Lyme Disease Support Group

By Crystal Phend, Senior Staff Writer, MedPage Today

Published: January 09, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and

Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

■This study of older adults without cognitive decline found that exercise decreased amyloid deposits in the brain among those carrying the apolipoprotein E (APOE) epsilon-4 genotype, a genetic risk factor for Alzheimer's disease.

■APOE carriers who exercised at or above American Heart Association-recommended levels had scans for amyloid deposits that resembled non-carriers, while sedentary APOE epsilon-4 carriers had elevated deposits.

Physical activity may help ward off Alzheimer's disease for individuals with genetic risk factors, researchers found.

Among carriers of the apolipoprotein E (APOE) epsilon-4 genotype, staying active appeared to put the brakes on accelerated buildup of amyloid plaques in the brain in a study by Denise Head, PhD, of Washington University in St. Louis, Mo., and colleagues.

At-risk individuals showed higher cortical amyloid levels on imaging studies overall (P<0.001), the group reported online in the Archives of Neurology.

But while that held true for sedentary adults, meeting American Heart Association recommendations for regular exercise wiped out the association.

The physically active genetic risk carriers didn't have higher brain amyloid levels as reflected by mean cortical binding potential on amyloid imaging compared with noncarriers overall (P=0.41) or active noncarriers (P=0.24).

For APOE epsilon-4 carriers, their "inherent neurophysiological disadvantage makes beneficial lifestyle factors, such as exercise, preferentially important," Head's group argued, though noting that the study couldn't draw a causal link.

Just how exercise might influence amyloid deposition isn't clear, though possibilities include an influence on metabolism and cerebral functioning, they suggested.

Their observational study included 201 individuals ages 45 to 88 who tested cognitively normal at a single Alzheimer's research center.

Among the 163 individuals imaged with a PET scan to measure amyloid deposits through binding of the amyloid imaging agent carbon 11–labeled Pittsburgh Compound B ([11C]Pi, 52 were APOE epsilon-4 carriers.

Carriers had significantly higher mean binding potential on that imaging as expected, although levels of a correlated marker known as beta-amyloid 42 in cerebrospinal fluid samples were actually lower than in noncarriers (both P<0.001).

Sedentary individuals -- regardless of carrier status -- also showed higher binding potential (P=0.005) and lower cerebrospinal beta-amyloid 42 (P=0.009) than those who were more active.

Carrier status and exercise level interacted significantly for amyloid imaging (P=0.008), though not on cerebrospinal fluid measures (P=0.41).

Being less active was associated with more cortical amyloid binding potential in APOE epsilon-4 carriers (P=0.013) but not in noncarriers (P=0.20).

Adjustment for potentially confounding factors, including age, sex, education, body mass index, hypertension, and diabetes, didn't change the results.

That the imaging and cerebrospinal fluid results differed so much was surprising, the researchers noted.

"The two largely reflect complimentary estimates of the same process of amyloid plaque development in the brain and are strongly associated," they explained.

One reason for the difference may have been that the two techniques identify different amyloid beta species and possibly reflect amyloid deposition in different regions of the brain, Head's group suggested.

Insufficient sample size was also a possibility, they noted. Other limitations were the possibility of residual confounding from factors such as ability to engage in physical activity that weren't measured in the study, as well as use of self-reported activity data.

Because the observational study couldn't determine causality or mechanisms, longitudinal and interventional studies are needed to determine if and how exercise impacts amyloid deposition and subsequent Alzheimer's disease, the group concluded.

The study was supported by National Institutes of Health grants.

Head reported having no conflicts of interest to disclose.

Co-authors reported links with AstraZeneca, Howrey & Associates, Pfizer, Genentech, Taconic, Bristol-Myers Squibb, Innogenetics, Medtronic, EnVivo, Satori, C2N Diagnostics, and Eli Lilly.

Primary source: Archives of Neurology

Source reference:

"Exercise engagement as a moderator of the effects of APOE genotype on amyloid deposition" Arch Neurol 2012; DOI: 10.1001/archneurol.2011.845.

http://www.medpagetoday.com/Geriatrics/AlzheimersDisease/ 30561?utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved

By MedPage Today Staff

Published: January 13, 2012

Lighting Up the Tangles

Several contrast agents are in development for imaging beta-amyloid plaques in patients with incipient Alzheimer's disease, but what about the disorder's other major pathology, neurofibrillary tangles?

Nothing suitable has yet come along for measuring these abnormalities in live patients.

That may now be changing, thanks to efforts by Masahiro Ono, PhD, and colleagues at Japan's Kyoto University.

In ACS Medicinal Chemistry Letters, they say they have identified a new agent that binds both to beta-amyloid plaques and to neurofibrillary tangles made of rogue tau proteins.

Studies in mice showed that the compound, based on fluorine-18, is stable enough in vivo to serve as a useful contrast agent. And, when applied to brain sections from deceased Alzheimer's disease patients, tangles as well as plaques lit up brightly in PET and SPECT scans.

-- J.G.

http://www.medpagetoday.com/Neurology/AlzheimersDisease/ 30657?utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc.[b]

By John Gever, Senior Editor, MedPage Today

Published: January 17, 2012

Another failure in phase III clinical testing has finally sent the investigational Alzheimer's disease drug dimebon to the trash heap, according to its commercial sponsors.

Pfizer and Medivation, which were co-developing the drug (also known as latrepirdine), announced Tuesday that they were stopping all development activities after the phase III CONCERT trial failed to demonstrate significant benefit in patients with mild to moderate Alzheimer's disease.

The companies are also terminating an open-label extension study that followed the main trial, which had randomized 1,003 patients to receive dimebon or placebo in addition to donepezil (Aricept) for one year.

A phase III trial called CONNECTION completed in 2010 had also failed to show a benefit for dimebon.

The two negative trials offset favorable results seen in an earlier phase III trial reported in 2008.

Dimebon originated in Russia decades ago, where it was long sold as an antihistamine for nasal congestion, leading to observations of apparent benefit in Alzheimer's disease patients. The drug was never approved or sold in the U.S.

Pfizer and Medivation promised that full results from CONCERT would be submitted for presentation at a future scientific meeting.

http://www.medpagetoday.com/Neurology/AlzheimersDisease/ 30717?utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved

By John Gever, Senior Editor, MedPage Today

Published: January 18, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and

Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

■A new guideline for the National Institute on Aging and the Alzeimer's Association recommends the "ABC" system for standardizing neuropathologic staging of Alzheimer's brain pathology on autopsy.

■Note that the "ABC" system scores beta-amyloid plaques, neurofibrillary tangles, and neuritic plaques for an assessment of neuropathologic changes of Alzheimer's independent of premortem cognitive impairment.

Individuals who were cognitively normal at the time of death can nevertheless be diagnosed with Alzheimer's disease on the basis of autopsy findings alone, according to new guidelines endorsed by the National Institute on Aging (NIA) and the Alzheimer's Association.

The guidelines for postmortem assessment of Alzheimer's disease, which replace criteria issued in 1997, also call on pathologists to base diagnoses on an "ABC" risk score that combines assessments of beta-amyloid plaques, neurofibrillary tangles, and neuritic plaques.

Also new to the guidelines are specific protocols for evaluating other pathologies related to cognitive impairment and dementia, such as Lewy body disease, vascular brain injury, and hippocampal sclerosis.

The new guidelines were developed by a team led by Thomas Montine, MD, of the University of Washington in Seattle, and Bradley Hyman, MD, of Massachusetts General Hospital in Boston.

They were published in two papers:

one in the January issue of Acta Neuropathologica describing the practical assessment, and another online in Alzheimer's & Dementia that reviewed the evidence base for the update.

The 1997 criteria had stipulated that patients whose brains had the plaques and tangles characteristic of Alzheimer's disease could not receive a formal postmortem diagnosis unless they also had had clinical dementia before death.

In contrast, the new guidelines are focused solely on histological and biochemical abnormalities found at autopsy, without reference to symptoms shown while patients were still living.

"There is consensus to disentangle the clinicopathologic term 'Alzheimer's disease' from [Alzheimer-associated] neuropathologic change," the guideline team wrote in the Alzheimer's & Dementia paper.

Key to the new attitude has been a raft of recent research documenting that plaques and tangles can infest patients' brains long before they develop clinical symptoms.

This has been demonstrated from autopsy findings and from imaging studies in LIVE patients using tracers that highlight beta-amyloid plaques.

One consequence of the new approach is that it emphasizes "the continuum of Alzheimer's disease neuropathologic change," as the Acta Neuropathologica paper put it, with grading schemes that provide for intermediate degrees of pathology as well as determinations of "preclinical" Alzheimer's disease in asymptomatic patients.

The old guidelines were geared instead toward providing a yes-no answer to whether a patient had Alzheimer's disease at death.

One of the more important elements in the revision is the use of "ABC" scores to measure the degree of Alzheimer's-related pathology.

The name refers to the evaluation of amyloid plaques, the Braak system for grading tau protein-based tangles, and the CERAD system for quantifying neuritic plaques.

Another addition is a suggestion to measure biomarkers, such as genetic risk factors (e.g. APOE genotype) and blood or cerebrospinal fluid proteins, when the autopsies are intended for research purposes, rather than in routine postmortem evaluations.

"We recognize that this is a rapidly advancing field of investigation and that in the future some combination of genetic testing and biomarkers may be useful as a surrogate for neuropathologic changes or functional decline," Hyman and colleagues wrote in Alzheimer's & Dementia.

The guidelines also set standards for the more mundane aspects of analyzing brain pathology, such as sites to be sampled and methods for detecting and measuring the variety of abnormalities that may be found in the aging brain.

For example, the Acta Neuropathologica paper advises that Lewy body disease is frequently present in the olfactory bulb, which "should be sampled when possible."

These guidelines are distinct from, though consistent with, recommendations for clinical diagnosis of Alzheimer's disease in LIVE patients, issued last April by the NIA and the Alzheimer's Association.

Development of the guidelines was supported by the National Institute on Aging, the Alzheimer's Association, and private foundation grants.

Guideline authors disclosed no relevant financial interests.

Primary source: Acta Neuropathologica

Source reference:

Montine T, et al "National Institute on Aging -- Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach" Acta Neuropathol 2012; 123: 1-11.

Additional source: Alzheimer's & Dementia

Source reference:

Hyman B, et al "National Institute on Aging -- Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease" Alzheimer's & Dementia 2012; DOI: 10.1016/j.jalz.2011.10.007.

http://www.medpagetoday.com/Neurology/AlzheimersDisease/ 30731?utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

***********************************

bettyg note: BRAD HYMAN was my late SIL's neurologist at IOWA CITY UNIVERSITY HOSPITAL when my brother's family was trying to find out what was wrong with her. he treated her for severe depression.

later he went to MAYO CLINIC OR out east to present position.

he was involved in 4-5 MONTH EARLY ONSET BRAIN AUTOPSY on my SIL. dx early onset AD. she died at age 40; yes 40, having the illness 8-14 yrs. prior!

they had frozen tissue to test for future developments especially if their young kids might INHERIT the gene causing early onset AD.

bettyg, leader; this was the worst disease watching my SIL, brother, and her 2 young kids go thru! her son never knew her healthy whatsoever!

By Crystal Phend, Senior Staff Writer, MedPage Today

Published: January 23, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor

University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

1 comment(s)

Action Points

This study of healthy older individuals found that those with greater early and middle-life cognitive activity had lower beta-amyloid deposition.

Although greater cognitive activity was associated with greater physical exercise, there was no association between exercise and amyloid deposition.

Keeping the brain in gear throughout life with reading, games, and other mental activities cuts down on beta-amyloid plaques thought to cause Alzheimer's disease, researchers found.

Brain imaging turned up a significant impact of greater mental activity across the lifespan, but particularly before middle age (P<0.001), Susan M. Landau, PhD, of the University of California Berkeley, and colleagues reported online in the Archives of Neurology.

The most cognitively active older adults in the small study had the amyloid levels of someone a quarter of their age, whereas mental couch potatoes, despite being cognitively intact, looked like their brains had Alzheimer's.

Thus a mentally stimulating lifestyle may prevent or slow deposition of the plaques, which adds to direct evidence backing the use-it-or-lose-it epidemiological findings in cognitive decline, Landau's group noted.

The mechanism may be that the mental exercise makes neural processing run more efficiently, which regulates beta-amyloid secretion and thus deposition, they suggested.

But mental activity clearly isn't the only factor contributing to Alzheimer's disease, "which is a complex disease with many potential pathogenetic processes," they wrote.

Their study compared 65 cognitively normal older adults in the Berkeley Aging Cohort (mean age 76.1) with 10 Alzheimer's disease patients (mean age 74.8) and 11 college students as controls (mean age 24.5).

Along with cognitive tests and questionnaires on lifestyle habits through life, a PET scan was done to measure amyloid deposits through binding of the amyloid imaging agent carbon 11–labeled Pittsburgh Compound B ([11C]Pi.

Individuals' current mentally stimulating activities didn't predict cortical amyloid levels significantly (P=0.09). But the mental activities did correlate with physical activity; study participants in the highest cognitive activity tertile expended more energy than the middle and lowest tertiles.

As well, greater mental exercise in the past did correlate with reduced amyloid buildup, even after adjustment for age, sex, and education and when additionally controlling for current memory performance (both P<0.001).

And when all these factors, along with physical activity, were included in the same model, cognitive activity earlier in life from age 6 to 40 emerged as the sole independent predictor of amyloid levels (P=0.002).

Among cognitively normal older adults, the least mentally active tertile -- those who reported activities like reading books or newspapers, writing emails or letters, going to the library, or playing games less than a few times a month -- had amyloid levels similar to patients with Alzheimer's disease.

They also had more amyloid plaque than the middle and top third of the cohort for cognitive activity -- who participated in such activities more than a few times a month or week, respectively (P=0.04 and P=0.001).

The regions of the brain where these amyloid differences primarily showed up were in the lateral and medial prefrontal cortex, parietal cortex, and lateral temporal cortex.

Amyloid levels didn't correlate with memory performance in the cohort, which the researchers noted was likely because the participants all had intact cognition.

They cautioned that their measure of cognitive activity "is likely just one of a variety of interrelated lifestyle factors that are difficult to quantify," such as the broader tendency to get involved in intellectual, occupational, social, and recreational activities.

The study looked specifically at mental activities that would be available to all without regard to socioeconomic status, such as writing letters and email or going to the library.

But other, unmeasured factors could have accounted for both propensity to participate in such activities and amyloid buildup, Landau's group noted.

"Cognitive activity is just one component of a complex set of lifestyle practices linked to Alzheimer's disease risk that may be examined in future work," they concluded.

The study was supported by grants from the National Institutes of Health and the Alzheimer's Association.

The researchers reported having no conflicts of interest to disclose.

Primary source: Archives of Neurology

Source reference:

Landau SM, et al "Association of lifetime cognitive engagement and low beta-amyloid deposition" Arch Neurol 2012; DOI: 10.1001/archneurol.2011.2748.

http://www.medpagetoday.com/Geriatrics/AlzheimersDisease/ 30803?utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.© 2012 Everyday Health, Inc. All rights reserved.© 2012 Everyday Health, Inc. All rights reserved.

By Todd Neale, Senior Staff Writer, MedPage Today

Published: January 25, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor

University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

1 comment

Action Points

This study found that the incidence of mild cognitive impairment (MCI) was substantial and was higher in men.

Higher rates of MCI were observed in persons with lower education and who were not married.

Men are more likely than women to develop mild cognitive impairment (MCI), with and without memory problems, researchers found.

In a cohort of older individuals living in Olmsted County, Minn., about one in every five who was cognitively normal at baseline developed mild cognitive impairment within three or four years, according to Rosebud Roberts, MBChB, of the Mayo Clinic in Rochester, Minn., and colleagues.

Compared with women, men had higher rates of both amnestic MCI -- which involves a memory deficit -- and nonamnestic impairment, which does not, the researchers reported in the Jan. 31 issue of Neurology.

"Differences in incidence rates by clinical subtype and by sex suggest that risk factors for MCI should be investigated separately for amnestic MCI and nonamnestic MCI, and in men and women," they wrote.

In an accompanying editorial, Kenneth Rockwood, MD, of Dalhousie University in Halifax, Nova Scotia, said that "finding a difference between men and women in the incidence of MCI is not a small thing."

"That is because much of the interest in MCI stems from its widely confirmed status as a risk for progression to dementia," he wrote. "Given that women tend to have a higher risk of dementia than do men, and that even in Olmsted County, dementia incidence is similar between men and women, it is unclear how to square more men in the at-risk state not translating into more men with dementia."

To explore the sex differences, Roberts and colleagues turned to the Mayo Clinic Study of Aging, which used data from the Rochester Epidemiology Project to prospectively assess the development of MCI in individuals ages 70 to 89 who were cognitively normal at baseline.

Every 15 months, the participants underwent evaluations that included the Clinical Dementia Rating Scale, a neurologic evaluation, and neuropsychological testing. The analysis included 1,450 individuals who completed at least one follow-up evaluation.

Through a median of 3.4 years, 19.6% of the participants developed mild cognitive impairment and 0.8% developed dementia.

The rate of MCI was higher for men than for women (72.4 versus 57.3 per 1,000 person-years; HR 1.40, P=0.004) and for the amnestic versus nonamnestic subtype (37.7 versus 14.7 per 1,000 person-years).

For both amnestic and nonamnestic MCI, rates were higher for men and for individuals who completed fewer than 13 years of education.

In addition, individuals who were never married were more likely to develop nonamnestic MCI compared with their married counterparts (HR 2.92, 95% CI 1.10 to 7.75).

About one-third of participants who tested positive for MCI at one assessment subsequently tested as cognitively normal.

In his editorial, Rockwood proposed two explanations for the higher rate of MCI among men, even though women have a higher rate of dementia. First, he said, men generally cannot tolerate deficits as well as women.

"While women might have more things wrong at any age, they can live with them longer than men do; for men, deficits more often are fatal," he wrote.

"In consequence, the risk of death might be higher for men with MCI, thereby not allowing them to live long enough to develop dementia."

Another possible explanation, though, is a difference between the sexes in how cognition evolves over time.

"Why men have a higher incidence of MCI but a lower incidence of dementia may come about from how they express the later-life dynamics of cognition," Rockwood wrote.

"For some men, MCI represents incomplete disease expression; alternately, they resist dementia development more," he wrote. "In that way, MCI in men could lend some insight into what prevented dementia might look like.

Whether this explanation holds depends, as the authors propose, on further investigation of risk factors for MCI separately in men and in women."

Roberts and colleagues acknowledged some limitations of the study, including possible nonparticipation bias and the relatively homogeneous population of Olmsted County (mostly of European ancestry).

The study was supported by the National Institutes of Health (NIH), the Robert Wood Johnson Foundation, and the Robert H. and Clarice Smith and Abigail van Buren Alzheimer's Disease Research Program, and was made possible by the Rochester Epidemiology Project.

Roberts receives research support from the NIH and Abbott. Her co-authors reported relationships with numerous companies, organizations, and publications,

including the Robert Wood Johnson Foundation, Neurology, Eli Lilly and Company, Elan/Janssen AI, Baxter International, Forest Laboratories, GE Healthcare, the Alzheimer's Association, Purdue Pharma, Amgen, MD Net Guide, Journal of the American Medical Directors Association, and Novartis.

Rockwood reported links with the Canadian Institutes of Health Research, the Nova Scotia Health Research Foundation, the Alzheimer Society of Canada, the Dalhousie Medical Research Foundation,

NUMCIO Plc, Elan Corporation/Wyeth, Bristol-Myers Squibb, Neuroepidemiology, Journal of Gerontology-Medical Sciences, Alzheimer's Research & Therapy, BMC Medicine, the Chinese Journal of Geriatrics, DementiaGuide, the National Natural Science Foundation of China, Eisai, and Pfizer Canada.

Primary source: Neurology

Source reference:

Roberts R, et al "The incidence of MCI differs by subtype and is higher in men: the Mayo Clinic Study of Aging" Neurology 2012; 78: 342-351.

Additional source: Neurology

Source reference:

Rockwood K "Is the development of late-life cognitive impairment more dynamic than sexy?" Neurology 2012; 78: 300-301.

http://www.medpagetoday.com/Neurology/Dementia/30851? utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

tom hennessy

01/27/12

Another reason for the higher rates of dementia in men may be due to their lower iron levels in women.

A recent study shows women who have hysterectomies have the same buildup of iron in their brains as men.

Women who did not have hysterectomies had brain iron levels which do not rise.

The researchers believe this is due to the lack of iron lowering menses found in women who did not have hysterectomies.

Hysterectomies cause a woman to lose her iron lowering menses. Iron in the brain has been linked to neurodegeneration.

"Premenopausal hysterectomy is associated with increased brain ferritin iron."

"The results suggest that menstruation-associated blood loss is a source of gender differences in brain iron.

It is possible that brain iron can be influenced by peripheral iron levels and may thus be a modifiable risk factor for age-related degenerative diseases.".

© 2012 Everyday Health, Inc. All rights reserved.

By Nancy Walsh, Staff Writer, MedPage Today

Published: February 02, 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

1 comment(s)

action Points

Researchers found that a simple questionnaire can help differentiate individuals experiencing normal age-related memory loss from those likely to be developing dementia.

Note that those who often repeated questions, statements, and stories on the same day also were at very high risk for the development of amnestic mild cognitive impairment.[/b]

A simple questionnaire can help differentiate individuals experiencing normal age-related memory loss from those at risk for developing dementia, [b]most notably by their orientation to time and patterns of repetitive speech, researchers found.

On the 21-item Alzheimer's Questionnaire, patients having trouble remembering the day, month, year, and time of day were almost 18 times more likely to have amnestic mild cognitive impairment, a precursor to dementia (OR 17.97, 95% CI 2.63 to 122.77, P=0.003), according to Michael Malek-Ahmadi, MSPH, and colleagues from the Banner Sun Health Research Institute in Sun City, Ariz.

Those who often repeated questions, statements, and stories on the same day also were at very high risk (OR 13.12, 95% CI 3.02 to 57.66, P=0.001), the researchers reported online in BMC Geriatrics.

Distinguishing mild cognitive impairment, particularly when associated with memory loss rather than loss of other functional domains, can be clinically challenging and time consuming, and brief screening tools are sorely needed as the aging population expands, according to the researchers.

"Additionally, as new therapies for Alzheimer's disease transition from being symptomatic to disease-modifying, identifying individuals who are at risk or in the earliest stages of the disease will be crucial in determining and improving disease outcome," they wrote.

A pilot study by these researchers recently showed good sensitivity and specificity for the Alzheimer's Questionnaire, with responses about various aspects of memory and related cognitive concerns being provided by caregivers or other informants.

To see if certain components of the questionnaire were particularly accurate in pinpointing these types of impairments, Malek-Ahmadi's group compared responses among 47 patients who had been diagnosed with amnestic mild cognitive impairment and 51 controls who were participants in a program involving posthumous brain and body donation.

The diagnosis of cognitive impairment had been made clinically and with neuropsychological testing, with scores on verbal memory recall measures falling 1.5 standard deviations below normal ranges for age and educational attainment.

Cognitively normal participants all scored higher than 1.5 standard deviations on the neuropsychological tests.

The Alzheimer's Questionnaire assesses memory, language, orientation, visuospatial competence, and functional capacity by a series of yes/no questions such as, "Does the patient have trouble remembering to take medications?"

On almost all questions, significantly more "yes" responses were seen for the cognitive impairment group.

Regression analysis determined that, along with repetitive speech and disorientation as to time, two other questions were highly predictive.

One was whether the patient has trouble dealing with financial matters such as paying bills (OR 11.60, 95% CI 2.10 to 63.99, P=0.005), and the second was if the patient showed an impaired sense of direction (OR 5.84, 95% CI 1.09 to 32.30, P=0.04), according to the researchers.

Further analysis indicated that the coefficient of determination (R2) was 0.71, which meant that the four identified items could account for a substantial proportion of the variance between patients with amnestic mild cognitive impairment and those who were cognitively normal.

The researchers then calculated that the four items together had a sensitivity of 80.3% and a specificity of 81.8%, with the area under the curve being 0.94.

"These data indicate that problems with orientation to time, repeating statements and questions, difficulty managing finances, and trouble with visuospatial orientation may accompany memory deficits in amnestic mild cognitive impairment," the researchers stated.

Limitations of the study included the wide confidence intervals for the four items' odds ratios and the possibility of bias in the R2 approximation.

In addition, the study sample was ethnically homogeneous.

The study was funded by the Banner Sun Health Research Institute, the National Institute on Aging, the Arizona Department of Health Services, and the Arizona Alzheimer's Research Consortium.

The authors declared no competing interests.

Primary source: BMC Geriatrics

Source reference:

Malek-Ahmadi M, et al "Informant-reported cognitive symptoms that predict amnestic mild cognitive impairment" BMC Geriatrics 2012.

http://www.medpagetoday.com/Geriatrics/AlzheimersDisease/ 30995?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: February 02, 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

Action Points

This study found that even in cognitively healthy adults, higher levels of the protein beta-amyloid on PET imaging were associated with harmful effects on some aspects of cognition.

Among the 18 people with elevated beta-amyloid, 38% had the ApoE4 gene, compared with 15% of the remaining volunteers.

Even in cognitively healthy adults, too much of the protein linked to Alzheimer's disease appears to affect some aspects of cognition, researchers reported.

In a cross-sectional analysis of adults ages 30 through 89, the protein beta-amyloid increased with age, and higher levels were associated with deterioration of some cognitive functions, according to Kristen Rodrigue, PhD, of the University of Texas Dallas, and colleagues.

And about one in five of those over 60 had markedly elevated deposition of the protein based on PET imaging for beta-amyloid, with a corresponding decline in some functions, Rodrigue and colleagues reported online and in the Feb. 7 issue of Neurology.

The researchers noted that beta-amyloid deposition in the brain is a hallmark of Alzheimer's and plays a key role in most theories about the origins of the disease.

Beta-amyloid deposition begins before the clinical signs of Alzheimer's are apparent, they noted, but the effect of those early deposits on cognition are not well understood.

To help clarify the issue, Rodrigue and colleagues enrolled volunteers who were taking part in a larger study, the Dallas Lifespan Brain Study, and asked them to have a PET scan for beta-amyloid and also take several tests of cognitive function.

The researchers also tested for the apolipoprotein E4 gene, which is associated with an increased risk of Alzheimer's disease.

The 137 participants who volunteered were well-educated (with an average of more than 16 years of schooling) and cognitively healthy (with an average score on the Mini-Mental State Examination of 29.3).

The cognitive function tests – taken twice by each participant -- covered five domains: processing speed, working memory, episodic memory, crystallized abilities, and fluid reasoning.

The researchers found that beta-amyloid levels increased in a linear fashion with age, but not with sex or the combination of age and sex. The age association was significant at P<0.001.

The sample population included a subset – 18 people older than 60 -- whose beta-amyloid levels were higher than the upper limit of the 95% confidence interval for the age analysis.

But even with those people removed, the researchers still found a significant effect (at P<0.001) of age. However, the effect became non-significant (at P=0.08) when those 60 and under were excluded.

Analysis of cognitive function showed a dose-response effect – with higher levels linked to worse performance – on processing speed and fluid reasoning that was significant at P=0.04 and P<0.05, respectively.

There was no effect on working memory, episodic memory, or crystallized abilities, Rodrigue and colleagues found.

In the subgroup with elevated beta-amyloid, the researchers found a significant affect on three domains -- processing speed, working memory, and fluid reasoning.

But in the full sample – excluding the elevated subgroup – the only domain affected was fluid reasoning, they reported.

Interestingly, among the 18 people with elevated beta-amyloid, 38% had the ApoE4 gene, compared with 15% of the remaining volunteers.

The researchers cautioned that the study group might not reflect the population as a whole. In particular, many 70-to-89-year-olds in the general population might not meet the cognitive and physical criteria for the study, and might be more likely to have elevated beta-amyloid.

The study was supported by the National Institutes of Health and the Alzheimer's Association.

The ligand was provided to the study at no charge by Avid Radiopharmaceuticals, Inc.

Rodrigue reported no financial links with industry.

Primary source: Neurology

Source reference:

Rodrigue KM, et al. "Β-Amyloid burden in healthy aging: Regional distribution and cognitive consequences" Neurology 2012; 78: 387-395.

http://www.medpagetoday.com/Neurology/AlzheimersDisease/ 30978?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: February 07, 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

Action Points

The recent revision in criteria for mild cognitive impairment (MCI) has blurred the distinction between this condition and early Alzheimer's disease.

Point that even among those now diagnosed with a more symptomatic degree of mild Alzheimer's disease dementia, 92.7% could be reclassified as having MCI.

The recent revision in criteria for mild cognitive impairment (MCI) has blurred the distinction between this condition and early Alzheimer's disease, a researcher argued in the current issue of the Archives of Neurology.

For instance, 99.8% of patients now classified as having very mild Alzheimer's disease dementia, based on their home and community functioning, could be diagnosed by the new criteria as having MCI, according to John C. Morris, MD, of Washington University in St. Louis.

And even among those now diagnosed with a more symptomatic degree of mild Alzheimer's disease dementia, 92.7% could be reclassified as having MCI, Morris wrote.

"An early etiologic diagnosis is advocated for other devastating neurodegenerative diseases, such as amyotrophic lateral sclerosis, without resorting to terms such as 'minimal motor impairment' and thus allows patients and families to initiate planning to cope with the illness and enable therapeutic interventions early in the disease course.

An analogous approach should be implemented for [Alzheimer's disease]," he stated.

The definition of MCI has evolved over time from being an intermediate state between cognitive changes related to normal aging and dementia, to cognitive impairment that was limited to the memory domain.

It was updated to include cognitive impairments in multiple domains, and now includes some degree of functional impairment.

The 2011 revised criteria for MCI require the following:

Cognitive changes recognized by the patient or observers

Impairments in at least one domain of cognition

Independent functioning, which can include assistance by others

No dementia

The broadening of what is meant by independent functioning is an important change, according to Morris.

To explore the effects of these changes, he looked at functional status of more than 17,000 patients with data collected by the National Alzheimer's Coordinating Center, comparing patients whose Clinical Dementia Ratings were 0 (no impairment), 0.5 (very mild impairment), or 1 (mild impairment).

He found that allowing patients who could perform daily activities with assistance to be considered independent meant that only 41.8% of patients who had been diagnosed with Alzheimer's disease with dementia scores of 0.5 would be considered functionally impaired, and that 79.4% of those with Alzheimer's disease diagnoses and dementia scores of 1 would be considered impaired (P<0.001).

In addition, 68.3% of those diagnosed as having MCI, and whose functional scores were 0.5, were considered to be functioning normally in community affairs, as were 23.9% of those diagnosed with Alzheimer's disease who had scores of 0.5.

And when scores on the four-point Functional Activities Questionnaire as high as 2 (performing with assistance) and 3 (dependent) on function were permitted for more difficult activities such as paying checks and assembling tax records, fewer than three-quarters (73.8%) of those with dementia scores of 0.5 and 94.7% of those with dementia scores of 1 would be considered impaired (P<0.001).

In the past, most definitions of MCI were based on neuropsychological testing, with a cutoff for memory impairment being 1.5 standard deviations below the mean for age.

The finding that broadening the criteria for MCI has removed the distinction between mild Alzheimer's disease and MCI has significant implications, according to Morris.

"The elimination of the functional boundary between MCI and [Alzheimer's disease] dementia means that their distinction will be based solely on the individual judgment of clinicians, resulting in nonstandard and ultimately arbitrary diagnostic approaches to MCI," he wrote.

He pointed out that far fewer physicians are willing to provide the diagnosis of dementia than terminal cancer (30% to 60% versus 94%), possibly because of concerns about anxiety, distress, and even suicide.

He believes this does a disservice. "Patients and families have consistently indicated that receiving a diagnosis of dementia is very important to them to indicate that the cognitive symptoms have an identifiable cause and to plan for the future," Morris wrote.

In providing "a nonconformist's view of [Alzheimer's disease]," he summarized his definition as being a process of neurodegeneration that progresses from slight to severe and results in worsening function, with symptomatic Alzheimer's disease ranging from "prodromal" to clinical dementia.

He further noted that an international working group on Alzheimer's disease diagnosis has supported avoidance of the term MCI for patients with a recognizable clinical phenotype and positive biomarkers.

That diagnosis should be reserved for patients whose disease cannot be classified and may be of non-Alzheimer's etiology, he argued.

He concluded that Alzheimer's disease patient care and research needs to be advanced by accepting that the diagnosis 'MCI due to Alzheimer's disease' is more appropriately recognized as the earliest symptomatic stage of Alzheimer's disease.

The study was supported by the National Institute on Aging and the National Alzheimer's Coordinating Center.

The author reported no financial disclosures.

Primary source: Archives of Neurology

Source reference:

Morris J "Revised criteria for mild cognitive impairment may compromise the diagnosis of Alzheimer disease dementia" Arch Neurol 2012; DOI:10.1001/archneurol.2011.3152.+

http://www.medpagetoday.com/Neurology/AlzheimersDisease/ 31049?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

By Crystal Phend, Senior Staff Writer, MedPage Today

Published: February 14, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor

University of Pennsylvania School of Medicine.

Action Points

The probe [18 F] FDDNP is a molecular PET probe that binds to both amyloid and tau with binding patterns consistent with neuropathologic determinations of plaque and tangle accumulation.

This study suggests that binding patterns of this probe predict future cognitive decline. This type of PET scanning may have practical utility in identifying people at risk for future cognitive decline and thus may be able to track effectiveness of novel interventions designed to delay such decline.

A new imaging marker for the protein plaques and tangles in the brain associated with Alzheimer's disease may act as an early warning for progressive cognitive decline, researchers found.

An increase in cortical binding of the chemical marker on PET scans predicted declining memory over two years among middle-age and older adults (P=0.03 to P=0.01), Gary W. Small, MD, of the University of California Los Angeles, and colleagues reported in the February issue of the Archives of Neurology.

Among individuals with mild cognitive impairment, the marker known as 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile, or [18F]FDDNP for short, was most accurate at predicting conversion to Alzheimer's disease.

Accuracy for predicting a diagnostic change from mild cognitive impairment to Alzheimer's disease was 68% for medial temporal [18F]FDDNP binding, 84% for frontal binding, 81% for parietal binding, and 88% for frontal and parietal binding.

PET scans with the marker "may not only assist in predicting future cognitive decline and identifying individuals more likely to benefit from prevention treatments, but it may also track the effectiveness of such treatments to accelerate drug discovery efforts," the group suggested.

Two other imaging markers have also been developed in the past decade to enable researchers to "see" evidence of Alzheimer's disease in the brain.

Both carbon 11–Pittsburgh Compound B and fluorine 18-labeled florbetapir measure only amyloid plaques, though. The novel marker [18F]FDDNP is the first to measure amyloid together with neurofibrillary tau tangles.

Small's group followed a cohort of 43 middle-age or older individuals without dementia at baseline who had been previously studied with the new marker.

Follow-up PET imaging a median of two years later showed a mean 2.7% increase in global cortical binding of the marker among the 21 participants with mild cognitive impairment at baseline, indicating greater buildup of amyloid and tau (P<0.001).

The 22 individuals studied with normal cognition didn't have significant increases in [18F]FDDNP binding over time in any area of the brain or globally.

Altogether, changes in memory scores from baseline to follow-up correlated with changes in [18F]FDDNP binding globally and in the frontal cortex (both P=0.01) and in the anterior cingulate (P=0.03).

This association didn't differ between the mild cognitive impairment and normal cognitive aging groups.

Higher amyloid and tau levels measured by [18F]FDDNP at baseline predicted greater decline in cognitive performance in domains including executive function, language, attention and information processing speed, and visuospatial function.

Alzheimer's disease was diagnosed during follow-up in six of the 21 individuals (29%) who started with mild cognitive impairment. Their baseline [18F]FDDNP binding was higher than that of the nonconverters for:

Frontal (P=0.03)

Parietal (P=0.04)

Global (P=0.03)

At the optimal cutoffs, [18F]FDDNP frontal and parietal binding had a sensitivity of 100% and specificity of 67% for conversion from mild cognitive impairment to Alzheimer's disease.

Medial temporal region binding had 83% sensitivity and 60% specificity for the same outcome in the mild cognitive impairment group.

"Thus, the pattern of [18F]FDDNP binding in mild cognitive impairment, consistent with known disease progression observed at autopsy, may provide useful information for physicians when individual patients are evaluated," Small's group concluded.

In the normal aging group, two of the three participants who developed mild cognitive impairment had the highest baseline regional [18F]FDDNP binding levels seen in the group.

While the numbers were too small to be definitive, this finding suggested that the marker may be promising in picking out patients at high risk for progression to mild cognitive impairment, the investigators suggested.

Other limitations were the well-educated sample and binding level cutoffs optimized for the patient group studied that may not be representative of other or general populations.

This study was supported by grants from the

National Institutes of Health;

a contract from the Department of Energy;

the General Clinical Research Centers Program;

the Fran and Ray Stark Foundation Fund for Alzheimer's Disease Research;

the Ahmanson Foundation;

the Larry L. Hillblom Foundation;

the Lovelace Foundation;

the Sence Foundation;

the McMahan Foundation;

the Judith Olenick Elgart Fund for Research on Brain Aging; and the Elizabeth and Thomas Plott Endowment in Gerontology.

Small and two co-authors receive royalties on a patent held by UCLA on methods for labeling beta-amyloid plaques and neurofibrillary tangles using the approach outlined in the study.

Small also reported links with Dakim, Eisai, Forest, Lily, Medivation, Novartis, and Pfizer.

Primary source: Archives of Neurology

Source reference:

Small GW, et al "Prediction of cognitive decline by positron emission tomography of brain amyloid and tau" Arch Neurol 2012; 69: 215-222.

http://www.medpagetoday.com/Neurology/Dementia/31173? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.