Explain that a cohort study found that cognitively normal individuals who had frequent awakenings during the night and/or spent more time awake in bed were more likely to have biomarkers of amyloid plaque accumulation than those with better sleep habits.
Note that the associations found in this study could not be deemed to be causative.
NEW ORLEANS -- Disturbed sleep is associated with preclinical signs of Alzheimer's disease, researchers found.
In a small cohort study in cognitively normal people, frequent awakenings and a habit of lying awake were linked to higher levels of markers of the brain plaques that are a hallmark of Alzheimer's disease, according to Yo-El Ju, MD, of Washington University School of Medicine in St. Louis, and colleagues.
The full study is slated for presentation at the annual meeting of the American Academy of Neurology in New Orleans in April, but some of the data were released early.
Ju and colleagues cautioned that it's not clear if there's a cause-and-effect relationship or, if there is, which way it runs.
"Further research is needed to determine why this is happening and whether sleep changes may predict cognitive decline," Ju said in a statement.
Alzheimer's disease begins long before there any symptoms, the researchers noted, but signs of the beta-amyloid plaques that build up in the brains of Alzheimer's patients can be detected in some cognitively normal people.
There is also evidence from animal studies that sleep disruption causes a build-up in those beta-amyloid markers, they said.
To investigate the link in humans, they turned to the Adult Children Study, a cohort of which half the members have a family history of Alzheimer's. For this analysis, 100 participants, ages 45 to 80, were given standardized assessments and shown to be cognitively normal.
Participants wore an actigraph for 14 days to measure sleep in an objective fashion; sleep diaries and questionnaires were used to gather subjective measures.
The researchers also measured levels of amyloid beta-42 in cerebrospinal fluid and looked for increased retention of Pittsburgh compound B during amyloid imaging by positron emission tomography -- 25% of participants had preclinical signs of Alzheimer's.
On average, participants spent about eight hours in bed, as measured by both actigraph results and subjective reports, but average sleep time on the actigraph was 6.5 hours (significantly shorter at P<0.05) because of brief awakenings during the night.
Those who woke up more than five times an hour were more likely to have abnormal biomarkers indicating amyloid pathology.
And more of those with low sleep efficiency – defined as sleep time divided by time in bed of less than 85% -- had such signs compared with those with high sleep efficiency.
Such research is critical for the study of Alzheimer's disease, commented Judy Willis, MD, an educator and neurologist in Santa Barbara, Calif., and a member of the neurology academy.
"Interventions, once the disease has progressed to symptomatic diagnosis, are limited," Willis told MedPage Today in an email, "and there is no cure or even strong support for any treatment that can reverse the development of amyloid plaques in humans once they form."
But it may be possible to intervene at an earlier stage, especially if it turns out the disordered sleep actually causes the amyloid pathology, Willis said.
"Studies finding correlation are inadequate to confirm causality," she noted, adding it's equally possible that disrupted sleep has a role in the development of the disease or that it's an early sign of a disease already developing.
But studies in mice have found that interfering with their sleep led to increases in amyloid pathology. Although mice do not get Alzheimer's, that finding suggests that improved sleep might be a pathway to better mental health.
Even if disrupted sleep is just a predictor, it could be useful in pointing people toward future clinical trials, Willis said.
Ju said longer studies following sleep over years will be needed to tease out the cause-and-effect relationship.
"Our study lays the groundwork for investigating whether manipulating sleep is a possible strategy in the prevention or slowing of Alzheimer's disease," she said.
The study was supported by the Ellison Foundation and the NIH.
The authors did not report any financial conflicts.
Willis did not report any conflicts.
Primary source: American Academy of Neurology
Ju Y, et al "Sleep disruption and risk of preclinical Alzheimer disease" AAN 2012; Abstract.
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
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Explain that walking speed and hand-grip strength during middle age correlated with cognitive function and stroke risk in older adults, suggesting simple tests might aid diagnosis of the two conditions.
Note that grip strength did not influence stroke risk in the overall cohort, but a higher baseline grip strength was associated with a 42% reduction in stroke risk among individuals 65 and older.
NEW ORLEANS --
Walking speed and hand-grip strength during middle age correlated with cognitive function and stroke risk in older adults, suggesting simple tests might aid diagnosis of the two conditions, according to data from a large cohort study.
During 11 years of follow-up, slower walking speed at baseline was associated with a 50% rise in the hazard for dementia.
Brain volume and performance on a variety of tests of cognitive function also were significantly lower in slower walkers.
Grip strength did not influence stroke risk in the overall cohort, but a higher baseline grip strength was associated with a 42% reduction in stroke risk among individuals 65 and older, as will be reported here in April at the American Academy of Neurology meeting.
"These are basic office tests [that] can provide insight into the risk of dementia and stroke and can be easily performed by a neurologist or general practitioner," Erica C. Camargo, MD, PhD, of Boston Medical Center, said in a statement.
"While frailty and lower physical performance in elderly people have been associated with an increased risk of dementia, we weren't sure until now how it impacted people of middle age," she added.
The findings came from an analysis of data from the Framingham Offspring Cohort, children of the original participants in the long-running study of the natural history of cardiovascular disease.
Camargo and colleagues analyzed data for 2,410 participants in the offspring cohort study, mean age 62, all of whom were stroke- and dementia-free at baseline. The initial workup included assessments of walking speed, grip strength, and cognitive function, as well as MRI scans of the brain.
The investigators statistically related age-standardized grip strength and walking speed with baseline cerebral volume estimated by MRI, with age- and education-standardized cognitive function and with stroke and dementia incidence.
During follow-up, 34 participants developed dementia, and 79 had strokes or transient ischemic attacks (TIAs).
Slower walking speed had a significant correlation with:
Increased stroke risk (HR 1.50, P=0.020)
Lower total cerebral volume (P=0.007)
Poorer performance on tests of various aspects of memory (visual reproduction, P=0.009; paired associate learning, P<0.001; executive function, P=0.004; visuo-perceptual function, P=0.002; and language, P=0.006)
Greater hand-grip strength was associated with a significant reduction in stroke risk (HR 0.58, P=0.013) in the subgroup of 784 participants who were older than 65 at baseline.
Increasing grip strength also was associated with:
Total cerebral brain volume (P<0.001)
Visual reproduction (P<0.001)
Executive function (P=0.009)
Visuo-perceptional function (P<0.001)
Better abstraction (P=0.009)
Acknowledging the need for more studies, Camargo and colleagues concluded that "walking speed and hand-grip strength might serve as clinical markers of the need for a more detailed assessment of brain function."
The study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute on Aging.
Camargo and co-investigators had no relevant disclosures.
From the American Heart Association:
Science News from International Stroke Conference 2012
Guidelines for the Primary Prevention of Stroke
Primary source: American Academy of Neurology
Camargo EC, et al "Walking speed, handgrip strength and risk of dementia and stroke: The Framingham Offspring Study" AAN 2012; Abstract.
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: February 16, 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
This meta-analysis found that mentally stimulating group activities boost cognition in mild to moderate dementia.
Quality of life, communication, and social interaction also improved with these programs, although mood, behavior, and disability did not.
Mentally stimulating group activities -- including such things as discussion groups, games, and gardening -- boost cognition in mild to moderate dementia, a Cochrane review determined.
Cognitive function showed consistent improvements for individuals in cognitive stimulation programs, with a standardized mean difference (the difference in means divided by a standard deviation) of 0.41 compared with controls (P<0.00001), Bob Woods, PhD, of Bangor University in Bangor, Wales, and colleagues found.
Quality of life, communication, and social interaction also improved with these programs, although mood, behavior, and disability did not, the group reported in the Cochrane Library.
"People with dementia and their caregivers are often advised that 'mental exercise' may be helpful in slowing down the decline in memory and thinking," they wrote, and that appears to be the case.
These programs stem from a practice that started in the 1950s known as "reality orientation" that drilled dementia patients on what day it was, where they were, and other similar items, but has fallen out of favor as insensitive and confrontational, Woods' group pointed out.
Modern cognitive stimulation efforts focus more on making the mental exercise enjoyable.
"This involves a wide range of activities that aim to stimulate thinking and memory generally, including discussion of past and present events and topics of interest, word games, puzzles, music and practical activities such as baking or indoor gardening," the reviewers explained.
The review included 15 trials with a total of 718 patients randomized to either cognitive stimulation or control groups.
The participants typically fell in the mild to moderate range for cognitive impairment, though some trials included more severe cases or Alzheimer's disease patients.
The cognitive interventions typically used sessions of 30 to 90 minutes (median 45) undertaken one to five times a week (median three).
The benefit on cognitive function from cognitive stimulation was seen both at the end of treatment and through follow-up one to three months afterward.
The number needed to treat was six to 14 to significantly slow cognitive decline, boosting the Alzheimer's Disease Assessment Scale - Cognitive score by at least four points, which the researchers pointed out was broadly comparable with those seen in trials with the acetylcholinesterase inhibitors.
Patients' self-reported quality of life and well-being improved as well -- by a standardized mean difference of 0.38 compared with controls -- in the four trials that evaluated it as a secondary outcome (P=0.006).
Pooling results of the four studies that reported on how the programs impacted communication and social interaction as rated by staff, the standardized mean difference between groups was 0.44 (P=0.002).
Mood didn't change, though, whether self-reported or staff-rated.
Nor was there any significant advantage to cognitive simulation for activities of daily living and basic self-care, general behavioral function, or problem behavior, such as irritability and being demanding and difficult.
The programs didn't appear to make things easier on family caregivers.
But "importantly, there was no indication of increased strain on family caregivers in the one study where they were trained to deliver the intervention," Woods' group pointed out.
They cautioned that the trials included in the review had small sample sizes and low quality in some cases.
"Other outcomes need more exploration, but improvements in self-reported quality of life and well-being were promising," their review concluded.
The reviewers reported having produced various training materials in dementia care, including cognitive stimulation therapy manuals, with royalties going to the Dementia Services Development Center Wales.
One co-author reported receiving fees for providing training in cognitive stimulation approaches.
Primary source: The Cochrane Library
Woods B, et al "Cognitive stimulation to improve cognitive functioning in people with dementia" Cochrane Library 2012; DOI: 10.1002/14651858.CD005562.pub2.
The Department of Health and Human Services (HHS) has released a detailed roadmap for fulfilling President Barack Obama's promise to find effective treatments for Alzheimer's disease by 2025 and expanding support for patients and their caregivers.
The 63-point draft plan, developed by the agency's Advisory Council on Alzheimer's Research, Care, and Services, covers research on new treatments and preventive measures, quality and efficiency of care for Alzheimer's patients, public awareness, and data collection.
"This is the first National Plan," according to the draft's preamble. It is the outgrowth of legislation enacted in January 2011 called the National Alzheimer's Project Act, directing HHS to develop a coherent and detailed strategy for coping with a surge in Alzheimer's disease cases expected to result from current demographic trends.
The Alzheimer's Association estimates that there were already 5.4 million Alzheimer's disease patients in the U.S. in 2011, with the count expected to approach 8 million by 2030.
Under the draft plan released late Wednesday, the National Institute on Aging will convene a scientific summit this May to advise on research priorities and develop goals and milestones for Alzheimer's disease treatment development.
Federally-sponsored research on the disease is to be expanded, with new studies of its basic pathology as well as more money set aside for clinical trials.
Imaging and biomarker studies aimed at identifying patients early in the disease process will also receive additional support.
Also to be addressed in the project are other dementias, with a scientific workshop to be held next year.
A major part of the plan is to step up coordination between the federal health and research agencies, the private sector, and public and private entities in other countries.
In the care-quality and care-quantity arenas, the project will focus on increasing the number of healthcare professionals trained in Alzheimer's disease care, including but not limited to physicians. Educating patients and their families as well as providers is a significant focus.
The project also intends to use the Affordable Care Act's establishment of an innovation research unit, within the Centers for Medicare and Medicaid Services, to explore new models of Alzheimer's disease care.
Two relevant projects are already underway in this unit:
A study of medical home model
A demonstration project called Independence at Home
Project funds will be used to support subgroup analyses in these studies focusing on Alzheimer patients and caregivers.
Services and education for caregivers is part of the project as well.
The plan notes that "maintaining their own health and well-being" is critical to prevent burnout.
It includes 16 separate strategies for aiding caregivers -- not only family members, but other non-health professionals, such as attorneys, who may serve Alzheimer patients.
HHS also wants to beef up data collection so that progress in the plan's various components can be tracked.
Missing from the draft, however, is a long-range budget.
Earlier this month, Obama announced that $50 million would be added to the $450 million already allocated this year by the National Institutes of Health for Alzheimer's disease research, with $80 million in new funding for fiscal 2013.
Obama's fiscal year 2013 budget also included $26 million to support other elements of the project. Beyond 2013, however, HHS has not tallied likely costs for the multitude of initiatives it is proposing.
The Alzheimer's Association called the HHS draft plan "another positive step," but pointed to the lack of budget specifics.
"The Alzheimer's Association urges the administration to specify the level of resource commitment that will be needed to meet the goal to prevent and effectively treat the disease by 2025," according to a statement from the group.
"The Alzheimer's Association values the initial plan's attention to evaluation and assessment, but looks forward to moving quickly from assessment of current efforts and programs to action for the growing number of families facing the disease."
Another advocacy group, the Alzheimer's Foundation of America, was more enthusiastic about the plan.
"AFA applauds HHS for making tremendous efforts and headway in capturing the unprecedented opportunity afforded by the National Alzheimer's Project Act to address the multiple challenges of Alzheimer's disease," it said in a statement.
"We are pleased that the draft plan includes solid education and care-related strategies in addition to aggressive research initiatives.
Meeting daily care-related challenges and costs are critical aspects of coping with Alzheimer's disease now as we all await realization of the plan's goal 'to develop effective prevention and treatment modalities by 2025."
HHS said it would accept public comments on the draft plan through March 30.
An Advisory Council on Alzheimer's Research, Care, and Services, established as part of the National Alzheimer's Project Act, will review the comments before issuing a final version of the plan.
By Michael Smith, North American Correspondent, MedPage Today
Published: February 23, 2012
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.
Explain that in elderly residents receiving antipsychotic drugs in nursing homes, there is variation in the risk of death according to the type of drug used.
Note that haloperidol/[b]HALDOL had the highest mortality risk.
Quetiapine (Seroquel) appeared to be the safest among six medications studied.[/b]
The risk of death associated with the use of antipsychotic drugs in older dementia patients varies depending on the drug, researchers found.
In fact, the risk of death associated with haloperidol (Haldol) is so high that its use "cannot be justified because of the excess harm," according to Krista Huybrechts, PhD, of Brigham and Women's Hospital in Boston, and colleagues.
Quetiapine (Seroquel) appeared to be the safest among six medications studied in a large cohort of people 65 and older in U.S. nursing homes, Huybrechts and colleagues reported online in BMJ.
While antipsychotics are not approved for people with dementia, they are widely used to help control aggression, the researchers noted. The FDA placed a black box warning on the so-called atypical antipsychotics in 2005 and followed suit three years later with a similar warning on the others.
But the comparative safety of individual drugs remains unclear, although the issue is important because off-label use seems likely to climb, Huybrechts and colleagues noted.
To help clarify the issue, they studied all-cause mortality (except for cancer deaths) among the 75,445 nursing home residents who were 65 or older, eligible for Medicaid, and who were new users of antipsychotic drugs from 2001 through 2005.
Deaths were included if they occurred within the first six months after starting the new drug.
Database analysis showed that risperidone (Risperdal) was the most commonly used, so it served as the comparator for the other five drugs studied – haloperidol, quetiapine, aripiprazole (Abilify), olanzapine (Zyprexa), and ziprasidone (Geodon, Zeldox).
Other antipsychotics, such as chlorpromazine (Thorazine), were excluded because they collectively formed less than 1% of prescriptions, the researchers noted.
Compared with risperidone, they found:
Risk of death associated with haloperidol was doubled (HR 2.07, 95% CI, 1.89 to 2.26)
Quetiapine was associated with a decreased risk (HR 0.81, 95% CI, 0.75 to 0.88)
The other three drugs were associated with risks that were not significantly different from risperidone
The mortality rate per 100 person-years during the first 180 days after the start of treatment was 37.1 overall, ranging from 26.2 for aripiprazole to 109.1 for haloperidol. The rate for risperidone was 36.2 deaths per 100 person-years.
The researchers found that the risks were highest early in treatment, were still present regardless of dose, and were seen for all of the causes of death that were studied, such as circulatory or respiratory.
They cautioned that unmeasured confounders might have affected the results, although sensitivity analyses suggested it was unlikely.
They also noted that – although the study population consisted of people in a nursing home – the findings should apply to other groups, as long as socioeconomic status doesn't modify the effect of the drugs themselves.
Although the risks of antipsychotics have been known for years, the drugs are still used in elderly demented patients, largely because physicians may not see good alternative choices, according to Jenny McCleery, MRCPsych, of the Oxford Health NHS Foundation Trust in Oxford, England, and Robin Fox, MBBS, of the Health Centre in Bicester, England.
"Few clinical problems place doctors in as tangled a web of clinical evidence, social policy, and ethical concerns as how to manage behavioral problems in patients with dementia," they argued in an accompanying editorial.
Guidelines urge nondrug interventions, but doctors may be under pressure to prescribe drugs, and they may also think that the resources needed to avoid drugs are lacking, they said.
Huybrechts and colleagues have added to the evidence of differential risk, they noted, but "use of any antipsychotic in dementia is undesirable" given both their risks and limited efficacy.
Instead, McCleery and Fox argued, future research should focus on ways to implement nondrug-based interventions "as simply and efficiently as possible."
This study was supported the Agency for Healthcare Research and Quality, the FDA, and the National Institute of Mental Health.
The journal said the authors had no financial conflicts.
The journal said editorial author McCleery reported a financial link with Lilly.
Primary source: BMJ
Huybrechts KF, et al "Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study" BMJ 2012; 344: e977.
Additional source: BMJ
McCleery J, Fox R "Antipsychotic prescribing in nursing homes" BMJ 2012; 344: e1093.
Adding Second Drug, but adding memantine (Namenda) No Help in Alzheimer's
By Todd Neale, Senior Staff Writer, MedPage Today
Published: March 08, 2012
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.
In moderate-to-severe Alzheimer's disease, continuing treatment with donepezil, a cholinesterase inhibitor, had some benefits, but adding memantine (Namenda) did not.
Note that memantine yielded similar benefits compared with placebo but the combination of memantine and donepezil was no better than donepezil alone.
For patients with moderate-to-severe Alzheimer's disease, continuing treatment with donepezil -- a cholinesterase inhibitor -- has some benefits, a randomized trial showed.
Compared with stopping donepezil, continuing treatment for a year resulted in significant improvements in cognition and performance of the activities of daily living (P<0.001 for both), according to Robert Howard, MD, of King's College London, and colleagues.
Memantine yielded similar benefits compared with placebo but the combination of memantine and donepezil was no better than donepezil alone, the researchers reported in the March 8 issue of the New England Journal of Medicine.
In an accompanying editorial, Lon Schneider, MD, of the University of Southern California in Los Angeles, said the results with donepezil in the trial may not apply to other cholinesterase inhibitors because of differences in pharmacokinetics and mechanisms of action.
"Nor should the ... results be interpreted as evidence of the efficacy of indefinite treatment with donepezil," he noted.
"More research is needed to assess the long-term benefits, the potential for harm and physiological tolerance, and the safe discontinuation of cholinesterase inhibitors as Alzheimer's disease progresses."
Cholinesterase inhibitors -- including donepezil -- have shown some benefits in patients with mild-to-moderate Alzheimer's disease, although no treatments have been able to halt disease progression.
When the disease worsens, clinicians must make a decision about continuing treatment, which is complicated by a greater risk of adverse outcomes, the need for permanent pacemakers, and hip fractures when treatment is not stopped.
In the DOMINO study, Howard and colleagues evaluated the effects of continuing donepezil with or without the addition of memantine in 295 patients with moderate-to-severe Alzheimer's disease who had been treated with donepezil for at least three months.
The patients were living in the community and either had a live-in caregiver or someone who visited them at least once a day.
The researchers assigned the patients to one of four groups for one year:
Continue donepezil at a dose of 10 mg daily and start placebo memantine
Continue donepezil and start memantine at a dose increasing to 20 mg daily
Gradually discontinue donepezil and receive placebo donepezil and placebo memantine
Gradually discontinue donepezil, receive placebo donepezil, and start memantine
The coprimary outcomes of the trial were changes on the Standardized Mini-Mental State Examination (SMMSE) and on the caregiver-rated Bristol Activities of Daily Living Scale (BADLS).
The minimum clinically important differences were defined as 1.4 points and 3.5 points, respectively.
Compared with patients who stopped donepezil, those who continued treatment scored 1.9 points better on the SMMSE and 3 points better on the BADLS. Only the difference on the SMMSE exceeded the minimum clinically important threshold.
In his editorial, Schneider said the 1.9-point difference "is potentially important because many of the patients were severely impaired, on the cusp for needing nursing home care, and slightly worse cognitive function could affect their ability to remain at home."
Compared with patients who received placebo memantine, those who started the drug scored 1.2 points better on the SMMSE and 1.5 points better on the BADLS (P≤0.02 for both), although both figures fell short of being clinically important.
Combining donepezil and memantine was not superior to donepezil alone.
"Although memantine appears to be helpful for the treatment of moderate-to-severe Alzheimer's disease when used alone or when replacing donepezil, the results of the DOMINO trial do not support the typical use in the U.S., and an FDA-approved use, as add-on therapy to established donepezil treatment," according to Schneider, who noted that the finding conflicts with a previous, shorter trial.
Howard and colleagues pointed out that neither donepezil nor memantine halted the overall loss of cognitive function and functional abilities.
Compared with the changes in patients who received placebo for both drugs, the gains seen in the SMMSE score with donepezil and memantine represented just 32% and 20%, respectively, of the total decline during the study. The figures for the BADLS scores were 23% and 11%, respectively.
There were 188 serious adverse events, but only six were considered possibly related to the study drugs. Rates did not differ between groups.
The study was supported by the U.K. Medical Research Council and Alzheimer's Society.
Pfizer and Lundbeck donated drugs and placebo but had no involvement in the design or conduct of the study or the analysis or reporting of the data.
Howard reported that he had no conflicts of interest.
His co-authors reported relationships with Abbott, Novartis, i3 Innovus, Medivation, Novartis NEURONET, Janssen, Eisai, Pfizer, Arnold Press, John Wiley, Lundbeck, Merz Pharmaceuticals, Lilly, GE Healthcare, Bayer Healthcare, Servier, Shire, Johnson & Johnson, Bristol-Myers Squibb, Acadia, UCB Pharma, GlaxoSmithKline, Solvay, and TauRx Therapeutics.
Schneider reported relationships with Forest Laboratories, Pfizer/Wyeth, Novartis, Johnson & Johnson, Merz, Lundbeck, and the Cochrane Collaboration.
Primary source: New England Journal of Medicine
Howard R, et al "Donepezil and memantine for moderate-to-severe Alzheimer's disease" N Engl J Med 2012; 366: 893-903.
Additional source: New England Journal of Medicine
Schneider L "Discontinuing donepezil or starting memantine for Alzheimer's disease" N Engl J Med 2012; 366: 957-959.
This year, the bill for Alzheimer's disease and other dementias in the U.S. will reach an estimated $200 billion, according to a report from the Alzheimer's Association.
That total includes the direct costs of caring for patients, including healthcare, long-term care, and hospice.
Roughly half will be paid by Medicare ($104.5 billion), with the rest covered by Medicaid ($33.5 billion), out-of-pocket spending ($33.8 billion), and other sources ($26.2 billion), which includes private insurance, health maintenance organizations, other managed care organizations, and uncompensated care.
In the absence of advances in prevention and treatment, the cost of caring for patients with Alzheimer's disease and other dementias could reach $1.1 trillion (in 2012 dollars) by 2050, a trend driven by an aging population, according to the report.
"Alzheimer's can't wait," said Robert Egge, the association's vice president of public policy, in a statement.
"The soaring costs, the escalating number of people living with the disease, and the challenges encountered by families and those who live alone with Alzheimer's all demand a meaningful, aggressive, and ambitious effort to solve this problem. Inattention is no longer an option."
Currently, about 5.4 million people in the U.S. have Alzheimer's disease, a figure that is estimated to increase to 11 to 16 million by the middle of the century.
Many of these individuals have other serious medical conditions, and the presence of dementia makes treating those conditions more difficult and expensive.
Highlighting the seriousness of the problem, the number of deaths related to Alzheimer's disease increased by a relative 66% from 2000 to 2008, during which time the number of deaths from other serious diseases -- including breast cancer, prostate cancer, heart disease, stroke, and HIV -- fell.
Alzheimer's disease remains the 6th leading cause of death in the U.S.
The report provided a special section on patients with Alzheimer's disease who live alone, estimating that at least one out of every seven patients in the community does not have a live-in companion. And up to half of those who live alone don't have a caregiver to provide assistance.
"Cognitive impairment and dementia do not rule out living alone, but all people with progressive dementia will be unable to safely live alone in the later stages of the disease," according to the authors.
Patients who live alone tend to be less impaired than those who don't, but they still remain at risk for having difficulty taking care of themselves, malnutrition, untreated medical conditions, social isolation, and accidents resulting in injury or death.
Aside from direct effects on patients, Alzheimer's disease also touches the lives of the estimated 15.2 million caregivers who assisted those with the disease. Last year, these caregivers -- mostly family members -- provided 17.4 billion hours of unpaid care, assisting in various activities of daily living.
Those responsibilities came with large amounts of emotional stress and depression, as well as sacrifices at work.
Scientists pinpoint how vitamin D may help clear amyloid plaques found in Alzheimer's
By Rachel ChampeauMarch 06, 2012
A team of academic researchers has identified the intracellular mechanisms regulated by vitamin D3 that may help the body clear the brain of amyloid beta, the main component of plaques associated with Alzheimer's disease.
Published in the March 6 issue of the Journal of Alzheimer's Disease, the early findings show that vitamin D3 may activate key genes and cellular signaling networks to help stimulate the immune system to clear the amyloid-beta protein.
Previous laboratory work by the team demonstrated that specific types of immune cells in Alzheimer's patients may respond to therapy with vitamin D3 and curcumin, a chemical found in turmeric spice, by stimulating the innate immune system to clear amyloid beta.
But the researchers didn't know how it worked.
"This new study helped clarify the key mechanisms involved, which will help us better understand the usefulness of vitamin D3 and curcumin as possible therapies for Alzheimer's disease," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System.
For the study, scientists drew blood samples from Alzheimer's patients and healthy controls and then isolated critical immune cells from the blood called macrophages, which are responsible for gobbling up amyloid beta and other waste products in the brain and body.
The team incubated the immune cells overnight with amyloid beta.
An active form of vitamin D3 called 1a,25–dihydroxyvitamin D3, which is made in the body by enzymatic conversion in the liver and kidneys, was added to some of the cells to gauge the effect it had on amyloid beta absorption.
Previous work by the team, based on the function of Alzheimer's patients' macrophages, showed that there are at least two types of patients and macrophages:
[b]Type I macrophages are improved by addition of 1a,25–dihydroxyvitamin D3 and curcuminoids (a synthetic form of curcumin),
while Type II macrophages are improved only by adding 1a,25–dihydroxyvitamin D3. [/b]
Researchers found that in both Type I and Type II macrophages, the added 1a,25–dihydroxyvitamin D3 played a key role in opening a specific chloride channel called "chloride channel 3 (CLC3)," which is important in supporting the uptake of amyloid beta through the process known as phagocytosis.
Curcuminoids activated this chloride channel only in Type I macrophages.
The scientists also found that 1a,25–dihydroxyvitamin D3 strongly helped trigger the genetic transcription of the chloride channel and the receptor for 1a,25–dihydroxyvitamin D3 in Type II macrophages.
Transcription is the first step leading to gene expression.
The mechanisms behind the effects of 1a,25–dihydroxyvitamin D3 on phagocytosis were complex and dependent on calcium and signaling by the "MAPK" pathway, which helps communicate a signal from the vitamin D3 receptor located on the surface of a cell to the DNA in the cell's nucleus.
The pivotal effect of 1a,25–dihydroxyvitamin D3 was shown in a collaboration between Dr. Patrick R. Griffin from the Scripps Research Institute and Dr. Mathew T. Mizwicki from UC Riverside.
They utilized a technique based on mass spectrometry, which showed that 1a,25–dihydroxyvitamin D3 stabilized many more critical sites on the vitamin D receptor than did the curcuminoids.
"Our findings demonstrate that active forms of vitamin D3 may be an important regulator of immune activities of macrophages in helping to clear amyloid plaques by directly regulating the expression of genes, as well as the structural physical workings of the cells," said study author Mizwicki, who was an assistant research biochemist in the department of biochemistry at UC Riverside when the study was conducted.
According to the team, one of the next stages of research would be a clinical trial with vitamin D3 to assess the impact on Alzheimer's disease patients.
Previous studies by other teams have shown that a low serum level of 25–hydroxyvitamin D3 may be associated with cognitive decline.
It is too early to recommend a definitive dosage of vitamin D3 to help with Alzheimer's disease and brain health, the researchers said.
The study was funded in part by the Alzheimer's Association and by the National Institutes of Health.
Other study authors included Danusa Menegaz and Antonio Barrientos-Duran of the department of biochemistry at UC Riverside;
Jun Zhang and Patrick R. Griffin of the department of molecular therapeutics at the Scripps Research Institute in Jupiter, Fla.;
Stephen Tse of the department of medicine at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System; and
John R. Cashman of the Human BioMolecular Research Institute in San Diego, Calif.
By Michael Smith, North American Correspondent, MedPage Today
Published: March 17, 2012
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania.
Note that this study found an association of retinopathy and cognitive impairment, along with larger ischemic lesion volumes.
The study raises the possibility that a retinal evaluation may be useful as a screening and/or predictive tool for cognitive decline associated with microvascular disease.
The eye of the patient may hold clues to the risk of dementia, researchers found.
In a prospective longitudinal study of older women, retinopathy was associated with poorer performance on a standard measure of cognition, according to Mary Haan, DrPH, of the University of California San Francisco, and colleagues.
Retinopathy was also associated with an increased volume of small ischemic areas in the brain, they reported online in Neurology.
"Problems with the tiny blood vessels in the eye may be a sign that there are also problems with the blood vessels in the brain that can lead to cognitive problems," Haan said in a statement.
"This could be very useful if a simple eye screening could give us an early indication that people might be at risk of problems with their brain health and functioning," she added.
Indeed, the study adds support to the notion that microvascular damage plays a role in the pathogenesis of some forms of dementia, according to Rebecca Gottesman, MD, PhD, of Johns Hopkins University School of Medicine, and Ge Li, MD, PhD, of the University of Washington in Seattle.
The data "support a vascular etiology or at least a vascular contribution to cognitive impairment," they argued in an accompanying editorial.
But more research into the effects of various degrees of retinopathy is still needed, they argued, something that the study was unable to tease out.
The findings come from analysis of 511 women, 65 and older, enrolled in the Women's Health Initiative, who also had cognitive assessments, structural brain scans, and standardized retinopathy evaluations as part of three ancillary substudies.
Participants had yearly cognitive testing, using the modified Mini-Mental State Examination.
An average of 3.8 years after enrollment, they were tested for retinopathy and an average of eight years after enrollment they had magnetic resonance imaging of the brain.
Haan and colleagues found:
39 women (7.6%) had retinopathy – eight classified as mild, 15 with only microaneurysms, two moderate, and one severe; 13 were classified as having fibrous proliferation.
Retinopathy was associated with significantly poorer scores on the cognitive tests, at P=0.019, over the 10-year follow-up period.
The difference was seen and remained significant in both visual and nonvisual aspects of the test.
Retinopathy was also associated with an average of 47% greater ischemic volume in the total brain (significant at P=0.04) and the 68% greater ischemic volume in the parietal lobe (significant at P=0.01).
Adjusting for high blood pressure and diabetes did not markedly affect the outcomes.
The retinopathy detected in the study was mild, they added, to the point that the women with retinopathy had similar scores on a test of visual acuity as the women without the disease.
The researchers cautioned that the study had "a relatively small sample size and a modest number of retinopathy cases," which limited their ability to pin down the aspects of the eye disease that were more important in influencing cognitive function or ischemic lesions.
Also, they noted, they were unable to evaluate specific cognitive domains.
The researchers had support from the National Heart, Lung and Blood Institute, the National Institute on Aging, and Wyeth Pharmaceuticals. The journal said Haan did not report any conflicts.
The journal said the editorial authors did not report any financial links with industry.
Primary source: Neurology
Haan M, et al "Cognitive function and retinal and ischemic brain changes: The Women's Health Initiative" Neurology 2012; 78: 942–949.
Additional source: Neurology
Gottesman RF, Li G "Is brain health in the eye of the beholder?" Neurology 2012; 78: 936–937.
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