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  Again, another study showing the importance of lifestyle factors in the development of protein buildups in the brain that are associated with the onset of Alzheimer's disease. Specifically, the study found that each one of several lifestyle factors—a healthy body mass index, physical activity and a Mediterranean diet, were linked to lower levels of plaques and tangles on brain scans in people who already had mild memory changes, (but not dementia). Other posts discussing Mediterranean diet and brain health (brain volume, etc.) are here, here, and here. Activity levels and brain health posts are here, here, and here. From Medical Xpress:

Diet and exercise can reduce protein build-ups linked to Alzheimer's

A study by researchers at UCLA's Semel Institute for Neuroscience and Human Behavior has found that a healthy diet, regular physical activity and a normal body mass index can reduce the incidence of protein build-ups that are associated with the onset of Alzheimer's disease.

In the study, 44 adults ranging in age from 40 to 85 (mean age: 62.6) with mild memory changes but no dementia underwent an experimental type of PET scan to measure the level of plaque and tangles in the brain. Researchers also collected information on participants' body mass index, levels of physical activity, diet and other lifestyle factors. Plaque, deposits of a toxic protein called beta-amyloid in the spaces between nerve cells in the brain; and tangles, knotted threads of the tau protein found within brain cells, are considered the key indicators of Alzheimer's.

The study found that each one of several lifestyle factors—a healthy body mass index, physical activity and a Mediterranean diet—were linked to lower levels of plaques and tangles on the brain scans. (The Mediterranean diet is rich in fruits, vegetables, legumes, cereals and fish and low in meat and dairy, and characterized by a high ratio of monounsaturated to saturated fats, and mild to moderate alcohol consumption.)

"The fact that we could detect this influence of lifestyle at a molecular level before the beginning of serious memory problems surprised us," said Dr. David Merrill, the lead author of the study, which appears in the September issue of the American Journal of Geriatric Psychiatry.

Earlier studies have linked a healthy lifestyle to delays in the onset of Alzheimer's. However, the new study is the first to demonstrate how lifestyle factors directly influence abnormal proteins in people with subtle memory loss who have not yet been diagnosed with dementia, Merrill said. Healthy lifestyle factors also have been shown to be related to reduced shrinking of the brain and lower rates of atrophy in people with Alzheimer's."The study reinforces the importance of living a healthy life to prevent Alzheimer's, even before the development of clinically significant dementia," Merrill said. 

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)

New research looked at people who "aged successfully" over a 10 year period compared with those who were "suboptimal agers" or had died. The successful agers were less likely to smoke, and have higher intakes of fiber from fruits, breads, and cereals (primarily from rolled oats and whole grain breads), but not from vegetables. Successful aging was defined as including an absence of disability, depressive symptoms, cognitive impairment, respiratory symptoms, and chronic diseases including cancer, coronary artery disease, and stroke. Fiber intake was more important for successful aging than glycemic index, glycemic load, carbohydrate intake, or sugar intake. From Medical Xpress:

Dietary fiber intake tied to successful aging, research reveals

A new paper—published in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences by scientists from The Westmead Institute for Medical Research—reports that eating the right amount of fiber from breads, cereals, and fruits can help us avoid disease and disability into old age

Using data compiled from the Blue Mountains Eye Study, a benchmark population-based study that examined a cohort of more than 1,600 adults aged 49 years and older for long-term sensory loss risk factors and systemic diseases, the researchers explored the relationship between carbohydrate nutrition and healthy aging.

They found that out of all the factors they examined—which included a person's total carbohydrate intake, total fiber intake, glycemic index, glycemic load, and sugar intake—it was the fiber that made the biggest difference to what the researchers termed "successful aging." Successful aging was defined as including an absence of disability, depressive symptoms, cognitive impairment, respiratory symptoms, and chronic diseases including cancer, coronary artery disease, and stroke.

"Out of all the variables that we looked at, fiber intake—which is a type of carbohydrate that the body can't digest—had the strongest influence," she said. "Essentially, we found that those who had the highest intake of fiber or total fiber actually had an almost 80 percent greater likelihood of living a long and healthy life over a 10-year follow-up. That is, they were less likely to suffer from hypertension, diabetes, dementia, depression, and functional disability."

While it might have been expected that the level of sugar intake would make the biggest impact on successful aging, Gopinath pointed out that the particular group they examined were older adults whose intake of carbonated and sugary drinks was quite low.

This study backs up similar recent findings by the researchers, which highlight the importance of the overall diet and healthy aging. In another study published last year in The Journals of Gerontology, Westmead Institute researchers found that, in general, adults who closely adhered to recommended national dietary guidelines reached old age with an absence of chronic diseases and disability, and had good functional and mental health status.

Another piece of the puzzle on how the brain ages. Vitamin B12 is important for brain health, and higher levels are associated with slower rates of brain changes associated with aging. And the opposite is true with homocysteine levels - increased levels are associated with faster rates of brain changes that are associated with aging (such as higher rates of total brain tissue volume loss). Keep in mind that these effects were modest, but this also raises the question of whether long-term B12 supplementation would benefit everyone or only those with a deficiency? From Medscape:

Vitamin B12 May Slow Brain Aging

Individuals with increased levels of circulating homocysteine have faster rates of brain changes associated with aging than other people, whereas higher levels of vitamin B12 are associated with slower rates of brain aging, new research suggests.

Babak Hooshmand, MD, PhD, Center for Alzheimer Research–Aging Research Center, Karolinska Institutet, Stockholm, Sweden, and colleagues found that total brain volume losses were lower in individuals with higher baseline vitamin B12 levels, whereas the opposite was true of those with increased homocysteine levels.

"Vitamin B12 and tHcy [total homocysteine] might be independent predictors of markers of brain aging in elderly individuals without dementia," the investigators write. They add, "[I]f the association is causal, supplementation with B vitamins may be effective for prevention of brain damage due to increased levels of total homocysteine. Adequately timed and powered randomized clinical trials are needed to determine efficient treatment guidelines." The research was published online April 27 in JAMA Psychiatry.

The researchers examined data on 501 participants aged 60 years and older from the Swedish National Study on Aging and Care, in Kungsholmen. All participants were free of dementia at baseline. Of these, 299 underwent repeated structural brain MRI between 2001 and 2009....Venous blood samples were collected at baseline, from which circulating levels of vitamin B12, red blood cell folate, and sulfur amino acids were determined. These were correlated with changes in brain tissue volumes and total white matter hyperintensity (WMH) over 6 years.

He also pointed to the single-center, randomized VITACOG study, in which 271 individuals older than 70 years who had mild cognitive impairment received supplementation with high-dose folic acid and vitamins B6 and B12. "They lost less brain compared to people who had normal homocysteine and normal vitamin levels, meaning that those with high levels of homocysteine or with clinical or biochemical vitamin deficiency can benefit from supplementation," said Dr Hooshmand.

This study found that people with high red meat intake, combined with low fruit and vegetable intake and a poor overall diet (which was found most frequently in males of low socioeconomic status) had biological markers indicating accelerated aging and poor renal function (early indicators of chronic kidney disease). Bottom line: eat less red meat, more whole grains, more fruits and vegetables for your health. From Medical Xpress:

Too much red meat and too few vegetables may increase your body's biological age

A diet containing too much red meat and not enough fruit and vegetables could increase your body's 'biological age' and contribute to health problems. Research led by the University of Glasgow and published today in Aging, has found that a moderate increase in serum phosphate levels caused by red meat consumption, combined with a poor overall diet, increases biological age (miles on the clock) in contrast to chronological age (years of age).
The study, which looked at participants from the most deprived to the least deprived in the NHS Greater Glasgow Health Board area, also demonstrates that deprived males were the worst affected.

Data from the study suggests that accelerated biological ageing, and dietary derived phosphate levels among the most deprived males, were directly related to the frequency of red meat consumption. Researchers believe that excess red meat particularly affects this group because of their poor diet and "sub-optimal fruit and vegetable intake".
The research, led by the Institute of Cancer Sciences in collaboration with the Karolinska Institutet (Stockholm, Sweden), also found that high phosphate levels in deprived males correlated with reduced kidney function and even underlying mild to moderate chronic kidney disease.

Phosphate is naturally present in basic foodstuffs, including meats, fish, eggs, dairy products and vegetables. Intestinal absorption of naturally occurring phosphate is minimally regulated, as absorption is efficient, hence high supplementation results in markedly elevated levels of serum phosphate, which can have adverse health consequences. Indeed high phosphate levels, as a consequence of dietary intake, have already been linked to higher all-cause and cardiovascular mortality risk, premature vascular ageing and kidney disease.

The researchers observed significant relationships between serum phosphate and biological age markers, including DNA content and telomere length(Original study.)

Another study showing big problems with anticholinergics, which are in many popular medicines - both non-prescription and prescription (e.g., Chlor-Trimeton, Benadryl, Tavist, Dimetapp). An earlier study with older adults found a dose-response link with dementia, but the current study explored this issue further. They followed 2 groups of  "cognitively normal older adults" in their early 70s for several years: those who took anticholinergic medicines and those who did not take anticholinergic medicines. They found that those who took anticholinergic medicines had reduced brain volume (brain shrinking) and cognitive decline (when compared to those who did not take anticholinergic medicines). The researchers summarized their findings as the "use of anticholinergic medication was associated with increased brain atrophy and dysfunction and clinical decline". This finding was greatest for those taking drugs with the most anticholinergic activity.

See a list of anticholinergic medicines  from the Aging Brain Program of the Indiana University Center for Aging Research. Definitely try to avoid medicines with a score of 2 (medium effect) or 3 (high effect), but I would even be cautious about score 1 (low effect) medicines - use all medicines only as long as absolutely needed. My one very important question is: If these effects are found in older adults, what do anticholinergics do to younger brains, especially the developing brains of children? From Medical Xpress:

Brain scans link physical changes to cognitive risks of widely used class of drugs

Older adults might want to avoid a using class of drugs commonly used in over-the-counter products such as nighttime cold medicines due to their links to cognitive impairment, a research team led by scientists at Indiana University School of Medicine has recommended. Using brain imaging techniques, the researchers found lower metabolism and reduced brain sizes among study participants taking the drugs known to have an anticholinergic effect, meaning they block acetylcholine, a nervous system neurotransmitter.

Previous research found a link between between the anticholinergic drugs and cognitive impairment and increased risk of dementia.....Drugs with anticholinergic effects are sold over the counter and by prescription as sleep aids and for many chronic diseases including hypertension, cardiovascular disease, and chronic obstructive pulmonary disease. A list of anticholinergic drugs and their potential impact is at http://www.agingbraincare.org/uploads/products/ACB_scale_-_legal_size.pdf.

Scientists have linked anticholinergic drugs and cognitive problems among older adults for at least 10 years. A 2013 study by scientists at the IU Center for Aging Research and the Regenstrief Institute found that drugs with a strong anticholinergic effect cause cognitive problems when taken continuously for as few as 60 days. Drugs with a weaker effect could cause impairment within 90 days.

The current research project involved 451 participants, 60 of whom were taking at least one medication with medium or high anticholinergic activity. The participants were drawn from a national Alzheimer's research project....and the Indiana Memory and Aging Study. To identify possible physical and physiological changes that could be associated with the reported effects, researchers assessed the results of memory and other cognitive tests, positron emission tests (PET) measuring brain metabolism, and magnetic resonance imaging (MRI) scans for brain structure.

The cognitive tests revealed that patients taking anticholinergic drugs performed worse than older adults not taking the drugs on short-term memory and some tests of executive function, which cover a range of activities such as verbal reasoning, planning, and problem solving. Anticholinergic drug users also showed lower levels of glucose metabolism—a biomarker for brain activity—in both the overall brain and in the hippocampus, a region of the brain associated with memory and which has been identified as affected early by Alzheimer's disease. The researchers also found significant links between brain structure revealed by the MRI scans and anticholinergic drug use, with the participants using anticholinergic drugs having reduced brain volume and larger ventricles, the cavities inside the brain.

Another study showing that higher physical activity (from a variety of activities) is "related to larger gray matter volume in the elderly, regardless of cognitive status", specifically in gray matter areas of the brain responsible for memory, learning, and cognition. In other words, higher levels of physical activity reduce brain atrophy that occurs with aging and improves cognitive function in elderly individuals.  There is also discussion of higher activity levels improving cerebral (brain) blood flow. Bottom line: get off your butt and move more for better brain health. From Medical Xpress:

Burning more calories linked with greater gray matter volume, reduced Alzheimer's risk

Whether they jog, swim, garden or dance, physically active older persons have larger gray matter volume in key brain areas responsible for memory and cognition, according to a new study by researchers at the University of Pittsburgh School of Medicine and UCLA.The findings, published today in the Journal of Alzheimer's Disease, showed also that people who had Alzheimer's disease or mild cognitive impairment experienced less gray matter volume reduction over time if their exercise-associated calorie burn was high.

A growing number of studies indicate physical activity can help protect the brain from cognitive decline, said investigator James T. Becker, Ph.D., professor of psychiatry, Pitt School of Medicine..... "Our study is one of the largest to examine the relationship between physical activity and cognitive decline, and the results strongly support the notion that staying active maintains brain health."

Led by Cyrus Raji, M.D., Ph.D., formerly a student at Pitt School of Medicine and now a senior radiology resident at UCLA, the team examined data obtained over five years from nearly 876 people 65 or older participating in the multicenter Cardiovascular Health Study. All participants had brain scans and periodic cognitive assessments. They also were surveyed about how frequently they engaged in physical activities, such as walking, tennis, dancing and golfing, to assess their calorie expenditure or energy output per week.

Using mathematical modeling, the researchers found that the individuals who burned the most calories had larger gray matter volumes in the frontal, temporal and parietal lobes of the brain, areas that are associated with memory, learning and performing complex cognitive tasks. In a subset of more than 300 participants at the Pitt site, those with the highest energy expenditure had larger gray matter volumes in key areas on initial brain scans and were half as likely to have developed Alzheimer's disease five years later.

"Gray matter houses all of the neurons in your brain, so its volume can reflect neuronal health," Dr. Raji explained. "We also noted that these volumes increased if people became more active over five years leading up to their brain MRI."

 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.

Brain aging can be viewed as having 2 parts: chronological age (normally  the brain grey matter volume slowly shrinks with advancing age) and a lifetime of exposures - which can be negative from unhealthy lifestyle and injuries, and positive from a healthy lifestyle and enriched environments. That's why after a lifetime there can be wide variation in the physiological age of our brains. These differences in the  brain (in the grey matter) can be measured with magnetic resonance imaging (MRIs).

The researchers in this study used the concept of physiological age - the difference between the chronological age and predicted age, as a marker of brain health. They looked at adults of varying ages,and found that the more flights of stairs a person climbs daily, and the more years of school a person had completed, the "younger" their brain physically appears.  This study was a cross-sectional study and so shows an association rather than a definite cause, but interestingly other forms of exercise did not show this link (walking/hiking, jogging, running, bicycling, aerobic exercise, lap swimming, tennis.squash/racquetball, low intensity exercise). From Science Daily:

Want a younger brain? Stay in school -- and take the stairs

Taking the stairs is normally associated with keeping your body strong and healthy. But new research shows that it improves your brain's health too -- and that education also has a positive effect. In a study recently published in the journal Neurobiology of Aging, researchers led by Jason Steffener, a scientist at Concordia University's Montreal-based PERFORM Centre, show that the more flights of stairs a person climbs, and the more years of school a person completes, the "younger" their brain physically appears.

The researchers found that brain age decreases by 0.95 years for each year of education, and by 0.58 years for every daily flight of stairs climbed -- i.e., the stairs between two consecutive floors in a building.

For the study, Steffener and his co-authors used magnetic resonance imaging (MRI) to non-invasively examine the brains of 331 healthy adults who ranged in age from 19 to 79. They measured the volume of grey matter found in participants' brains because its decline, caused by neural shrinkage and neuronal loss, is a very visible part of the chronological aging process. Then, they compared brain volume to the participants' reported number of flights of stairs climbed, and years of schooling completed. 

Results were clear: the more flights of stairs climbed, and the more years of schooling completed, the younger the brain. "This study shows that education and physical activity affect the difference between a physiological prediction of age and chronological age, and that people can actively do something to help their brains stay young," he says.

A new study has confirmed an association between proton pump inhibitors (PPIs) — drugs that treat heartburn, peptic ulcers, and other acid-related disorders of the upper gastrointestinal tract — and increased risk for dementia in older patients. An earlier study by the same researchers found the same link between PPI use and dementia risk. The drugs work by lowering the amount of acid produced by the stomach. PPIs are among the most frequently prescribed drugs, and include omeprazole (Losec), esomeprazole (Nexium), lansoprazole (Prevacid), and the over-the-counter medication Olex.

The U.S. Food and Drug Administration have warned people to take them for the shortest period possible, namely a few weeks, and only for serious acid reflux, ulcers, or stomach bleeding. Other problems linked to long-term use are: fractures, pneumonia, increased rates of C. difficile, low magnesium levels, and chronic kidney disease. From Science Daily:

Proton pump inhibitors may be associated with increased risk of Dementia

The use of proton pump inhibitors, the popular medications used to treat gastroesophageal reflux and peptic ulcers, may be associated with an increased risk of dementia in a study using data from a large German health insurer, according to an article published online by JAMA Neurology.  The use of proton pump inhibitors (PPIs) has increased among older patients and PPIs are among the most frequently used classes of drugs.

Britta Haenisch, Ph.D., of the German Center for Neurodegenerative Diseases, Bonn, Germany, and coauthors examined the association between the use of PPIs and the risk of dementia using data from 2004 to 2011 on inpatient and outpatient diagnoses and drug prescriptions. Regular PPI use was at least one PPI prescription in each quarter of an 18-month interval.

The study population included 218,493 individuals 75 or older before 144,814 individuals were excluded, leaving 73,679 individuals included in the final analysis. The authors identified 29,510 patients who developed dementia during the study period. Regular users of PPIs (2,950 patients, mostly female and average age nearly 84) had a 44 percent increased risk of dementia compared with those (70,729 patients, mostly female and average age 83) not receiving PPI medication, according to the results.

"The present study can only provide a statistical association between PPI use and risk of dementia. The possible underlying causal biological mechanism has to be explored in future studies.