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Vascular Functions and Brain Integrity in Midlife: Effects of Obesity and Metabolic Syndrome

DOI: 10.1155/2014/653482

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Intact cognitive function is the best predictor of quality of life and functional ability in older age. Thus, preventing cognitive decline is central to any effort to guarantee successful aging for our growing population of elderly. The purpose of the work discussed in this outlook paper is to bridge knowledge from basic and clinical neuroscience with the aim of improving how we understand, predict, and treat age- and disease-related cognitive impairment. Over the past six years, our research team has focused on intermediate neuroimaging phenotypes of brain vulnerability in midlife and isolating the underlying physiological mechanisms. The ultimate goal of this work was to pave the road for the development of early interventions to enhance cognitive function and preserve brain integrity throughout the lifespan. 1. Introduction The most rapidly rising threat to brain health in US adults is the clustering of obesity, high blood pressure, elevated fasting glucose, and abnormal lipid metabolism in a single individual, a condition known as metabolic syndrome. A staggering 34–45% of US adults currently fulfill criteria for metabolic syndrome [1]. These numbers are alarming as metabolic syndrome is associated not only with increased risk for cardiovascular disease and diabetes [2], but also with current cognitive dysfunction and risk for future cognitive decline, over and above the detrimental effects of its components [3–10]. While we have some information about each of the disrupted peripheral physiological mechanisms in turn, very little is known about the central mechanisms that connect metabolic syndrome to brain health and cognition. The goal of our work over the past six years has been to explore the underlying neural mechanisms of midlife brain vulnerability related to peripheral vascular and metabolic disturbances, before clinically significant and permanent cognitive dysfunction has developed. Understanding the preclinical stages of disease has the enormous advantage of presenting opportunities for early intervention, a task with much higher prospect of success than attempting to restore lost function later in life. Early identification of brain vulnerability is crucial; yet it presents a significant challenge due to the low sensitivity of clinical paper-and-pencil measures of cognitive impairment and lack of norms for tests with higher ceiling performance values. Our team has endeavored to solve this problem through combining sophisticated behavioral analyses with modern neuroimaging techniques. 2. Early Markers of Brain Vulnerability As noted

References

[1]  R. B. Ervin, “Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003–2006,” National Health Statistics Reports, no. 13, pp. 1–7, 2009.
[2]  K. G. M. M. Alberti, R. H. Eckel, S. M. Grundy et al., “Harmonizing the metabolic syndrome: A joint interim statement of the international diabetes federation task force on epidemiology and prevention; National heart, lung, and blood institute; American heart association; World heart federation; International atherosclerosis society; And international association for the study of obesity,” Circulation, vol. 120, no. 16, pp. 1640–1645, 2009.
[3]  T. N. Akbaraly, M. Kivimaki, M. J. Shipley et al., “Metabolic syndrome over 10 years and cognitive functioning in late midlife: the Whitehall II study,” Diabetes Care, vol. 33, no. 1, pp. 84–89, 2010.
[4]  S. Kalmijn, D. Foley, L. White et al., “Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men: the Honolulu-Asia aging study,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 10, pp. 2255–2260, 2000.
[5]  K. Yaffe, M. Haan, T. Blackwell, E. Cherkasova, R. A. Whitmer, and N. West, “Metabolic syndrome and cognitive decline in elderly latinos: findings from the Sacramento Area Latino Study of Aging Study,” Journal of the American Geriatrics Society, vol. 55, no. 5, pp. 758–762, 2007.
[6]  K. Yaffe, A. L. Weston, T. Blackwell, and K. A. Krueger, “The metabolic syndrome and development of cognitive impairment among older women,” Archives of Neurology, vol. 66, no. 3, pp. 324–328, 2009.
[7]  N. M. Gatto, V. W. Henderson, J. A. St. John, C. McCleary, H. N. Hodis, and W. J. Mack, “Metabolic syndrome and cognitive function in healthy middle-aged and older adults without diabetes,” Aging, Neuropsychology, and Cognition, vol. 15, no. 5, pp. 627–641, 2008.
[8]  M. G. Dik, C. Jonker, H. C. Comijs et al., “Contribution of metabolic syndrome components to cognition in older individuals,” Diabetes Care, vol. 30, no. 10, pp. 2655–2660, 2007.
[9]  M. Vanhanen, K. Koivisto, L. Moilanen et al., “Association of metabolic syndrome with Alzheimer disease: a population-based study,” Neurology, vol. 67, no. 5, pp. 843–847, 2006.
[10]  C. Raffaitin, H. Gin, J.-P. Empana et al., “Metabolic syndrome and risk for incident alzheimer's disease or vascular dementia,” Diabetes Care, vol. 32, no. 1, pp. 169–174, 2009.
[11]  M. M. Gonzales, T. Tarumi, H. Tanaka et al., “Functional imaging of working memory and peripheral endothelial function in middle-aged adults,” Brain and Cognition, vol. 73, no. 2, pp. 146–151, 2010.
[12]  M. M. Gonzales, T. Tarumi, S. C. Miles, H. Tanaka, F. Shah, and A. P. Haley, “Insulin sensitivity as a mediator of the relationship between BMI and working memory-related brain activation,” Obesity, vol. 18, no. 11, pp. 2131–2137, 2010.
[13]  M. M. Gonzales, T. Tarumi, D. E. Eagan, H. Tanaka, M. Vaghasia, and A. P. Haley, “Indirect effects of elevated body mass index on memory performance through altered cerebral metabolite concentrations,” Psychosomatic Medicine, vol. 74, no. 7, pp. 691–698, 2012.
[14]  A. P. Haley, M. M. Gonzales, T. Tarumi, and H. Tanaka, “Dyslipidemia links obesity to early cerebral neurochemical alterations,” Obesity, vol. 21, no. 10, pp. 2007–2013, 2013.
[15]  S. Y. Bookheimer, M. H. Strojwas, M. S. Cohen et al., “Patterns of brain activation in people at risk for Alzheimer's disease,” New England Journal of Medicine, vol. 343, no. 7, pp. 450–456, 2000.
[16]  L. Chang, O. Speck, E. N. Miller et al., “Neural correlates of attention and working memory deficits in HIV patients,” Neurology, vol. 57, no. 6, pp. 1001–1007, 2001.
[17]  A. J. Saykin, L. A. Flashman, S. A. Frutiger et al., “Neuroanatomic substrates of semantic memory impairment in Alzheimer's disease: patterns of functional MRI activation,” Journal of the International Neuropsychological Society, vol. 5, no. 5, pp. 377–392, 1999.
[18]  L. H. Sweet, S. M. Rao, M. Primeau, S. Durgerian, and R. A. Cohen, “Functional magnetic resonance imaging response to increased verbal working memory demands among patients with multiple sclerosis,” Human Brain Mapping, vol. 27, no. 1, pp. 28–36, 2006.
[19]  L. H. Sweet, S. M. Rao, M. Primeau, A. R. Mayer, and R. A. Cohen, “Functional magnetic resonance imaging of working memory among multiple sclerosis patients,” Journal of Neuroimaging, vol. 14, no. 2, pp. 150–157, 2004.
[20]  S. Ogawa, T. M. Lee, A. R. Kay, and D. W. Tank, “Brain magnetic resonance imaging with contrast dependent on blood oxygenation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 24, pp. 9868–9872, 1990.
[21]  R. Cabeza, N. D. Anderson, J. K. Locantore, and A. R. McIntosh, “Aging gracefully: compensatory brain activity in high-performing older adults,” NeuroImage, vol. 17, no. 3, pp. 1394–1402, 2002.
[22]  A. P. Haley, J. Gunstad, R. A. Cohen, B. A. Jerskey, R. C. Mulligan, and L. H. Sweet, “Neural correlates of visuospatial working memory in healthy young adults at risk for hypertension,” Brain Imaging and Behavior, vol. 2, no. 3, pp. 192–199, 2008.
[23]  L. H. Sweet, J. F. Paskavitz, A. P. Haley et al., “Imaging phonological similarity effects on verbal working memory,” Neuropsychologia, vol. 46, no. 4, pp. 1114–1123, 2008.
[24]  M. M. Gonzales, T. Tarumi, D. E. Eagan, H. Tanaka, F. O. Biney, and A. P. Haley, “Current serum lipoprotein levels and fMRI response to working memory in midlife,” Dementia and Geriatric Cognitive Disorders, vol. 31, no. 4, pp. 259–267, 2011.
[25]  K. F. Hoth, M. M. Gonzales, T. Tarumi, S. C. Miles, H. Tanaka, and A. P. Haley, “Functional MR imaging evidence of altered functional activation in metabolic syndrome,” The American Journal of Neuroradiology, vol. 32, no. 3, pp. 541–547, 2011.
[26]  A. P. Haley, D. E. Eagan, M. M. Gonzales, F. O. Biney, and R. A. Cooper, “Functional magnetic resonance imaging of working memory reveals frontal hypoactivation in middle-aged adults with cognitive complaints,” Journal of the International Neuropsychological Society, vol. 17, no. 5, pp. 915–924, 2011.
[27]  T. D. Wager and E. E. Smith, “Neuroimaging studies of working memory: a meta-analysis,” Cognitive, Affective and Behavioral Neuroscience, vol. 3, no. 4, pp. 255–274, 2003.
[28]  B. Segura, M. á. Jurado, N. Freixenet, C. Albuin, J. Muniesa, and C. Junqué, “Mental slowness and executive dysfunctions in patients with metabolic syndrome,” Neuroscience Letters, vol. 462, no. 1, pp. 49–53, 2009.
[29]  R. A. Cohen, A. Poppas, D. E. Forman et al., “Vascular and cognitive functions associated with cardiovascular disease in the elderly,” Journal of Clinical and Experimental Neuropsychology, vol. 31, no. 1, pp. 96–110, 2009.
[30]  A. P. Haley, L. H. Sweet, J. Gunstad et al., “Verbal working memory and atherosclerosis in patients with cardiovascular disease: an fMRI study,” Journal of Neuroimaging, vol. 17, no. 3, pp. 227–233, 2007.
[31]  J. D. Ragland, B. I. Turetsky, R. C. Gur et al., “Working memory for complex figures: an fMRI comparison of letter and fractal n-back tasks,” Neuropsychology, vol. 16, no. 3, pp. 370–379, 2002.
[32]  E. R. Danielsen and B. Ross, Magnetic Resonance Spectroscopy Diagnosis of Neurological Diseases, Marcel Dekker, New York, NY, USA, 1999.
[33]  B. D. Ross, “Biochemical considerations in 1H spectroscopy. Glutamate and glutamine; myo-inositol and related metabolites,” NMR in Biomedicine, vol. 4, no. 2, pp. 59–63, 1991.
[34]  M. Erecińska and I. A. Silver, “Metabolism and role of glutamate in mammalian brain,” Progress in Neurobiology, vol. 35, no. 4, pp. 245–296, 1990.
[35]  G. T. Berry, Z. J. Wang, S. F. Dreha, B. M. Finucane, and R. A. Zimmerman, “In vivo brain myo-inositol levels in children with Down syndrome,” Journal of Pediatrics, vol. 135, no. 1, pp. 94–97, 1999.
[36]  K. Kantarci, C. R. Jack Jr., Y. C. Xu et al., “Regional metabolic patterns in mild cognitive impairment and Alzheimer's disease: a 1H MRS study,” Neurology, vol. 55, no. 2, pp. 210–217, 2000.
[37]  G. Helms, C. Ciumas, S. Kyaga, and I. Savic, “Increased thalamus levels of glutamate and glutamine (Glx) in patients with idiopathic generalised epilepsy,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 77, no. 4, pp. 489–494, 2006.
[38]  Y. Pu, Q.-F. Li, C.-M. Zeng et al., “Increased detectability of alpha brain glutamate/glutamine in neonatal hypoxic-ischemic encephalopathy,” The American Journal of Neuroradiology, vol. 21, no. 1, pp. 203–212, 2000.
[39]  A. P. Haley, T. Tarumi, M. M. Gonzales, J. Sugawara, and H. Tanaka, “Subclinical atherosclerosis is related to lower neuronal viability in middle-aged adults: a 1H MRS study,” Brain Research, vol. 1344, pp. 54–61, 2010.
[40]  D. E. Eagan, M. M. Gonzales, T. Tarumi, H. Tanaka, S. Stautberg, and A. P. Haley, “Elevated serum C-reactive protein relates to increased cerebral myoinositol levels in middle-aged adults,” Cardiovascular Psychiatry and Neurology, vol. 2012, Article ID 120540, 9 pages, 2012.
[41]  A. P. Haley, M. M. Gonzales, T. Tarumi, and H. Tanaka, “Subclinical vascular disease and cerebral glutamate elevation in metabolic syndrome,” Metabolic Brain Disease, vol. 27, no. 4, pp. 513–520, 2012.
[42]  A. P. Haley, M. M. Gonzales, T. Tarumi, S. C. Miles, K. Goudarzi, and H. Tanaka, “Elevated cerebral glutamate and myo-inositol levels in cognitively normal middle-aged adults with metabolic syndrome,” Metabolic Brain Disease, vol. 25, no. 4, pp. 397–405, 2010.
[43]  I.-K. Penner, M. Rausch, L. Kappos, K. Opwis, and E. W. Radü, “Analysis of impairment related functional architecture in MS patients during performance of different attention tasks,” Journal of Neurology, vol. 250, no. 4, pp. 461–472, 2003.
[44]  W. Staffen, A. Mair, H. Zauner et al., “Cognitive function and fMRI in patients with multiple sclerosis: evidence for compensatory cortical activation during an attention task,” Brain, vol. 125, no. 6, pp. 1275–1282, 2002.
[45]  M. M. Gonzales, T. Tarumi, J. A. Mumford et al., “Greater BOLD response to working memory in endurance-trained adults revealed by breath-hold calibration,” Human Brain Mapping, vol. 35, no. 7, pp. 2898–2910, 2013.
[46]  G. F. Fletcher, G. Balady, S. N. Blair et al., “Statement on exercise: benefits and recommendations for physical activity programs for all Americans: a statement for health professionals by the committee on exercise and cardiac rehabilitation of the Council on Clinical Cardiology, American Heart Association,” Circulation, vol. 94, no. 4, pp. 857–862, 1996.
[47]  J. L. Etnier, W. Salazar, D. M. Landers, S. J. Petruzzello, M. Han, and P. Nowell, “The influence of physical fitness and exercise upon cognitive functioning: a meta-analysis,” Journal of Sport and Exercise Psychology, vol. 19, no. 3, pp. 249–277, 1997.
[48]  M. M. Gonzales, T. Tarumi, S. Kaur et al., “Aerobic fitness and the brain: increased N-acetyl-aspartate and choline concentrations in endurance-trained middle-aged adults,” Brain Topography, vol. 26, no. 1, pp. 126–134, 2013.
[49]  T. Tarumi, M. M. Gonzales, B. Fallow et al., “Central artery stiffness, neuropsychological function, and cerebral perfusion in sedentary and endurance-trained middle-aged adults,” Journal of Hypertension, vol. 31, no. 12, pp. 2400–2409, 2013.
[50]  T. Tarumi, M. M. Gonzales, B. Fallow et al., “Aerobic fitness and cognitive function in midlife: an association mediated by plasma insulin,” Metabolic Brain Disease, vol. 28, no. 4, pp. 727–730, 2013.
[51]  T. W. Buford, M. D. Roberts, and T. S. Church, “Toward exercise as personalized medicine,” Sports Medicine, vol. 43, no. 3, pp. 157–165, 2013.
[52]  F. Gonzalez-Lima, B. R. Barksdale, and J. C. Rojas, “Mitochondrial respiration as a target for neuroprotection and cognitive enhancement,” Biochemical Pharmacology, vol. 88, no. 4, pp. 584–593, 2014.
[53]  J. C. Rojas and F. Gonzalez-Lima, “Low-level light therapy of the eye and brain,” Eye and Brain, vol. 3, pp. 49–67, 2011.
[54]  J. C. Rojas and F. Gonzalez-Lima, “Neurological and psychological applications of transcranial lasers and LEDs,” Biochemical Pharmacology, vol. 86, no. 4, pp. 447–457, 2013.
[55]  A. M. Fulop, S. Dhimmer, J. R. Deluca et al., “A meta-analysis of the efficacy of laser phototherapy on pain relief,” Clinical Journal of Pain, vol. 26, no. 8, pp. 729–736, 2010.
[56]  D. W. Barrett and F. Gonzalez-Lima, “Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans,” Neuroscience, vol. 230, pp. 13–23, 2013.

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