citation: Journal of Alzheimer's Disease, vol. 74, no. 1, pp. 65-77, 2020
Authors: Silbert, Lisa C. | Lahna, David | Promjunyakul, Nutta-on | Boespflug, Erin | Ohya, Yusuke | Higashiuesato, Yasushi | Nishihira, Junko | Katsumata, Yuriko | Tokashiki, Takashi | Dodge, Hiroko H.
Article Type: Research Article
Abstract: Background: Cortical gray matter (GM) and white matter (WM) deterioration are signals of neurodegeneration and increased dementia risk; however, their specific etiologies in dementia-free aging is unclear. Objective: The objective of this study was to examine potentially modifiable risk factors of GM and WM degeneration in a well-characterized cohort of dementia-free elderly. Methods: 96 Okinawan elderly participants (age 83.6) from the Keys to Optimal Cognitive Aging Project (KOCOA) underwent MRI and cognitive evaluation. Serum markers of inflammation (interleukin-6 (IL-6), high sensitivity C-reactive protein), cerebrovascular disease (systolic blood pressure (SBP) 140+, hemoglobin A1C (HgbA1C), total cholesterol), and essential minerals (copper (Cu), …magnesium, and calcium) were examined in relation to mean cortical thickness (MCT) and white matter hyperintensities (WMH), adjusting for age and gender. Voxel-based morphometry (VBM) analyses identified relationships between regional GM density and the above markers. Results: Decreased MCT was associated with SBP 140 + (p = 0.029) and increased serum IL-6 (p = 0.036), HgbA1C (p = 0.002), and Cu (p = 0.025). In VBM analyses, increased IL-6, HgbA1C, and Cu were associated with decreased GM density in temporal lobe regions. HgbA1C (p = 0.004) was associated with greater WMH volume. Conclusions: Peripheral markers of Cu, CVD risk, and inflammation are associated with MRI-markers of decreased brain health in dementia-free Okinawan elderly, with regional cortical thinning in areas involved in early accumulation of Alzheimer’s disease pathology. Results identify potentially modifiable biomarkers as targets in the prevention of dementia in older individuals. Show more
Keywords: Aging, Alzheimer’s disease, atrophy, brain, cerebrovascular disorders, cognitive aging, copper, inflammation, magnetic resonance imaging, micronutrients, vascular disease
DOI: 10.3233/JAD-171153
Citation: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 365-372, 2018
Authors: Silbert, Lisa C. | Dodge, Hiroko H. | Lahna, David | Promjunyakul, Nutta-on | Austin, Daniel | Mattek, Nora | Erten-Lyons, Deniz | Kaye, Jeffrey A.
Article Type: Research Article
Abstract: Background: Computer use is becoming a common activity in the daily life of older individuals and declines over time in those with mild cognitive impairment (MCI). The relationship between daily computer use (DCU) and imaging markers of neurodegeneration is unknown. Objective: The objective of this study was to examine the relationship between average DCU and volumetric markers of neurodegeneration on brain MRI. Methods: Cognitively intact volunteers enrolled in the Intelligent Systems for Assessing Aging Change study underwent MRI. Total in-home computer use per day was calculated using mouse movement detection and averaged over a one-month period surrounding the MRI. Spearman’s …rank order correlation (univariate analysis) and linear regression models (multivariate analysis) examined hippocampal, gray matter (GM), white matter hyperintensity (WMH), and ventricular cerebral spinal fluid (vCSF) volumes in relation to DCU. A voxel-based morphometry analysis identified relationships between regional GM density and DCU. Results: Twenty-seven cognitively intact participants used their computer for 51.3 minutes per day on average. Less DCU was associated with smaller hippocampal volumes (r = 0.48, p = 0.01), but not total GM, WMH, or vCSF volumes. After adjusting for age, education, and gender, less DCU remained associated with smaller hippocampal volume (p = 0.01). Voxel-wise analysis demonstrated that less daily computer use was associated with decreased GM density in the bilateral hippocampi and temporal lobes. Conclusions: Less daily computer use is associated with smaller brain volume in regions that are integral to memory function and known to be involved early with Alzheimer’s pathology and conversion to dementia. Continuous monitoring of daily computer use may detect signs of preclinical neurodegeneration in older individuals at risk for dementia. Show more
Keywords: Alzheimer’s disease, assessment of cognitive disorders/dementia, cognitive aging, MRI, volumetric MRI
DOI: 10.3233/JAD-160079
Citation: Journal of Alzheimer's Disease, vol. 52, no. 2, pp. 713-717, 2016
