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Nice to hear that a new study found that across the lifespan, human brains are capable of producing new neurons (neurogenesis). Neurons are nerve cells, what we popularly call brain cells, and are the basic working unit of the nervous system. The human brain contains about 100 billion neurons.

The researchers did find some age differences (e.g. with age there was less neuroplasticity or the brain's ability to reorganize itself by forming new neural connections, and a decline in angiogenesis - the development of new blood vessels). But still... the findings are reassuring. Interesting how the researchers did the study. They examined 28 brains (specifically, newly formed neurons and the state of blood vessels within the hippocampus) right after death from previously healthy people (aged 14 to 79), who died suddenly.

While they found age differences, they did not find gender differences. The researchers summarized that healthy older subjects without cognitive impairment (meaning they were mentally healthy), neuropsychiatric disease, or treatment (e.g. depression drugs or psychotropic drugs) display preserved neurogenesis (produce new neurons) throughout life. From Science Daily:

Older adults grow just as many new brain cells as young people

Researchers show for the first time that healthy older men and women can generate just as many new brain cells as younger people.

There has been controversy over whether adult humans grow new neurons, and some research has previously suggested that the adult brain was hard-wired and that adults did not grow new neurons. This study, to appear in the journal Cell Stem Cell on April 5, counters that notion. Lead author Maura Boldrini, associate professor of neurobiology at Columbia University, says the findings may suggest that many senior citizens remain more cognitively and emotionally intact than commonly believed. ...continue reading "Some Good News About The Aging Brain"

This recent study adds to the body of knowledge of what negative major life events (resulting in lots of stress, anxiety, worry) does to a middle-aged person's health. Negative life events could be an interpersonal conflict (e.g. divorce), a death in the family, financial hardship, and serious medical emergencies. Using MRIs, the researchers found that each fateful life event (FLE), especially those that involve interpersonal relationships, accelerates brain aging about .37 years (about a third of a year). And the more negative life events, the bigger the effect. From Science Daily:

Negative fateful life events and the brains of middle-aged men

Conflict, a death in the family, financial hardship and serious medical crises are all associated with accelerated physical aging. In a new study, researchers at the University of California San Diego School of Medicine found that such negative fateful life events -- or FLEs -- appear to also specifically accelerate aging in the brain

Writing in the journal Neurobiology of Aging, a research team, led by senior author William S. Kremen, PhD, professor of psychiatry and co-director of the Center for Behavior Genetics of Aging at UC San Diego School of Medicine, found that major adverse events in life, such as divorce, separation, miscarriage or death of a family member or friend, can measurably accelerate aging in the brains of older men, even when controlling for such factors as cardiovascular risk, alcohol consumption, ethnicity and socioeconomic status, which are all associated with aging risk. 

Specifically, they found that on average, one FLE was associated with an increase in predicted brain age difference (PBAD) of 0.37 years. In other words, a single adverse event caused the brain to appear physiologically older by approximately one-third of a year than the person's chronological age, based upon magnetic resonance imaging (MRI). 

The researchers studied 359 men, ages 57 to 66 years old, participating in the Vietnam Era Twin Study of Aging (VETSA). Researchers asked participants to tally a list of life-changing events over the past two years .... All participants underwent MRI exams and further physical and psychological assessments within one month of completing the most recent self-reports. The MRIs assessed physiological aspects of the brain, such as volume and cortical thickness -- a measure of the cerebral cortex or outer layer of the brain linked to consciousness, memory, attention, thought and other key elements of cognition.

Hatton said exposure to chronic stress has long been associated with biological weathering and premature aging, linked, for example, to oxidative and mitochondrial damage in cells, impaired immune system response and genomic changes. The study's authors said their findings provide a possible link between molecular aging and brain structure changes in response to major stressful life events. They do note that the study was a snapshot of a narrow demographic: older, predominantly white, males. It is not known whether females or other ethnicities would show similar findings.

The last post dealt with the link between highly processed food and increased risk of cancer. Now an interesting article written by Dr. Lisa Mosconi (Associate Director of the Alzheimer’s Prevention Clinic at Weill Cornell Medical College/New York -Presbyterian Hospital) refers to that study when discussing research about lifestyles (and especially diet) and later Alzheimer's disease.

It'll be interesting to see how this research plays out - is her approach stressing diet (and avoiding ultra-processed food and trans fats) and lifestyle correct or not? Much of what she says definitely makes sense and is supported by research, such as the negative health effects of chronic inflammation, and how eating actual, real foods has beneficial health effects. On the other hand, vitamin, mineral, and fish oil supplements generally don't show those health benefits (as she discusses here).

Currently there are a number of theories about causes of Alzheimer's disease (including the role of microbes), as well as a number of drug treatments that so far have gone nowhere. If Dr. Mosconi's research interests you, then read the interview she did in 2017. [In the interview she talks about the importance of exercise, intellectual stimulation, social networks, and the benefits of eating real foods rather than supplements. She recommends: drink water, eat fish, eat vegetables and fruit, eat glucose rich foods, and don't eat highly processed and fast foods.]  From Quartz:

The road to Alzheimer’s disease is lined with processed foods

Dementia haunts the United States. There’s no one without a personal story about how dementia has touched someone they care for. But beyond personal stories, the broader narrative is staggering: By 2050, we are on track to have almost 15 million Alzheimer’s patients in the US alone. ... It’s an epidemic that’s already underway—but we don’t recognize it as such. The popular conception of Alzheimer’s is as an inevitable outcome of aging, bad genes, or both.  ...continue reading "Ultra-Processed Foods and Alzheimer’s?"

A number of recent studies and articles have discussed the effectiveness of diet in treating or preventing depression with the main conclusion that yes, it helps. Now an observational study (that will be presented in April) found that elderly people following the DASH diet most closely were 11% less likely to become depressed over time than those that did not.

Researchers studying 964 elderly participants over six and a half years found that those who followed the DASH diet, which emphasizes whole grains, fruits, and vegetables, had lower rates of depression, while those who ate a traditional Western diet were more prone to depression. The DASH (Dietary Approaches to Stop Hypertension) diet also emphasizes low sodium (salt) to lower blood pressure, as well as foods rich in nutrients (such as potassium, calcium, and magnesium) that are thought to lower blood pressure.

The study's lead author L. J. Cherian (at Rush Medical Center in Chicago) said that "we need to view food as medicine”. Yes. Eating more fruits and vegetables, whole grains, legumes, seeds, nuts have many health benefits (such as cardiovascular benefits, improving the gut microbes) -  a win-win. From Science Daily:

Diet shown to reduce stroke risk may also reduce risk of depression

People who eat vegetables, fruit and whole grains may have lower rates of depression over time, according to a preliminary study that will be presented at the American Academy of Neurology's 70th Annual Meeting in Los Angeles, April 21 to 27, 2018. The study found that people whose diets adhered more closely to the Dietary Approaches to Stop Hypertension (DASH) diet were less likely to develop depression than people who did not closely follow the diet. In addition to fruit and vegetables, the DASH diet recommends fat-free or low-fat dairy products and limits foods that are high in saturated fats and sugar. Studies have shown health benefits such as lowering high blood pressure and bad cholesterol (LDL), along with lowering body weight ...continue reading "DASH Diet Linked To Lower Rate of Depression"

Study after study has found negative health effects from frequent heavy drinking of alcohol, including a number of cancers. On the other hand, light to moderate drinking seems to have some health benefits (here and here). Recently a large study conducted in France found that chronic heavy drinking, which has resulted in alcohol use disorders (alcohol abuse, alcohol dependence, or alcoholism), is the biggest risk factor for developing dementia, especially early onset dementia. Only people with alcohol use disorders which resulted in them being hospitalized were included in the study.

But the surprising thing was that lower levels of "chronic heavy drinking" doesn't seem so much - it's daily consumption of more than 60 grams of pure alcohol  for men, and more than 40 grams of pure alcohol for women. In the United States, a standard drink contains about 14 grams of alcohol - which is a 12 ounce (350 ml) glass of beer, a 5 ounce (150 ml) glass of 12% wine, or a 1.5 ounce (44 ml) glass of spirits. In other words, drinking 3 glasses of wine daily (or more) is heavy drinking for a woman. (Note: The Centers for Disease Control (CDC) views moderate drinking as 1 glass of wine daily for women, and 2 glasses of wine daily for men).  ...continue reading "Heavy Drinking And Risk of Dementia"

Interesting new research found health benefits to the brain from daily low intake of alcohol (equivalent to about 2 1/2 drinks per day). The University of Rochester (in New York) researchers found that while low daily (chronic) levels of alcohol were beneficial to the brain's glymphatic system, higher daily levels or binge drinking was not. And the low daily levels of alcohol intake was also better for the glymphatic system than no alcohol at all (the control group). In 2015 this same research team described the glymphatic system as not just the brain’s “waste-clearance system,” but as potentially helping fuel the brain by transporting glucose, lipids, amino acids, and neurotransmitters.

I'm sure this study will be greeted by many as great news, but remember it was done with MICE, and not humans, so one should be cautious in generalizing the results. But the researchers think that it does apply to humans, and may explain why some studies find some health benefits to low levels of daily alcohol intake, even better than no alcohol, and many negative effects to higher levels of alcohol intake - thus the J-shaped curve of effects seen in studies. [NOTE: Studies also find that alcohol consumption can cause cancer, and this is dose related. Studies find the Mediterranean diet (which includes low to moderate levels of alcohol) beneficial for brain health.]

By the way - no, the mice didn't receive wine as the press release from the Univ. of Rochester says. The mice actually received "intraperitoneal injections of low, intermediate, and high doses of ethanol" or just plain saline (the control group). From Science Daily:

In wine, there's health: Low levels of alcohol good for the brain

While a couple of glasses of wine can help clear the mind after a busy day, new research shows that it may actually help clean the mind as well. The new study, which appears in the journal Scientific Reports, shows that low levels of alcohol consumption tamp down inflammation and helps the brain clear away toxins, including those associated with Alzheimer's disease.

"Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system," said Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and lead author of the study. "However, in this study we have shown for the first time that low doses of alcohol are potentially beneficial to brain health, namely it improves the brain's ability to remove waste." The finding adds to a growing body of research that point to the health benefits of low doses of alcohol. While excessive consumption of alcohol is a well-documented health hazard, many studies have linked lower levels of drinking with a reduced risk of cardiovascular diseases as well as a number of cancers.

Nedergaard's research focuses on the glymphatic system, the brain's unique cleaning process that was first described by Nedergaard and her colleagues in 2012. They showed how cerebral spinal fluid (CSF) is pumped into brain tissue and flushes away waste, including the proteins beta amyloid and tau that are associated with Alzheimer's disease and other forms of dementia. Subsequent research has shown that the glymphatic system is more active while we sleep, can be damaged by stroke and trauma, and improves with exercise.

The new study, which was conducted in mice, looked at the impact of both acute and chronic alcohol exposure. When they studied the brains of animals exposed to high levels of alcohol over a long period of time, the researchers observed high levels of a molecular marker for inflammation, particularly in cells called astrocytes which are key regulators of the glymphatic system. They also noted impairment of the animal's cognitive abilities and motor skills.

Animals that were exposed to low levels of alcohol consumption, analogous to approximately 2 ½ drinks per day, actually showed less inflammation in the brain and their glymphatic system was more efficient in moving CSF through the brain and removing waste, compared to control mice who were not exposed to alcohol. The low dose animals' performance in the cognitive and motor tests was identical to the controls.

"The data on the effects of alcohol on the glymphatic system seemingly matches the J-shaped model relating to the dose effects of alcohol on general health and mortality, whereby low doses of alcohol are beneficial, while excessive consumption is detrimental to overall health" said Nedergaard. "Studies have shown that low-to-moderate alcohol intake is associated with a lesser risk of dementia, while heavy drinking for many years confers an increased risk of cognitive decline. This study may help explain why this occurs. Specifically, low doses of alcohol appear to improve overall brain health." [Original study. Especially interesting is the Introduction & Discussion sections.]

The spice turmeric is a very popular supplement nowadays, believed to have all sorts of health benefits due to the curcumin in it (e.g. that it is anticancer, anti-Alzheimer's, anti inflammatory). And yes, studies in the lab (in vitro and in vivo) look very promising. However, a large 2017 review of existing studies also found evidence that "curcumin is unstable under physiological conditions and not readily absorbed by the body, properties that make it a poor therapeutic candidate". In other words, the hype for curcumin supplements is not matching the reality, especially or probably because it is so poorly absorbed by humans. But researchers keep trying. And keep in mind that turmeric has other compounds in it also - it is not just curcumin and nothing else.

A "double-blind, placebo-controlled clinical trial" is the best evidence for something being effective. That means a study where people are randomly assigned to groups, no one actually knows who is getting what, and there is a placebo group that is getting a "sham" treatment. A recent study did exactly that in testing a new formulation of curcumin (Theracurmin) that was easily absorbed (bioavailable) by the persons participating in the study.

And yes - they found health benefits, specifically improvements in memory and attention in those persons taking the curcumin supplements over a 18 month period (as compared to those taking a placebo and whose memory and attention deteriorated over that time). The subjects (who were between 50 and 90 years of age) did not have dementia at the start of the study, but were showing signs of "normal aging" or had mild neurocognitive disorder. Brain scans (before and after treatment) suggested that the behavioral and cognitive benefits from curcumin were associated with "decreases in plaque and tangle accumulation in brain regions moduating mood and memory" - so it had anti-inflammatory and/or anti-amyloid brain effects.

So...  Stay tuned. Meanwhile, perhaps frequent eating of foods containing turmeric may also have beneficial effects, as some studies suggest. From Science Daily:

Curcumin improves memory and mood

Lovers of Indian food, give yourselves a second helping: Daily consumption of a certain form of curcumin -- the substance that gives Indian curry its bright color -- improved memory and mood in people with mild, age-related memory loss, according to the results of a study conducted by UCLA researchers. .... Found in turmeric, curcumin has previously been shown to have anti-inflammatory and antioxidant properties in lab studies. It also has been suggested as a possible reason that senior citizens in India, where curcumin is a dietary staple, have a lower prevalence of Alzheimer's disease and better cognitive performance.

The double-blind, placebo-controlled study involved 40 adults between the ages of 50 and 90 years who had mild memory complaints. Participants were randomly assigned to receive either a placebo or 90 milligrams of curcumin twice daily for 18 months. All 40 subjects received standardized cognitive assessments at the start of the study and at six-month intervals, and monitoring of curcumin levels in their blood at the start of the study and after 18 months. Thirty of the volunteers underwent positron emission tomography, or PET scans, to determine the levels of amyloid and tau in their brains at the start of the study and after 18 months.

The people who took curcumin experienced significant improvements in their memory and attention abilities, while the subjects who received placebo did not, Small said. In memory tests, the people taking curcumin improved by 28 percent over the 18 months. Those taking curcumin also had mild improvements in mood, and their brain PET scans showed significantly less amyloid and tau signals in the amygdala and hypothalamus than those who took placebos. The amygdala and hypothalamus are regions of the brain that control several memory and emotional functions. [Original study.]

Many people look forward to retirement, thinking of all the wonderful things they will finally be able to do.  However, what no one expects is that retirement can have a negative effect on their cognitive functioning. This is what a long-term study carried out by the University of London in the United Kingdom found. The study tracked 3,433 civil servants for the 14 years before retirement, and then another 14 years afterward. The participants were given periodic examinations to assess their cognitive functioning (verbal memory, abstract reasoning, etc.).

The researchers found that when people did eventually retire, they experienced decline in their verbal memory 38 percent faster than before they stopped working. They concluded that the act of retirement significantly accelerates verbal memory decline. They also found that a higher employment grade was protective against verbal memory decline while people were still working, but this ‘protective effect’ was lost when individuals retired, resulting in a similar rate of decline after retirement across the different employment grades.

The researchers pointed out that the adverse effect of retirement on verbal memory is consistent with the results of other studies. That's why they stress how important it is to continue undertaking mentally stimulating activities after retirement in order to prevent this decline. The researchers felt that the study results supported the ‘use it or lose it’ hypothesis regarding verbal memory function. But the good news was that retirement seemed to have little impact on other domains of cognitive functions, such as abstract reasoning and verbal fluency. They just showed normal age-related declines over time.

From European Journal of Epidemiology: Effect of retirement on cognitive function: the Whitehall II cohort study

According to the ‘use it or lose it’ hypothesis, a lack of mentally challenging activities might exacerbate the loss of cognitive function. On this basis, retirement has been suggested to increase the risk of cognitive decline, but evidence from studies with long follow-up is lacking. We tested this hypothesis in a cohort of 3433 civil servants who participated in the Whitehall II Study, including repeated measurements of cognitive functioning up to 14 years before and 14 years after retirement. Piecewise models, centred at the year of retirement, were used to compare trajectories of verbal memory, abstract reasoning, phonemic verbal fluency, and semantic verbal fluency before and after retirement.

We found that all domains of cognition declined over time. Declines in verbal memory were 38% faster after retirement compared to before, after taking account of age-related decline. In analyses stratified by employment grade, higher employment grade was protective against verbal memory decline while people were still working, but this ‘protective effect’ was lost when individuals retired, resulting in a similar rate of decline post-retirement across employment grades. We did not find a significant impact of retirement on the other cognitive domains. In conclusion, these findings are consistent with the hypothesis that retirement accelerates the decline in verbal memory function. This study points to the benefits of cognitively stimulating activities associated with employment that could benefit older people’s memory.

Interesting study results - being overweight (a higher body mass index or BMI) is linked to dementia more than 20 years later, but in the few years before dementia onset body mass index (BMI) is lower in those who develop dementia than in those who don't develop dementia. The researchers hypothesize that 2 processes are going on:  A higher BMI (overweight or obese) in mid-life is harmful (a direct effect), and then there is weight loss during the preclinical dementia phase. Bottom line: best is a normal weight in mid-life to try to prevent dementia later on in life. From Science Daily:

Obesity increases dementia risk

People who have a high body mass index (BMI) are more likely to develop dementia than those with a normal weight, according to a new UCL-led study. The study, published in the Alzheimer's & Dementia journal, analysed data from 1.3 million adults living in the United States and Europe. The researchers also found that people near dementia onset, who then go on to develop dementia, tend to have lower body weight than their dementia-free counterparts.

"The BMI-dementia association observed in longitudinal population studies, such as ours, is actually attributable to two processes," said lead author of the study, Professor Mika Kivimäki (UCL Institute of Epidemiology & Health). "One is an adverse effect of excess body fat on dementia risk. The other is weight loss due to pre-clinical dementia. For this reason, people who develop dementia may have a higher-than-average body mass index some 20 years before dementia onset, but close to overt dementia have a lower BMI than those who remain healthy."

In this study, researchers from across Europe pooled individual-level data from 39 longitudinal population studies from the United States, the United Kingdom, France, Sweden, and Finland. A total of 1,349,857 dementia-free adults participated in these studies and their weight and height were assessed. Dementia was ascertained using linkage to electronic health records obtained from hospitalisation, prescribed medication and death registries.

A total of 6,894 participants developed dementia during up to 38 years of follow-up. Two decades before symptomatic dementia, higher BMI predicted dementia occurrence: each 5-unit increase in BMI was associated with a 16-33% higher risk of this condition (5 BMI units is 14.5 kg for a person 5'7" (170 cm) tall, approximately the difference in weight between the overweight and normal weight categories or between the obese and overweight categories). In contrast, the mean level of BMI during pre-clinical stage close to dementia onset was lower compared to that in participants who remained healthy. [Original study.]

It's reassuring to see that there are positive things one can do to maintain brain health as one ages. With normal aging, the brain typically shrinks a little with each passing decade  - starting from about the age of 40. But one recent Australian study, which reviewed the results of many other studies, found that exercise slows down this shrinkage in humans, specifically in the left hippocampus. That is, that aerobic exercise had a significant positive effect on the volume of the left hippocampus. This matches the result of animal studies.

The researchers pointed out that some studies found increases also in other parts of the human brain from exercise (e.g. in the white matter), but that they did not look at and review those studies. [See posts on research.] The good news is that positive effects were from exercise programs generally lasting less than 12 months. But it is unknown which type of exercise is best, or whether it is general "activity level and movement" that is most important. Bottom line: Get out there and move, move, move for brain health. And for cardiorespiratory fitness. It's all linked and it's all good. From Medical Xpress:

Exercise maintains brain size, new research finds

Aerobic exercise can improve memory function and maintain brain health as we age, a new Australian-led study has found. In a first of its kind international collaboration, researchers from Australia's National Institute of Complementary Medicine at Western Sydney University and the Division of Psychology and Mental Health at the University of Manchester in the UK examined the effects of aerobic exercise on a region of the brain called the hippocampus, which is critical for memory and other brain functions.

Brain health decreases with age, with the average brain shrinking by approximately five per cent per decade after the age of 40. Studies in mice and rats have consistently shown that physical exercise increases the size of the hippocampus but until now evidence in humans has been inconsistent.

The researchers systematically reviewed 14 clinical trials which examined the brain scans of 737 people before and after aerobic exercise programs or in control conditions. The participants included a mix of healthy adults, people with mild cognitive impairment such as Alzheimer's and people with a clinical diagnosis of mental illness including depression and schizophrenia. Ages ranged from 24 to 76 years with an average age of 66. The researchers examined effects of aerobic exercise, including stationary cycling, walking, and treadmill running. The length of the interventions ranged from three to 24 months with a range of 2-5 sessions per week.

Overall, the results – published in the journal NeuroImage– showed that, while exercise had no effect on total hippocampal volume, it did significantly increase the size of the left region of the hippocampus in humans.

"When you exercise you produce a chemical called brain-derived neurotrophic factor (BDNF), which may help to prevent age-related decline by reducing the deterioration of the brain," Mr Firth said. "Our data showed that, rather than actually increasing the size of the hippocampus per se, the main 'brain benefits' are due to aerobic exercise slowing down the deterioration in brain size. In other words, exercise can be seen as a maintenance program for the brain.".... Interestingly, physical exercise is one of the very few 'proven' methods for maintaining brain size and functioning into older age.