LIFE EXTENSION MAGAZINE
Contrary to common beliefs, the prevalence of dementia in older Americans continues to steeply decrease.
As we reported long ago, those who engage in healthy lifestyles may delay brain aging by 11 years while reducing Alzheimer's and vascular dementia risks.1
The latest data on this topic were published in the Proceedings of the National Academy of Sciences.
Using a new model of cognitive status, scientists found a statistically significant 30.1% decline in age-adjusted dementia prevalence in Americans over age 65 from years 2000-2016.2
A significant part of this dementia reduction is attributed to higher education levels.2 Previous studies found higher education3,4 along with better diet,5 lifestyle,6 and management of hypertension7 correlating with reduced dementia prevalence.
Overlooked in some media reports is that more highly educated people tend to follow healthier lifestyles and take steps to reduce cardiovascular risks that also accelerate brain aging.
Educated persons may also ingest nutrients that correlate with improved brain health.
This editorial describes some of the better-documented methods of preserving neurological function with age.
The term dementia refers to a decline in cognitive abilities that leads to loss of independent function.
An estimated 4-5 million older adults in the United States suffer severe neurological impairment.8 This total number is expected to triple in coming decades.9
Not all population groups equally suffer loss of cognitive abilities with age.
Dementia risk plummets in response to healthier dietary/lifestyle choices and better control of hypertension, diabetes, and lipids.10-12
In the famous Framingham Heart Study, the incidence of dementia among older Americans declined by about 20% per decade between 1977 and 2008.13
A British study found a 24% decline in the expected number of cases of dementia between 1991 and 2011 among older adults.14
More recent data confirm how humans can further slash dementia risk.
For instance, an international expert commission reported in The Lancet that more than 40% of global dementia cases may be preventable by correcting unhealthy factors that impact individual risk.15,16
Peer-reviewed published studies of humans and animals reveal methods that may further protect against neurodegeneration.6,11,17-19
Control Your Rate of Brain Aging
Maturing people can exert a degree of control over their rate of brain aging.
When it comes to preventing dementia, however, there is no single approach.
Everyone should strive for blood pressure in the lowest tolerable ranges. I target my blood pressure under 115/75 mmHg. Others require somewhat higher blood pressure to push blood through their aged/damaged circulatory systems.
Reducing chronic inflammation is essential for protecting aging brains. Most of you accomplish this via healthy behavior practices.
In a major finding we previously reported on, a group of elderly Americans underwent cognitive tests and MRI scans to assess brain function, and blood tests to assess nutrient status.21
The results identified five categories of plasma nutrients associated with enhanced cognitive performance.21These plasma nutrients include carotenoids (like lycopene), vitamin D, and homocysteine-lowering vitamins (folate and B12).
MRI imaging revealed enhanced brain network connectivity in those with higher plasma carotenoid status and healthy balances of omega-3 and omega-6 fatty acids.21
This study found that higher levels of nutrient combinations measured in blood plasma were associated with enhanced cognitive performance and improved brain network efficiency as follows:
- A proper balance of certain omega-3 and omega-6 fatty acids was associated with higher function of two domains of memory.
- Higher lycopene levels were correlated with better scores in three separate domains of memory.
- Higher omega-3 levels (EPA, DHA, and DPA) were strongly linked to better executive function and higher overall intelligence.
- Carotenoids including trans-lutein were positively associated with two measures of intelligence.
- Homocysteine-reducing B-vitamins (vitamin B2, folate, B12) and vitamin D were associated with better executive function.
- Functional MRI analysis revealed that three nutrient biomarker patterns significantly influenced the relationship between functional brain connectivity networks and measures of intelligence and cognitive function.
Readers of Life Extension Magazine® have supplemented with the above nutrients for many decades.
Restoring Brain Cell “Connectivity”
Our brain contains about 100 million cells called neurons.
In order for neurons to communicate they must connect to one another.
A synapse is the connection that allows information to pass from one neuron to the next.
Synapses are essential to neuronal function. Not only are synapses crucial to short-term memory in the young, but their structural integrity is imperative in aging individuals seeking to stave off cognitive impairments.22
When Synapses Degrade
Alzheimer's dementia is characterized by the pathological accumulation of non-functioning plaque in neurons and loss of normal neurotransmitter flow between neurons.
Before neurons encounter severe damage, scientists have found a marked decline in synaptic density.
This loss of synaptic density causes a decline in neuronal connectivity that correlates to the impairments observed in Alzheimer's.23,24
A consistent finding in the brains of Alzheimer's victims is a significant loss of synaptic contacts. This led a group of researchers to conclude:
"...synapse loss is an early event in the disease process and suggests that mild cognitive impairment may be a transitional stage between early Alzheimer's disease and no cognitive impairment… with synaptic loss a structural correlate involved in cognitive decline."25
Magnesium and Synaptic Density
In a series of animal studies, a highly absorbable form of magnesium was shown to increase magnesium brain concentrations.26
In response to this magnesium elevation there were significant increases in synaptic density and corresponding improvements in synaptic functioning and neuronal signaling.26
These favorable changes in synaptic structure/function translated into enhanced measures of cognitive function.
Short-Term Memory Restoration
An animal study found that 24 days of supplementation with magnesium-L-threonate produced an increase in cerebrospinal magnesium sufficient to boost short- and long-term memory scores. Other forms of magnesium did not significantly elevate brain magnesium compared to the control group.26
Another study on memory-impaired aged rats showed that magnesium-L-threonate could reverse the kind of cognitive dysfunction that occurs in normal aging humans. Magnesium-L-threonate was added to the rat's drinking water for one month. This enabled a significant improvement of short-term memory.26
Long-Term Memory Research
Young and old animals underwent maze training with a delay interval. Animals supplemented with magnesium-L-threonate learned to find the hidden platform in the maze faster than non-supplemented animals.
The degree of learning ability enhancement in the aged animals was greater than in young animals. This makes sense since aged animals suffer more loss of synaptic density that magnesium-L-threonate has been shown to restore.26
To test long-term spatial memory, a second trial test was performed 24 hours later. The unsupplemented "control" group forgot how to perform in the maze, whereas young and aged animals supplemented with magnesium-L-threonate retained their ability to navigate the maze. This might be equivalent to an older human being able to find their car in a crowded parking lot.
The researchers concluded, "Magnesium-L-threonate significantly enhanced hippocampus-dependent spatial learning and memory in both young and aged rats."26
Correlation Between Synaptic Density and Memory
Scientists next sought to verify that the mechanism behind improvements in memory and cognitive performance was due to increased density of the synapses.
Studies were done to precisely measure the various synaptic structural components in the brain.
Rats supplemented with magnesium-L-threonate showed across-the-board improvements in synaptic protein expression, function, and structure, along with long-term potentiation of synaptic strength.26
Reversal of Synaptic Decline
Several studies indicate that synaptic connections decline in the portion of the brain essential for memory. The degree of synaptic loss correlates with impairment of memory functions.27,28
To evaluate the impact in old animals, one group received magnesium-L-threonate while an un-supplemented group served as controls.
After one month, autopsy findings showed synaptic density was 67% higher in the group supplemented with magnesium-L-threonate. This study showed that even in old animals, magnesium-L-threonate increased the density of synaptic components essential for youthful neurotransmitter release.26
Human Findings
To further assess the effects of magnesium-L-threonate, MIT researchers designed a clinical trial of older people with early cognitive impairment.
The study subjects had some impairment in their ability to plan, adapt, focus, and make decisions (executive functions).
These human study subjects supplemented with magnesium L-threonate or a placebo daily for 12 weeks.
At the beginning of the study, the participants averaged 57.8 years of age. Their brain age based on cognitive function, however, was 68.3 years old. By the end of the trial, those receiving magnesium L-threonate decreased their brain age a remarkable nine years.29
Another human trial showed promising preliminary results in patients diagnosed with mild to moderate dementia. Even at this more advanced stage of cognitive decline, magnesium L-threonate led to improvements in cognition and executive function.30
An open-label pilot study found that nearly half of adults with moderate ADHD (attention deficit hyperactivity disorder) who received magnesium L-threonate for up to 12 weeks displayed clinical improvements.31
Modern Recognition of Magnesium
Magnesium supplementation rates are surging higher in the United States and are projected to almost double from years 2021 to 2028.32
This is happening as more consumers learn of its whole-body benefits and the National Institutes of Health statement that "magnesium is a nutrient that the body needs to stay healthy."33
Life Extension subscribers have been reading about magnesium for over 40 years and utilize a variety of magnesium supplements to guard their precious health.
For longer life,
William Faloon, Co-Founder, Life Extension®
Ways to Reduce Risk of Dementia
Lifestyle Habits
Exercise Regularly Eat A Healthy Diet Get Adequate Sleep Do Not Smoke
Health Care
Treat Any Heart Disease Control Blood Pressure Control Blood Sugar Correct Hearing Loss
Mental and Social
Well-Being Activities
Stay Curious and Interested Actively Learn New Things Stay Socially Engaged Participate in Group Activities
Diet and Lifestyle Choices Can Thwart Brain Aging
One of the most consistent findings in the published medical literature is the profound role of diet and lifestyle on dementia risk.
A study published in 2023 found that people who follow a Mediterranean diet reduce dementia risk by 23%...even in those genetically predisposed (APOe4 positive) to early-stage Alzheimer's.5
The "MIND" diet was created to identify the constituents of the Mediterranean and DASH diets that possess the greatest neuroprotective properties.
Ten brain-healthy food groups in the MIND diet are:34
- Green leafy vegetables
- Other vegetables
- Nuts
- Berries
- Beans
- Whole grains
- Fish
- Poultry
- Olive oil
- Wine (moderate drinking)
Consuming the above 10 healthy food groups conferred significant protection against Alzheimer's34 and mild cognitive impairment.5,34,35
The top five dangerous food groups are:34
- Red meats
- Butter and stick margarine
- Cheese
- Pastries and sweets
- Fried/fast food
By reducing one's intake of the five brain-damaging foods, significant protection against Alzheimer's and mild cognitive impairment was conferred.34
This does not mean one can never consume any of the five bad food groups. Individuals can still follow a MIND diet if they reduce consumption of the following brain-damaging foods:
- Pastries and sweets to under five servings per week,
- Red meat to under four servings per week,
- Cheese to under one serving per week,
- Butter or margarine to under one tablespoon per day, and
- Fried/fast foods to under one serving per week.
On a personal note, I don't find the above restrictions confining, and I don't think many readers of this magazine will either.
Researchers found that greater adherence to the MIND diet resulted in a markedly slower rate of cognitive decline. Strict adherence to the MIND diet reduced Alzheimer's incidence by 53%.34
Even study subjects with "middle-of-the-road" compliance with the MIND diet, such as ingesting some of the constituents of a brain-healthy diet like berries, had their dementia risk reduced by 35%.34
These large risk reductions in response to healthier eating patterns represent game changers as it relates to reducing the numbers of Americans who would otherwise suffer agonizing dementia-related deaths. By adhering to healthy dietary patterns, your brain might be the equivalent of 7.5 years younger in biological age.34
The problem is that relatively few people can stick solely to healthy dietary patterns. The encouraging news is that it may not matter because just ingesting some of the constituents of the MIND diet was shown to confer considerable protection against neurodegenerative disease.36
The graphic below highlights the multiple ways that aging humans can reduce their dementia risk.
References
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- Hudomiet P, Hurd MD, Rohwedder S. Trends in inequalities in the prevalence of dementia in the United States. Proc Natl Acad Sci U S A. 2022 Nov 16;119(46):e2212205119.
- Sharp ES, Gatz M. Relationship between education and dementia: an updated systematic review. Alzheimer Dis Assoc Disord. 2011 Oct-Dec;25(4):289-304.
- Takasugi T, Tsuji T, Hanazato M, et al. Community-level educational attainment and dementia: a 6-year longitudinal multilevel study in Japan. BMC Geriatr. 2021 Nov 23;21(1):661.
- Shannon OM, Ranson JM, Gregory S, et al. Mediterranean diet adherence is associated with lower dementia risk, independent of genetic predisposition: findings from the UK Biobank prospective cohort study. BMC Med. 2023 Mar 14;21(1):81.
- Dhana K, Evans DA, Rajan KB, et al. Healthy lifestyle and the risk of Alzheimer dementia: Findings from 2 longitudinal studies. Neurology. 2020 Jul 28;95(4):e374-e83.
- Sierra C. Hypertension and the Risk of Dementia. Front Cardiovasc Med. 2020;7:5.
- Available at: https://www.nytimes.com/2016/11/21/health/dementia-rates-united-states.html. Accessed September 26, 2023.
- Alzheimer's Association. 2022 Alzheimer's disease facts and figures. Alzheimers Dement. 2022 Apr;18(4):700-89.
- Larson EB, Yaffe K, Langa KM. New insights into the dementia epidemic. N Engl J Med. 2013 Dec 12;369(24):2275-7.
- Langa KM, Larson EB, Crimmins EM, et al. A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012. JAMA Intern Med. 2017 Jan 1;177(1):51-8.
- Available at: https://www.cdc.gov/aging/publications/features/dementia-risk-reduction-june-2022/index.html. Accessed September 28, 2023.
- Satizabal CL, Beiser AS, Chouraki V, et al. Incidence of Dementia over Three Decades in the Framingham Heart Study. N Engl J Med. 2016 Feb 11;374(6):523-32.
- Matthews FE, Arthur A, Barnes LE, et al. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet. 2013 Oct 26;382(9902):1405-12.
- Available at: https://aaic.alz.org/releases_2017/AAIC17-Thurs-briefing-Lancet-Global-health-policy.asp. Accessed September 26, 2023.
- Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020 Aug 8;396(10248):413-46.
- Satizabal CL, Beiser AS, Chouraki V, et al. Incidence of Dementia over Three Decades in the Framingham Heart Study. N Engl J Med. 2016 Feb 11;374(6):523-32.
- Matthews FE, Arthur A, Barnes LE, et al. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet. 2013 Oct 26;382(9902):1405-12.
- Perneczky R. Dementia prevention and reserve against neurodegenerative disease. Dialogues Clin Neurosci. 2019 Mar;21(1):53-60.
- Manton KC, Gu XL, Ukraintseva SV. Declining prevalence of dementia in the U.S. elderly population. Adv Gerontol. 2005;16:30-7.
- Zwilling CE, Talukdar T, Zamroziewicz MK, et al. Nutrient biomarker patterns, cognitive function, and fMRI measures of network efficiency in the aging brain. Neuroimage. 2019 Mar;188:239-51.
- Available at: https://lpi.oregonstate.edu/mic/health-disease/cognitive-function-in-brief#:~:text=Cognition%20basically%20means%20using%20your,problem%20solving%2C%20and%20multitasking). Accessed September 28, 2023.
- Cardozo PL, de Lima IBQ, Maciel EMA, et al. Synaptic Elimination in Neurological Disorders. Curr Neuropharmacol. 2019;17(11):1071-95.
- Carson RE, Naganawa M, Toyonaga T, et al. Imaging of Synaptic Density in Neurodegenerative Disorders. J Nucl Med. 2022 Jun;63(Suppl 1):60S-7S.
- Scheff SW, Price DA, Schmitt FA, et al. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging. 2006 Oct;27(10):1372-84.
- Slutsky I, Abumaria N, Wu LJ, et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010 Jan 28;65(2):165-77.
- Subramanian J, Savage JC, Tremblay ME. Synaptic Loss in Alzheimer's Disease: Mechanistic Insights Provided by Two-Photon in vivo Imaging of Transgenic Mouse Models. Front Cell Neurosci. 2020;14:592607.
- Martinez-Serra R, Alonso-Nanclares L, Cho K, et al. Emerging insights into synapse dysregulation in Alzheimer's disease. Brain Commun. 2022;4(2):fcac083.
- Liu G, Weinger JG, Lu ZL, et al. Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. J Alzheimers Dis. 2016;49(4):971-90.
- Wroolie TE, Watson K, Chen K, et al. Open Label Trial of Magnesium L-Threonate in Patients with Dementia. Innov Aging. 2017Jul Jun 30;1(Suppl 1):170. doi: 10.1093/geroni/igx004.661. eCollection 2017 Jul.
- Surman C, Vaudreuil C, Boland H, et al. L-Threonic Acid Magnesium Salt Supplementation in ADHD: An Open-Label Pilot Study. J Diet Suppl. 2021;18(2):119-31.
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- Morris MC, Tangney CC, Wang Y, et al. MIND diet associated with reduced incidence of Alzheimer's disease. Alzheimers Dement. 2015 Sep;11(9):1007-14.
- Dhana K, James BD, Agarwal P, et al. MIND Diet, Common Brain Pathologies, and Cognition in Community-Dwelling Older Adults. J Alzheimers Dis. 2021;83(2):683-92.
- Cherian L, Wang Y, Fakuda K, et al. Mediterranean-Dash Intervention for Neurodegenerative Delay (MIND) Diet Slows Cognitive Decline After Stroke. J Prev Alzheimers Dis. 2019;6(4):267-73.
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