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Another article was published this month raising the issue of whether Alzheimer's disease is caused by a microbe - which can explain why all the medicines and experimental drugs aimed at treating the "tangles" or amyloid plaques in the brain are not working as a treatment (because that's the wrong approach). The microbe theory of Alzheimer's disease has been around for decades, but only recently is it starting to be taken seriously. Some of the microbes found in patients with Alzheimer's disease (from analyses of both normal brains and Alzheimer patient brains after death): fungi, Borrelia burgdorferi (Lyme disease), herpes simplex virus Type 1 (HSV1), and Chlamydia pneumoniae.

The general hypotheses seem to be that Alzheimer’s disease is caused by infection, but it isn't linked to any one pathogenic microbe.  Instead, the evidence seems to support that "following infection, certain pathogens gain access to brain, where immune responses result in the accumulation of amyloid-β, leading to plaque formation". So the microbes act as "triggers" for Alzheimer's disease - the microbes get into the brain, and immune responses somehow eventually result in the amyloid plaques and Alzheimer's disease. From The Scientist:

Do Microbes Trigger Alzheimer’s Disease?

In late 2011, Drexel University dermatology professor Herbert Allen was astounded to read a new research paper documenting the presence of long, corkscrew-shape bacteria called spirochetes in postmortem brains of patients with Alzheimer’s disease. Combing data from published reports, the International Alzheimer Research Center’s Judith Miklossy and colleagues had found evidence of spirochetes in 451 of 495 Alzheimer’s brains. In 25 percent of cases, researchers had identified the spirochete as Borrelia burgdorferi, a causative agent of Lyme disease. Control brains did not contain the spirochetes.

Allen had recently proposed a novel role for biofilms—colonies of bacteria that adhere to surfaces and are largely resistant to immune attack or antibiotics—in eczema....  Allen knew of recent work showing that Lyme spirochetes form biofilms, which led him to wonder if biofilms might also play a role in Alzheimer’s disease. When Allen stained for biofilms in brains from deceased Alzheimer’s patients, he found them in the same hippocampal locations as amyloid plaquesToll-like receptor 2 (TLR2), a key player in innate immunity, was also present in the same region of the Alzheimer’s brains but not in the controls. He hypothesizes that TLR2 is activated by the presence of bacteria, but is locked out by the biofilm and damages the surrounding tissue instead.

Spirochetes, common members of the oral microbiome, belong to a small set of microbes that cross the blood-brain barrier when they’re circulating in the blood, as they are during active Lyme infections or after oral surgery. However, the bacteria are so slow to divide that it can take decades to grow a biofilm. This time line is consistent with Alzheimer’s being a disease of old age, Allen reasons, and is corroborated by syphilis cases in which the neuroinvasive effects of spirochetes might appear as long as 50 years after primary infection.

Allen’s work contributes to the revival of a long-standing hypothesis concerning the development of Alzheimer’s. For 30 years, a handful of researchers have been pursuing the idea that pathogenic microbes may serve as triggers for the disease’s neuropathology..... In light of continued failures to develop effective drugs, some researchers, such as Harvard neurobiologist Rudolph Tanzi, think it’s high time that more effort and funding go into alternative theories of the disease. “Any hypothesis about Alzheimer’s disease must include amyloid plaques, tangles, inflammation—and, I believe, infection.”

Herpes simplex virus type 1 (HSV1) can acutely infect the brain and cause a rare but very serious encephalitis. In the late 1980s, University of Manchester molecular virologist Ruth Itzhaki noticed that the areas of the brain affected in HSV1 patients were the same as those damaged in patients with Alzheimer’s disease. Knowing that herpes can lie latent in the body for long periods of time, she began to wonder if there was a causal connection between the infection and the neurodegenerative disorder.

Around the same time, neuropathologist Miklossy, then at the University of Lausanne in Switzerland, was detailing the brain damage caused by spirochetes—both in neurosyphilis and neuroborrelia, a syndrome caused by Lyme bacteria. She happened upon a head trauma case with evidence of bacterial invasion and plaque formation, and turned her attention to Alzheimer’s. She isolated spirochetes from brain tissue in 14 Alzheimer’s patients but detected none in 13 age-matched controls. In addition, monoclonal antibodies that target the amyloid precursor protein (APP)—which, when cleaved, forms amyloid-β—cross-reacted with the spirochete species found, suggesting the bacteria might be the source of the protein.

Meanwhile, in the U.S., a third line of evidence linking Alzheimer’s to microbial infection began to emerge. While serving on a fraud investigation committee, Alan Hudson, a microbiologist then at MCP-Hahnemann School of Medicine in Philadelphia, met Brian Balin.... Soon, Balin began to send Hudson Alzheimer’s brain tissue to test for intracellular bacteria in the Chlamydia genus. Some samples tested positive for C. pneumoniae: specifically, the bacteria resided in microglia and astrocytes in regions of the brain associated with Alzheimer’s neuropathology, such as the hippocampus and other limbic system areas. Hudson had a second technician repeat the tests before he called Balin to unblind the samples. The negatives were from control brains; the positives all had advanced Alzheimer’s disease. "We were floored,” Hudson says.

Thus, as early as the 1990s, three laboratories in different countries, each studying different organisms, had each implicated human pathogens in the etiology of Alzheimer’s disease. But the suggestion that Alzheimer’s might have some microbial infection component was still well outside of the theoretical mainstream. Last year, Itzhaki, Miklossy, Hudson, and Balin, along with 29 other scientists, published a review in the Journal of Alzheimer’s Disease to lay out the evidence implicating a causal role for microbes in the disease.

The microbe theorists freely admit that their proposed microbial triggers are not the only cause of Alzheimer’s disease. In Itzhaki’s case, some 40 percent of cases are not explained by HSV1 infection. Of course, the idea that Alzheimer’s might be linked to infection isn’t limited to any one pathogen; the hypothesis is simply that, following infection, certain pathogens gain access to brain, where immune responses result in the accumulation of amyloid-β, leading to plaque formation.

Surprised...is how I felt after reading this study. According to the study, activity levels and exercise in mid-life are not linked to cognitive fitness and dementia later on in life. Instead, higher levels of physical activity and exercise has a beneficial effect on the brain in the short term (e.g., within 2 years or so). This finding of no long-term benefits, but only short-term benefits to the brain from exercise, is contrary to some other (cross-sectional) studies, but is supported by another recent study ("no evidence of a neuroprotective effect of physical activity").

The beauty of this study is that it followed 646 people for 30 years (from a median age of 46 years in 1978 and 77 years in 2008). The negative is that according to this study, physical exercise in mid-life does not seem to delay or prevent the onset of dementia and Alzheimer's later on in life. Eh... From Medical Xpress:

Physical activity in midlife not linked to cognitive fitness in later years, long-term study shows

A study led by Johns Hopkins Bloomberg School of Public Health researchers that tracked activity levels of 646 adults over 30 years found that, contrary to previous research, exercise in mid-life was not linked to cognitive fitness in later yearsThe finding suggests that physical activity may not help maintain cognitive function, or help avoid or delay the onset of the debilitating conditions like dementia and Alzheimer's

The study, which appears online in the Journal of Alzheimer's Disease, did find that activity levels among study participants in the later years were associated with high cognitive function two years later. This supports earlier research findings that exercise may help to maintain cognitive fitness in the short term.

There is no known treatment or cure for Alzheimer's or dementia, syndromes that involves declining memory, confusion and eventually limited ability to perform daily tasks. To date, there are no preventive measures, such as physical exercise, brain games or a diet regimen, that have been proven to help delay or altogether prevent its onset. The researchers undertook the study because of a growing consensus that physical activity levels helps prevent Alzheimer's, however much of the evidence for this thinking is based on cross-sectional studies that compare responses from one group of participants with another at a given point in time or within a very short duration, typically several years..... That's where longitudinal studies, which look at the same group of participants over a long time, are more helpful.

The researchers used data from the Johns Hopkins Precursors study.... The researchers used responses from 1978 through 2008 from 646 participants (598 men, 48 women) to calculate so-called metabolic equivalents, which quantify physical activity levels. Participants were also asked whether they regularly exercise to a sweat. The team administered cognitive tests in 2008, and, using participants' medical records, scored for dementia through 2011. The researchers identified 28, or 4.5 percent of the cohort, to have Alzheimer's.

No physical activity measure in mid-life was associated with late-life cognitive fitness or onset of dementia. The study confirmed findings of other cross-sectional studies, that higher levels of physical activity and exercise measured close in time to the cognitive testing were associated with better cognitive functioning. The authors also looked at whether patterns of change in physical activity levels over the life span were associated with cognitive health and found no relationships.

The idea that exercise might play a role in preventing or limiting Alzheimer's makes sense, the researchers say, because physical activity, at least in mouse models, has shown less accumulation of B-amyloid plaques, which are thought to play a role in dementia, including Alzheimer's. In addition, physical activity improves blood flow to the brain, which is linked to better cognitive performance. This may explain why studies find that exercise may contribute to cognitive fitness in the short term.

 This post is more on the theme of nanoparticles and human health. My last post was about a study that examined how inhaled nanoparticles  (for example, from air pollution) travel from the lungs to the bloodstream. Well, today's post is about a pretty shocking 2016 air pollution nanoparticle study which examined the brains (brain tissue) of 45 dead people  (ages 3 to 92) who had lived for a long time in two places with heavy  particulate air pollution - Mexico City and Manchester, England. Some of the British people also had Alzheimer's disease or dementia.

The researchers found evidence that minute nano-sized particles of magnetite from air pollution can find their way into the brain. There are 2 forms of magnetite (which is an iron ore) - one naturally occurring (jagged edges in appearance), and one found commonly in air pollution (smooth and rounded - from being created in the high temperatures of vehicle engines or braking systems). The researchers are concerned that the air pollution nanoparticles may increase the risk for brain diseases such as Alzheimer's.

One of the researchers (Prof Barbara Maher) has previously identified magnetite particles in samples of air gathered beside a busy road in Lancaster, England and outside a power station. She suspected that similar particles may be found in the brain samples, and that is what happened. "It's dreadfully shocking. When you study the tissue you see the particles distributed between the cells and when you do a magnetic extraction there are millions of particles, millions in a single gram of brain tissue - that's a million opportunities to do damage."..."It's a whole new area to investigate to understand if these magnetite particles are causing or accelerating neurodegenerative disease." However, it must be stressed that at this time there is no proven link between these magnetite particles and any neurodegenerative diseases. They're just wondering.... they call finding these pollution nanoparticles "suggestive observations".

From Medical Xpress: Toxic air pollution nanoparticles discovered in the human brain

Tiny magnetic particles from air pollution have for the first time been discovered to be lodged in human brains – and researchers think they could be a possible cause of Alzheimer's disease. Researchers at Lancaster University found abundant magnetite nanoparticles in the brain tissue from 37 individuals aged three to 92-years-old who lived in Mexico City and Manchester. This strongly magnetic mineral is toxic and has been implicated in the production of reactive oxygen species (free radicals) in the human brain, which are associated with neurodegenerative diseases including Alzheimer's disease.

Professor Barbara Maher, from Lancaster Environment Centre, and colleagues (from Oxford, Glasgow, Manchester and Mexico City) used spectroscopic analysis to identify the particles as magnetite. Unlike angular magnetite particles that are believed to form naturally within the brain, most of the observed particles were spherical, with diameters up to 150 nm, some with fused surfaces, all characteristic of high-temperature formation – such as from vehicle (particularly diesel) engines or open fires. The spherical particles are often accompanied by nanoparticles containing other metals, such as platinum, nickel, and cobalt.

Professor Maher said: "The particles we found are strikingly similar to the magnetite nanospheres that are abundant in the airborne pollution found in urban settings, especially next to busy roads, and which are formed by combustion or frictional heating from vehicle engines or brakes."

Other sources of magnetite nanoparticles include open fires and poorly sealed stoves within homes. Particles smaller than 200 nm are small enough to enter the brain directly through the olfactory nerve after breathing air pollution through the nose.....The results have been published in the paper 'Magnetite pollution nanoparticles in the human brain' by the Proceedings of the National Academy of Sciences.

A good discussion of the study in The Scientist: Environmental Magnetite in the Human Brain

Fig. S11. Image of magnetite nanoparticles from the exhaust plume of a diesel engine. Credit: Maher et al study, 2016.

09_05_magnetic_01  A microscopic image shows magnetic nanoparticles in the human brain. Credit: Barbara Maher et al study, 2016.

Image result for tea A study found that daily drinking of  tea (either black tea/oolong or green tea) is associated with a lower risk of "neurocognitive disorders" - in cognitive impairment in women, and in a lower risk of Alzheimer's disease in both men and women who are genetically predisposed to the disease (apolipoprotein E (APOE) genotype) - when compared to those who never or rarely drank tea. The researchers called long-term daily tea drinking as "neuroprotective".

The study followed 957 residents of Singapore for several years. All were "cognitively normal" when the study started (average age 64 1/2 years), but 72 people or 7.5% had developed neurocognitive disorders by the second follow-up (after 4 years). The study found that there was a dose-dependent relationship - the more tea that was drunk daily, the more protective it appeared to be. And it was most protective in those who consistently drank tea at both time points - when the study started and till the end. However, there was a gender difference - it seemed to protect women from neurocognitive disorders, but not men. But in those who were genetically predisposed to Alzheimer's - tea drinking was protective for both males and females. Further studies will follow up to see if the gender difference holds - they couldn't explain it.

The researchers also point out that tea drinking has a long history in Chinese culture as an natural "attention enhancer" and strong tea is drunk as to maintain alertness and concentration. Sounds a lot like why people drink coffee. From Medical Xpress:

Daily consumption of tea protects the elderly from cognitive decline

Tea drinking reduces the risk of cognitive impairment in older persons by 50 per cent and as much as 86 per cent for those who are genetically at risk of Alzheimer's. A cup of tea a day can keep dementia away, and this is especially so for those who are genetically predisposed to the debilitating disease, according to a recent study led by Assistant Professor Feng Lei from the Department of Psychological Medicine at National University of Singapore's (NUS) Yong Loo Lin School of Medicine. The longitudinal study involving 957 Chinese seniors aged 55 years or older has found that regular consumption of tea lowers the risk of cognitive decline in the elderly by 50 per cent, while APOE e4 gene carriers who are genetically at risk of developing Alzheimer's disease may experience a reduction in cognitive impairment risk by as much as 86 per cent.

He added, "Based on current knowledge, this long term benefit of tea consumption is due to the bioactive compounds in tea leaves, such as catechins, theaflavins, thearubigins and L-theanine. These compounds exhibit anti-inflammatory and antioxidant potential and other bioactive properties that may protect the brain from vascular damage and neurodegeneration. Our understanding of the detailed biological mechanisms is still very limited so we do need more research to find out definitive answers.

Image result for eggs Remember all the dietary advice that for years told us to avoid or limit consumption of eggs - that since they were high in cholesterol, they were bad for us and would increase our risk for heart disease? And the nonsense that we should only eat the egg whites while throwing out the yolks? Hah...That advice was wrong, which another recent study confirms.

Eggs are an amazingly nutritious food. They’re loaded with high quality protein, healthy fats, vitamins, minerals, high in choline (a brain nutrient), biotin, antioxidants, lutein, and zeaxanthin. One review of studies (involving millions of people) looked at whole egg consumption  and found that high egg consumption (up to one egg per day) is not associated with increased risk of coronary heart disease or stroke, and in fact there was a reduced risk of hemorrhagic stroke. Only among diabetics was there an elevated risk of coronary heart disease with high egg consumption (up to 1 egg per day). Another study found a lower risk of type 2 diabetes in middle-aged men (see post).

A recent study from Finland found that neither cholesterol nor egg intake (eating one egg per day) is associated with an increased risk of dementia or Alzheimer's disease in Finnish men who were followed for 22 years. Instead, eating eggs was associated with better cognitive performance in certain areas such as executive function, which includes memory, problem solving, and planning (they were given neuropsychological tests). From Science Daily:

High cholesterol intake and eggs do not increase risk of memory disorders

A new study from the University of Eastern Finland shows that a relatively high intake of dietary cholesterol, or eating one egg every day, are not associated with an elevated risk of dementia or Alzheimer's disease. Furthermore, no association was found in persons carrying the APOE4 gene variant that affects cholesterol metabolism and increases the risk of memory disorders. APOE4 is common in Finland.

The dietary habits of 2,497 men aged between 42 and 60 years and with no baseline diagnosis of a memory disorder were assessed at the onset the Kuopio Ischaemic Heart Disease Risk Factor Study, KIHD, in 1984-1989 at the University of Eastern Finland. During a follow-up of 22 years, 337 men were diagnosed with a memory disorder, 266 of them with Alzheimer's disease. 32.5 per cent of the study participants were carriers of APOE4.

The study found that a high intake of dietary cholesterol was not associated with the risk of dementia or Alzheimer's disease -- not in the entire study population nor in the carriers of APOE4. Moreover, the consumption of eggs, which are a significant source of dietary cholesterol, was not associated with the risk of dementia or Alzheimer's disease. On the contrary, the consumption of eggs was associated with better results in certain tests measuring cognitive performance

 Recently some studies have found that a diminished sense of smell occurs in persons with mild cognitive impairment and Alzheimer's disease. Doctors have long observed that patients with Alzheimer's frequently complain that food doesn't taste good anymore (because they can't smell what they are eating). This is because odor signals from the nose are processed in areas of the brain that are among the first to be affected by Alzheimer's disease. It is thought that as dementia starts and progresses, the parts of the brain that distinguish odors start to deteriorate.

This is why various odor tests have been devised. One such odor test (used in the following study) is called "Sniffin Sticks", which tests for 16 odors such as orange, peppermint, leather, banana, garlic, rose, fish, and coffee. However, note that other degenerative brain diseases (including Parkinson's) can also affect odor detection, and the ability to smell can be diminished by smoking, certain head injuries, and even normal aging. From Medical Xpress:

Study confirms 'sniff test' may be useful in diagnosing early Alzheimer's disease

Tests that measure the sense of smell may soon become common in neurologists' offices. Scientists have been finding increasing evidence that the sense of smell declines sharply in the early stages of Alzheimer's, and now a new study from the Perelman School of Medicine at the University of Pennsylvania published today in the Journal of Alzheimer's Disease confirms that administering a simple "sniff test" can enhance the accuracy of diagnosing this dreaded disease. The sniff test also appears to be useful for diagnosing a pre-dementia condition called mild cognitive impairment (MCI), which often progresses to Alzheimer's dementia within a few years.

Roalf and his colleagues used a simple, commercially available test known as the Sniffin' Sticks Odor Identification Test, in which subjects must try to identify 16 different odors. They administered the sniff test, and a standard cognitive test (the Montreal Cognitive Assessment), to 728 elderly people. The subjects had already been evaluated by doctors at Penn with an array of neurological methods, and according to expert consensus had been placed in one of three categories: "healthy older adult," "mild cognitive impairment," or "Alzheimer's dementia." Roalf and his team used the results from the cognitive test alone, or combined with the sniff test, to see how well they identified subjects in each category.

As researchers report, the sniff test added significantly to diagnostic accuracy when combined with the cognitive test. For example, the cognitive test alone correctly classified only 75 percent of people with MCI, but that figure rose to 87 percent when the sniff test results were added. Combining the two tests also enabled more accurate identification of healthy older adults and those with Alzheimer's dementia. The combination even boosted accuracy in assigning people to milder or more advanced categories of MCI.

Prompted by prior studies that have linked a weakening sense of smell to Alzheimer's, doctors in a few larger dementia clinics already have begun to use smell tests in their assessments of elderly patients. Part of the reason the practice has not yet become common is that the tests that seem most useful take too long to administer. 

 Eating several servings of seafood (especially fish) weekly has beneficial health effects throughout life, and now research finds another benefit in older adults. Seafood contains both EPA and DHA, which are two types of omega-3 fatty acids. DHA or docosahexanoic acid has "neuroprotective qualities" and is found in both the gray and white matter of the brain. Higher DHA levels (measured in the blood) was associated with better memory, less brain atrophy (better brain volume), and fewer amyloid plaques (which are associated with Alzheimer's) in cognitively healthy older adults. From Medscape:

Higher Serum DHA Linked to Less Amyloid, Better Memory

New research supports neuroprotectant effects of docosahexaenoic acid (DHA) in the aging brain. In a small cross-sectional study of cognitively healthy older adults, higher serum DHA levels were associated with less cerebral amyloidosis, better memory scores, and less regional brain atrophy.

"The interesting finding was the association of low serum DHA levels with cerebral amyloidosis (amyloid plaques) in older adults without evidence of dementia," Hussein N. Yassine, MD, Department of Medicine, University of Southern California, Los Angeles, told Medscape Medical News. "This association was predominantly driven by persons at the lowest quartile of serum DHA levels who likely have limited intake of seafood." "This study adds to the existing evidence on the benefit of seafood consumption on [Alzheimer's disease] AD risk factors," Dr Yassine added.

The study was published online August 8 in JAMA Neurology. In a linked editorial, Joseph F. Quinn, MD, Department of Neurology, Oregon Health and Science University, Portland, notes that DHA is "the most abundant polyunsaturated fatty acid in the brain, playing an important structural role in synapses while also modulating a number of signaling pathways. "Brain DHA levels are also modulated by dietary intake, so it is plausible for dietary DHA to alter brain concentrations and affect downstream targets including brain pathology and function."

Dr Yassine and colleagues assessed serum DHA levels, measures of amyloid burden based on positron emission tomography with Pittsburgh compound B, brain volume, and neuropsychological test scores in 61 adults without dementia in the Aging Brain Study.

They found that serum DHA levels (percentage of total fatty acids) were 23% lower in those with cerebral amyloidosis relative to those without. Serum DHA levels were inversely correlated with brain amyloid load, independent of age, sex, years of education, and apolipoprotein E genotype. They also noted a positive correlation between serum DHA levels and brain volume in several subregions affected by AD, in particular the left subiculum and the left entorhinal volumes.

Clinically, there was a significant association between serum DHA levels and nonverbal memory. This association persisted after adjustment for age but not after adjustment for apolipoprotein E genotype. Serum DHA levels were not associated with measures of global cognition, executive function, or verbal memory scores.

 Get out there and start getting active NOW - the earlier you start in life, the better for your brain decades later. All physical activity or exercise is good, including regular walks. From Medical Xpress:

Regular exercise protects against cognitive decline in later years

Regular exercise in middle age is the best lifestyle change a person can make to prevent cognitive decline in the later years, a landmark 20-year study has found.

University of Melbourne researchers followed 387 Australian women from the Women's Healthy Ageing Project for two decades. The women were aged 45 to 55-years-old when the study began in 1992. The research team made note of their lifestyle factors, including exercise and diet, education, marital and employment status, number of children, mood, physical activity and smoking....They were also asked to learn a list of 10 unrelated words and attempt to recall them half an hour later, known as an Episodic Verbal Memory test.

When measuring the amount of memory loss over 20 years, frequent physical activity, normal blood pressure and high good cholesterol were all strongly associated with better recall of the words. Study author Associate Professor Cassandra Szoeke, who leads the Women's Healthy Ageing Project, said once dementia occurs, it is irreversible. "In our study more weekly exercise was associated with better memory." 

"We now know that brain changes associated with dementia take 20 to 30 years to develop," Associate Professor Szoeke said. "The evolution of cognitive decline is slow and steady, so we needed to study people over a long time period. We used a verbal memory test because that's one of the first things to decline when you develop Alzheimer's Disease."
Regular exercise of any type, from walking the dog to mountain climbing, emerged as the number one protective factor against memory loss. Asoc Prof Szoeke said that the best effects came from cumulative exercise, that is, how much you do and how often over the course of your life.  (Original study)

 A study by researchers showing troubling effects from certain pesticides (especially a class of fungicides) raises all sorts of questions: What is the long-term effect of chronic low doses of these fungicides in the foods we eat? How much of these chemicals are we getting exposed to? The Univ. of North Carolina researchers studied the effect of 294 chemicals (all common food-use pesticides or other environmental chemicals) on "mouse cortical neurons" (mouse brain cells). They found that one group of chemicals, which they referred to as "cluster 2", "mimics brain disorders" such as autism, advanced age, Alzheimer's, Parkinson's disease, and other neurodegenerative disorders. The chemicals (all pesticides, and mainly fungicides) causing these effects are: fenamidone, pyraclostrobin, famoxadone, trifloxystrobin, fenpyroximate, azoxystrobin, fluoxastrobin pyridaben and rotenone. Even though this study was done on mouse cortical neurons (in vitro), it is meaningful because of the similarities with human brain cells.

Very little is known about human exposure to these chemicals (how much is our exposure?) and their effects on humans, but the data suggest effects similar to that in neurological disorders. The researchers point out that many of the chemical residues in this cluster were found on conventionally raised foods, especially leafy green vegetables, and were detected at relatively high levels, especially pyraclostrobin. Most of these fungicides only came into use after 2000 and usage of these fungicides has been increasing in the U.S, with the exception of pyridaben (decreasing use) and rotenone (very low use). "These data suggest significant human exposure potential to many of the chemicals in cluster 2".

They point out that these fungicide residues have not been detected on organically produced foods (EPA and USDA data), which suggests a way to minimize exposure. None of these chemicals can be used by organic farmers in the U.S. Possible exposure is also from gardens and lawns (if used), contaminated water, and for farm workers in conventional agriculture. From Science Daily:

Could new class of fungicides play a role in autism, neurodegenerative diseases?

Scientists at the UNC School of Medicine have found a class of commonly used fungicides that produce gene expression changes similar to those in people with autism and neurodegenerative conditions, including Alzheimer's disease and Huntington's disease.

Mark Zylka, PhD, senior author of the study and associate professor of cell biology and physiology at UNC, and his team exposed mouse neurons to approximately 300 different chemicals.... "Based on RNA sequencing, we describe six groups of chemicals," Zylka said. "We found that chemicals within each group altered expression in a common manner. One of these groups of chemicals altered the levels of many of the same genes that are altered in the brains of people with autism or Alzheimer's disease." Chemicals in this group included the pesticides rotenone, pyridaben, and fenpyroximate, and a new class of fungicides that includes pyraclostrobin, trifloxystrobin, fenamidone, and famoxadone. Azoxystrobin, fluoxastrobin, and kresoxim-methyl are also in this fungicide class.

"We cannot say that these chemicals cause these conditions in people," Zylka cautioned. "Many additional studies will be needed to determine if any of these chemicals represent real risks to the human brain." Zylka, a member of the UNC Neuroscience Center, and his group found that these chemicals reduced the expression of genes involved in synaptic transmission -- the connections important for communication between neurons. If these genes are not expressed properly, then our brains cannot function normally. Also, these chemicals caused an elevated expression of genes associated with inflammation in the nervous system. This so-called neuroinflammation is commonly seen in autism and neurodegenerative conditions.

The researchers also found that these chemicals stimulated the production of free radicals -- particles that can damage the basic building blocks of cells and that have been implicated in a number of brain diseases. The chemicals also disrupted neuron microtubules. "Disrupting microtubules affects the function of synapses in mature neurons and can impair the movement of cells as the brain develops," Zylka said. "We know that deficits in neuron migration can lead to neurodevelopmental abnormalities. We have not yet evaluated whether these chemicals impair brain development in animal models or people."

Jeannie T. Lee, MD, PhD, professor of genetics at Harvard Medical School and Massachusetts General Hospital, who was not involved in this research, said, "This is a very important study that should serve as a wake-up call to regulatory agencies and the general medical community. The work is timely and has wide-ranging implications not only for diseases like autism, Parkinson's, and cancer, but also for the health of future generations. I suspect that a number of these chemicals will turn out to have effects on transgenerational inheritance."

Zylka's group also analyzed information from the U.S. Geological Survey, which monitors countywide pesticide usage, as well as the Food and Drug Administration and the U.S. Department of Agriculture, which test foodstuffs yearly for pesticide residues. Of the chemicals Zylka's team studied, only the usage of pyridaben has decreased since 2000. Rotenone use has remained the same since 2000. However, the use of all the fungicides in this group has increased dramatically over the past decade.

Indeed, a study from the Environmental Protection Agency found that pyraclostrobin is found on foods at levels that could potentially affect human biology, and another study linked pyraclostrobin usage to honeybee colony collapse disorder. The pesticide rotenone was previously implicated in Parkinson's disease through replicated animal experiments and through human epidemiological studies.....Previous work has also shown that a single dose of the fungicide trifloxystrobin reduced motor activity for several hours in female rats and for days in male rats. Disrupted motor function is a common symptom of Parkinson's disease and other neurological disorders. The related fungicide picoxystrobin impaired motor activity in rats at the lowest dose tested.

Zylka added, "The real tough question is: if you eat fruits, vegetables or cereals that contain these chemicals, do they get into your blood stream and at what concentration? That information doesn't exist." Also, given their presence on a variety of foodstuffs, might long term exposure to these chemicals -- even at low doses -- have a cumulative effect on the brain?

Zylka noted that conventionally grown leafy green vegetables such as lettuce, spinach, and kale have the highest levels of these fungicides. But due to each chemical's effectiveness at reducing fungal blights and rust, crop yields have increased and farmers are expanding their use of these chemicals to include many additional types of food crops.

Zylka's team hopes their research will encourage other scientists and regulatory agencies to take a closer look at these fungicides and follow up with epidemiological studies. "Virtually nothing is known about how these chemicals impact the developing or adult brain," Zylka said. "Yet these chemicals are being used at increasing levels on many of the foods we eat."

 Applying fungicide to apple orchard. Credit: Univ. of Kentucky Agriculture Extension

 Two articles about the link between Alzheimer's disease (AD) and microbes this past week: a study linking periodontal disease and Alzheimer's, and the other a journal editorial (written by an international team of 31 researchers) suggesting that we need to more closely look at the role of microbes in Alzheimer's disease, especially herpes virus, chlamydia and spirochaete bacteria.

This team is suggesting an "infectious cause" for Alzheimer's, an example being the reactivation of herpes simplex virus type 1 (HSV1) in the person. The researchers state that "regarding HSV1, about 100 publications by many groups indicate directly or indirectly that this virus is a major factor in the disease".  The team also mentions the possibility of fungi infection in some cases (see my November 6, 2015 post about a study finding fungal involvement). Both articles mention that treatment of the diseases with some form of antimicrobials or antivirals could possibly treat Alzheimer's disease, and that trails now need to be done.

From Science Daily: Link between gum disease and cognitive decline in Alzheimer’s

A new study has found a link between gum disease and greater rates of cognitive decline in people with early stages of Alzheimer's Disease. Periodontitis or gum disease is common in older people and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Higher levels of antibodies to periodontal bacteria are associated with an increase in levels of inflammatory molecules elsewhere in the body, which in turn has been linked to greater rates of cognitive decline in Alzheimer's disease in previous studies.

The presence of gum disease at baseline was associated with a six-fold increase in the rate of cognitive decline in participants over the six-month follow-up period of the study. Periodontitis at baseline was also associated with a relative increase in the pro-inflammatory state over the six-month follow-up period. The authors conclude that gum disease is associated with an increase in cognitive decline in Alzheimer's Disease, possibly via mechanisms linked to the body's inflammatory response.....However, growing evidence from a number of studies links the body's inflammatory response to increased rates of cognitive decline, suggesting that it would be worth exploring whether the treatment of gum disease might also benefit the treatment of dementia and Alzheimer's Disease.

From Journal of Alzheimer's Disease: Microbes and Alzheimer’s Disease

We are researchers and clinicians working on Alzheimer’s disease (AD) or related topics, and we write to express our concern that one particular aspect of the disease has been neglected, even though treatment based on it might slow or arrest AD progression. We refer to the many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and several types of spirochaete, in the etiology of AD [1–4]. Fungal infection of AD brain [5, 6] has also been described, as well as abnormal microbiota in AD patient blood [7]. The first observations of HSV1 in AD brain were reported almost three decades ago [8]. The ever-increasing number of these studies (now about 100 on HSV1 alone) warrants re-evaluation of the infection and AD concept.

AD is associated with neuronal loss and progressive synaptic dysfunction, accompanied by the deposition of amyloid-β (Aβ) peptide, a cleavage product of the amyloid-β protein precursor (AβPP), and abnormal forms of tau protein, markers that have been used as diagnostic criteria for the disease [9, 10]. These constitute the hallmarks of AD, but whether they are causes of AD or consequences is unknown. We suggest that these are indicators of an infectious etiology. In the case of AD, it is often not realized that microbes can cause chronic as well as acute diseases; that some microbes can remain latent in the body with the potential for reactivation, the effects of which might occur years after initial infection; and that people can be infected but not necessarily affected, such that ‘controls’, even if infected, are asymptomatic [2].

Regarding HSV1, about 100 publications by many groups indicate directly or indirectly that this virus is a major factor in the disease....The only opposing reports, two not detecting HSV1 DNA in elderly brains and another not finding an HSV1–APOE association, were published over a decade ago [76–78]. However, despite all the supportive evidence, the topic is often dismissed as ‘controversial’. One recalls the widespread opposition initially to data showing that viruses cause some types of cancer, and that a bacterium causes stomach ulcers.

In summary, we propose that infectious agents, including HSV1, Chlamydia pneumonia, and spirochetes, reach the CNS and remain there in latent form. These agents can undergo reactivation in the brain during aging, as the immune system declines, and during different types of stress (which similarly reactivate HSV1 in the periphery). The consequent neuronal damage— caused by direct viral action and by virus-induced inflammation— occurs recurrently, leading to (or acting as a cofactor for) progressive synaptic dysfunction, neuronal loss, and ultimately AD.

AD causes great emotional and physical harm to sufferers and their carers, as well as having enormously damaging economic consequences. Given the failure of the 413 trials of other types of therapy for AD carried out in the period 2002–2012 [79], antiviral/antimicrobial treatment of AD patients, notably those who are APOE ɛ 4 carriers, could rectify the ‘no drug works’ impasse. We propose that further research on the role of infectious agents in AD causation, including prospective trials of antimicrobial therapy, is now justified.