HOW DOES THE BRAIN WORK?
The human brain is made up of 100 billion specialized cells called neurons (1). These neurons receive neurochemical signals through branch-like structures called dendrites. The main body of the cell then processes these signals and provides the energy, proteins, and chemicals necessary to relay additional signals. These additional signals are passed down axons as electrical impulses until they reach terminals. The terminals respond, in turn, by releasing neurochemicals (2).
Neurons can live for more than 100 years. As a result, they must constantly maintain and repair themselves. For this purpose, the brain also contains about 40-130 billion supporting cells called neuroglia (3). These cells clear away cellular debris, provide nutrients to and insulate the neurons, support the blood-brain barrier, and protect against pathogens (4).
WHAT HAPPENS TO THE BRAIN AS WE AGE?
As we age, changes in our brains can affect our cognitive ability. These age-associated changes are generally the result of one of two things:
- The natural maturation process (referred to as normal aging)
- Non-normative factors like disease or trauma (referred to as pathological aging) (5,6)
Both kinds of aging are associated with structural (7), chemical (8,9), physiological (10,11,12), and genetic (13,14,15) changes in the brain.
Defining the line between normal brain aging and pathological brain aging is difficult, and it is not yet entirely clear where one ends and the other begins. Generally, the following occurs as the brain ages.
- Reduced blood flow and decreased vasculature in certain areas of the brain. Damage to brain vasculature and to the blood-brain barrier are also common, but these are regarded as pathological changes (i.e. from high blood pressure etc.)
- Decreased glucose uptake and reduced glucose transportation (i.e. by insulin-sensitive transporters)
- Increased mitochondrial dysfunction and damage
- Increased reactive oxygen species and subsequent oxidative stress
- DNA damage in neurons and mitochondria
- Increased inflammation of the brain
- Certain neurochemicals and neurochemical receptors also decrease in the aging brain (7,8,9,10,11,12,13,14,15)
RISK FACTORS FOR AN AGING BRAIN
- Increased age
- Low education
- Medical conditions like diabetes, hypertriglyceridemia, or hypertension
- Excessive alcohol intake or smoking
- Limited physical activity
- Poor diet
- Chronic inflammation (16,17,18,19)
SYMPTOM OF AN AGING BRAIN
The symptoms are generally the same whether normal or pathological aging occurs. However, symptoms in pathological aging are generally more severe.
- Reduced ability to tune out or ignore irrelevant information
- Difficulty multitasking
- Difficulty processing and learning new information
- Increased difficulty finding words and recalling names
- Mild decreases in the ability to pay attention
- Slower processing speed (20,21)
AGING BRAIN FACTS AND STATISTICS
It has been estimated that the number of Americans over the age of 65 will double between 2010 and 2030 compared to the year 2000. By 2030 there will be about 72.1 million seniors in the United States which is twice the number from 2007 (22).
According to the United Nations, 1 out of every 10 people globally is age 60 or older, and the United Nations predicts that this number will grow to 1 in 5 by 2050 and 1 in 3 by 2150 (23).
The brain loses about 0.2-0.5% of its weight or volume every year after age 40. Age-related decline in volume is not uniform across the brain and certain regions seem to shrink at a faster rate than others (24).
Alzheimer’s is the most common cause of dementia among older adults. In 2013 an estimated 5 million Americans were living with Alzheimer’s disease. The number of people living with Alzheimer’s doubles every 5 years beyond age 65 (25)
MEDICAL TREATMENT OF AN AGING BRAIN
Treatment depends on what type of aging occurs. There is little treatment for those who experience normal aging. However, treatment of pathological aging varies greatly based on what disease someone is experiencing (26).
The following medications are usually prescribed for the diseases below:
- Alzheimer’s disease: Cholinesterase inhibitors sold under trade names Aricept, Exelon, and Razadyne, as well as memantine which is sold under the trade name Namenda, are prescribed to treat the cognitive symptoms of Alzheimer’s disease. Cholinesterase inhibitors are usually prescribed for the early stages of the disease, while memantine is prescribed for the later stages of the disease (27).
- Parkinson’s disease: Levodopa is the single most effective medication to treat the symptoms of Parkinson’s disease, but not the disease itself (28).
- Huntington’s disease: Tetrabenazine, Haloperidol, and Chlorpromazine are usually prescribed to suppress certain involuntarily movements, hence their primary role is to suppress the symptoms and not cure the disease. At this point, no medication for the treatment of the disease is identified (29,30,31).
NATURAL WAYS TO SUPPORT AN AGING BRAIN
Practices to Help Support an Aging Brain:
- Education: The most important and widely agreed upon item is education (32,33) and staying mentally active into years of elder life (34). Education has been shown to slow down age-related cortical thinning which in turn affects many cognitive functions (33).
- Physical activity: Exercise is another important factor which leads to increasing the neuroplasticity in the brain and hence improve cognitive function such as working memory, reasoning, response time and task switching (35,36,37,38). Physical exercise, when paired with mental exercise was shown to help increase the amount of gray matter and hence improve cognitive functions with a different mechanism (39,40). In fact, even in elderly with a sedentary lifestyle, short-term aerobic exercise is shown to boost cognitive performance (41). Exercise is also shown to fight neurodegenerative disease in early stages (42).
- Training: Brain training for certain cognitive function was shown to improve that function in long-term. Examples of such cognitive functions are selective attention and auditory attention (43).
- Early screening for neurodegenerative disease also helps with mediating the symptoms in pathological aging (44)
- Avoid smoking (45)
Natural Supplements to Support an Aging Brain:
- Phosphatidylserine (28,29,30,46)
- Vinpocetine (35,36,37)
- Bacopa (38,47,48,49,50,51)
- Ginkgo biloba (52,53)
- Ginger (54,55,56)
- Spearmint extract (57,58)
- Acetyl-L-carnitine (59,60,61)
- Ginseng Panax (62,63)
- How does the brain work? Pubmed Health. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072486/.Accessed August 2, 2018.
- Bringing the Power of Science to Bear on Drug Abuse and Addiction. https://www.drugabuse.gov/publications/teaching-packets/power-science/section-i/3-how-neuron-works. Accessed August 2, 2018.
- von Bartheld CS, Bahney J, Herculano-Houzel S. The Search for True Numbers of Neurons and Glial Cells in the Human Brain: A Review of 150 Years of Cell Counting. J Comp Neurol. 2016 Dec 15; 524(18): 3865–3895. doi:10.1002/cne.24040
- Neuroscience. Neuroglial Cells.https://www.ncbi.nlm.nih.gov/books/NBK10869/. Accessed August 2, 2018.
- How the aging brain affects thinking. National Institute on Aging. https://www.nia.nih.gov/health/how-aging-brain-affects-thinking. Accessed May 16, 2018.
- Reese CM, Cherry KE, Copland AL. Knowledge of normal versus pathological memory aging in younger and older adults. Aging, Neuropsych, & Cogn. 2000;7(1):1-8. doi.10.1076/anec.220.127.116.119.
- Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW. Mapping cortical change across the human life span. Nat Neurosci. 2003;6(3):309-315. doi:10.1038/nn1008
- Grachev ID, Swarnkar A, Szeverenyi NM, Ramachandran TS, Apkarian A V. Aging alters the multichemical networking profile of the human brain: an in vivo (1)H-MRS study of young versus middle-aged subjects. J Neurochem. 2001;77(1):292-303.
- Yamamoto M, Suhara T, Okubo Y, et al. Age-related decline of serotonin transporters in living human brain of healthy males. Life Sci. 2002;71(7):751-757. doi:10.1016/S0024-3205(02)01745-9
- Rossini PM, Rossi S, Babiloni C, Polich J. Clinical neurophysiology of aging brain: From normal aging to neurodegeneration. Prog Neurobiol. 2007;83(6):375-400. doi:10.1016/j.pneurobio.2007.07.010
- Peters R. Ageing and the brain. Postgrad Med J. 2006;82(964):84-88. doi:10.1136/pgmj.2005.036665
- Rossini P, Noris Ferilli M, Rossini L, Ferreri F. Clinical Neurophysiology of Brain Plasticity in Aging Brain. Curr Pharm Des. 2013;19(36):6426-6439. doi:10.2174/1381612811319360004
- Gene Expression in the Aging Brain. PLoS Biol. 2005;3(9):e313. doi:10.1371/journal.pbio.0030313
- Lodato MA, Rodin RE, Bohrson CL, et al. Aging and neurodegeneration are associated with increased mutations in single human neurons. Science. 2018;359(6375):555-559. doi:10.1126/science.aao4426
- Kumar A, Gibbs JR, Beilina A, et al. Age-associated changes in gene expression in human brain and isolated neurons. Neurobiol Aging. 2013;34(4):1199-1209. doi:10.1016/j.neurobiolaging.2012.10.021
- What Causes Alzheimer’s Disease? https://www.nia.nih.gov/health/what-causes-alzheimers-disease. Accessed July 27, 2018.
- Fjell AM, McEvoy L, Holland D, Dale AM, Walhovd KB. What is normal in normal aging? Effects of aging, amyloid and Alzheimer’s disease on the cerebral cortex and the hippocampus. Progress in Neurobiology. 2014. http://neuro.pathology.pitt.edu/conferences/jclub/JClub6-11-14WILEY.pdf.
- Boccardi V, Comanducci C, Baroni M, Mecocci P. Of Energy and Entropy: The Ineluctable Impact of Aging in Old Age Dementia. Int. J. Mol. Sci. 2017, 18(12), 2672; doi:10.3390/ijms18122672.
- Healthy Aging. https://memory.ucsf.edu/healthy-aging. Accessed July 27, 2018
- How the Aging Brain Affects Thinking. https://www.nia.nih.gov/health/how-aging-brain-affects-thinking. Accessed July 27, 2018.
- Healthy Aging. https://memory.ucsf.edu/healthy-aging. Accessed July 27, 2018.
- The Aging Population. https://www.asha.org/slp/clinical/aging/. Accessed July 27, 2018.
- Martin JE, Sheaf MT. The pathology of ageing: concepts and mechanisms. J Pathol 2007; 211: 111–113. DOI: 10.1002/path.2122
- Fjell AM, McEvoy L, Holland D, Dale AM, Walhovd KB. What is normal in normal aging? Effects of Aging, Amyloid and Alzheimer’s Disease on the Cerebral Cortex and the Hippocampus. Prog Neurobiol. 2014 Jun; 117: 20–40. doi:10.1016/j.pneurobio.2014.02.004
- Alzheimer’s Disease. https://www.cdc.gov/aging/aginginfo/alzheimers.htm. Accessed July 27, 2018.
- Aging Brain Clinic. https://my.clevelandclinic.org/health/treatments/16723-aging-brain-clinic. Accessed July 27, 2018.
- Alzheimer’s Association – Medications for Memory Loss. https://m.alz.org/medications-for-memory-loss.asp. Accessed April 30, 2018.
- Approved Medications | American Parkinson Disease Assoc. https://www.apdaparkinson.org/what-is-parkinsons/treatment-medication/medication/. Accessed April 30, 2018.
- Yero T, Rey JA. Tetrabenazine (Xenazine), An FDA-Approved Treatment Option For Huntington’s Disease-Related Chorea. P T. 2008;33(12):690-694.
- Haloperidol: MedlinePlus Drug Information. https://medlineplus.gov/druginfo/meds/a682180.html. Accessed April 30, 2018.
- Chlorpromazine: MedlinePlus Drug Information. https://medlineplus.gov/druginfo/meds/a682040.html. Accessed April 30, 2018.
- Archer JA, Lee A, Qiu A, Chen S-HA. Working memory, age and education: A lifespan fMRI study. He H, ed. PLoS One. 2018;13(3):e0194878. doi:10.1371/journal.pone.0194878
- Kim JP, Seo SW, Shin HY, et al. Effects of education on aging-related cortical thinning among cognitively normal individuals. Neurology. 2015;85(9):806-812. doi:10.1212/WNL.0000000000001884
- Roldán-Tapia MD, Cánovas R, León I, García-Garcia J. Cognitive Vulnerability in Aging May Be Modulated by Education and Reserve in Healthy People. Front Aging Neurosci. 2017;9:340. doi:10.3389/fnagi.2017.00340
- Szapáry L, Horváth B, Alexy T, et al. [Effect of vinpocetin on the hemorheologic parameters in patients with chronic cerebrovascular disease]. Orv Hetil. 2003;144(20):973-978.
- Valikovics A, Csányi A, Németh L. [Study of the effects of vinpocetin on cognitive functions]. Ideggyogy Sz. 2012;65(3-4):115-120.
- Ogunrin A. Effect of vinpocetine (cognitolTM) on cognitive performances of a nigerian population. Ann Med Health Sci Res. 2014;4(4):654-661. doi:10.4103/2141-9248.139368
- Nemetchek MD, Stierle AA, Stierle DB, Lurie DI. The Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain. J Ethnopharmacol. 2017;197:92-100. doi:10.1016/j.jep.2016.07.073
- Anderson-Hanley CP, Barcelos NP, ZIMMERMAN EAM, et al. The Aerobic and Cognitive Exercise Study (ACES) for community-dwelling older adults with or at-risk for Mild Cognitive Impairment (MCI): Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial. Front Aging Neurosci. 2018;10:76. doi:10.3389/FNAGI.2018.00076
- Churchill JD, Galvez R, Colcombe S, Swain RA, Kramer AF, Greenough WT. Exercise, experience and the aging brain. Neurobiol Aging. 2002;23(5):941-955.
- Chapman SB, Aslan S, Spence JS, et al. Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging. Front Aging Neurosci. 2013;5:75. doi:10.3389/fnagi.2013.00075
- Fisher BE, Li Q, Nacca A, et al. Treadmill exercise elevates striatal dopamine D2 receptor binding potential in patients with early Parkinson’s disease. Neuroreport. 2013;24(10):509-514. doi:10.1097/WNR.0b013e328361dc13
- O’Brien JL, Lister JJ, Fausto BA, Clifton GK, Edwards JD. Cognitive Training Enhances Auditory Attention Efficiency in Older Adults. Front Aging Neurosci. 2017;9:322. doi:10.3389/fnagi.2017.00322
- National Institute for Aging. Natl Institue Aging. https://www.nia.nih.gov/health/assessing-cognitive-impairment-older-patients. Accessed August 2, 2018.
- Karama S, Ducharme S, Corley J, et al. Cigarette smoking and thinning of the brain’s cortex. Mol Psychiatry. 2015;20(6):778-785. doi:10.1038/mp.2014.187
- Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC. Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991;41(5):644-649.
- Pase MP, Kean J, Sarris J, Neale C, Scholey AB, Stough C. The Cognitive-Enhancing Effects of Bacopa monnieri : A Systematic Review of Randomized, Controlled Human Clinical Trials. J Altern Complement Med. 2012;18(7):647-652. doi:10.1089/acm.2011.0367
- Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res. 2013;16(4):313-326. doi:10.1089/rej.2013.1431
- Peth-Nui T, Wattanathorn J, Muchimapura S, et al. Effects of 12-Week Bacopa monnieri Consumption on Attention, Cognitive Processing, Working Memory, and Functions of Both Cholinergic and Monoaminergic Systems in Healthy Elderly Volunteers. Evidence-Based Complement Altern Med. 2012;2012:1-10. doi:10.1155/2012/606424
- Calabrese C, Gregory WL, Leo M, Kraemer D, Bone K, Oken B. Effects of a Standardized Bacopa monnieri Extract on Cognitive Performance, Anxiety, and Depression in the Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial. J Altern Complement Med. 2008;14(6):707-713. doi:10.1089/acm.2008.0018
- Zhang L-N, Sun Y-J, Pan S, et al. Na + -K + -ATPase, a potent neuroprotective modulator against Alzheimer disease. Fundam Clin Pharmacol. 2013;27(1):96-103. doi:10.1111/fcp.12000
- Howes M-JR, Houghton PJ. Ethnobotanical treatment strategies against Alzheimer’s disease. Curr Alzheimer Res. 2012;9(1):67-85.
- Hashiguchi M, Ohta Y, Shimizu M, Maruyama J, Mochizuki M. Meta-analysis of the efficacy and safety of Ginkgo biloba extract for the treatment of dementia. J Pharm Heal Care Sci. 2015;1(1):14. doi:10.1186/s40780-015-0014-7
- Saenghong N, Wattanathorn J, Muchimapura S, et al. Zingiber officinale Improves Cognitive Function of the Middle-Aged Healthy Women. Evidence-Based Complement Altern Med. 2012;2012:1-9. doi:10.1155/2012/383062
- Lee D-H, Kim D-W, Jung C-H, Lee YJ, Park D. Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells. Toxicol Appl Pharmacol. 2014;279(3):253-265. doi:10.1016/j.taap.2014.06.030
- Azam F, Amer AM, Abulifa AR, Elzwawi MM. Ginger components as new leads for the design and development of novel multi-targeted anti-Alzheimer’s drugs: a computational investigation. Drug Des Devel Ther. 2014;8:2045-2059. doi:10.2147/DDDT.S67778
- Herrlinger KA, Nieman KM, Sanoshy KD, et al. Spearmint Extract Improves Working Memory in Men and Women with Age-Associated Memory Impairment. J Altern Complement Med. 2018;24(1):37-47. doi:10.1089/acm.2016.0379
- Cook C, Herringer K, et al. Effects of a Proprietary Spearmint Extract on Cognitive Function and Tolerance Parameters in Men and Women with Age-Associated Memory Impairment | The FASEB Journal. 2015;29(1).
- Spagnoli A, Lucca U, Menasce G, et al. Long-term acetyl-L-carnitine treatment in Alzheimer’s disease. Neurology. 1991;41(11):1726-1732.
- Thal LJ, Carta A, Clarke WR, et al. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer’s disease. Neurology. 1996;47(3):705-711.
- Sano M, Bell K, Cote L, et al. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer’s disease. Arch Neurol. 1992;49(11):1137-1141.
- Lee S-T, Chu K, Sim J-Y, Heo J-H, Kim M. Panax Ginseng Enhances Cognitive Performance in Alzheimer Disease. Alzheimer Dis Assoc Disord. 2008;22(3):222-226. doi:10.1097/WAD.0b013e31816c92e6
- Heo J-H, Lee S-T, Chu K, et al. An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimers disease. Eur J Neurol. 2008;15(8):865-868. doi:10.1111/j.1468-1331.2008.02157.x