aging

Better physical fitness and lower aortic stiffness key to slower brain aging

  • A study found that physical fitness & arterial stiffness accounted for a third of the cognitive differences between older adults, completely erasing age as a factor.

An Australian study involving 102 older adults (60-90) has concluded that physical fitness and arterial stiffness account for a great deal of age-related memory decline.

The study that, while both physical fitness and aortic stiffness were associated with spatial working memory performance, the two factors affected cognition independently. More importantly, and surprisingly, statistical modelling found that, taking BMI and gender into account, fitness and aortic stiffness together explained a third (33%) of the individual differences in spatial working memory — with age no longer predicting any of the differences.

While physical fitness didn’t seem to affect central arterial stiffness, the researchers point out that only current fitness was assessed and long term fitness might be a better predictor of central arterial stiffness.

It's also worth noting that only one cognitive measure was used. However, this particular measure should be a good one for assessing cognition untainted by the benefits of experience — a purer measure of the ability to process information, as it were.

It would also be interesting to extend the comparison to younger adults. I hope future research will explore these aspects.

Nevertheless, the idea that age-related cognitive decline might be largely, or even entirely, accounted for by one's physical fitness and the state of one's arteries, is an immensely appealing one.

Fitness was assessed with the Six-Minute Walk test which involved participants walking back and forth between two markers placed 10 metres apart for six minutes. Only participants who completed the full six minutes were included in the analysis.

https://www.eurekalert.org/pub_releases/2018-06/ip-bpf061118.php

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Belly fat in older adults linked with cognitive impairment

  • A large Irish study found that belly fat was linked to poorer cognition in older adults, while BMI was not, probably because it doesn't distinguish between muscle and fat.

Data from over 5,000 individuals found that a measure of belly fat (waist:hip ratio) was associated with reduced cognitive function in older Irish adults (60+). Body mass index (BMI), however, was found to protect cognitive function.

BMI is a crude measure of body fat and cannot differentiate between fat and muscle — the muscle component is likely to be the protective factor.

Research indicates that as we age, our fat becomes less efficient at producing a hormone that helps support the growth and survival of neurons and helps regulate their activity.

That hormone is adiponectin, which is made by fat cells, circulates in our blood and enters our brain. Inside fat cells, its production is regulated by PPAR-γ (peroxisome proliferator-activated receptor gamma).

Adiponectin is anti-inflammatory and can help regulate neuronal activity, including turning activity of some neurons up and others down. However, adiponectin is reduced in Alzheimer’s patients. Delivering adiponectin to the brain has been shown to improve cognition in mice.

Chronic stress can also decrease fat's production of PPAR-γ and adiponectin.

Fat cells become less efficient at making adiponectin in obesity, and with age. One theory is that fat cells start making inflammation-promoting signals called cytokines and this inflammation then inhibits adiponectin production.

The shift from beneficial subcutaneous fat to unhealthy fat that piles up on our bellies and around the organs inside our abdominal cavity is one that naturally occurs with age, but it is of course worse if you have a lot of excess weight around your abdomen.

Genetic variations in PPAR-γ and adiponectin as well as low blood levels of adiponectin are associated with an increased Alzheimer's risk.

https://www.eurekalert.org/pub_releases/2018-08/tcd-mob080118.php

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Choline linked to better memory & healthier brains

  • A large, long-running study of middle-aged men found that higher dietary intake of choline was linked to a lower risk of dementia and better memory & verbal abilities.
  • A mouse study found that offspring of those given high amounts of choline showed better memory. Both mother and offspring showed lower levels of inflammation in the hippocampus.

Dietary choline linked to reduced dementia risk & better cognition

Data from a large, long-running Finnish study, involving some 2,500 men aged 42-60, has found that dietary intake of phosphatidylcholine was associated with a reduced risk of dementia (the risk was 28% lower in men with the highest intake compared to the lowest). Men with the highest intake of dietary phosphatidylcholine also excelled in tests measuring their memory and linguistic abilities.

The key sources of phosphatidylcholine in the study population's diet were eggs (39%) and meat (37%).

Choline is necessary for the formation of the neurotransmitter acetylcholine. Earlier studies have linked choline intake with cognitive processing, and adequate choline intake may play a role in the prevention of cognitive decline and Alzheimer's disease.

There was no interaction with the APOE4 gene.

https://www.eurekalert.org/pub_releases/2019-08/uoef-dca080619.php

Choline helps fight Alzheimer's across generations

A study using genetically engineered mice found that when they were given high choline in their diet, their offspring showed improved in spatial memory.

Study of the hippocampus found the choline had reduced microglial activation, and thus brain inflammation, and reduced levels of homocysteine by converting it into the more helpful chemical methionine. These effects, achieved through gene modification, passed on to the next generation.

It has long been recognized that choline is particularly important in early brain development.

https://www.eurekalert.org/pub_releases/2019-01/asu-enm010719.php

Reference: 

Ylilauri, Maija P.T. et al. 2019. Associations of dietary choline intake with risk of incident dementia and with cognitive performance: the Kuopio Ischaemic Heart Disease Risk Factor Study.
American Journal of Clinical Nutrition, published online July 30, 2019, https://doi.org/10.1093/ajcn/nqz148

[4504] Velazquez, R., Ferreira E., Winslow W., Dave N., Piras I. S., Naymik M., et al.
(2019).  Maternal choline supplementation ameliorates Alzheimer’s disease pathology by reducing brain homocysteine levels across multiple generations.
Molecular Psychiatry. 1 - 10.

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Does mental stimulation help fight age-related cognitive decline?

  • A large study found that mentally stimulating activities in mid-life and later were linked to a lower risk or delay of MCI.
  • A very large study found that the more regularly older adults played puzzles such as crosswords and Sudoku, the better they performed on tasks assessing attention, reasoning and memory.
  • A review of 32 studies has concluded that mind-body exercises such as tai chi do help improve cognition in older adults.

Can computer use, crafts and games slow or prevent age-related memory loss?

A study involving 2,000 healthy older adults (average age 78) found that mentally stimulating activities were linked to a lower risk or delay of MCI, and that the timing and number of these activities may also play a role.

During the study, 532 participants developed MCI.

Using a computer in middle-age (50-65) was associated with a 48% lower risk of MCI, while using a computer in later life was associated with a 30% lower risk, and using a computer in both middle-age and later life was associated with a 37% lower risk.

Engaging in social activities, like going to movies or going out with friends, or playing games, like doing crosswords or playing cards, in both middle-age and later life were associated with a 20% lower risk of developing MCI.

Craft activities were associated with a 42% lower risk, but only in later life.

Those who engaged in two activities were 28% less likely to develop MCI than those who took part in no activities, while those who took part in three activities were 45% less likely, those with four activities 56% percent less likely and those with five activities were 43% less likely.

It should be noted that activities in middle-age were assessed by participants’ memory many years later.

https://www.eurekalert.org/pub_releases/2019-07/aaon-ccu071019.php

Regular crosswords & sudoku linked to sharper brain in later life

Data from the PROTECT online platform, involving 19,000 healthy older adults (50-96), found that the more regularly older adults played puzzles such as crosswords and Sudoku, the better they performed on tasks assessing attention, reasoning and memory.

In some areas the improvement was quite dramatic, for example, on measures of problem-solving, people who regularly do these puzzles performed equivalent to an average of eight years younger compared to those who don't.

https://www.eurekalert.org/pub_releases/2019-05/uoe-rca051419.php

Mind-body exercises improve cognitive function in older adults

A meta-analysis of 32 randomized controlled trials with 3,624 older adults with or without cognitive impairment has concluded that mind-body exercises, especially tai chi and dance mind-body exercise, help improve global cognition, cognitive flexibility, working memory, verbal fluency, and learning in older adults.

https://www.eurekalert.org/pub_releases/2018-12/w-mem121718.php

Reference: 

Krell-Roesch, J., Syrjanen, J. A., Vassilaki, M., Machulda, M. M., Mielke, M. M., Knopman, D. S., … Geda, Y. E. (2019). Quantity and quality of mental activities and the risk of incident mild cognitive impairment. Neurology, 93(6), e548. https://doi.org/10.1212/WNL.0000000000007897

Brooker, H., Wesnes, K. A., Ballard, C., Hampshire, A., Aarsland, D., Khan, Z., … Corbett, A. (2019). The relationship between the frequency of number-puzzle use and baseline cognitive function in a large online sample of adults aged 50 and over. International Journal of Geriatric Psychiatry, 34(7), 932–940. https://doi.org/10.1002/gps.5085

Brooker, H., Wesnes, K. A., Ballard, C., Hampshire, A., Aarsland, D., Khan, Z., … Corbett, A. (2019). An online investigation of the relationship between the frequency of word puzzle use and cognitive function in a large sample of older adults. International Journal of Geriatric Psychiatry, 34(7), 921–931. https://doi.org/10.1002/gps.5033

Wu, C., Yi, Q., Zheng, X., Cui, S., Chen, B., Lu, L., & Tang, C. (2019). Effects of Mind-Body Exercises on Cognitive Function in Older Adults: A Meta-Analysis. Journal of the American Geriatrics Society, 67(4), 749–758. https://doi.org/10.1111/jgs.15714

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Education & IQ linked to later cognitive decline & dementia

  • A large, long-running study found those with a college education maintained good cognition substantially longer than those who didn't complete high school.
  • A very large online study found that higher levels of education were strong predictors of better cognitive performance across all ages (15-60 years), but this was more true for types of cognition such as reasoning and less true for processing speed.
  • A large study of older men found that their cognitive ability at age 20 was a stronger predictor of cognitive function later in life than other factors, such as higher education, occupational complexity or engaging in late-life intellectual activities.

Americans with a college education live longer without dementia and Alzheimer's

Data from the large, long-running U.S. Health and Retirement Study found that healthy cognition characterized most of the people with at least a college education into their late 80s, while those who didn’t complete high school had good cognition up until their 70s.

The study found that those who had at least a college education lived a much shorter time with dementia than those with less than a high school education: an average of 10 months for men and 19 months for women, compared to 2.57 years (men) and 4.12 years (women).

The data suggests that those who graduated high school can expect to live (on average) at least 70% of their remaining life after 65 with good cogntion, compared to more than 80% for those with a college education, and less than 50% for those who didn't finish high school.

The analysis was based on a sample of 10,374 older adults (65+; average age 74) in 2000 and 9,995 in 2010.

https://www.eurekalert.org/pub_releases/2018-04/uosc-awa041618.php

https://academic.oup.com/psychsocgerontology/article/73/suppl_1/S20/4971564 (open access)

More education linked to better cognitive functioning later in life

Data from around 196,000 subscribers to Lumosity online brain-training games found that higher levels of education were strong predictors of better cognitive performance across the 15- to 60-year-old age range of their study participants, and appear to boost performance more in areas such as reasoning than in terms of processing speed.

Differences in performance were small for test subjects with a bachelor's degree compared to those with a high school diploma, and moderate for those with doctorates compared to those with only some high school education.

But people from lower educational backgrounds learned novel tasks nearly as well as those from higher ones.

https://www.eurekalert.org/pub_releases/2017-08/l-mel082117.php

http://www.futurity.org/higher-education-cognitive-peak-1523712/

Youthful cognitive ability strongly predicts mental capacity later in life

Data from more than 1,000 men participating in the Vietnam Era Twin Study of Aging revealed that their cognitive ability at age 20 was a stronger predictor of cognitive function later in life than other factors, such as higher education, occupational complexity or engaging in late-life intellectual activities.

All of the men, now in their mid-50s to mid-60s, took the Armed Forces Qualification Test at an average age of 20. The same test of general cognitive ability (GCA) was given in late midlife, plus assessments in seven cognitive domains.

GCA at age 20 accounted for 40% of the variance in the same measure at age 62, and approximately 10% of the variance in each of the seven cognitive domains. Lifetime education, complexity of job and engagement in intellectual activities each accounted for less than 1% of variance at average age 62.

The findings suggest that the impact of education, occupational complexity and engagement in cognitive activities on later life cognitive function simply reflects earlier cognitive ability.

The researchers speculated that the role of education in increasing GCA takes place primarily during childhood and adolescence when there is still substantial brain development.

https://www.eurekalert.org/pub_releases/2019-01/uoc--yca011819.php

Reference: 

[4484] Crimmins, E. M., Saito Y., Kim J. Ki, Zhang Y. S., Sasson I., & Hayward M. D.
(2018).  Educational Differences in the Prevalence of Dementia and Life Expectancy with Dementia: Changes from 2000 to 2010.
The Journals of Gerontology: Series B. 73(suppl_1), S20 - S28.

Guerra-Carrillo, B., Katovich, K., & Bunge, S. A. (2017). Does higher education hone cognitive functioning and learning efficacy? Findings from a large and diverse sample. PLOS ONE, 12(8), e0182276. https://doi.org/10.1371/journal.pone.0182276

[4485] Kremen, W. S., Beck A., Elman J. A., Gustavson D. E., Reynolds C. A., Tu X. M., et al.
(2019).  Influence of young adult cognitive ability and additional education on later-life cognition.
Proceedings of the National Academy of Sciences. 116(6), 2021.

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Low social engagement linked to cognitive decline & dementia risk

  • A very large, very long-running British study found that higher social contact at age 60 was associated with a significantly lower risk of developing dementia.
  • A 3-year study of older adults found that lower social engagement was only associated with greater cognitive decline in those with higher amyloid-beta levels.

Socially active 60-year-olds face lower dementia risk

Data from the Whitehall II study, tracking 10,228 participants for 30 years, found that increased social contact at age 60 is associated with a significantly lower risk of developing dementia later in life. Someone who saw friends almost daily at age 60 was 12% less likely to develop dementia than someone who only saw one or two friends every few months.

While previous studies have found a link between social contact and dementia risk, the long follow-up in the present study strengthens the evidence that social engagement could protect people from dementia (rather than precursors of dementia bringing about a decline in social engagement).

https://www.eurekalert.org/pub_releases/2019-08/ucl-sa6073119.php

Low social engagement plus high amyloid linked to cognitive decline

A three-year study of 217 healthy older adults (63-89) enrolled in the Harvard Aging Brain Study, has found that higher amyloid-beta levels in combination with lower social engagement was associated with greater cognitive decline over three years. Lower social engagement wasn’t associated with cognitive decline in those with a lower amyloid-beta burden.

https://www.eurekalert.org/pub_releases/2019-06/bawh-scl062819.php

Reference: 

Sommerlad, A., Sabia, S., Singh-Manoux, A., Lewis, G., & Livingston, G. (2019). Association of social contact with dementia and cognition: 28-year follow-up of the Whitehall II cohort study. PLOS Medicine, 16(8), e1002862. https://doi.org/10.1371/journal.pmed.1002862

Biddle, K et al, "Social Engagement and Amyloid-b-Related Cognitive Decline in Cognitively Normal Older Adults." American Journal of Geriatric Psychiatry. DOI: https://doi.org/10.1016/j.jagp.2019.05.005

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Sleep problems linked to age-related cognitive problems

  • A very large Canadian study found that older adults with chronic insomnia performed significantly worse on cognitive tests.
  • A small study links older adults' increasing difficulties with consolidating memories to poorer synchronization of brainwaves during sleep.
  • A fruitful study shows that oxidative stress drives sleep, and that this is regulated by a specific molecule that monitors the degree of oxidative stress.

Chronic insomnia linked to memory problems

Data from 28,485 older Canadians (45+) found that those with chronic insomnia performed significantly worse on cognitive tests than those who had symptoms of insomnia without any noticable impact on their daytime functioning and those with normal sleep quality. The main type of memory affected was declarative memory (memory of concepts, events and facts).

Chronic insomnia is characterized by trouble falling asleep or staying asleep at least three nights a week for over three months with an impact on daytime functioning (mood, attention, and daytime concentration).

https://www.eurekalert.org/pub_releases/2019-05/cu-cia051519.php

Poor brainwave syncing behind older adults failure to consolidate memories

We know that memories are consolidated during sleep, and that for some reason this consolidation becomes more difficult with age. Now a new study shows why.

To consolidate memories (move them into long-term storage), low and speedy brain waves have to sync up at exactly the right moment during sleep. These brain rhythms synchronize perfectly in young adults, but in old age, it seems, slow waves during non-rapid eye movement (NREM) sleep are not so good at making timely contact with the speedy electrical bursts known as “spindles.”

These difficulties are thought to be due to atrophy of the gray matter in the medial frontal cortex.

The study compared the overnight memory of 20 healthy young adults to that of 32 healthy older adults (mostly in their 70s). Before going to sleep, participants learned and were then tested on 120 word sets. They were tested again in the morning. EEG results from their sleeping brains showed that in older people, the spindles consistently peaked early in the memory-consolidation cycle and missed syncing up with the slow waves.

http://www.futurity.org/memories-sleep-older-adults-1633432/

https://www.eurekalert.org/pub_releases/2017-12/uoc--obd121417.php

Oxidative stress governs sleep

A fruitfly study has shown how oxidative stress leads to sleep. Fruitflies (and, it is believed, humans) have sleep-control neurons that act like an on-off switch: if the neurons are electrically active, the fly is asleep; when they are silent, the fly is awake. The switch is triggered, it appears, by an electrical current that flows through two ion channels, and this, it now appears, is regulated by a small molecule called NADPH.

The state of NADPH reflects the degree of oxidative stress. Sleeplessness causes oxidative stress, driving the behavior of NADPH.

I'm wildly speculating here, but is it possible that increased sleep problems often found with age are linked to a growing inability of this molecule to sensitively monitor the degree of oxidative stress, perhaps due to high levels of oxidative stress??

https://www.eurekalert.org/pub_releases/2019-03/uoo-saa032119.php

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How blood flow is controlled in the brain

  • A study shows that blood is stored in the blood vessels in the space between the brain and skull, and its flow  is closely linked to the flow of cerebrospinal fluid in and out of the brain's ventricles.
  • A second study shows that capilleries, the smallest blood vessels in the brain, monitor the flow of blood within the brain and actively direct it to the areas that need it the most.

Increases in brain activity are matched by increases in blood flow. Neurons require a huge amount of energy, but can’t store it themselves, so must rely on blood to deliver the nutrients they need.

Two new studies help explain how blood flow is controlled.

The first study found blood appears to be stored in the blood vessels in the space between the brain and skull.

When the heart pumps blood into cranium, only a fraction of it flows into the capillaries that infuse the brain. The arteries in the cranium expand to store the excess blood. This expansion pushes out cerebrospinal fluid into the spinal column. When the heart relaxes, the drop in the pressure pushing blood through the arteries causes them to contract and the blood is pushed into the brain's capillaries. This in turn forces used blood out of the brain into the veins between it and the skull. These cerebral veins expand to store this blood as it leaves the brain.

Crucially, the study shows that the flow of blood in the veins leading out of the cranium is closely linked to the flow of cerebrospinal fluid in and out of the brain's ventricles.

The second study looked at what happens further down the track.

It had been thought that capillaries were passive tubes and the arterioles were the source of action — but the area covered by capillaries vastly surpasses the area covered by arterioles. So new findings make sense: that capillaries actively control blood flow by acting like a series of wires, transmitting electrical signals to direct blood to the areas that need it most.

To do this, capillaries rely on a protein (an ion channel) that detects increases in potassium during neuronal activity. Increased activity of this channel facilitates the flow of ions across the capillary membrane, thereby creating a small electrical current that communicates the need for additional blood flow to the arterioles, resulting in increased blood flow to the capillaries.

If the potassium level is too high, however, this mechanism can be disabled. This may be involved in a broad range of brain disorders.

https://www.eurekalert.org/pub_releases/2017-05/lbu-ffi050217.php

https://www.eurekalert.org/pub_releases/2017-03/lcom-ei032417.php

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Inflammation linked to brain health

  • Study indicates APOE4 carriers are only at greater Alzheimer's risk if they have chronic inflammation.
  • Large study finds increasing inflammation linked to more white matter damage.
  • Common causes of chronic inflammation include cardiovascular disease, heart failure, diabetes, high blood pressure and infections.

Link found between chronic inflammation and Alzheimer's gene risk

Data from the Framingham Heart Study has found carriers of the ApoE4 gene were much more likely to develop Alzheimer’s if they also had chronic low-grade inflammation. Indeed, the researchers suggest that, in the absence of inflammation, there might be no difference of Alzheimer's risk between ApoE4 and non-ApoE4 carriers.

https://www.eurekalert.org/pub_releases/2018-10/buso-lfb101818.php

Mid- to late-life increases in chronic inflammation age brain

Data from 1,532 participants in a long-running study, in which participants were tested five times every 3 years (on average), found that those who showed increasing inflammation had greater abnormalities in the brain's white matter structure.

90 people transitioned from low to persistently elevated C-reactive protein during midlife, indicating increasing inflammation. Their brains appear similar to that of a person 16 years older, researchers estimate.

Common causes of chronic inflammation include cardiovascular disease, heart failure, diabetes, high blood pressure and infections such as hepatitis C or HIV.

61% of participants were women, and 28% were African-American. At the final visit, participants were an average age of 76.

https://www.eurekalert.org/pub_releases/2018-07/jhm-mtl070218.php

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Smoking, hypertension, diabetes & obesity each linked to poor brain health

  • A large study has found that smoking, high blood pressure, diabetes, and obesity are each linked to more brain atrophy, and damage to white matter.
  • The more of these you have, the greater the shrinkage and damage.

Brain scans of 9,772 people aged 44 to 79, who were enrolled in the UK Biobank study, have revealed that smoking, high blood pressure, high pulse pressure, diabetes, and high BMI — but not high cholesterol — were all linked to greater brain shrinkage, less grey matter and less healthy white matter.

Smoking, high blood pressure, and diabetes were the most important factors, but there was also a compound effect, with the number of vascular risk factors being associated with greater damage to the brain. On average, those with the highest vascular risk had nearly 3% less volume of grey matter, and one-and-a-half times the damage to their white matter, compared to people who had the lowest risk.

The brain regions affected were mainly those involved in ‘higher-order’ thinking, and those known to be affected early in the development of dementia.

The associations were as strong for middle-aged adults as for older ones, suggesting the importance of tackling these factors early.

While the effect size was small, the findings emphasize how vulnerable the brain is to vascular factors even in relatively healthy adults. This also suggests the potential of lifestyle changes for fighting cognitive decline.

Although this study didn't itself examine cognitive performance in its participants, other studies have shown links between cognitive impairment and vascular risk factors, particularly diabetes, obesity, hypertension, and smoking.

https://www.eurekalert.org/pub_releases/2019-03/esoc-shb030719.php

Cognitive decline in type 2 diabetes linked to white matter hyperintensities

While type 2 diabetes has been associated with cognitive problems, the mechanism has been unclear. Now a study involving 93 people with type 2 diabetes has found that greater white matter hyperintensities (indicative of cerebral small vessel disease) were associated with decreased processing speed (but not with memory or executive function).

https://www.eurekalert.org/pub_releases/2018-09/w-rem091818.php

Reference: 

Cox, Simon R. et al. 2019. Associations between vascular risk factors and brain MRI indices in UK Biobank. European Heart Journal. doi:10.1093/eurheartj/ehz100

[4395] Mankovsky, B., Zherdova N., van den Berg E., Biessels G.-J., & de Bresser J.
(2018).  Cognitive functioning and structural brain abnormalities in people with Type 2 diabetes mellitus.
Diabetic Medicine. 35(12), 1663 - 1670.

 

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