Combating Age-Related Brain DeteriorationOctober 2011
By Eric R. Braverman, MD, with Dale Kiefer, BS
Strategies for Preserving and Enhancing Brain Function
Scientists recently published the results of a controlled trial that examined the effects of aerobic exercise on cognition and other biomarkers of Alzheimer’s disease among older adults diagnosed with mild cognitive impairment. Subjects were randomly assigned to engage in intensive aerobic exercise for 45 to 60 minutes per day, four days a week, for six months. Control subjects underwent supervised stretching sessions for equivalent periods, but did not engage in vigorous exercise. Results showed that aerobic exercise, but not simple stretching, acted as a “potent [non-drug-induced] intervention that improves executive control processes for older women at high risk of cognitive decline.”38 Another recent study conducted by the Mayo Clinic on more than 1,300 subjects concluded, “Any frequency of moderate exercise performed in midlife or late life was associated with a reduced odds of having mild cognitive impairment.”37
The benefits of exercise are achieved through a variety of mechanisms, including enhanced production of key neurotransmitters.43,44 As I note in my book Younger You: Unlock the Hidden Power of Your Brain to Look and Feel 15 Years Younger (McGraw-Hill, 2006), serotonin is an important brain chemical messenger associated with the regulation of mood and sleep. Deficiencies yield depression, fatigue, and poor sleep. Acetylcholine is a key neurotransmitter involved in cognition, memory, and learning. A deficit in acetylcholine, and its receptors, is associated with dementia and Alzheimer’s disease. Dopamine affects the body’s ability to regulate weight, experience pleasure, and feel energetic. When dopamine levels fall, obesity, addiction, and fatigue may result. Gamma-aminobutyric acid (GABA) is a crucial neurotransmitter that has a stabilizing effect on the brain’s other chemical messengers. GABA controls the brain’s rhythm, affecting one’s ability to handle stress and to function mentally and physically at a calm, steady pace.49
In addition to these four foundational neurotransmitters, studies have shown that exercise increases production of a substance known as brain-derived neurotrophic factor, which has been associated, at least in women, with enhanced cognitive function and brain plasticity.44,50-52 Exercise also encourages angiogenesis, or the formation of new blood supply structures. This is important for growing new brain cells and their supporting structures.50,53,54
The Power of Neurogenesis: New Brain Growth and Life
When I attended medical school, we learned that many types of cells regenerate more or less constantly throughout life; in essence, entire organs are eventually renewed as old cells are replaced. But the brain and central nervous system represented a notable exception. Brain cells are finite, we were told, and soon after birth the ability to grow and regenerate neurons is irrevocably lost. Furthermore, dogma held, the myriad pathways and connections among adult brain cells are “fixed and immutable,” incapable of further adaptation, and certainly incapable of new growth.
We now know this is incorrect.55-58 Research conducted since the 1970s has shown that the growth of new nerves (a process known as neurogenesis) does occur. This growth plays an important role in the brain’s plasticity, or ability to remodel, especially in key areas of the brain, such as the hippocampus, which is responsible for some of the most important higher cognitive functions, including memory and emotion. It’s no coincidence that Alzheimer’s disease strikes the hippocampus first, eroding long-term memory.
While the hippocampus is vulnerable to the ravages of Alzheimer’s disease, it also responds to better nutrition and increased exercise, thereby promoting neurogenesis. In fact, scientists are only beginning to fully appreciate the dramatic implications of this discovery, which may yield new treatments for conditions ranging from mental illness and addiction to age-associated declines in memory and cognition.55,59-62
Exercise Improves Sleep
One of the chief complaints among many of my elderly patients is poor sleep quality. Fortunately, exercise also improves sleep. And better sleep is also associated with increased neurogenesis in the adult brain.63 Conversely, poor sleep may restrict neurogenesis. By engaging in regular aerobic exercise you’ll sleep better, age more slowly and improve the architecture, and thus health, of your brain.
Robust Brain Function, Robust Libido
A healthy brain correlates with better mental acuity—but also better sex. There’s a common saying that “the brain is the greatest erogenous zone.” This is truer than most of us realize. When the brain is alive, so are the sex organs. I’ve treated patients who came to me complaining of multiple problems, including failing memory and declining cognition, not to mention poor sleep quality and sluggish libido. My patients have experienced remarkable success reversing these declines using treatments ranging from nutrients, to better dietary habits, to electrocranial stimulation, to bioidentical hormone replacement therapy. In some cases it is necessary to treat underlying conditions such as hypertension, which is a contributing factor in vascular dementia, before success is achieved. After treatment, patients experience improved memory, reasoning and intellect, and they have been known to rave about their reignited sex lives.
Maintaining youthful cognitive function is a crucial challenge of aging, both in terms of cognitive function and structural deterioration or “brain wasting.” Declining memory function may begin as early as age 30 and is often evident after 50 years of age. Fortunately, it is possible to take proactive steps to maintain youthful cognition with aging. Maintaining a healthy body weight and body fat percentage may help preserve healthy brain structure and function. Frail bones have been linked with cognitive decline in women. Hormonal balance may promote healthy cognitive function. Traumatic brain injury is a common yet overlooked cause of cognitive difficulties. Exercise increases blood flow to the brain and may decrease the risk of cognitive decline, while promoting healthy sleep. A healthy diet and extra nutritional support further enhance cognitive function.
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1. Bugg JM, Head D. Exercise moderates age-related atrophy of the medial temporal lobe. Neurobiol Aging. 2011 Mar;32(3):506-14.
2. Alzheimer’s Association. 2009 Alzheimer’s disease facts and figures. Alzheimers Dement. 2009 May;5(3):234-70.
3. Pavlović DM, Pavlović AM. Mild cognitive impairment. Srp Arh Celok Lek. 2009 Jul-Aug;137(7-8):434-9.
4. Pike KE, Savage G. Memory profiling in mild cognitive impairment: can we determine risk for Alzheimer’s disease? J Neuropsychol. 2008 Sep;2(Pt 2):361-72.
5. Swartz RH, Stuss DT et al. Independent cognitive effects of atrophy and diffuse subcortical and thalamico-cortical cerebrovascular disease in dementia. Stroke. 2008 Mar;39(3):822-30.
6. Braverman ER, Chen TJ, Prihoda TJ, et al. Plasma growth hormones, P300 event-related potential and test of variables of attention (TOVA) are important neuroendocrinological predictors of early cognitive decline in a clinical setting: evidence supported by structural equation modeling (SEM) parameter estimates. Age (Dordr). 2007 Sep;29(2-3):55-67.
7. Dahl A, Hassing LB, et al. Being overweight in midlife is associated with lower cognitive ability and steeper cognitive decline in late life. J Gerontol A Biol Sci Med Sci. 2010 Jan;65(1):57-62.
8. Raji CA, Ho AJ, et al. Brain structure and obesity. Hum Brain Mapp. 2010 Mar;31(3):353-64.
9. Geiger BM, Behr GG, et al. Evidence for defective mesolimbic dopamine exocytosis in obesity-prone rats. FASEB J. 2008 Aug;22(8):2740-6.
10. Geiger BM, Haburcak M, et al. Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity. Neuroscience. 2009 Apr 10;159(4):1193-9.
11. Margolin D, Hammerstad J, Orwoll E, McClung M, Calhoun D. Intracranial calcification in hyperparathyroidism associated with gait apraxia and parkinsonism. Neurology. 1980 Sep;30(9):1005-7.
12. Bilge I, Sadikoĝlu B, Emre S, Sirin A, Tatli B. Brain calcification due to secondary hyperparathyroidism in a child with chronic renal failure. Turk J Pediatr. 2005 Jul-Sep;47(3):287-90.
13. Vidal JS, Sigurdsson S, Jonsdottir MK, et al. Coronary artery calcium, brain function and structure: the AGES-Reykjavik Study. Stroke. 2010 May;41(5):891-7.
14. Lui LY, Stone K, Cauley JA, Hillier T, Jaffe K. Bone loss predicts subsequent cognitive decline in older women: the study of osteoporotic fractures. J Am Geriatr Soc. 2003 Jan; 51(1):38-43.
15. Braverman ER, Chen TJ, Chen AL, et al. Age-related increases in parathyroid hormone may be antecedent to both osteoporosis and dementia. BMC Endocr Disord. 2009 Oct 13;9:21.
16. Farrag AK, Khedr EM, et al. Effect of surgical menopause on cognitive functions. Dement Geriatr Cogn Disord. 2002;13(3):193-8.
17. Blum K, Sheridan PJ, Wood RC, et al. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. J R Soc Med. 1996 Jul;89(7):396-400.
18. Blum K, Chen AL, Chen TJ, et al. Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary. Theor Biol Med Model. 2008 Nov 12;5:24.
19. Blum K, Braverman ER, Holder JM, et al. Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors. J Psychoactive Drugs. 2000 Nov;32 Suppl:i-iv, 1-112.
20. Dowling GJ, Weiss SR, Condon TP. Drugs of abuse and the aging brain. Neuropsychopharmacology. 2008 Jan;33(2):209-18.
21. Colliver JD, Compton WM, Gfroerer JC, Condon T. Projecting drug use among aging baby boomers in 2020. Ann Epidemiol. 2006 Apr;16(4):257-65.
22. Pedraza C, García FB, Navarro JF. Neurotoxic effects induced by gammahydroxybutyric acid (GHB) in male rats. Int J Neuropsychopharmacol. 2009 Oct;12(9):1165-77.
23. Lecacheux M, Karila L, et al. Cognitive modifications associated with tobacco smoking. Presse Med. 2009 Sep;38(9):1241-52.
24. Banakar MK, Kudlur NS, George S. Fetal alcohol spectrum disorder (FASD). Indian J Pediatr. 2009 Nov;76(11):1173-5.
25. Loeber S, Duka T, Welzel H, et al. Impairment of cognitive abilities and decision making after chronic use of alcohol: the impact of multiple detoxifications. Alcohol Alcohol. 2009 Jul-Aug;44(4):372-81.
26. Majewska MD. Cocaine addiction as a neurological disorder: implications for treatment. NIDA Res Monogr. 1996;163:1-26.
27. Karila L, Lowenstein W, Coscas S, Benyamina A, Reynaud A. Complications of cocaine addiction. Rev Prat. 2009 Jun 20;59(6):825-9.
28. Jager G, Ramsey NF. Long-term consequences of adolescent cannabis exposure on the development of cognition, brain structure and function: an overview of animal and human research. Curr Drug Abuse Rev. 2008 Jun;1(2):114-23.
29. Indlekofer F, Piechatzek M, Daamen M, et al. Reduced memory and attention performance in a population-based sample of young adults with a moderate lifetime use of cannabis, ecstasy and alcohol. J Psychopharmacol. 2009 Jul;23(5):495-509.
30. Gruber SA, Silveri MM, Yurgelun-Todd DA. Neuropsychological consequences of opiate use. Neuropsychol Rev. 2007 Sep;17(3):299-315.
31. Cadet JL, Krasnova IN. Molecular bases of methamphetamine-induced neurodegeneration. Int Rev Neurobiol. 2009;88:101-19.
32. Available at: http://www.cdc.gov/ncipc/pub-res/tbi_in_us_04/tbi_ed.htm. Accessed July 12, 2011.
33. Langlois J, Rutland-Brown W, Wald M. The epidemiology and impact of traumatic brain injury: A brief overview. J Head Trauma Rehab. 2006;21(5):375-8.
34. Ainslie PN, Cotter JD, George KP, et al. Elevation in cerebral blood flow velocity with aerobic fitness throughout healthy human ageing. J Physiol. 2008 Aug 15;586(16):4005-10.
35. Deslandes A, Moraes H, Ferreira C, et al. Exercise and mental health: many reasons to move. Neuropsychobiology. 2009;59(4):191-8.
36. Crawford JG. Alzheimer’s disease risk factors as related to cerebral blood flow. Med Hypotheses. 1996 Apr;46(4):367-77.
37. Geda YE, Roberts RO, Knopman DS, et al. Physical exercise, aging, and mild cognitive impairment: a population-based study. Arch Neurol. 2010 Jan;67(1):80-6.
38. Baker LD, Frank LL, Foster-Schubert K, et al. Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol. 2010 Jan;67(1):71-9.
39. Clark PJ, Brzezinska WJ, Puchalski EK, Krone DA, Rhodes JS. Functional analysis of neurovascular adaptations to exercise in the dentate gyrus of young adult mice associated with cognitive gain. Hippocampus. 2009 Oct;19(10):937-50.
40. Van Praag H. Neurogenesis and exercise: past and future directions. Neuromolecular Med. 2008;10(2):128-40.
41. Fabel K, Kempermann G. Physical activity and the regulation of neurogenesis in the adult and aging brain. Neuromolecular Med. 2008;10(2):59-66.
42. Lautenschlager NT, Cox KL, Flicker L, et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA. 2008 Sep 3;300(9):1027-37.
43. Garraux G. Preserve brain function...through physical exercice? Rev Med Liege. 2008 May-Jun;63(5-6):293-8.
44. Ma Q. Beneficial effects of moderate voluntary physical exercise and its biological mechanisms on brain health. Neurosci Bull. 2008 Aug;24(4):265-70.
45. Lange-Asschenfeldt C, Kojda G. Alzheimer’s disease, cerebrovascular dysfunction and the benefits of exercise: from vessels to neurons. Exp Gerontol. 2008 Jun;43(6):499-504.
46. Linkis P, Jørgensen LG, Dynamic exercise enhances regional cerebral artery mean flow velocity. J Appl Physiol. 1995 Jan;78(1):12-6.
47. Yaffe K, Fiocco AJ, et al. Predictors of maintaining cognitive function in older adults: the Health ABC study. Neurology. 2009 Jun 9;72(23):2029-35.
48. Reichman WE. Nondegenerative dementing disorders. In: Coffey CE, Cummings JL, eds. The American Psychiatric Press Textbook of Geriatric Neuropsychiatry. 2nd ed. Washington, DC: American Psychiatric Press; 2000:491-507.
49. Braverman ER. Younger You: Unlock the Hidden Power of Your Brain to Look and Feel 15 Years Younger. New York, NY: McGraw-Hill; 2006.
50. Lista I, Sorrentino G. Biological mechanisms of physical activity in preventing cognitive decline. Cell Mol Neurobiol. 2010 May;30(4):493-503.
51. Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002 Jun;25(6):295-301.
52. Komulainen P, Pedersen M, Hanninen T, et al. BDNF is a novel marker of cognitive function in ageing women: the DR’s EXTRA Study. Neurobiol Learn Mem. 2008 Nov;90(4):596-603.
53. Van der Borght K, Kóbor-Nyakas DE, Klauke K, et al. Physical exercise leads to rapid adaptations in hippocampal vasculature: temporal dynamics and relationship to cell proliferation and neurogenesis. Hippocampus. 2009 Oct;19(10):928-36.
54. Pereira AC, Huddleston DE, Brickman AM, et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5638-43.
55. Balu DT, Lucki I. Adult hippocampal neurogenesis: regulation, functional implications, and contribution to disease pathology. Neurosci Biobehav Rev. 2009 Mar;33(3):232-52.
56. Elder GA, De Gasperi R, Gama Sosa MA. Research update: neurogenesis in adult brain and neuropsychiatric disorders. Mt Sinai J Med. 2006 Nov;73(7):931-40.
57. Paizanis E, Kelaï S, Renoi T, Hamon T, Lanfumey L. Life-long hippocampal neurogenesis: environmental, pharmacological and neurochemical modulations. Neurochem Res. 2007 Oct;32(10):1762-71.
58. Lee E, Son H. Adult hippocampal neurogenesis and related neurotrophic factors. BMB Rep. 2009 May 31;42(5):239-44.
59. Eisch AJ, Cameron HA, et al. Adult neurogenesis, mental health, and mental illness: hope or hype? J Neurosci. 2008 Nov 12;28(46):11785-91.
60. Kempermann G, Krebs J, Fabel K. The contribution of failing adult hippocampal neurogenesis to psychiatric disorders. Curr Opin Psychiatry. 2008 May;21(3):290-5.
61. Paizanis E, Kelai S, Renoir T, Hamon M, Lanfumey L. Life-long hippocampal neurogenesis: environmental, pharmacological and neurochemical modulations. Neurochem Res. 2007 Oct;32(10):1762-71.
62. Lazarov O, Mattson MP, Peterson DA, Pimplikar SW, van Praag H. When neurogenesis encounters aging and disease. Trends Neurosci. 2010 Dec;33(12):569-79.
63. Meerlo P, Mistlberger RE, et al. New neurons in the adult brain: the role of sleep and consequences of sleep loss. Sleep Med Rev. 2009 Jun;13(3):187-94.
64. Querido JS, Sheel AW. Regulation of cerebral blood flow during exercise. Sports Med. 2007;37(9):765-82.
65. Ploughman M. Exercise is brain food: the effects of physical activity on cognitive function. Dev Neurorehabil. 2008 Jul;11(3):236-40.
66. Floel A, Ruscheweyh R, Kruger K, et al. Physical activity and memory functions: Are neurotrophins and cerebral gray matter volume the missing link? Neuroimage. 2010 Feb 1;49(3):2756-63.
67. Takechi R, Galloway S, Pallebage-Gamarallage MM, Lam V, Mamo JC. Dietary fats, cerebrovasculature integrity and Alzheimer’s disease risk. Prog Lipid Res. 2009 Nov 5.
68. Lee Y, Back JH, Kim J. Systematic review of health behavioral risks and cognitive health in older adults. Int Psychogeriatr. 2010 Mar;22(2):174-87.
69. Pasinetti GM, Eberstein JA. Metabolic syndrome and the role of dietary lifestyles in Alzheimer’s disease. J Neurochem. 2008 Aug;106(4):1503-14.
70. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Mediterranean diet and health status: meta-analysis. BMJ. 2008 Sep 11;337:a1344.
71. Cole GM, Frautschy SA. DHA may prevent age-related dementia. J Nutr. 2010 Apr;140(4):869-74.
72. Shah K, Qureshi SU, Johnson M, Parikh M, Shulz PE, Kunik ME. Does use of antihypertensive drugs affect the incidence or progression of dementia? A systematic review. Am J Geriatr Pharmacother. 2009 Oct;7(5):250-61.
73. Castro JE, Varea E, Marquez C, Cordero MI, Poirier G, Sandi C. Role of the amygdala in antidepressant effects on hippocampal cell proliferation and survival and on depression-like behavior in the rat. PLoS One. 2010 Jan 8;5(1):e8618.
74. Boldrini M, Underwood MD, Hen R, et al. Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacology. 2009 Oct;34(11):2376-89.