Lyme Disease Support Group

By Crystal Phend, Senior Staff Writer, MedPage Today

Published: March 19, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

6 comment(s)

Action Points

Antioxidant supplements don't appear to have an impact on cerebrospinal fluid biomarkers related to Alzheimer's disease.

Note that the popular antioxidant coenzyme Q (CoQ) had no significant impact on any CSF measures in the antioxidant biomarker trial.

Antioxidant supplements don't appear to have an impact on cerebrospinal fluid (CSF) biomarkers related to Alzheimer's disease, a clinical trial determined.

The combination of vitamin E, vitamin C, and alpha-lipoic acid did not lower levels of the amyloid and tau proteins that make up the plaques and tangles seen in the brain with Alzheimer's disease, Douglas R. Galasko, MD, of the University of California San Diego, and colleagues found.

The combination did reduce CSF levels of the oxidative stress biomarker F2-isoprostane by 19% but raised a safety concern with faster decline in cognitive scores, they reported online in the Archives of Neurology.

The popular antioxidant coenzyme Q (CoQ) had no significant impact on any CSF measures in the Alzheimer's Disease Cooperative Study antioxidant biomarker trial.

Oxidative damage is widespread in the brain in Alzheimer's disease and contributes to neuronal damage, Galasko's group explained.

Some prior observational evidence has pointed to lower Alzheimer's risk with an antioxidant-rich diet, although prevention trials with supplements have had mixed results, they noted.

Their study included 78 adults with mild to moderate Alzheimer's randomly assigned to double-blind treatment over 16 weeks with the combination of 800 IU vitamin E, 500 mg vitamin C, and 900 mg of alpha-lipoic acid once a day; CoQ alone at a dose of 400 mg three times a day; or placebo.

Vitamins C and E act as antioxidants by controlling dangerous free radicals produced when oxygen reacts with certain molecules,

while alpha-lipoic acid spurs production of many antioxidant enzymes in the body.

CoQ is an antioxidant that helps protect mitochondria from oxidation.

Serial CSF specimens collected from 66 of the participants showed only small changes from baseline.

Beta-amyloid 42, which accumulates to forms plaques in the Alzheimer's brain, declined by 8 pg/mL from a baseline of 190 pg/mL with the antioxidant combination and by 15 pg/mL from a baseline of 185 in the CoQ group, but neither was a significant difference from placebo.

Tau protein, which forms neurofibrillary tangles in the brain with Alzheimer's, fell by 23 pg/mL with the antioxidant combination from a baseline of 123 and by 9 pg/mL from a baseline of 109 in the CoQ group, but again neither differed from changes with placebo.

Levels of tau phosphorylated at a specific site (P-tau181) likewise declined slightly over the study period for the two antioxidant groups but without a significant difference from placebo.

The one significant change was in CSF levels of the oxidative marker F2-isoprostane, which is stable oxidized arachidonic acid.

The vitamin C and E plus alpha-lipoic acid group saw a 7 pg/mL reduction in F2-isoprostane from a baseline of 38 over the 16 weeks of treatment (P=0.04). The other groups showed no change.

"It is unclear whether the relatively small reduction in CSF F2-isoprostane level seen in this study may lead to clinical benefits in Alzheimer disease," the group cautioned.

Cognition, measured with the Mini-Mental State Examination, didn't improve in any of the groups. In fact, the decline in scores appeared accelerated in the antioxidant combination group, with a change of -4.6 points over the 16 weeks compared with -2.3 to -2.4 in the other two groups.

The researchers highlighted that as a potential safety concern that needs further careful assessment if longer-term trials are considered. The antioxidants were otherwise well tolerated.

Function, as measured on the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale, didn't change in any group.

The study was supported by a National Institute on Aging grant.

The researchers reported having no conflicts of interest regarding the study; the specific antioxidants studied or the company that makes them, Vitaline, which supplied both study drugs and placebo; or the CSF assays that were measured.

Galasko reported serving as editor of Alzheimer's Disease Research and Treatment, serving on data safety monitoring boards for Elan and Janssen, being an investigator in clinical trials sponsored by Eli Lilly and Avid, and receiving research support from National Institutes of Health grants.

Primary source: Archives of Neurology

Source reference:

Galasko D, et al "Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures" Arch Neurol 2012; DOI:10.1001/archneurol.2012.85.

http://www.medpagetoday.com/Neurology/AlzheimersDisease/ 31721?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

A parasite often picked up from cats and better known for its threat to pregnancy appears to block neurodegeneration from Alzheimer's disease, a mouse study suggested.

The study used mice engineered to produce Alzheimer-like deposits of beta-amyloid protein. When infected with Toxoplasma gondii, they showed less inflammation, damage to neurons, and plaque deposition. Infected mice also navigated mazes better, suggesting their cognition was protected.

In people, chronic infections with the parasite usually stay in the brain, where they cause no overt symptoms but suppress CNS immune responses, including the inflammatory cytokines that play a role in Alzheimer's disease.

Thus, these results suggest "that the neuroprotection induced by T. gondii infection before the onset of Alzheimer's disease could inhibit the beta-amyloid accumulation and neurodegeneration that probably diminish cognitive abilities," the researchers concluded in PLoS One.

-- C.P.

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© 2012 Everyday Health, Inc. All rights reserved.

Elderly men and women with mild Alzheimer’s disease and cataracts can benefit from cataract surgery, a new report shows. The surgery led to improvements in thinking, sounder sleep, better mood and other benefits.

"We wanted to learn whether significant vision improvement would result in positive mood and behavior changes, or might instead upset these patients' fragile coping strategies," said Dr. Brigitte Girard, the lead author of the study and a researcher at Tenon Hospital in Paris, France. Surgery produced improvements in many of the patients studied.

The findings are important, since cataracts, which cloud the lens in the eye, are very common in older people. With the advance of lasers and other technologies, cataract surgery has become a relatively simple procedure that can produce dramatic improvements in vision.

The results underline the importance of good vision and medical care for anyone with Alzheimer’s disease.

The study is the first to address whether cataract surgery is helpful specifically for people with Alzheimer’s disease. Earlier studies have shown that older people in general show improvements in thinking and mood after cataract surgery to correct vision loss.

For the study, the researchers enrolled 38 men and women with mild Alzheimer’s disease whose average age was 85. All of the study participants had cataracts in at least one eye that severely impaired their vision.

All underwent cataract surgery, involving removal of the faulty lens and replacement with a new, clear lens. After the surgery, all but one of the patients showed dramatic improvements in their vision.

They were also assessed for psychological and cognitive health one month and three months after the surgery. One in four patients showed improvements in thinking and memory skills.

Many also showed an easing of symptoms of depression. They did not, however, show improvements in day-to-day functioning.

Most of the participants also slept better after the surgery. They also had fewer nighttime outbursts and behavior problems, a common problem in people with Alzheimer’s.

The researchers speculate that the improved sleep may be due to better processing of melatonin, a hormone involved in sleep. Other studies have shown that cataract surgery can improve melatonin levels.

"In future studies we intend to learn what factors, specifically, led to the positive effects we found, so that we can boost the quality of life for Alzheimer's patients, their families and caregivers," Dr. Girard said. The findings were reported at the American Academy of Ophthalmology's 2011 Annual Meeting in Orlando, Fla.

By www.ALZinfo.org, The Alzheimer's Information Site.

Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University

Source: The 115th Annual Meeting of the American Academy of Ophthalmology, Oct. 23 to 25, Orange County Convention Center, Orlando, Fla.

https://www.alzinfo.org/02/articles/prevention-and-wellness/ cataract-surgery-ease-alzheimers-symptoms

no copyright shown

New evidence suggests that enduring stress can contribute to the early pathologic events leading to Alzheimer's disease, researchers reported in the Proceedings of the National Academy of Sciences.

In a series of experiments in which mice were repeatedly exposed to an emotional stressor, hyperphosphorylated tau proteins accumulated in their brains.

The stressor was 30 minutes of physical restraint for the mice, which is thought to have similar results in the murine brain as chronic fear and anxiety do in the human brain, according to lead investigator Robert A. Rissman, PhD, of the University of California at San Diego.

A single exposure to the stressor did not result in tau aggregation, the researchers found.

Tau deposition was most pronounced in the hippocampus, an area of the brain closely involved in memory formation and storage, and was regulated by the corticotropin-releasing factor receptor. Moreover, an antagonist of this receptor blocked the effects of the repeated stress, suggesting a possible treatment target in Alzheimer's disease.

Such antagonists are currently under development, and may have applications to other neurodegenerative conditions such as amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease, the researchers noted.

-- N.W.

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© 2012 Everyday Health, Inc. All rights reserved

By Kristina Fiore, Staff Writer, MedPage Today

Published: April 02, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, Nurse Planner

Action Points

Treatment with the [b]monoclonal antibody bapineuzumab significantly lowered levels of phosphorylated tau (P-tau) in the cerebrospinal fluid of Alzheimer's patients.

Note that there were no changes, however, in cerebrospinal fluid (CSF) levels of amyloid-beta, the protein that bapineuzumab targets for removal in the brain.[/b]

Treatment with the monoclonal antibody bapineuzumab significantly lowered levels of phosphorylated tau (P-tau) in the cerebrospinal fluid of Alzheimer's patients, researchers found.

In a pooled analysis from two earlier phase II studies, P-tau levels fell significantly for those on bapineuzumab compared with controls (P=0.03), and there was also a trend toward diminished total-tau levels in these patients, Kaj Blennow, MD, PhD, of the University of Gothenburg in Sweden, and colleagues reported online in the Archives of Neurology.

There were no changes, however, in cerebrospinal fluid (CSF) levels of amyloid-beta, the protein that bapineuzumab targets for removal in the brain.

The findings may indicate that the monoclonal antibody has some downstream effects on the degenerative process, but whether these effects translate to clinical improvements remains to be seen, the researchers said.

Bapineuzumab is an investigational antibody against amyloid-beta, a protein plaque that builds up, along with neurofibrillary (tau) tangles, in the brains of Alzheimer's patients.

Patients with Alzheimer's disease typically have lower levels of amyloid-beta in their CSF fluid, while levels of tau proteins are increased in CSF.

The drug is still being evaluated in a phase III trial and has previously hit some setbacks, with questions about links with amyloid-beta imaging abnormalities of edema (ARIA-E) that led to the highest dose of the agent being dropped from the study.

To evaluate bapineuzumab's effects on CSF biomarkers, Blennow and colleagues conducted an exploratory, post-hoc analysis of two phase-II, randomized, double-blind, placebo-controlled trials, each a year long, involving a total of 46 patients from the U.S., the U.K., and Finland, who had mild to moderate Alzheimer's disease.

A total of 27 patients were given bapineuzumab while 19 were given placebo.

The researchers found a significant drop in CSF P-tau from baseline (-9.9 pg/mL, P=0.001) but no change in levels in the placebo group, which amounted to a significant difference between groups (P=0.03).

While levels of total tau (T-tau) in CSF also fell significantly for treated patients (-72.3 pg/mL, P=0.03) with no significant difference from baseline in the placebo group, the difference between groups wasn't significant but only indicated a trend, the researchers said (P=0.09).

Blennow and colleagues wrote that the declines in P-tau levels may reflect a drop in the formation of tau tangles in the brain.

"These findings may indicate downstream effects of bapineuzumab treatment on the degenerative process," they wrote.

However, there were no clear-cut differences on CSF levels of amyloid beta. That may be due to clearance of cortical amyloid-beta through other pathways, they said, or the binding of amyloid-beta to the antibody may mask a change in CSF levels of the protein.

Overall, they warned that it remains unclear whether the changes seen in tau levels in CSF actually correlate with clinical benefit.

They also noted that the study was limited because it was based on pooled analysis of two prior trials.

The study was supported by Elan and Pfizer.

The researchers reported relationships with Elan, Pfizer, Janssen, which acquired some assets related to Elan's Alzheimer Immunotherapy Program in 2009, AstraZeneca, Athena, Avid-Lilly, Baxter, Bristol-Myers Squibb,

Eisai, Sanofi, Medivation, Merck-Serono, Bayer, GE, Genentech, Adamas, American Life Science Pharmaceuticals, Biogen-Idec, Helicon, Eli Lilly, Intellect Neurosciences, Johnson & Johnson, and Teva.

Some co-authors are employees of Janssen and Pfizer.

Primary source: Archives of Neurology

Source reference:

Blennow K, et al "Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease" Arch Neurol 2012; DOI: 10.1001/archneurol.2012.90.

http://www.medpagetoday.com/Neurology/AlzheimersDisease/ 31987?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved

By Michael Smith, North American Correspondent, MedPage Today

Published: April 09, 2012

The FDA has approved the radioactive diagnostic agent florbetapir (Amyvid) for evaluation of the causes of cognitive decline, including Alzheimer's disease, according to Eli Lilly, developer of the compound.

Florbetapir is used in conjunction with positron emission tomography to evaluate the burden of amyloid plaques in the brain, according to Daniel Skovronsky, MD, PhD, the company's brand development leader for the product.

The main value of the test, Skovronsky told MedPage Today during a telephone media briefing, will be in ruling out Alzheimer's disease.

Although amyloid plaques are considered to be a hallmark of Alzheimer's, he said, they also appear in other forms of dementia and in the course of normal aging.

And many patients diagnosed with Alzheimer's – as many as one in five – do not show amyloid plaques during autopsy, he noted.

A florbetapir scan showing few or no amyloid plaques would rule out the disease, he said, adding "in those patients, physicians can then focus on looking for other causes of dementia."

The approval of the product is a "great advancement in nuclear medicine practice," said Edward Coleman, MD, of Duke University Medical Center.

"It may help give physicians additional information when evaluating patients with cognitive decline," he told reporters during the media briefing

Coleman cautioned that the compound does add to a patient's cumulative exposure to radiation.

He also added that, in response to FDA concerns about the reliability of the test, the results of the PET scan should only be interpreted by a physician who has gone through a "reader training program" that's now available online.

The company said florbetapir was evaluated in three main clinical studies that examined healthy adult patients, patients with a range of cognitive disorders, and some terminally ill patients who had agreed to have their brains evaluated post mortem.

In one study, the company said in a release, post-mortem cortical amyloid burden was highly correlated with median scores on the florbetapir scans, with a correlation coefficient of r=0.78 and a significance level of P<0.0001.

Florbetapir scans had a median sensitivity of 92% and specificity of 95% for readers who had in-person training and 82% and 95%, respectively, for readers trained online.

The most common patient adverse effect in the clinical trials was headache, reported by 1.8% of participants, followed by musculoskeletal pain, fatigue, and nausea.

http://www.medpagetoday.com/Neurology/AlzheimersDisease/ 32088?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

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2young2dieMom

LymeNet Contributor

Member # 25434

posted 04-24-2012 12:12 PM

I've heard lyme might be the cause of Alzheimer's Disease. Does anyone know of any studies done on the subject?

I lost both my mom and father in law to Alzheimer's. Both lasted 10+ years but starved to death in the end. Heartbreaking.

t9im

LymeNet Contributor

Member # 25489

posted 04-24-2012 12:27 PM

I believe there are many causes of Alzheimer's but Dr. M in NY showed a link between spirochetes and Alzheimers when he analyzed 10 Alzheimer brains from the Harvard Brain Bank and 7 of the 10 had spirochetes.

From the spriochetes I've seen in gum infections I would not limit it to Lyme.

Keebler

Honored Contributor (10K+ posts)

Member # 12673

posted 04-24-2012 12:51 PM

-

I agree with t9im. I think there can be many different causes & influences.

However, borrelia certainly seems to be a prime suspect. The work of Dr. Alan MacDonald in this area has been brilliant.

-------------------------------------

http://www.molecularalzheimer.org/

Molecular Alzheimer.org

Many Images presented on this site hold copyrights - by other authors , and other publishers and by Alan B. MacDonald, MD

The Research support has been provided by: Turn the Corner Foundation, New York, NY;

and St Catherine of Siena Medical Center, Smithtown, New York

================================

http://www.ilads.org/search/search.php?zoom_sort=0&zoom_query=MacDonald&zoom_per_page=20&zoom_and=0

Search at ILADS for “MacDonald” - 13 results

================================

http://www.underourskin.com/

Documentary "UNDER OUR SKIN" in which Dr. MacDonald was one of many doctors interviewed about lyme & tick-borne disease.

Sadly, a bad turn of his health required him to fully resign, leaving his research behind for others to carry on.

http://www.underourskin.com/characters

½ down, you can see a bit of background for Dr. MacDonald’s work. ( His “research into Lyme disease began over 25 years ago . . .”).

http://www.hulu.com/search?query=Under+Our+Skin&st=0&fs=

HULU - "Under Our Skin" links

nefferdun

Frequent Contributor (1K+ posts)

Member # 20157

posted 04-24-2012 01:03 PM

Other things to look for are FL1953; protomyxzoa, which is linked to a lot of things including Alzheimer's, chronic fatigue, fibromyalgia, ALS, MS and other auto immune diseases.

Methyl cycle mutations are connected to all of the above as well. MTHFR reduces the ability to absorb folic acid which is a precursor to glutathione.

It causes hypercoagulation,( thick blood) which means less oxygen gets to the cells, and there is a decreased ability to detox harmful substances out of the body.

Another common mutation is linked to reduced B12, a deficiency of which is know to cause dementia. I would get the complete methyl cycle panel test done if I were you because the mutations are easy to treat with diet and supplements.

There are so many ways these mutations are linked to neurological/ psychological illness that you just have to try to decipher it yourself. Here is a link:

http://www.heartfixer.com/AMRI-Nutrigenomics.htm

Then there is high ferritin (stored iron) which can cause lesions on the brain as well as harm the liver, heart and pancreas. The genetic mutation that causes it is called hemocrhomatosis and is most commonly linked to Scotch/Irish ancestry.

Chronic infections can also cause the body to store iron as it tries to hide it from the pathogens that also use it. Infections can also cause hypercoagulation. So it all works together against you, but if you have any of the genetic mutations then you are already in the hole and it is much harder for you to recover.

My mother had Alzheimer's also, as did my grandmother on my father's side. Very scary.

© 1994-2011 The Lyme Disease Network of New Jersey, Inc.

All Rights Reserved.

By John Gever, Senior Editor, MedPage Today

Published: April 20, 2012

NEW ORLEANS -- Significant progress against multiple sclerosis, Parkinson's disease, and Alzheimer's disease is slated to be reported at the American Academy of Neurology's annual meeting here.

With abstracts for all presentations made public prior to the meeting -- including the late-breakers, which were released earlier this week -- the neurology community already has a good idea of what to expect and is looking forward to the details that the investigators have saved for their presentations.

Among the most eagerly awaited will be results from the so-called REFLEXION trial of interferon beta-1a (Rebif) for delaying onset of definite multiple sclerosis (MS) in patients with early signs of the disease.

The abstract indicated that only about 27% of those taking the drug after an initial demyelinating event progressed to clinically definite MS within three years, versus 41% of those who took placebo for the first two years before switching to interferon treatment.

Reducing 'Off' Time in Parkinson's disease

Another study likely to attract attention is about a combination of levodopa and carbidopa formulated as an intestinal gel, aimed at avoiding the peaks and troughs in blood levels that result from oral administration in Parkinson's disease.

According to that abstract, patients receiving the gel in a randomized, blinded trial had significantly less "off" time -- that is, the resumption of tremor, stiffness, and other symptoms that are suppressed by dopamine-based drugs -- than those treated with standard oral medication.

The gel cut "off" time by nearly two hours per 16-hour waking day, on average.

Similar results were also reported in the abstract for a placebo-controlled study of a transdermal form of rotigotine (Neupro), with about a two-hour reduction in "off" time each day.

Alzheimer's Disease Imaging Agents

Three of the late-breaker studies (dubbed "Emerging Science" in the meeting program) address imaging agents for detecting beta-amyloid plaques in the brains of live patients.

One such product, florbetapir (Amyvid), was just approved by the FDA, but competing products are not far behind.

Meeting attendees will hear new results with two of these, florbetaben and flutemetamol.

Like florbetapir, both are 18F-labeled compounds that bind selectively to beta-amyloid plaques and light up on PET scans.

The florbetaben study abstract indicates that findings on PET scans in near-death patients correlated strongly with their actual plaques measured at autopsy a short time later.

A similar study with flutemetamol came up with similar results, according to its abstract.

In a study with possibly more clinical relevance, flutemetamol binding in the brains of 11 community-dwelling older people with memory loss correlated significantly with their performance on a cognition test.

DMD Drug Trial

Also closely watched will be a presentation on a possible disease-modifying drug for Duchenne muscular dystrophy (DMD) called eteplirsen.

DMD results from any of several loss-of-function mutations in the gene for dystrophin, an important muscle component. Eteplirsen causes the gene transcription mechanism to skip over certain of these mutations, such that a shortened but still functional form of dystrophin is produced.

A clinical trial involving 12 boys with DMD is to be reported at the meeting. The abstract provided no results, but the drug's manufacturer indicated in a press release earlier this month that the agent appeared to boost dystrophin production significantly. On the other hand, after 24 weeks, there was no sign of functional improvement.

The presentation at AAN will be the first in a scientific venue -- clinicians and patients will be watchful for newer data on the drug's clinical effects, or lack thereof.

Repetitive Head Injuries in Sport

Concussions in football and hockey players have been big news stories in the past two years, but the risks to those athletes likely pale in comparison to risks faced by boxers and martial-arts fighters.

Researchers at the Cleveland Clinic are scheduled to report on a study of more than 75 active fighters, comparing the total number and frequency of their bouts with results of brain-volume measurements and cognition tests.

Brain shrinkage was more pronounced with longer fighting histories and more frequent fights, according to the abstract.

But when it came to cognitive impairment, there was a clear demarcation between those who had been fighting for more than nine years and those with shorter fight histories.

In those with more than 9 years, cognitive performance was significantly related to the number of years of fighting and the frequency of fights. No such relationship was seen, however, in those with less time in their combative sports.

The investigators suggested in the abstract that "there may be [a] threshold at which continued repetitive head trauma begins to produce measurable changes in cognition, despite volumetric brain changes that can be detected earlier.

Other Studies of Interest

The following will also be featured in the "Emerging Science" session, slated for late Wednesday afternoon here:

Pregabalin (Lyrica) for treating neuropathic pain following spinal cord injury

Acomparison of pregabalin and pramipexole (Mirapex) in restless legs syndrome

A confirmation trial of fingolimod (Gilenya) in relapsing-remitting MS

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© 2012 Everyday Health, Inc. All rights reserved.

By Michael Smith, North American Correspondent, MedPage Today

Published: April 23, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

This single-blinded, randomized study found that older women with mild cognitive impairment displayed improved executive function after twice-weekly resistance training compared to a control group that worked on balance and toning.

Note that a third group doing aerobic training showed improved balance and cardiovascular capacity, but no change in memory function.

Pumping iron also pumps up the memory of older women with mild cognitive impairment, researchers reported.

In a randomized, single-blind trial, women who lifted weights had significant improvements in memory tasks after 6 months, compared with women in a control group who worked on balance and stretching, according to Teresa Liu-Ambrose, PhD, of the University of British Columbia in Vancouver, and colleagues.

Women in a third group, who worked on aerobic training, saw their fitness improve but got no cognitive benefit compared with the control group, Liu-Ambrose and colleagues reported in a letter published in the April 23 issue of Archives of Internal Medicine.

Exercise is a "promising strategy" for controlling cognitive decline, the researchers noted.

Indeed, both aerobic and resistance training have been shown to improve cognitive performance and functional plasticity in healthy seniors living in the community as well as those with mild cognitive impairment, they noted.

But the comparative efficacy of the two modes of exercise hasn't been examined in people with mild cognitive impairment. To help fill the gap, they enrolled 86 community-dwelling women ages 70 to 80 with subjective memory complaints and a score lower than 26 out of 30 on the Montreal Cognitive Assessment.

They were randomly allocated to twice-weekly sessions of resistance, aerobic, or balance and tone training. Those in the resistance group used machines and free weights, while those in the aerobic group undertook an outdoor walking program.

The balance and tone sessions consisted of stretching, range of motion and balance exercises, and relaxation techniques; the patients in this last group served as controls.

The primary outcome was performance on the Stroop Test, which measures selective attention and conflict resolution, but the researchers also tested other aspects of executive cognitive function, including set shifting and working memory, as well as measuring associative memory and everyday problem-solving ability.

They used functional magnetic resonance imaging on 22 of the participants (7 to 8 from each group) to assess regional patterns of functional brain plasticity during the associative memory tests.

The investigators also assessed general balance and mobility and cardiovascular capacity.

Compared with the balance and tone group, they found:

The resistance training group had significantly improved performance on the Stroop Test and the associative memory task (P=0.04 and P=0.03, respectively).

During the encoding and recall of associations, those in the resistance training group also had significant functional changes in three cortical regions -- the right lingual and occipital-fusiform gyri and the right frontal pole (P=0.03, P=0.02, and P=0.03, respectively).

They also had a significant positive correlation between change in hemodynamic activity in the right lingual gyrus and change in behavioral associative memory performance (correlation coefficient r=0.51, P=0.02).

The aerobic training group significantly improved general balance and mobility and cardiovascular capacity (P=0.03 and P=0.04, respectively).

The analysis provides "novel evidence" that resistance training has several benefits in terms of cognition, the researchers argued, at least for older women. They cautioned that the results might not apply to men or to women of other ages.

The study was supported by the Pacific Alzheimer's Research Foundation.

The journal said the authors made no financial disclosures.

Primary source: Archives of Internal Medicine

Source reference:

Nagamatsu LS, et al "Resistance training promotes cognitive and functional brain plasticity in seniors with probable mild cognitive impairment" Arch Intern Med 2012; 172(8): 666-668.

http://www.medpagetoday.com/Geriatrics/Dementia/32305? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

By Nancy Walsh, Staff Writer, MedPage Today

Published: April 23, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

Recent studies suggest that the use of cerebrospinal fluid and amyloid imaging can detect the presence of amyloid deposition beginning as early as 10 to 15 years prior to the onset of any clinically detectable cognitive decline from Alzheimer's disease.

In this study, researchers found that cognitive decline in older individuals who have amyloid-beta deposition only occurs when they also have high levels of a specific tau protein.

Cognitive decline in older individuals who have amyloid-beta deposition only occurs when they also have high levels of a specific tau protein, a longitudinal study found.

Having amyloid-beta peptides 1-42 present in the cerebrospinal fluid was associated with changes on the clinical dementia rating scale exclusively among patients who also had phosphorylated (p) tau181p present at elevated levels (β1=0.06, P=0.01), according to Rahul S. Desikan, MD, PhD, of the University of California San Diego, and colleagues.

In contrast, individuals who were positive for amyloid-beta1-42 but negative for p-tau181p showed no evidence of decline (β1= −0.02, P=0.35), the researchers reported online in the Archives of Neurology.

"Our results indicate that in clinically normal older individuals, amyloid-beta deposition by itself is not associated with clinical decline; the presence of p-tau represents a critical link between amyloid-beta deposition and accelerated clinical decline," they stated.

Previous research has demonstrated a clear association between amyloid-beta deposition and the later development of Alzheimer's disease, even 10 to 15 years before signs of dementia begin to appear.[/b]

However, recent animal studies have suggested that the protein tau also contributes to the injury to neurons and synapses characteristic of Alzheimer's disease, and that low levels of tau appear to be protective.

To see if clinical decline correlated with the two proteins, Desikan and colleagues obtained cerebrospinal fluid samples from 107 participants in the Alzheimer's Disease Neuroimaging Initiative who were cognitively normal at baseline, following them for 3 years.

Average age was 76, and more than two-thirds were men.

At follow-up, cognition was assessed on the global clinical dementia rating scale; the sum of boxes test, which summarizes function in various domains such as memory and problem-solving; and the Alzheimer Disease Assessment Scale-cognitive subscale.

P-tau181p positivity was defined as a level above 23 pg/mL, and amyloid-beta1-42 positivity was defined as a level above 192 pg/mL.

The researchers first analyzed the correlation between amyloid-beta positivity and cognitive decline, and found significant associations on all three measures.

On this background, they then examined the specific influence of p-tau. As with the global dementia score, they found that only patients who also had high levels of this protein experienced declines on the sum of boxes test (β1=0.24, P=0.04).

No change on the sum of boxes score was evident in p-tau-negative individuals (β1=−0.003, P=0.94).

Similarly, on the Alzheimer's disease cognitive subscale, changes were seen only among those who had high levels of p-tau (β1=0.94, P=0.004).

The researchers then considered whether total tau, as opposed to the phosphorylated subtype, correlated with decline and found that the clinical dementia rating score among amyloid-beta-positive individuals was not associated with total tau, although associations were seen on the Alzheimer's cognitive subscale.

Total tau is elevated in other degenerative neurologic disorders, but p-tau appears to be more specific for Alzheimer's disease in that it "correlates with increased neurofibrillary pathology," they observed.

"It is feasible that although amyloid-beta initiates the degenerative cascade, elevated levels of tau may represent a second phase of the [Alzheimer's disease] pathologic process where neurodegenerative changes occur largely independent of amyloid-beta," Desikan and colleagues suggested.

Accordingly, tau may represent a therapeutic target, and future clinical trials should consider participants' levels of both amyloid-beta and p-tau.

Limitations of the study included its reliance on the two indirect biomarkers that may not represent the full extent of Alzheimer's pathology, and the possibility that other markers such as visinin-like protein also may have a role in preclinical dementia.

Also, the findings need to be replicated in a representative cohort of community-dwelling elderly individuals.

In an editorial accompanying the article, David M. Holtzman, MD, of Washington University in St. Louis argued in favor of using these biomarkers in the design of Alzheimer's prevention trials, because without markers indicating that individuals are at risk for dementia, "trial size would be enormous and cost prohibitive, and individuals may be subjected to treatments that have the potential for toxicity with no clear benefit."

Clinical research into prevention of Alzheimer's disease should follow the pattern established in cancer and cardiovascular disease, he stated.

"While it will not be easy, this is the most likely way to make a real, lasting, and important clinical impact," Holtzman said.

The study was funded by the National Institutes of Health and the San Diego chapter of the Alzheimer's Association.

[b]Several of the researchers receive research support and act as consultants for various companies, including Eli Lilly, Esai, Wyeth, Roche, Amgen, Pfizer, Novartis, NeuroPhage, Merck, and Baxter International.

Primary source: Archives of Neurology

Source reference:

Desikan R, et al "Amyloid-β-associated clinical decline occurs only in the presence of elevated p-tau" Arch Neurol 2012; DOI: 10.1001/archneurol.2011.3354.

Additional source: Archives of Neurology

Source reference:

Holtzman D "CSF biomarkers for secondary prevention trials" Arch Neurol 2012; DOI: 10.1001/archneurol.2012.587.

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